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J Scholes

Publications and source records attributed to J Scholes.

At least 19 recordsLinked to original sources
PubMed2001

Differential expression of the cell-adhesion molecule Nr-CAM in hyperplastic and neoplastic human pancreatic tissue.

Nr-CAM is a member of the immunoglobulin superfamily of neural cell-adhesion molecules initially thought to be expressed mainly in the brain. Here we show the presence of Nr-CAM protein in normal human pancreas and characterize its expression in hyperplastic and neoplastic human pancreatic tissue. Nr-CAM is expressed on the cell surface in normal pancreatic acini with enhanced staining at cell-cell junctions, and weak or no surface staining is seen on normal ductal cells. Nr-CAM expression is markedly up-regulated in intraductal hyperplasia. Expression was well maintained in well or moderately differentiated carcinoma but was reduced or absent from most poorly differentiated tumors. In addition, 4 of 4 human pancreatic adenocarcinoma cell lines tested demonstrated little or no Nr-CAM expression. This differential regulation of Nr-CAM expression suggests that it may be involved in the pathogenesis and invasive/metastatic behavior of pancreatic cancers. HUM PATHOL 32:396-400.

Biomarkers, Tumor↗
PubMed2000

Differences between the clearance of apoptotic cells by professional and non-professional phagocytes.

Both professional and non-professional phagocytes [1] participate in clearing the massive numbers of cells that undergo apoptosis during animal development [2], but it is not known how they divide this task. Using time-lapse recordings of cells in culture, we show that professional phagocytes (brain macrophages or microglia) are highly motile, ingest apoptotic cells immediately, and digest them quickly. Non-professionals such as BHK and lens epithelial cells are sessile, often recognize apoptotic cells as soon as they die by showing characteristic palpating movements, but delay ingestion until several hours later. By pre-ageing apoptotic cells, we show that this delay is because the apoptotic cells must undergo further changes before non-professionals can ingest them. The difference was also apparent in vivo, using immunofluorescence and electron microscopy of the developing central nervous system. This arrangement favours prompt clearance by professionals if present in adequate numbers; if they are scarce, however, non-professional bystanders will reluctantly clear the apoptotic cells.

Animals↗
PubMed2000

Obesity potentiates AOM-induced colon cancer.

Obesity and diet affect the incidence and severity of various types of cancer, including colon cancer. It is not known whether obesity, independent of diet, is a risk factor for colon adenocarcinoma. We used azoxymethane (AOM) to induce colon cancer in mature genetically obese male Zucker rats (fa/fa) on low-fat crude diet (LFC, 10% fat) and their lean counterparts (Fa/fa and Fa/fa) on high-fat crude diet (HFC, 40% fat) for three months. At death visible tumors, histopathology, and colonic aberrant crypt (AC) formation were studied by blinded investigators. At death the obese animals were heavier (719 +/- 19 g; mean +/- SEM) than lean animals regardless of diet or genotype (Fa/fa-LFC:451 = 6 g; Fa/fa-HFC:441 +/-10 g; Fa/Fa-HFC:412 +/- 9 g; P < 0.001 vs fa/fa by ANOVA). All AOM-treated rats developed AC, compared to none of the saline-injected controls. Macroscopic adenocarcinoma developed in 8/9 obese rats on LFC (P < 0.001), compared to none in lean rats regardless of diet. Obese rats had significantly more AC (876 +/- 116) than any of the lean rats (Fa/fa-LFC:550 +/- 99; Fa/fa-HFC:325 +/- 37; Fa/Fa-HFC:360 +/- 36; P < 0.05 vs fa/fa). We conclude that obesity more than exposure to high-fat diet was associated with colon carcinogenesis in these rats.

Adenocarcinoma↗
PubMed2000

Schwann cells in the regenerating fish optic nerve: evidence that CNS axons, not the glia, determine when myelin formation begins.

