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Biomedical subjects

K Olson

Publications and source records attributed to K Olson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Using Reiki to manage pain: a preliminary report.

The purpose of this study was to explore the usefulness of Reiki as an adjuvant to opioid therapy in the management of pain. Since no studies in this area could be found, a pilot study was carried out involving 20 volunteers experiencing pain at 55 sites for a variety of reasons, including cancer. All Reiki treatments were provided by a certified second-degree Reiki therapist. Pain was measured using both a visual analogue scale (VAS) and a Likert scale immediately before and after the Reiki treatment. Both instruments showed a highly significant (p < 0.0001) reduction in pain following the Reiki treatment.

Adult↗
PubMed1997

Critique of the National Cancer Institute of Canada's framework for cancer control.

This paper offers a critique of the National Cancer Institute of Canada's (NCIC) framework for cancer control. The critique has been prepared by researchers who used the framework to review the literature in 5 substantive areas. These reviews, published in the current and previous issues of CPC, were designed to begin to outline a research agenda for the Sociobehavioural Cancer Research Network. In this paper, the authors reflect on the strengths and limitations of the framework. Perceived strengths are that the framework (a) facilitates systematic thinking about research options and priorities, (b) helps foster clear communication, (c) links science and practice, (d) may assist grant review panels to place proposed studies in context and (e) emphasizes important values. Perceived concerns include the following: (a) potential users are not familiar with the framework, (b) lack of clarity of definitions and classification criteria, (c) the utility of the framework is not immediately self-evident to potential users, (d) the framework lacks emphasis on environmental and policy interventions and (e) it is not clear how the values espoused are to be integrated with other dimensions of the framework. The concerns were seen as remediable. In short, the framework was seen to be valuable in its current form; refinement may enhance its value.

Canada↗
PubMed1996

Confirmation by mass spectrometry of a trisulfide variant in methionyl human growth hormone biosynthesized in Escherichia coli.

A sulfur-containing compound found in acid hydrolysates of proteins was identified 30 years ago as a trisulfide: bis-(2-amino-2-carboxyethyl) trisulfide (cysteine2S3). At that time, studies concerning the chemistry of sulfur-transferring enzyme systems suggested that cysteine2S3 also existed in biological systems. Two decades later, a cystine trisulfide structure was postulated in the regulator protein molecule for the activation of delta-aminolevulinate synthetase. Recently, a trisulfide bond was reported to occur in the minor loop disulfide at Cys182-Cys189 in human growth hormone. We have detected a trisulfide structure in methionyl human growth hormone in the major loop disulfide Cys53-Cys165. The development of mass spectral analyses of high molecular weight molecules, such as proteins, led to the eventual identification of the modification. A tandem mass spectral analysis on a Sciex electrospray instrument localized an addition of 32 Da to the Cys53-Cys165 fragment. Elemental composition was determined by accurate mass measurement obtained by peak matching to a synthetic peptide and established that an extra sulfur atom was involved.

Amino Acid Sequence↗
PubMed1996

Long-acting growth hormones produced by conjugation with polyethylene glycol.

Derivatives of human growth hormone (hGH) of increasing size were produced by reaction with the N-hydroxysuccinimide ester of polyethylene glycol-5000 (PEG5000), a 5-kDa reagent that selectively conjugates to primary amines. By adjusting the reaction conditions and purification procedure, it was possible to isolate hGH derivatives containing up to seven PEG moieties that altered the Stokes radius and thereby the effective molecular masses of the unmodified hormone from 22 to 300 kDa. Fortunately, the most reactive amines were ones that did not lie in either of the two sites important for receptor binding. Nonetheless, increasing the level of PEG modification linearly reduced the affinity of hGH for its receptor and increased the EC50 in a cell-based assay up to 1500-fold. Most of the reduction in affinity was the result of slowing the association rate for the receptor. The clearance rate of hGH in rats was inversely proportional to effective molecular weight and closely fit a filtration model. We have tested the potency of these analogs by injecting them daily or every 6 days into hypophysectomized rats and determining the effects on body and organ growth. The efficacy of these analogs was optimal for hGH conjugated with 5 eq of PEG5000, and the potency was increased by about 10-fold compared with unmodified hGH. Such PEG-hGH derivatives show promise as long-acting alternatives to daily injections of hGH. More generally these studies show that improving hormone clearance properties, even at the expense of reducing receptor binding affinity, can lead to dramatic increases in hormone efficacy.

