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Biomedical subjects

M Grant

Publications and source records attributed to M Grant.

At least 55 records · Page 3Linked to original sources
PubMed2000

Myostatin and insulin-like growth factor-I and -II expression in the muscle of rats exposed to the microgravity environment of the NeuroLab space shuttle flight.

The mechanism of the loss of skeletal muscle mass that occurs during spaceflight is not well understood. Myostatin has been proposed as a negative modulator of muscle mass, and IGF-I and IGF-II are known positive regulators of muscle differentiation and growth. We investigated whether muscle loss associated with spaceflight is accompanied by increased levels of myostatin and a reduction in IGF-I and -II levels in the muscle, and whether these changes correlate with an increase in muscle proteolysis and apoptosis. Twelve male adult rats sent on the 17-day NASA STS-90 NeuroLab space flight were divided upon return to earth into two groups, and killed either 1 day later (R1) or after 13 days of acclimatization (R13). Ground-based control rats were maintained for the same periods in either vivarium (R3 and R15, respectively), or flight-simulated cages (R5 and R17, respectively). RNA and protein were isolated from the tibialis anterior, biceps femoris, quadriceps, and gastrocnemius muscles. Myostatin, IGF-I, IGF-II and proteasome 2c mRNA concentrations were determined by reverse transcription/PCR; myostatin and ubiquitin mRNA were also measured by Northern blot analysis; myostatin protein was estimated by immunohistochemistry; the apoptotic index and the release of 3-methylhistidine were determined respectively by the TUNEL assay and by HPLC. Muscle weights were 19-24% lower in the R1 rats compared with the control R3 and R5 rats, but were not significantly different after the recovery period. The myostatin/beta-actin mRNA ratios (means+/-s.e.m. ) were higher in the muscles of the R1 rats compared with the control R5 rats: 5.0-fold in tibialis (5.35 +/- 1.85 vs 1.07 +/- 0.26), 3.0-fold in biceps (2.46+/-0.70 vs 0.81 +/- 0.04), 1.9-fold in quadriceps (7.84 +/- 1.73 vs 4.08 +/- 0.52), and 2.2-fold in gastrocnemius (0.99 +/- 0.35 vs 0.44 +/- 0.17). These values also normalized upon acclimatization. Our antibody against a myostatin peptide was validated by detection of the recombinant human myostatin protein on Western blots, which also showed that myostatin immunostaining was increased in muscle sections from R1 rats, compared with control R3 rats, and normalized upon acclimatization. In contrast, IGF-II mRNA concentrations in the muscles from R1 rats were 64-89% lower than those in R3 animals. With the exception of the gastrocnemius, IGF-II was also decreased in R5 animals maintained in flight-simulated cages, and normalized upon acclimatization. The intramuscular IGF-I mRNA levels were not significantly different between the spaceflight rats and the controls. No increase was found in the proteolysis markers 3-methyl histidine, ubiquitin mRNA, and proteasome 2C mRNA. In conclusion, the loss of skeletal muscle mass that occurs during spaceflight is associated with increased myostatin mRNA and protein levels in the skeletal muscle, and a decrease in IGF-II mRNA levels. These alterations are normalized upon restoration of normal gravity and caging conditions. These data suggest that reciprocal changes in the expression of myostatin and IGF-II may contribute to the multifactorial pathophysiology of muscle atrophy that occurs during spaceflight.

Analysis of Variance↗
PubMed2000

Beyond the Supreme Court decision: nursing perspectives on end-of-life care.

PURPOSE/OBJECTIVES: To describe nurses' views of care of the terminally ill. DESIGN: Descriptive cross-sectional survey. SAMPLE: 300 nurses who completed a survey published in Nursing98 and Nursing Management and 2,033 nurses randomly selected from the Oncology Nursing Society (N = 2,333). METHODS: Mailed end-of-life (EOL) care survey. MAIN RESEARCH VARIABLES: Dilemmas, barriers, and effectiveness of EOL care and education and attitudes regarding assisted suicide and euthanasia. FINDINGS: EOL care dilemmas are common in nursing practice, and many barriers exist to providing quality EOL care. Issues of euthanasia and assisted suicide are particularly significant to nurses who struggle to provide pain and symptom relief amid a system characterized by deficiencies in EOL care. CONCLUSIONS: Improved care is contingent on adequate education of nurses as the primary caregivers of patients and families who are facing the end of life. Study findings provide direction for improved care of the terminally ill. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are centrally involved in care of the terminally ill. Major reform is needed to provide quality EOL care.

