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Biomedical subjects

N Warren

Publications and source records attributed to N Warren.

At least 37 records · Page 2Linked to original sources

A comparison of the effects of concentric versus eccentric exercise on force and position sense at the human elbow joint.

It is generally accepted that our sense of limb position and movement is provided, in part, by signals from muscle spindles, while the sense of muscle force derives from signals in tendon organs. Experiments are described here, using human subjects, in which the effects of eccentric and concentric exercise of elbow flexor muscles are compared on the sense of forearm position and the sense of tension in elbow flexors. Subjects were required to compress a preloaded spring with one arm, carrying out a concentric contraction in elbow flexors, then flexors of the other arm released the spring from compression and thereby carried out an eccentric contraction. The force of the spring was adjusted to be 20% maximum voluntary contraction (MVC), and each subject carried out a minimum of 120 contractions. Position sense was measured in blindfolded subjects by placing one forearm at a set angle and asking subjects to match it by positioning the other arm. Over 4 days postexercise, subjects placed the eccentrically exercised arms in a more extended position than the concentrically exercised arm suggesting that they thought the muscle was shorter than it actually was. In a force-matching task, subjects systematically undershot the target 10% MVC with their eccentrically exercised arm. Since it is known that eccentric exercise is associated with damage to muscle fibres, it is postulated that this leads to a disturbance of muscle receptors, the muscle spindles and tendon organs.

Adolescent↗

Changes in cell adhesion and extracellular matrix molecules in spontaneous spinal neural tube defects in avian embryos.

Quail embryos (embryonic days 2-2.5) with spontaneous neural tube defects (NTDs), along with age-matched normal embryos, were examined immunocytochemically for the extracellular matrix (ECM) molecules laminin, fibronectin, and chondroitin sulfate proteoglycan, the cell adhesion molecules (CAMs) E- and N-cadherin and neural CAM (NCAM), and the neural crest marker HNK-1. The embryos with NTDs were at the lower limit of the normal stage range and the affected region was about 25% shorter than in normal embryos. Open NTDs occurred in cervical and upper thoracic level, although often the ventral neural tube was morphologically normal. Widened, irregular but closed neural tubes (lower thoracic to sacral levels) showed disorganized mesenchyme-like cells centrally and often multiple lumens. Finger-like tabs projecting from the ectoderm over the neural tube also occurred at lower thoracic to sacral levels. In open NTDs, the E-cadherin-labeled epidermis was incomplete dorsally, and was continuous with the N-cadherin-labeled neural tissue, with a sharp demarcation between E- and N-cadherin-expressing regions, as in the early stages of normal primary neurulation. A sharp inverted peak of epidermis extended ventrally, closely applied to the side of the neural tissue. The intervening matrix labeled less intensely for chondroitin sulfate proteoglycan relative to laminin and fibronectin, in comparison to control embryos. In closed NTDs, the dorsal superficial cell layer (i.e., positionally epidermis) was not separated from the underlying neural tissue by a band of matrix as in control embryos. In addition, this layer expressed E-cadherin (as in normal embryos), but coexpressed N-cadherin and NCAM, which are not normally found here at this stage. This overlap region resembled the mid-dorsal tissue at earlier stages in normal secondary neurulation in the tail-bud. The tabs of tissue appeared to be localized hypertrophy of the epidermal and neural ectoderm, and also showed codistribution of E- and N-cadherin. In all these defects, matrix molecules occurred within (rather than around) the neural and epidermal epithelia. HNK-1-labeled neural crest cells were frequently absent in regions of NTDs, in contrast to control embryos. These results show that matrix and cell adhesion molecules are disturbed in spontaneous NTDs at the time of neurulation, and therefore could be involved in the generation of the defects by altering cell adhesion-dependent morphogenetic events.

Animals↗

The cystic fibrosis delta F508 gene mutation and cancer.

Following the observation that relatives of cystic fibrosis (CF) patients have an increased mortality due to leukaemia, a study was initiated to determine whether leukaemia patients had an increased prevalence of the delta F508 CF mutation. No increase in carriers were found among leukaemias; however the carrier frequency of the delta F508 mutation appeared to be reduced in patients with malignant melanoma analysed as a control group compared to the normal population. This paper extends our previous study and investigates several other common human tumours, including those of the colon, breast, and lymphoma tissue. Fewer than expected carriers remained among the melanoma group from South Wales. There were fewer than expected carriers among patients with colon cancer compared to the normal population. The prevalence of the delta F508 mutation was normal in lymphomas and leukaemias.

Alleles↗

Roles of Pax-6 in murine diencephalic development.