Animals↗
PubMed1995

Monosomy 7 and activating RAS mutations accompany malignant transformation in patients with congenital neutropenia.

Individuals with severe forms of congenital neutropenia suffer from recurrent infections. The therapeutic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to increase the neutrophil count is associated with fewer infections and an improved quality of life. However, the long-term effects of this new therapy are largely unknown. In particular, it is unclear if myeloid leukemia, a known complication of some forms of congenital neutropenia, will occur with increased frequency among patients who receive long-term treatment with hematopoietic growth factors. We report 13 patients with congenital disorders of myelopoiesis who developed leukemic transformation with either myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) and 1 who acquired a clonal cytogenetic abnormality without evidence of MDS or AML while receiving rhG-CSF. The bone marrows of 10 patients showed monosomy 7 and 5 had activating RAS mutations. These abnormalities were not detected in pretreatment bone marrows and cessation of rhG-CSF was not associated with either clinical improvement or cytogenetic remission. We conclude that patients with severe forms of congenital neutropenia are at relatively high risk of developing MDS and AML. The occurrence of monosomy 7 and RAS mutations in these cases suggests that the myeloid progenitors of some patients are genetically predisposed to malignant transformation. The relationship between therapeutic rhG-CSF and leukemogenesis in patients with severe chronic neutropenia is unclear.

Adolescent↗
PubMed1995

Molecular analysis at the NF1 locus in astrocytic brain tumors.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are at increased risk for developing malignant neural crest tumors and juvenile myeloid leukemia. Although the normal allele of the NF1 tumor-suppressor gene is frequently deleted in some of the malignant tumors that arise in patients with NF1, the role of NF1 alterations in the sporadic forms of these cancers is unclear. METHODS: A series of intragenic sequence polymorphisms was used to investigate lymphocyte and tumor DNA samples from 22 adults with high grade malignant gliomas for loss of heterozygosity (LOH) at NF1. In addition, an assay based on the polymerase chain reaction was used to screen these tumors for point mutations at codon 1423. RESULTS: One recurrent anaplastic astrocytoma showed LOH within NF1 but not with a flanking marker located near the gene. Of 21 informative tumors, none showed point mutations affecting codon 1423 of NF1. CONCLUSION: These data suggest that LOH at NF1 is uncommon in sporadic high grade astrocytoma, and codon 1423 is not a "hot spot" for activating point mutations in these tumors.

Adult↗
PubMed1995

Molecular evidence that childhood monosomy 7 syndrome is distinct from juvenile chronic myelogenous leukemia and other childhood myeloproliferative disorders.

The observation that juvenile chronic myelogenous leukemia (JCML) and childhood bone marrow monosomy 7 syndrome (Mo 7) are similar in many clinical and epidemiologic respects suggests a shared pathogenic basis and raises the possibility that the bone marrows of patients with JCML might lose chromosome 7 alleles by mechanisms that do not result in detectable cytogenetic deletions. We used a series of polymorphic markers mapped to chromosome 7 to test this hypothesis in 22 children with MPS and MDS, including 19 with JCML. All MPS and MDS samples demonstrated allelic heterozygosity with at least one chromosome 7 marker; 16 were heterozygous with probes from both 7p and 7q. Furthermore, the percentage of patient bone marrow samples heterozygous at each locus tested was similar to the frequency observed in the normal population. Whereas these data demonstrate that submicroscopic loss of large segments of chromosome 7 alleles is uncommon in children with MPS and MDS who do not have Mo 7, they do not exclude small deletions around an uncharacterized tumor-suppressor locus. Our results suggest that a number of distinct molecular events contribute to leukemogenesis, and we propose a multistep model to explain the similarities and differences between the major subtypes of childhood MPS and MDS.