Fish optic nerve fibres quickly regenerate after injury, but the onset of remyelination is delayed until they reach the brain. This recapitulates the timetable of CNS myelinogenesis during development in vertebrate animals generally, and we have used the regenerating fish optic nerve to obtain evidence that it is the axons, not the myelinating glial cells, that determine when myelin formation begins. In fish, the site of an optic nerve injury becomes remyelinated by ectopic Schwann cells of unknown origin. We allowed these cells to become established and then used them as reporters to indicate the time course of pro-myelin signalling during a further round of axonal outgrowth following a second upstream lesion. Unlike in the mammalian PNS, the ectopic Schwann cells failed to respond to axotomy and to the initial outgrowth of new optic axons. They only began to divide after the axons had reached the brain. Shortly afterwards, small numbers of Schwann cells began to leave the dividing pool and form myelin sheaths. More followed gradually, so that by 3 months remyelination was almost completed and few dividing cells were left. Moreover, remyelination occurred synchronously throughout the optic nerve, with the same time course in the pre-existing Schwann cells, the new ones that colonised the second injury, and the CNS oligodendrocytes elsewhere. The optic axons are the only common structures that could synchronise myelin formation in these disparate glial populations. The responses of the ectopic Schwann cells suggest that they are controlled by the regenerating optic axons in two consecutive steps. First, they begin to proliferate when the growing axons reach the brain. Second, they leave the cell cycle to differentiate individually at widely different times during the ensuing 2 months, during the critical period when the initial rough pattern of axon terminals in the optic tectum becomes refined into an accurate map. We suggest that each axon signals individually for myelin ensheathment once it completes this process.

Animals↗
PubMed2000

A formula for diversity: a review of critical care curricula.

This paper is based on a documentary analysis and literature review of critical care nursing commissioned by the English National Board for Nursing, Midwifery and Health Visiting. Five critical care programmes were included in the analysis: ENB 100, 124, 199, 176/183, and 415. In total, 105 curricula were reviewed from 30 institutions. Data were extracted and analysed using an adapted grounded theory approach. The documentary analysis was supplemented by two telephone surveys with lecturers (n = 84) and clinical managers (n = 81). There was great diversity in the programmes in terms of the academic level at which the courses were set, module configuration, approaches to practice assessment and the amount of student effort for the same professional award. Diversity arose because of different university module formulae, different methods to differentiate level 2 and level 3 practice, different views about the purpose of the course, and an attempt to make the programmes increasingly flexible to accommodate a heterogeneous student population. Documentary analysis has its limitations, and although the research team were able to check out issues with lecturers throughout the analysis, they were unable to capture the lived experience of the curriculum. A second study has been commissioned by the ENB to explore how these issues influence practice.

Critical Care↗
PubMed2000

Clinical exchange: one model to achieve culturally sensitive care.

This paper reports on a clinical exchange programme that formed part of a pre-registration European nursing degree run by three collaborating institutions in England, Holland and Spain. The course included: common and shared learning including two summer schools; and the development of a second language before the students went on a three-month clinical placement in one of the other base institutions' clinical environments. The aim of the course was to enable students to become culturally sensitive carers. This was achieved by developing a programme based on transcultural nursing principles in theory and practice. Data were gathered by interview, focus groups, and questionnaires from 79 exchange students, fostering the strategies of illuminative evaluation. The paper examines: how the aims of the course were met; the factors that inhibited the attainment of certain goals; and how the acquisition of a second language influenced the students' learning about nursing. A model is presented to illustrate the process of transformative learning from the exchange experience.

Culture↗
PubMed2000

Balancing stakeholder needs: a review of ENB 100 and 415 courses. English National Board for Nursing, Midwifery and Health Visiting.