Pax-6 is one of the earliest regulatory genes to be expressed in the diencephalon. We tested whether normal Pax-6 protein is required for early diencephalic development by examining morphology, precursor proliferation and patterns of regulatory gene expression in the embryonic diencephalon of Small-eye mice (Pax-6 mutants). In Small-eye mice, diencephalic morphology was abnormal at all the embryonic ages studied (days 10.5, 12.5 and 14.5). Regional differences in diencephalic cell density were lost, the diencephalon/mesencephalon boundary was unclear and the third ventricle was enlarged. We estimated diencephalic proliferative rates after labelling with bromodeoxyuridine and found that they were abnormally low in mutants aged embryonic day 10.5. In older mutants, the diencephalon contained fewer cells than normal. In wild-type E14.5 diencephalon, Pax-6, Dlx-2 and Wnt-3 are expressed in discrete regions along the rostrocaudal and dorsoventral axes. In situ hybridizations for these genes in E14.5 Small-eye mice revealed discrete zones of diencephalic expression that had similar relative positions to those in wild-type mice. Some differences of detail in their expression were seen: Pax-6 had an expanded rostral domain of expression and an abnormally indistinct caudal boundary; Dlx-2 had a diffuse, rather than a sharp, caudal boundary of expression; the normally high dorsal midline expression of Wnt-3 was lost. We conclude that normal expression of Pax-6 is required for the correct regulation of diencephalic precursor proliferation. Pax-6 may also control some aspects of diencephalic differentiation, but its mutation in Small-eye mice does not preclude the development of a degree of diencephalic regionalization resembling that in normal mice.

Animals↗

Advice for beginning nurse researchers.

Heideggerian hermeneutics was used to illuminate the advice of six nurse researchers who were interviewed by the authors. The advice given to us as beginning researchers included identifying a planned program of research with a topic that we "love" and conducting research that is meaningful. Additional advice included keeping an idea log, networking, mentoring, and developing collegial relationships. The words of these researchers are intended for future investigators, yet much wisdom exists for all nurses.

Documentation↗

Nurse abuse.

Explore the source record for details and available documents.

Ethics, Nursing↗

The roles of growth factors and neural activity in the development of the neocortex.

Previous research on primarily the peripheral nervous system has shown that soluble growth factors help control key developmental events by contributing to dynamic autocrine and paracrine signalling systems. Much less is known about the roles of these substances in neocortical development. Using cell and tissue culture paradigms, we have demonstrated that soluble growth factors are produced by the neocortex and its subcortical targets, and that these tissues can respond to them. There are several possible functions for these factors in neocortical development in vivo: they may initiate axonal growth from neocortical neurons and/or their afferents; accelerate or guide that growth; and/or play a role in the later refinement of connections. Although none of these possibilities can be excluded, the existing evidence strengthens the hypothesis that soluble growth factors are important for the early postnatal growth and refinement of neocortical connections, when their levels of release may be regulated by neocortical activity. At present we do not know which growth factors are involved in these processes, but the results of preliminary experiments indicate that neurotrophins and fibroblast growth factor are prime candidates.

Animals↗

RAS and FMS mutations following cytotoxic therapy for childhood acute lymphoblastic leukaemia.

Patients who have received cytotoxic therapy for primary neoplastic disease are at an increased risk of developing secondary (therapy-related) acute myeloid leukaemia (AML) or myelodysplasia (MDS). RAS and FMS mutations have been observed in patients with AML and MDS. It has been suggested that the mutational status within these genes may be predictive of early secondary leukaemic disease. In this study we have screened 50 haematologically normal patients in complete remission from childhood acute lymphoblastic leukaemia (ALL) for activating point mutations in the RAS and FMS proto-oncogenes. Such patients may be considered at risk of therapy-related disease. Codons 12, 13 and 61 were screened in RAS and codon 969 in FMS using the polymerase chain reaction (PCR) followed by oligonucleotide hybridization (ONH). Three of the 50 patients (6%) were found to harbour N12 RAS mutations. One of these three patients (2%) had both a N12 RAS and FMS 969 mutation. Upon sequencing the RAS mutations, substitutions of serine, cysteine and aspartic acid for glycine were identified. The FMS 969 mutation was also confirmed, by sequencing, as a histidine substitution. RAS mutations were not detected in presentation samples indicating that these lesions have been somatically acquired presumably subsequent to cytotoxic therapy for the primary disease. Continued follow-up of these patients may indicate a role for these mutations in the development of secondary malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Human immunodeficiency virus infection care is unavailable to inmates on release from jail.