Child, Preschool↗
PubMed1995

Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins.

Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP695) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levels of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. No extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in approximately 20% of nontransgenic mice when they reach mid- to late-adult life, suggesting that APP overexpression may accelerate a naturally occurring age-related CNS disorder in FVB/N mice.

Aging↗
PubMed1995

Comparison of Mycoplasma arthritidis strains by enzyme-linked immunosorbent assay, immunoblotting, and DNA restriction analysis.

Twenty Mycoplasma arthritidis strains or isolates were compared by a combination of enzyme-linked immunosorbent assay by an antiserum adsorption technique, Western immunoblotting, and restriction analysis of chromosomal DNA. Antigenic markers that defined strains related to strains 158p10p9, PG6, and H606 were identified. In addition, restriction analysis allowed all 20 strains to be divided into six groups. Results of restriction analysis corresponded generally with antigenic similarities, although the former did not allow grouping with as fine a precision as the latter. However, intrastrain antigenic variability, which is common among many Mycoplasma species, including M. arthritidis, introduced a complicating factor into our attempts at antigenic analysis. While serologic and antigenic analyses remain useful, we recommend that they be used with caution and in combination with other techniques for identifying and characterizing new isolates and newly acquired strains. Combinations of these techniques have proven to be useful in our laboratory for quality control and for uncovering interesting relationships among strains subjected to animal passage and their less virulent antecedents and among strains originally classified as the same but obtained from different sources and maintained, sometimes for decades, in different laboratories.

Animals↗
PubMed1995

Molecular genetic manipulation of mosquito vectors.

Despite their central role in disease transmission, relatively little is known of the molecular biology of arthropod vectors. Modern molecular approaches will undoubtedly provide considerable information about gene regulation and expression in vectors and consequently a much better understanding of the biology and molecular biology of vectors. Such knowledge is essential for developing effective control strategies for vector-borne diseases. In this review, we focus upon techniques and approaches used at the Arthropod-Borne and Infectious Diseases Laboratory (AIDL) at Colorado State University to bioengineer mosquitoes with reduced vector competence. We have developed technologies and procedures that allow genetic manipulation of mosquitoes, including RNA and DNA virus gene-delivery vehicles and efficacious antiviral constructs, which will facilitate the development of pathogen-resistant, transformed mosquitoes. Many of the approaches, constructs, and technologies developed at AIDL will be applicable to molecular manipulation of other arthropod genomes.

Animals↗
PubMed1994

Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras.

Children with neurofibromatosis, type 1 (NF-1) are at increased risk of developing malignant myeloid disorders and their bone marrows frequently show loss of the normal allele of the NF1 tumor-suppressor gene. NF1 encodes a protein called neurofibromin, which accelerates guanosine triphosphate (GTP) hydrolysis on the p21ras (Ras) family of signaling proteins. We used a genetic approach to test the hypothesis that NF1 negatively regulates myeloid cell growth through its effect on Ras. This model predicts that, if RAS mutations and loss of NF1 function deregulate myeloid growth by the same biomechanical mechanism, then activating RAS mutations will be restricted to children with malignant myeloid disorders who do not have NF-1. We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS. The incidence of RAS mutations was 21% (12 of 55) in patients without NF-1 and 0% (zero of 16) in children with NF-1 (P = .04). Among the 55 patients who did not have NF-1, we found RAS mutations in four of 27 with Mo 7, in five of 24 with JCML, in two of 3 with AML, and in a patient with myeloproliferative syndrome (MPS). These data from primary human cancer cells provide strong genetic evidence that NF1 limits the growth of myeloid cells by regulating Ras.

Alleles↗
PubMed1994

Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders.