This paper reports the findings of a documentary analysis and literature review of general and paediatric intensive care unit (ICU) courses (ENB 100 and ENB 415). The findings are part of a larger review of critical care courses commissioned by the English National Board for Nursing, Midwifery and Health Visiting (ENB), also incorporating operating department, coronary care and accident and emergency courses. It was important to set the curriculum review in the context of intensive care practice and education, hence the study also comprised interviews with lecturers and ICU managers. The study findings reveal diversity in major aspects of the critical care courses, including the academic level of the programmes and credits they attracted; the assessment strategies for theory and practice, the extent of shared learning and the amount of student effort. Many factors influenced this diversity including contrary opinion among stakeholders about the purpose of the course: to prime the students for working in the specialty; or to consolidate previous experience (in some cases up to 15 years). Course structure and content have changed in response to local university requirements and directives from the statutory bodies, as well as in response to the higher level of academic credit awarded for pre-registration programmes (qualification inflation). The perceived shift in course content as well as the diversity across programmes had led a group of ICU managers to define their own list of competencies (Crunden 1998). However, the majority of the managers interviewed for this study (63% of General ICU managers (n = 19) and 83% (n = 6) of Paediatric ICU managers) were generally satisfied with the competencies and skills of the nurses who had undertaken the ENB course. The authors conclude from the diverse nature of the courses that there is little national comparability in the courses although this finding might be an artefact of documentary analysis. The extent to which this (apparent) diversity results in different levels of competence in practice requires further exploration.

Attitude of Health Personnel↗
PubMed2000

Cd44: a marker of squamous differentiation in adenosquamous neoplasms.

OBJECTIVE: To test the hypothesis that CD44 standard (CD44[s]) and its other variants, CD44v6 and CD44v7-8, might be useful markers of squamous differentiation in epithelial tumors. DESIGN: We studied expression of CD44(s), CD44v6, and CD44v7-8 using immunohistochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, pancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplastic tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 33 adenosquamous tumors were used. All were stained with monoclonal antibodies against a conserved portion of CD44(s) and its variants, CD44v6 and CD44v7-8, using the avidin-biotin peroxidase method. RESULTS: CD44(s) and its variants consistently and strongly stained areas of tumors with well-developed squamous differentiation. These markers also consistently and strongly stained normal squamous mucosa. Reactivity for CD44 and its variants was lacking in normal glandular type epithelium and in adenocarcinomas composed entirely of well-differentiated mucin-producing glands. Areas of well-differentiated carcinoma, both squamous and adenocarcinoma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with well-differentiated squamous foci being consistently positive, well-differentiated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less intense with the variants, it followed the same staining pattern as found for CD44(s). No differences in the extent or intensity of staining were identified in the metastatic versus primary tumor foci, nor was any difference identified between superficial and deeply invasive areas of primary tumors. CONCLUSIONS: Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epithelium and tumors, and that these markers can identify areas of well- to moderately differentiated elements in adenosquamous neoplasms. However, poorly differentiated tumors show an inconsistent staining pattern with CD44, such that it cannot be used as a reliable and practical marker of squamous differentiation in poorly differentiated neoplasms.

Adenocarcinoma↗
PubMed1997

B-cell gene rearrangement in benign and malignant lymphoid proliferations of mucosa-associated lymphoid tissue and lymph nodes.

The polymerase chain reaction (PCR) with polyacrylamide gel electrophoresis was used to study patterns of immunoglobulin heavy chain (IgH) gene rearrangement (GR) in formalin-fixed, paraffin-embedded specimens of lymphomas and reactive conditions of mucosa-associated lymphoid tissue (MALT) and lymph node. DNA amplification was performed directly on sections obtained from paraffin blocks. Five patterns of PCR products were observed: a single band, two or more discrete bands, smearing, a single band overlying a smear, and two or more bands over a smear. A pure polyclonal pattern (smear) was observed in all of the reactive lymph nodes but in only 15% of cases of Helicobacter pylori (HP) gastritis with lymphoid hyperplasia, 25% of cases of HP gastritis without lymphoid hyperplasia, and 37% of colonic specimens of various types. Patterns consisting of multiple bands with or without background smearing were common in gastritis, colitis, and gastric lymphomas. Single bands or dominant bands were present in all lymph node and salivary gland lymphomas, 12 of 14 cases of gastric lymphoma, and 17 of 20 cases of HP gastritis with lymphoid hyperplasia. These bands were reproducible in deeper sections from the same paraffin block or similar areas sampled in different blocks in all of the lymph node and salivary gland lymphomas, 11 of 12 gastric lymphomas, but only 1 of 17 cases of HP gastritis with lymphoid hyperplasia. Bands were also found in 3 of 20 cases of HP gastritis without lymphoid hyperplasia and 17 of 38 colonic specimens, but these were not reproducible. The complexity of patterns of IgH GR in acquired MALT compared with lymph nodes may be the result of a relative paucity of B-cell clones or preferential proliferation of B-cell clones with a limited area of distribution.

