Search PubMed⌕ Search

Biomedical subjects

D Arnold

Publications and source records attributed to D Arnold.

At least 73 records · Page 4Linked to original sources
PubMed1996

Expression levels of stress protein gp96 are not limiting for major histocompatibility complex class I-restricted antigen presentation.

Immunization of mice with gp96 induces CTL with specificity for proteins that are expressed in the cells from which gp96 was isolated (Arnold et al., J. Exp. Med. 1995. 182: 885, Udono et al., Proc. Natl. Acad. Sci. USA 1994. 91: 3077). Recently, it has been shown that gp96 from cells transfected with vesicular stomatitis virus (VSV) nucleocapsid protein as well as gp96 loaded in vitro with peptides containing an epitope of this protein are taken up by phagocytic cells which obtain thereby the capacity for stimulating VSV-specific cytotoxic T lymphocytes (Suto and Srivastava, Science 1995. 269: 1585). The immunization experiments together with the peptide transfer from gp96/peptide complexes to major histocompatibility complex (MHC) class I molecules of phagocytic cells are consistent with the hypothesis that the endoplasmic reticulum-resident protein gp96 plays a crucial role in the antigen presentation of a cell (Srivastava et al., Immunogenetics 1994. 29: 93). To examine the involvement of gp96 in class I-restricted antigen presentation, we reduced gp96 RNA and protein levels by transfecting P13.1 cells with a vector containing part of gp96 cDNA in antisense orientation to the promotor. We found that antisense clones expressing strongly reduced levels of gp96 mRNA and gp96 protein show normal levels of MHC class I molecules on the cell surface and are recognized by T cells to the same extent as wild-type cells. Thus, our results show that normal levels of gp96 expression in a cell are not limiting for class I-restricted antigen presentation.

Amino Acid Sequence↗
PubMed1996

The role of the nurse practitioner in a urology service.

OBJECTIVE: To evaluate the role of the nurse practitioner in urology and to determine the impact on the work of junior doctors. METHODS: Written criteria were defined before the postholder was appointed and subsequent performance was assessed against these criteria. Training was provided and the quality of work was assessed by direct observation. Senior House Officers (SHOs) were asked whether the post had increased their opportunities to attend theatre, outpatients and post-graduate training sessions and had decreased the number of 'inappropriate' tasks they had to perform. RESULTS: The nurse practitioner accomplished all the tasks that were defined before the appointment. The assessment of patients in pre-admission and haematuria clinics was satisfactory. The continuity of information, care of patients and counselling for patients receiving complex surgery were improved. Sixty-three per cent of all patients seen in the pre-admission clinic and all patients in a haematuria clinic were assessed initially by the nurse practitioner. Because the nurse practitioner was involved in setting up intravenous drug administration and infusions, administrative tasks and in obtaining results from the laboratory, the number of 'inappropriate' tasks performed by the SHOs decreased and they were able to attend more sessions of training and education. CONCLUSIONS: The nurse practitioner in clinical urological practice constitutes an effective use of resources and relieves junior medical staff from other tasks, allowing them to receive a more focused training. In addition, the quality of patient care was thought to be improved in some areas. The framework of a job plan for a nurse practitioner is described.

Humans↗
PubMed1996

[Nursing and power--use of the so-called poststructuralism theory for the analysis of the power-relationships in the "female" nursing professional].

Nursing and power. Poststructuralism and its application to the power-relationships in the "female" occupation of nursing The theory of Foucault is used to outline a "genealogy" of nursing, historically a female occupation, subordinate to medicine. Foucault's ideas about power, discourse and panopticon are analysed in relation to nursing. The concept of discourse enables the writer to see the "feminine ideology" of society as the effect of power on the identity, behaviour and expression of emotion of women in nursing. The hospital and the "Mutterhaus" can be understood as panoptical institutions. Hospital nurses are in a position in which they have powers of disciplining patients and at the same time are themselves subject to surveillance and normalisation. As a concrete example, the techniques of using power, which originate from monasteries, form "norm-traps" when applied to nursing. Finally, not only the question of power, but also that of resistance to power, is addressed. Professionalisation and the move towards science-based nursing can be seen as "counter discourse". This is meant to set up the nurses' own knowledge base, their understanding of the nurse-patient relationship and of nursing practice, against the view of nursing as a profession subordinate to medicine. Foucault's view of power and resistance leads the writer to align herself with "the other side", in this case professionalisation in nursing. But at the same time one is invited to take the offensive in the debate of old and new contradictions.