Adolescent↗
PubMed2000

Analysis of palliative care content in nursing textbooks.

Overall, this study demonstrates significant deficiencies in end-of-life care content in nursing textbooks. Defining palliative care, quality of life at the end of life, and issues of policy, ethics, and law are the foundation of end-of-life care. Analysis of these topics revealed a need to clarify concepts and to apply them within the context of end-of-life care. The analysis also demonstrated a need to transfer findings from palliative care research and concepts from hospice into basic education. In March 1999 the investigators convened a conference in New York in collaboration with a group of medical investigators analyzing EOL content in medical textbooks. The conference was also attended by publishers, editors, and authors of textbooks. The investigators were very encouraged by their interest in and commitment to correcting any weaknesses in their books. The investigators provided them with specific recommendations for improvement and resources for locating both appropriate content and authors with palliative care expertise. These resources are also made available on the City of Hope Pain Resource Center Web site (http:@mayday.coh.org). Achieving the overall project goal of strengthened nursing education in end-of-life care will be reached through a variety of measures. Improving textbooks is but one important step. The various disciplines involved in palliative care can contribute to this project by working in collaboration with textbook publishers.

Education, Nursing↗
PubMed2000

Dignity in dying.

Barriers to effective end-of-life care encompass patient, professional, and system issues. Learn the findings of a landmark study on how well nurses meet the needs of dying patients.

Attitude of Health Personnel↗
PubMed1999

Probing the agonist domain of the nicotinic acetylcholine receptor by cysteine scanning mutagenesis reveals residues in proximity to the alpha-bungarotoxin binding site.

We have constructed a series of cysteine-substitution mutants in order to identify residues in the mouse muscle nicotinic acetylcholine receptor (AChR) that are involved in alpha-bungarotoxin (alpha-Bgtx) binding. Following transient expression in HEK 293-derived TSA-201 cells, covalent modification of the introduced cysteines with thiol-specific reagents reveals that alpha subunit residues W187, V188, F189, Y190, and P194 are solvent accessible and are in a position to contribute to the alpha-Bgtx binding site in native receptors. These results with the intact receptor are consistent with NMR studies of an alpha-Bgtx/receptor-dodecapeptide complex [Basus, V., Song., G., and Hawrot, E. (1993) Biochemistry 32, 12290-12298]. We pursued a more detailed analysis of the F189C mutant as this site varies substantially between AChRs that bind Bgtx and certain neuronal AChRs that do not. Treatment of intact cells expressing F189C with either bromoacetylcholine (BrACh) or [2-(trimethylammonium)ethyl] methane-thiosulfonate (MTSET), both methylammonium-containing thiol-modifying reagents with agonist properties, results in a marked decrease ( approximately 55-70%) in the number of alpha-Bgtx binding sites, as measured under saturating conditions. The decrease in sites appears to affect both alpha/gamma and alpha/delta sites to the same extent, as shown for alphaW187C and alphaF189C which were the two mutants examined on this issue. In contrast to the results obtained with MTSET and BrACh, modification with reagents that lack the alkylammonium entity, such as methylmethanethiosulfonate (MMTS), the negatively charged 2-sulfonatoethyl methane-thiosulfonate (MTSES), or the positively charged aminoethyl methylthiosulfonate (MTSEA), has little or no effect on the maximal binding of alpha-Bgtx to the alphaW187C, alphaV188C, or alphaF189C mutant receptors. The striking alkylammonium dependency suggests that an interaction of the tethered modifying group with the negative subsite within the agonist binding domain is primarily responsible for the observed blockade of toxin binding.

Acetylcholine↗
PubMed1999

Early events in host-pathogen interactions.

Research focused on early events in host-pathogen interactions has provided new insights into fundamental aspects of microbial pathogenicity and plant responses. Considerable progress has been made in understanding regulation of the delivery of pathogenicity determinants from bacteria into plant cells, signal cascades involved in fungal pathogenicity, the co-ordinating role of the plant cytoskeleton in plant defence and calcium flux as a primary signalling function during the hypersensitive reaction.

Bacteria↗
PubMed1999

Analysis of symptom assessment and management content in nursing textbooks.