DNA, Neoplasm↗
PubMed1997

The Pax protein Noi is required for commissural axon pathway formation in the rostral forebrain.

No-isthmus (Noi) is a member of the zebrafish Pax family of transcriptional regulators that is expressed in restricted domains of the developing CNS. In the developing eye and optic nerve, the Noi+ cells are primitive glial cells that line the choroid fissure and optic stalk/nerve to its junction with the optic tract. This pattern of Noi expression is retained in the adult, defining the optic nerve astroglia, which wrap the left and right nerves separately at the midline, thus forming the bodily crossed optic chiasm found in fish. In embryos carrying mutations in the noi gene, the choroid fissure fails to close, glial cells of the optic nerve fail to differentiate and optic axons exhibit abnormal trajectories exiting the eye and at the midline of the diencephalon. Optic axons select inappropriate pathways into the contralateral optic nerve, rostrally towards the anterior commissure and along the ipsilateral optic tract. Noi+ cells also border the pathway of axons in the postoptic commissure, which is located adjacent to the optic chiasm. These postoptic commissural axons are defasciculated and also exhibit pathfinding defects in noi- embryos. These results indicate that Noi is required in cells that line the pathways taken by optic and non-optic commissural axons for guidance across the midline of the diencephalon. We find that expression of two members of the Netrin family of axon guidance molecules and the signalling protein Sonic hedgehog is disturbed in noi- embryos, whereas several members of the Eph family of receptors and ligands show no obvious alterations in expression at the diencephalic midline.

Animals↗
PubMed1995

Detection of K-ras oncogene mutations in bronchoalveolar lavage fluid for lung cancer diagnosis.

BACKGROUND: Lung cancer is the leading cause of cancer deaths in the United States. A long-standing goal of cancer researchers has been to develop tests that would facilitate earlier diagnosis and treatment of lung cancer and thereby decrease mortality from this disease. Because cancer results from the accumulation of a variety of genetic events (e.g., mutations, rearrangements, and deletions) in genes controlling cell growth and differentiation, these changes might serve as diagnostically useful molecular markers. Activation of the K-ras oncogene by point mutations in codon 12, which occurs in many cases of lung adenocarcinoma, may serve as one such clinically useful molecular marker. For detection of K-ras point mutations in bronchoalveolar lavage fluid, in which small numbers of malignant cells are mixed with a population of predominantly genetically normal cells, the sensitivity of commonly used assays for ras mutations risks false-negative results. PURPOSE: By applying a highly sensitive assay, we investigated whether detection of K-ras codon 12 mutations in samples of bronchoalveolar lavage fluid could be clinically useful in diagnosing lung cancer. METHODS: We developed a highly sensitive assay for detecting K-ras codon 12 mutations based on an enriched polymerase chain reaction (PCR) technique. This technique was applied to 87 specimens of bronchoalveolar lavage fluid specimens that were obtained from 86 patients, and associated tumor biopsy specimens obtained from 35 of these patients who underwent diagnostic bronchoscopy for clinically suspected lung cancer. Statistical comparisons were performed by using the two-tailed Fisher's exact test [corrected]. RESULTS: Of 52 patients with confirmed lung cancer, samples of bronchoalveolar lavage fluid from 16 patients contained K-ras codon 12 mutations, including 14 (56%) of 25 patients with lung adenocarcinomas, one (33%) of three with bronchoalveolar carcinomas, one (20%) of five with large-cell carcinomas, and none of the 14 with squamous cell carcinomas. Mutations were detected in four additional cases in which cancer was suspected but had not been histologically confirmed. Tissue samples from 35 of the patients all yielded the identical K-ras codon 12 genotype found in the corresponding samples of bronchoalveolar lavage fluid. No mutation was found in any sample from 30 patients with diagnoses other than non-small-cell lung cancer. Thus, for those cases in which tissue was available and tested, the sensitivity and specificity of detecting K-ras mutations in bronchoalveolar lavage fluid for diagnosing K-ras mutation-positive lung cancer were both 100%. For nine patients, K-ras mutations were detected in bronchoalveolar lavage fluid obtained during otherwise nondiagnostic bronchoscopies. CONCLUSIONS: Our data demonstrate that sensitive detection of K-ras codon 12 mutations can serve as an important adjunct to cytology in the diagnosis of lung cancer. IMPLICATIONS: Detection of these mutations could lead to earlier cancer diagnosis and less need for invasive diagnostic procedures.