Existentialism↗
PubMed1995

Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96.

Vaccination of mice with heat shock proteins isolated from tumor cells induces immunity to subsequent challenge with those tumor cells the heat shock protein was isolated from but not with other tumor cells (Udono, H., and P.K. Srivastava. 1994. J. Immunol. 152:5398-5403). The specificity of this immune response is caused by tumor-derived peptides bound to the heat shock proteins (Udono., H., and P.K. Srivastava. 1993. J. Exp. Med. 178:1391-1396). Our experiments show that a single immunization with the heat shock protein gp96 isolated from beta-galactosidase (beta-gal) expressing P815 cells (of DBA/2 origin) induces cytotoxic T lymphocytes (CTLs) specific for beta-gal, in addition to minor H antigens expressed by these cells. CTLs can be induced in mice that are major histocompatibility complex (MHC) identical to the gp96 donor cells (H-2d) as well as in mice with a different MHC (H-2b). Thus gp96 is able to induce "cross priming" (Matzinger, P., and M.J. Bevan. 1977. Cell. Immunol. 33:92-100), indicating that gp96-associated peptides are not limited to the MHC class I ligands of the gp96 donor cell. Our data confirm the notion that samples of all cellular antigens presentable by MHC class I molecules are represented by peptides associated with gp96 molecules of that cell, even if the fitting MHC molecule is not expressed. In addition, we extend previous reports on the in vivo immunogenicity of peptides associated gp96 molecules to two new groups of antigens, minor H antigens, and proteins expressed in the cytosol.

Animals↗
PubMed1995

Late-onset mitochondrial myopathy.

In the majority of patients with mitochondrial encephalomyopathies, signs and symptoms appear in the first three decades of life. Here we report on a group of 9 older patients (> 69 years old) with late-onset skeletal myopathy characterized by focal accumulations of deleted mitochondrial DNAs (mtDNAs) and altered muscle energy status, suggestive of a primary mitochondrial disease. The clinical phenotype was somewhat variable. However, all patients shared a common feature of insidious moderate proximal muscle weakness; some also showed fatigability and axial muscle weakness. In situ hybridization analysis demonstrated accumulations of messenger RNAs transcribed from deleted mtDNAs in a relatively large number of muscle fibers in the patient group. These fiber segments appeared as ragged red with the modified Gomori trichrome stain and hyperreactive with a modified succinate dehydrogenase stain. Most were negative for cytochrome c oxidase activity. On transverse sections their mean frequency was 0.69% (trichrome) and 1.97% (succinate dehydrogenase) significantly above control levels. Multiple mtDNA deletions were demonstrated by the polymerase chain reaction in both the patients and an age-matched control group, but not in younger control subjects. Phosphorus 13 magnetic resonance spectroscopy of resting muscle showed a decreased phosphocreatine-inorganic phosphate ratio in the patient group. The myopathy in this group of patients appears to result from mitochondrial dysfunction related to the clonal expansion of different mtDNA deletions in individual fiber segments. While the origin of the mtDNA mutations is not clear, the phenotype seems to represent an exaggerated form of what is observed in the normal aging process.

Aged↗
PubMed1995

Familial myopathy with conspicuous depletion of mitochondria in muscle fibers: a morphologically distinct disease.

Three patients (two of them siblings) presented with easy fatiguability and prominent postexercise pain. Muscle biopsy showed that large areas of about one third of the type II fibers were completely devoid of mitochondria. The remaining mitochondria were unusually large in size, but otherwise normal ultrastructurally. In two patients, 31P in vivo MRS showed low phosphocreatine (PCr), high ADP, low phosphorylation potential at rest and slow ADP and PCr recovery after aerobic exercise. This appears to be a pathologically unique form of metabolic myopathy. The cause of the focal mitochondrial depletion is not known. It should be distinguished from the mtDNA depletion syndrome in which muscle mitochondria are not reduced, but proliferate.

Adenosine Diphosphate↗
PubMed1994

A strategy for the analysis of gene expression during neural development.