BACKGROUND: The human immunodeficiency virus (HIV) seroprevalence in urban jails is higher than that in the general community. METHODS: We interviewed a cohort of HIV-infected inmates in a jail in New York, NY, during incarceration and after release to assess the accessibility of medical and social services. RESULTS Of the 170 inmates who were interviewed and released into the community, 40 (24%) came to a follow-up interview. Of the 40, 25 (62%) had not received an appointment with an infectious disease clinic by the time of the new interview. Only eight (27%) of the 32 who received zidovudine in jail obtained zidovudine; and only one of the 13 who received isoniazid prophylaxis in jail obtained isoniazid prophylaxis. Twenty (65%) had applied for but not yet received Medicaid. CONCLUSION: Inmates infected with HIV may encounter difficulties obtaining medical care and social services on release into the community, which can potentially lead to active infectious tuberculosis. Family physicians may encounter HIV-positive patients who are newly released from jail and who need follow-up medical care, and they must help address the needs of HIV-positive, formerly incarcerated people.

AIDS-Related Opportunistic Infections↗

Are HIV-infected injection drug users taking HIV tests?

OBJECTIVES: Knowledge of infection is essential for human immunodeficiency virus-type 1 (HIV-1) treatment initiation and epidemic control. This study evaluates infection knowledge among infected injection drug users and acceptance of confidential testing among injection drug users, particularly those infected with HIV-1. METHODS: A total of 810 injection drug users entering treatment in Contra Costa County, Calif, were examined. Clients were tested with unlinked (blinded) tests and simultaneously counseled and offered voluntary confidential HIV-1 antibody testing. Data on confidential testing acceptance, previous testing, drug use, and demographic information were collected. RESULTS: Of the 810 tested, 105 (13.0%) were infected. The current confidential test was accepted by 507 (62.6%). HIV seroprevalence in the unlinked survey was four times greater than in the voluntary survey (13% and 3.5%, respectively). HIV-1 infection was associated with refusal of a confidential test largely because most infected injection drug users (n = 58; 55.2%) already knew of their infection. Of the 47 injection drug users who were not aware of their infection, 12 (25.5%) accepted the test. Although African-American injection drug users presented with a higher infection rate (37.3%), they were three times less likely to know of their infection. CONCLUSIONS: "In-clinic" HIV-1 testing is highly accepted, and most infected clients in treatment will learn their status. Nevertheless, voluntary testing data are likely to yield considerable underestimates of the true rate of infection among injection drug users.

AIDS Serodiagnosis↗

A promoter of Epstein-Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection.

A viral promoter that functions on recombinant plasmids in cells immortalized by Epstein-Barr virus was identified and characterized. It is identical to that mapped on the viral genome by Bodescot et al. (M. Bodescot, M. Perricaudet, and P.J. Farrell, J. Virol. 61:3424-3430, 1987) which functions during the latent phase of the viral life cycle in some but not all cells to encode several latent viral gene products. Experiments with these plasmids indicated that this promoter requires the enhancer within oriP of Epstein-Barr virus in cis to function efficiently. They also indicated that it requires the EBNA-1 gene in trans to function efficiently. The EBNA-1 gene therefore positively affects both viral DNA replication (J.L. Yates, N. Warren, and B. Sugden, Nature [London] 313:812-815, 1985) and viral transcription.

Antigens, Viral↗

Plasmid origin of replication of Epstein-Barr virus, oriP, does not limit replication in cis.

Two plasmids encoding resistance to hygromycin-B or to the analog of neomycin, G418, and containing either one or two copies of the plasmid origin of replication, oriP, of Epstein-Barr virus (EBV) were introduced into an EBV-positive B-lymphoblastoid cell line. Two clones of cells containing both plasmids were analyzed for the number of copies of each plasmid when the cells were propagated in the absence or in the presence of one or both selective agents. Under all conditions tested, the plasmid with two copies of oriP behaved in cells as did the plasmid with one copy of this plasmid origin of replication.

B-Lymphocytes↗

Selection of imagery in the relief of chronic and acute clinical pain.

This study examined the effects of pleasant imagery and type of pleasant imagery on the relief of acute and chronic pain. Two images were used in alternation, both selected from five images generated by the patient. The first image was the one most preferred by the patient; the second was the one determined by the experimenter to represent the most successful mastery of developmental stages according to the schemata outlined by Erickson (International Encyclopedia of Social Sciences, Vol. 9, McMillan, 1968). It was hypothesized that an image associated with successful phases of life would be less likely to provoke anxiety disruptive of the relaxation procedure and thus be more effective in the relief of pain. Both images were successful in reducing reported pain relief over a three-day period, but as predicted, the developmentally-selected image was more effective. The general effectiveness of these images held only for patients with acute pain.

Acute Disease↗