Bronchoalveolar Lavage Fluid↗
PubMed1995

CT in patients with scirrhous carcinoma of the GI tract: imaging findings and value for tumor detection and staging.

OBJECTIVE: The purposes of this study were to analyze the CT features of scirrhous carcinoma of the gastrointestinal (GI) tract and to assess the usefulness of CT in detecting and staging these lesions. MATERIAL AND METHODS: This is a retrospective evaluation of 31 proven cases of scirrhous carcinoma (linitis plastica) of the GI tract imaged in our institution from 1986 to 1994. Twenty-two patients had primary gastric carcinoma, and nine had carcinoma of the colon (rectosigmoid in eight and right colon in one). CT examinations were reviewed and correlated with pathologic and/or surgical findings in all patients and with barium examinations in 19 cases. A modified Dukes classification was used to stage these lesions without knowledge of the pathologic and surgical results. RESULTS: Four gastric lesions were missed during the initial CT examination. Seventeen patients had extensive circumferential lesions, and five had focal plaquelike lesions. The wall thickness ranged from 1 to 3 cm (mean, 1.8 cm). Homogeneous enhancement was seen in 17 patients, slightly heterogeneous enhancement was seen in one, a target configuration was present in two patients, and intramural calcification was present in one patient. All colonic lesions were circumferential, homogeneously enhancing with a wall thickness ranging from 1 to 3 cm (mean, 2 cm). CT scans showed limitations in evaluating local parameters. Compared with surgical and pathologic staging, CT correctly staged 26 patients, understaged four patients, and overstaged one patient. Among the 19 patients with pathologically proven stage D lesions (61%), CT correctly staged 17 patients (89%) and had a 100% positive predictive value. One case of hepatic metastases, 13 cases of malignant ascites, and 11 cases of omental and peritoneal metastases were found. CONCLUSION: CT is an important complimentary imaging technique to detect scirrhous carcinoma. The sensitivity of detection depends on the size of the lesion and the quality of the examination. CT has limitations in staging early lesions but shows a high sensitivity (89%) in detecting Dukes stage D lesions. Accurate CT staging in these individuals (61% in this series) allows a more adequate treatment strategy and avoids unnecessary exploratory laparotomies.

Adenocarcinoma, Scirrhous↗
PubMed1995

Gastrointestinal emergencies in the patient with AIDS.

The clinical importance of gastrointestinal disorders among patients with acquired immunodeficiency syndrome (AIDS) is enormous. Estimates of gastrointestinal complaints among AIDS patients range from 30% to 90%. Many of these patients may be chronically ill and have multiple simultaneous opportunistic pathogens and neoplasms. The diagnosis and management of serious gastrointestinal complications that often occur in the setting of chronic illness represent major challenges in the care of patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1994

Myelin repair by Schwann cells in the regenerating goldfish visual pathway: regional patterns revealed by X-irradiation.

In the regenerating goldfish optic nerves, Schwann cells of unknown origin reliably infiltrate the lesion site forming a band of peripheral-type myelinating tissue by 1-2 months, sharply demarcated from the adjacent new CNS myelin. To investigate this effect, we have interfered with cell proliferation by locally X-irradiating the fish visual pathway 24h after the lesion. As assayed by immunohistochemistry and EM, irradiation retards until 6 months formation of new myelin by Schwann cells at the lesion site, and virtually abolishes oligodendrocyte myelination distally, but has little or no effect on nerve fibre regrowth. Optic nerve astrocyte processes normally fail to re-infiltrate the lesion, but re-occupy it after irradiation, suggesting that they are normally excluded by early cell proliferation at this site. Moreover, scattered myelinating Schwann cells also appear in the oligodendrocyte-depleted distal optic nerve after irradiation, although only as far as the optic tract. Optic nerve reticular astrocytes differ in various ways from radial glia elsewhere in the fish CNS, and our observations suggest that they may be more permissive to Schwann cell invasion of CNS tissue.