This article reports on one goal of a project designed to improve end-of-life (EOL) care in nursing education. The goal was to improve the content regarding pain and EOL care included in major textbooks used in nursing education. A descriptive study design was selected using content analysis of 50 texts selected from a potential of over 700 texts. The 50 texts included 45,683 pages. The text review was conducted using an analysis framework encompassing 9 essential areas of EOL care. The study methods included content analysis as well as quantification of the content present in the texts. The 9 areas of the analysis framework were: palliative care defined; quality of life; pain; other symptom assessment/management; communication with dying patients and families; role/needs of family caregivers in EOL care; death; issues of policy, ethics, and law; and bereavement. This article reports on the findings of the analysis related to symptom assessment/management. Nursing texts have limited content on symptom assessment and management. Increased attention to this area, a critical role of nursing, is essential to improved care for patients at EOL.

Journal Article↗
PubMed1999

Family caregiving in cancer pain management.

The experience of cancer pain is known to greatly affect family caregivers as well as patients. There are many demands placed on caregivers of cancer patients with pain at home as a result of the shifting of care from the acute setting to the home. These complex demands significantly affect caregiver quality of life. The purpose of this study was to describe the experience of pain management from the perspective of family caregivers of patients with cancer amidst the current healthcare environment. This quasi-experimental study involved 231 family caregivers of patients with cancer pain receiving home care. Family caregivers were assessed in conjunction with a pain education program that provided patient and. family education regarding pain assessment, drug and nondrug interventions. Assessment measures used were the Quality of Life (QOL)-Family Caregiver Tool, Knowledge and Attitudes about Pain (K&A) Tool, and Caregiver Finances Tool. Study findings reveal disruption to family caregiver quality of life in the areas of physical, psychological, social, and spiritual well-being. There is also a continued need for education regarding cancer pain management. Comparison between patients and family caregivers demonstrates that pain impacts both the patient experiencing it and their caregivers.

Journal Article↗
PubMed1999

Improving cancer pain management using a performance improvement framework.

Pain is an important issue in quality of care and is increasingly cited as an outcome used to evaluate effectiveness of nursing care. Research indicates that nurses are not well prepared to care for patients with pain. Thus many patients are inadequately assessed and treated and consequently receive less than optimal pain management. The article describes the development, implementation, and evaluation of a pain education program designed to provide clinical nurses with the knowledge necessary to use appropriate pain management techniques. Program content stresses the use of a performance improvement framework for changing clinical practice in individual clinical settings.

Adult↗
PubMed1999

Molecular weight effects on chain pull-out fracture of reinforced polymeric interfaces.

Using Brownian dynamics, we simulate the fracture of polymer interfaces reinforced by diblock connector chains. We consider the mushroom regime, where connector chains are grafted with low surface density, for the case of large pulling velocities. We find that for short chains the interface fracture toughness depends linearly on the degree of polymerization N of the connector chains, while for longer chains the dependence becomes N(3/2). Based on the geometry of the initial chain configuration, we propose a scaling argument that accounts for both short and long chain limits and the crossover between them.

Journal Article↗
PubMed1999

Evolution of speckle during spinodal decomposition.

Time-dependent properties of the speckled intensity patterns created by scattering coherent radiation from materials undergoing spinodal decomposition are investigated by numerical integration of the Cahn-Hilliard-Cook equation. For binary systems which obey a local conservation law, the characteristic domain size is known to grow in time tau as R=[Btau](n) with n=1/3, where B is a constant. The intensities of individual speckles are found to be nonstationary, persistent time series. The two-time intensity covariance at wave vector k can be collapsed onto a scaling function Cov(deltat,t), where deltat=k(1/n)B(tau(2)-tau(1)) and t=k(1/n)B(tau(1)+tau(2))/2. Both analytically and numerically, the covariance is found to depend on deltat only through deltat/t in the small-t limit and deltat/t (1-n) in the large-t limit, consistent with a simple theory of moving interfaces that applies to any universality class described by a scalar order parameter. The speckle-intensity covariance is numerically demonstrated to be equal to the square of the two-time structure factor of the scattering material, for which an analytic scaling function is obtained for large t. In addition, the two-time, two-point order-parameter correlation function is found to scale as C(r/(B(n)sqaureroot[tau1(2n)+tau2(2n)]),tau1/tau2), even for quite large distances r. The asymptotic power-law exponent for the autocorrelation function is found to be lambda approximately 4.47, violating an upper bound conjectured by Fisher and Huse.