The delineation of cis-acting elements regulating stage-specific gene expression has played a critical role in the definition of the transcriptional circuitry regulating differentiation. In complex tissues such as the central nervous system, differentiation often requires temporally and spatially dynamic epigenetic cues that cannot be reproduced in cell culture. In these cases, identification of critical regulatory sequences and subsequent characterization of cognate transcription factors have been limited by lack of a rapid and efficient assay system for gene expression. We report a methodology that combines particle-bombardment transfection procedures and organotypic slice culture techniques to provide an acute assay system for transcriptional control in the developing central nervous system. Using this system, we demonstrate that cell-specific regulation of the brain lipid-binding protein (BLBP) gene in Bergmann glia, astrocytes, and migrating granule cells is conferred by 1.7 kb of 5' flanking sequences and that Purkinje cell-specific expression of the calbindin D28k gene in cerebellar cortex can be achieved with 1.1 kb of flanking DNA. Nearly 100% cotransfection of multiple DNAs can be achieved, allowing the design of precisely internally controlled experiments and providing the potential for rapid and efficient genetic analysis of gene function in single cells in a wild-type environment.

Aging↗
PubMed1994

Long-term effects of Aroclor 1254 (PCBs) on plasma lipid and carnitine concentrations in rhesus monkey.

Sixty-seven female rhesus monkeys (Macaca mulatta) were orally dosed daily for 152 weeks with 0, 5, 20, 40, and 80 micrograms Aroclor 1254 (PCB)/kg body wt. Blood polychlorinated biphenyl (PCB) concentrations were highly positively correlated (r = 0.92, P < 0.001) with doses of PCB administered. A comprehensive analysis of plasma lipids/lipoproteins revealed a PCB-associated increase in plasma triglycerides and decreases in plasma total cholesterol, high-density lipoprotein cholesterol (HDL-chol), very-low plus low-density lipoprotein cholesterol (VLDL+LDL-chol), and total carnitine (which is involved in fatty acid metabolism). All of the lipid/lipoprotein changes were significantly (P < or = 0.05) correlated with blood PCB concentration. These data, obtained after 152 weeks of continuous daily exposure of a primate model to PCB support a causal relationship between plasma lipid changes and PCB intake. Previously, causality has been refuted on the premise that the commonly observed elevation of triglycerides with increasing concentration of blood PCB is a reflection, not of PCB dose, but of the partitioning of PCB between tissues (adipose) and blood in proportion to the blood lipid present. The mechanism of the plasma lipid changes was not investigated in this study but the altered lipid/lipoprotein pattern is discussed with respect to known cardiovascular risk profiles.

Administration, Oral↗
PubMed1994

Hereditary spherocytosis associated with protein band 3 defect in a Swiss kindred.

A kindred with hereditary spherocytosis, in which 10 individuals were affected, was investigated. Gel electrophoresis of membrane proteins revealed a protein band 3 defect (densitometric reduction 14.4 +/- 7.0%). The erythrocyte morphology of unsplenectomized patients showed so-called pincered erythrocytes (about 1%), which were not present in the five splenectomized patients. Splenectomy also reduced anisocytosis and all parameters of haemolysis, while haemoglobin increased. The osmotic resistance was reduced in patients with protein band 3 deficiency. Erythrocyte filterability through 3 microns pores was decreased. A significant correlation was found between osmotic resistance and filterability. The membrane elastic modulus of erythrocytes was not affected. These results on structural and functional properties of protein band 3 deficient erythrocytes may contribute to a better understanding of this newly discovered form of hereditary spherocytosis.

Adolescent↗
PubMed1994

Health at work in the NHS feature.

Almost 20 million people are in paid employment in England today, spending up to 60 per cent of their waking hours in their places of work, many for 40 years or more. Workplaces are, therefore, a major influence on health and provide an invaluable setting for health promotion.

Health Promotion↗
PubMed1994

Benign familial nocturnal alternating hemiplegia of childhood.

In infancy, two brothers developed recurrent attacks of alternating or bilateral hemiplegia arising exclusively out of sleep. The episodes were terminated by even brief sleep. Neither child had hypotonia, dystonic attacks, paroxysmal eye movement abnormalities, or other features characteristic of the now-classic form of alternating hemiplegia of childhood (AHC). The development of the brothers has so far remained normal. Both parents have a history of migraine. In the older boy, magnetic resonance spectroscopy (MRS) of muscle showed increased inorganic phosphate similar to what is found in children with AHC. In the younger brother and parents, MRS of muscle was normal. Other investigations were unrevealing. Flunarizine greatly reduced the duration of attacks. This genetically determined disorder represents a specific entity that is probably migraine-related and is easily misdiagnosed as AHC. Because of its benign course, particularly as far as mental development is concerned, it must be distinguished from classic AHC, which has a terrible prognosis.

Adult↗