Animals↗
PubMed1994

The reflective dialogue and repertory grid: a research approach to identify the unique contribution of nursing, midwifery or health visiting to the therapeutic milieu.

This paper seeks to demonstrate the use of two research methods within the interpretive paradigm: the reflective dialogue and the repertory grid. At first sight, the use of these two methods might appear contradictory; however this paper seeks to demonstrate the complementary fashion in which both techniques elicit rich and contextualized data. Both methods use extended interviews to illuminate practitioners' perceptions about their unique contribution to the therapeutic milieu. The approach primarily seeks to identify how practitioners' perceptions alter in the light of contextual change and seeks to enable practitioners to identify their developmental needs to meet future challenges. Fundamental assumptions underpin the approach: reciprocity, the equality of researcher and participant, and that research can be an act of empowerment and education. These issues are explored throughout the paper which closes with an invitation to add to the debate about the evolution of such an approach.

Community Health Nursing↗
PubMed1993

Lymphocytes and macrophages outnumber oligodendroglia in normal fish spinal cord.

As shown by staining with a monoclonal antibody against fish CD45, leukocytes are present in very large numbers in the fish central nervous system. Their subtypes were distinguished by electron microscopy and found to include all major hematogenous forms except thrombocytes, the most numerous being tissue macrophages and lymphocytes. As a population, they differ fundamentally from ramified microglia, the restricted form of myeloid cells present in the central nervous system in mammals. They are rare in most grey matter regions but are concentrated in myelinated fiber tracts as well as in certain strata of the radial glial network. The macrophages engulf discarded myelin and outnumber the oligodendrocytes in normal spinal cord white matter, where the density of lymphocytes is > 5000-fold greater than reported in rat.

Animals↗
PubMed1991

Diversity amongst the microglia in growing and regenerating fish CNS: immunohistochemical characterization using FL.1, an anti-macrophage monoclonal antibody.

We have immunohistochemically characterized the forms and distribution of microglia--the macrophages of the CNS--in fish, using a new monoclonal antibody (mAb), FL.1. This mAb specifically reacts with resident macrophages throughout the body in Oreochromine fish, including Kuppfer cells, gut-associated myeloid cells, and peritoneal macrophages, as well as with microglia, but circulating monocytes are not labelled with FL.1. The FL.1-epitope, which is lost following treatment with reducing agents, has an extracellular location and is associated with three integral membrane glycoprotein variants. FL.1-staining shows that microglia are extremely abundant throughout the fish CNS. For example, they comprise a third of the glia in the optic nerve, and 30% of all cells, including neurons, in the spinal cord, i.e., fish have about tenfold more microglia than mammals. Two forms of FL.1-positive microglia are predominant in fish, one resembling their mammalian counterparts, but less ramified, and the other comprising smaller rounded cells with very little cytoplasm, which are most numerous in the ependymal region of the optic tectum. Apart from the conventional microglia, the optic nerves also contain large lipid-laden macrophages which comprise a third form of FL.1-positive cell in the CNS. Fish optic nerves contain astrocytes of a distinct type which form reticular networks, but lack connections to capillaries (Maggs and Scholes, J. Neurosci. 1990;10:1600-1614). The co-distribution of foamy macrophages may have a metabolic role that is performed by ordinary astrocytes elsewhere in the CNS. An antiserum against the beta 2 subunit of the human leukocyte integrins (Kishimoto et al., Cell 1987a; 50:193-202) was found selectively to recognize the foamy macrophages in Oreochromis. Following lesion to the optic nerve, FL.1-labelling shows that microglia proliferate throughout the visual pathway. In the optic tectum, the additional FL.1-positive cells are concentrated in the vicinity of degenerating retinal axons and their terminals. Most of the microglia in the injured optic nerve have amoeboid morphologies, and the foamy macrophages become depleted.

Animals↗