BACKGROUND: Children with type 1 neurofibromatosis (NF-1) are at increased risk for malignant myeloid disorders. Analysis of the NF-1 gene (NF1) suggests that the function of its product, neurofibromin, is reduced in affected persons and that NF1 belongs to the tumor-suppressor class of recessive cancer genes. This model is consistent with evidence that neurofibromin accelerates the intrinsic guanosine triphosphate-hydrolyzing activity of the Ras family of regulatory proteins. Loss of constitutional heterozygosity has not been reported in the benign tumors associated with NF-1, however, and has only been detected in a few malignant neural-crest tumors and in some tumor-derived cell lines. METHODS: We studied DNA extracted from the bone marrow of 11 children with NF-1 in whom malignant myeloid disorders developed and from parental leukocytes. We used a series of polymorphic markers within and near NF1 to determine whether leukemogenesis was associated with structural alterations of the gene. RESULTS: Bone marrow samples from five patients showed loss of heterozygosity. In each case, the NF1 allele was inherited from a parent with NF-1 and the normal allele was deleted. CONCLUSIONS: These data provide evidence of NF1 may function as a tumor-suppressor allele in malignant myeloid diseases in children with NF-1 and that neurofibromin is a regulator of ras in early myelopoiesis.

Alleles↗
PubMed1994

LOCALIZATION OF ANGIOTENSIN II RESPONSES IN THE TROUT CARDIOVASCULAR SYSTEM

The renin/angiotensin system (RAS) is a tonic anti-drop regulator of arterial blood pressure in many teleosts. In trout, angiotensin II (ANG II) has no direct constrictor effect on large arteries or veins and the identity of specific cardiovascular pressor effectors is unknown. Potential targets of angiotensin activation were examined in the present experiments using perfused organs and isolated tissues from the rainbow trout Oncorhynchus mykiss. Perfused gill (arches 2 and 3), perfused skeletal muscle-kidney (via the dorsal aorta; PDA) and perfused splanchnic (via the celiacomesenteric; PCM) circulations vasoconstrict in response to salmonid ANG II in a dose-dependent manner. ANG II was significantly (P&frac34;0.05) more potent in the PCM than in the PDA, and both preparations were more responsive than the gills: pD2=8.0&plusmn;0.20 (10) for PCM; pD2=7.5&plusmn;0.07 (13) for PDA; pD2=6.9 &plusmn;0.21 (8) for gill arch 3; pD2=6.7&plusmn;0.23 (8) for gill arch 2; mean &plusmn; s.e.m. (N), respectively. Salmonid angiotensin I (ANG I) also produced a dose-dependent constriction of the PDA and PCM. Angiotensin converting enzyme (ACE) activated nearly 100 % of ANG I to ANG II in a single pass through the PDA, whereas PCM conversion was estimated to be less than 10 %. Inhibitors of adrenergic constriction partially prevented ANG II responses in the PDA but did not affect PCM responses. ANG II did not affect paced rings of ventricular muscle in the presence of high or low [Ca2+] or epinephrine concentrations, nor did it have any inotropic or chronotropic effects in the in situ perfused heart. Red blood cell swelling was unaffected by ANG II. Similarly, the effects of ANG II on gut, urinary bladder and gall bladder smooth muscle were negligible or non-existent; thus, an increase in splanchnic resistance due to extravascular compression can be discounted. These results indicate that, in trout, the systemic microcirculation is the major cardiovascular effector of angiotensin-mediated pressor responses. In addition, the RAS has little direct effect on non-vascular smooth muscle or the heart. From an evolutionary perspective, the initial site of direct systemic RAS action appears to be the vascular microcirculation.

Journal Article↗
PubMed1994

Research utilization in critical care: an exemplar.

The authors describe the process and outcome of implementing a research-based pain management protocol in four adult critical care units at a large, Midwestern tertiary care center. The project was initiated and directed by members of the divisional research committee. Strategies used to change practice included determining if pain management was a problem via quality assessment monitors, surveying nurses regarding their knowledge and attitude toward pain management, educating staff members about the research base for the practice change, using change champions in each unit, and developing a core group of nurses in each unit to facilitate the change. Outcomes of this research utilization project include a 41% decline in the number of patients in pain, a 44% decline in pain intensity, and improvement in nurses knowledge about pain.

Clinical Nursing Research↗