Journal Article↗
PubMed1999

Analysis of end-of-life content in nursing textbooks.

PURPOSE/OBJECTIVES: To determine the amount and types of content regarding pain and end-of-life (EOL) care included in major textbooks used in nursing education. DESIGN: Descriptive. SAMPLE: 50 texts (45,683 pages) selected from a potential of more than 700 texts. METHODS: Content analysis and quantification of nine essential areas of EOL care content present in the texts. MAIN RESEARCH VARIABLES: Nine areas of EOL care: palliative care defined; quality of life, pain; other symptom assessment/management; communication with dying patients and families; role/needs of family caregivers in EOL care; death; issues of policy, ethics, and law; and bereavement. FINDINGS: Only 2% of the overall content and 1.4% of chapters in nursing texts were related to EOL care. Based on the analysis, many deficiencies were identified in the texts, including inaccurate information and a lack of information regarding critical EOL topics. CONCLUSIONS: Nursing texts contain limited content regarding EOL care. Increased attention to this area is essential in preparing nurses to care for patients at EOL. IMPLICATIONS FOR NURSING PRACTICE: Nursing practice is based on the foundation of nursing education. Changes in nursing school curriculum and provision of continuing education for practicing nurses are essential for improved EOL care.

Curriculum↗
PubMed1998

A novel gastrin-binding protein in the human eosinophil.

A specific and saturable interaction between 125I-gastrin and eosinophils was discovered in autoradiographs of human gastric mucosal tissue and confirmed in isolated and enriched preparations of WBC's. Gastrin displaced 125I-gastrin from eosinophils in a dose-dependent manner with a D50 = 11 uM. Scatchard analysis of the saturation curve indicated a single binding site of low affinity (Kd = 4.14 uM) and high capacity (Bmax = 430 umoles/mg protein). The gastrin binding protein was localized to the granular core of the eosinophil and found to have a molecular weight of approximately 15 kDa following chemical crosslinking of radioligand to granules and SDS/PAGE. Based on its molecular weight and granular location and the charge characteristics of gastrin, the gastrin binding protein in the human eosinophil is most likely major basic protein. In vivo this interaction might act to limit the cytotoxic potential of MBP on tissues and/or attentuate gastrin concentrations thereby helping regulate gastric acid secretion and mucosal growth.

Autoradiography↗
PubMed1998

Competition alters the perception of noxious stimuli in male and female athletes.

The ability of athletes to continue to compete despite sustaining painful injury is often interpreted as evidence for the activation of endogenous analgesia mechanisms. However, alterations in perception of noxious stimuli during competition have not yet been systematically investigated. This experiment evaluated experimental pain sensitivity in male and female athletes 2 days before, immediately following, and 2 days after competition. Non-athlete controls were evaluated at the same intervals. Competition dramatically reduced pain report on the cold-pressor test in all athletes. Withdrawal latencies to noxious heat also were altered by competition, with finger withdrawal latency decreasing and arm withdrawal latency increasing in most athletes. No changes in pain report were observed across time in non-athlete controls. Competition induces both hyperalgesic and analgesic states that are dependent on the body region tested and pain assessment methodology used.

Adult↗
PubMed1998

Improving end-of-life care education in home care.

A training program for home care professionals, HOPE (Home care Outreach for Palliative care Education), was designed to improve the knowledge and skills of those providing care to patients and family caregivers at home. This article presents an overview of the pilot HOPE training program and a case study to illustrate the complex end-of-life (EOL) care needs in nonhospice home care settings. HOPE was designed as five training modules based on a needs assessment survey completed by 134 home care agencies. The training modules were composed of (a) General Overview of End of Life Care; (b) Pain Management; (c) Symptom Management; (d) Communication with Patients and Families; and (e) the Death Event. The program was implemented for clinical staff (N = 52), predominantly nurses, in two home care agencies and evaluated with pre- and postcourse surveys. Pre- and postcourse evaluations demonstrated an increase in the overall rating of EOL care from a mean rating of 5.97 to 7.42 for self-assessment and from 6.59 to 7.94 for agency assessment (on a scale of 0 = not at all effective to 10 = very effective). Future palliative care education should also include evaluation of the impact of such programs on patient care. We concluded that increasing palliative care knowledge of home care professionals is necessary to improve patient care at the EOL.

Journal Article↗