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Biomedical subjects

K Olson

Publications and source records attributed to K Olson.

At least 19 recordsLinked to original sources
PubMed2001

The human CD8 coreceptor effects cytotoxic T cell activation and antigen sensitivity primarily by mediating complete phosphorylation of the T cell receptor zeta chain.

Recognition of antigen by cytotoxic T lymphocytes (CTL) is determined by interaction of both the T cell receptor and its CD8 coreceptor with peptide-major histocompatibility complex (pMHC) class I molecules. We examine the relative roles of these receptors in the activation of human CTL using mutations in MHC class I designed to diminish or abrogate the CD8/pMHC interaction. We use surface plasmon resonance to determine that point mutation of the alpha3 loop of HLA A2 abrogates the CD8/pMHC interaction without affecting the affinity of the T cell receptor/pMHC interaction. Antigen-presenting cells expressing HLA A2 which does not bind to CD8 fail to activate CTL at any peptide concentration. Comparison of CTL activation by targets expressing HLA A2 with normal, abrogated, or diminished CD8/pMHC interaction show that the CD8/pMHC interaction enhances sensitivity to antigen. We determine that the biochemical basis for coreceptor dependence is the activation of the 23-kDa phosphoform of the CD3zeta chain. In addition, we produce mutant MHC class I multimers that specifically stain but do not activate CTL. These reagents may prove useful in circumventing undesirable activation-related perturbation of intracellular processes when pMHC multimers are used to phenotype antigen-specific CD8+ lymphocytes.

Amino Acid Sequence↗
PubMed2001

Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses.

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263-272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation in four patients carrying HLA-B27. In three of these patients the mutation occurred late, coinciding with disease progression. In another it occurred within 1 yr of infection and was associated with a virus of syncytium-inducing phenotype. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. After the loss of the cytotoxic T lymphocyte (CTL) response to this epitope and in the presence of high viral load, reversion to wild-type sequence was observed. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. Phylogenetic analyses indicated that these substitutions emerged under natural selection rather than by genetic drift or linkage. Outgrowth of CTL escape viruses required high viral loads and additional, possibly compensatory, mutations in the gag protein.

Arginine↗
PubMed2001

Superselective intra-arterial carboplatin for treatment of intracranial neoplasms: experience in 100 procedures.

BACKGROUND: The results of animal studies suggest that superselective intra-arterial infusion allows the permeation of a high concentration of chemotherapeutic agents within intracranial neoplasms. In the present report, we review our clinical experience with the 100 intra-arterial infusions of carboplatin in intracranial neoplasms not responsive to other treatment modalities. METHODS: Carboplatin was infused in 100 separate sessions (24 patients) as a mean dose of 286+/-60 mg/m2 (range 34-377 mg/m2). RMP-7, a bradykinin analog, was used as an adjunct in 28 sessions (6 patients). The infusions were performed through superselective microcatheterization of the following arteries: internal carotid (n = 39), middle cerebral (n = 61), posterior cerebral (n = 21) and anterior cerebral (n = 10). The frequency of neurological and non-neurological complications, and survival were recorded. In a subset of 10 patients, tumor volume was measured by serial magnetic resonance images to assess therapeutic response to therapy. RESULTS: The mean age of the patients was 44.5 years (range 26-67 years); 13 were men. The tumors were classified as glioblastoma multiforme (n = 12), metastatic tumor (n = 1), high-grade astrocytoma (n = 6), and anaplastic mixed glioma (n = 5). Follow-up was available for 23 patients (mean 22 months, range 2-69 months). Survival beyond 1 year after initiation of intra-arterial carboplatin therapy was documented in 12 of the 23 patients. A total of 13 neurological complications including seizures (n = 7), transient neurological deficits (n = 5), and ischemic stroke (n = 1) were observed in 100 procedures. A lower frequency of complications occurred in men and in patients who received adjunctive RMP-7. Volumetric analysis of serial magnetic resonance images demonstrated tumor mass reduction in 3 out of 10 patients. An increase in tumor mass ranging from 23% to 230% was observed in the other 7 patients over a period ranging from 2.3 to 37.7 months since initiation of carboplatin therapy. CONCLUSIONS: Superselective intra-arterial administration of carboplatin appears feasible and was associated with predominantly transient neurological complications. The addition of RMP-7 to carboplatin therapy appears to be at least as safe as the administration of carboplatin alone and requires further investigation as a means of chemotherapeutic dose intensification.

Adenocarcinoma↗
PubMed2001

Variations in treatment benefits influence smoking cessation: results of a randomised controlled trial.

OBJECTIVE: To assess the impact and costs of coverage for tobacco dependence treatment benefits with no patient cost sharing for smokers with employer sponsored coverage in two large independent practice association (IPA) model health maintenance organisations (HMOs) in California, USA. METHODS: A randomised experimental design was used. 1204 eligible smokers were randomly assigned either to the control group, which received a self-help kit (video and pamphlet), or to the treatment group, which received the self-help kit and fully covered benefits for over the counter (OTC) nicotine replacement therapy (NRT) gum and patch, and participation in a group behavioural cessation programme with no patient cost sharing. RESULTS: The quit rates after one year of follow up were 18% in the treatment group and 13% in the control group (adjusted odd ratio (OR) 1.6, 95% confidence interval (CI) 1.1 to 2.4), controlling for health plan, sociodemographics, baseline smoking characteristics, and use of bupropion. Rates of quit attempts (adjusted OR 1.4, 95% CI 1.1 to 1.8) and use of nicotine gum or patch (adjusted OR 2.3, 95% CI 1.6 to 3.2) were also higher in the treatment group. The annual cost of the benefit per user who quit ranged from $1495 to $965 or from $0.73 to $0.47 per HMO member per month. CONCLUSIONS: Full coverage of a tobacco dependence treatment benefit implemented in two IPA model HMOs in California has been shown to be an effective and relatively low cost strategy for significantly increasing quit rates, quit attempts, and use of nicotine gum and patch in adult smokers.

Adult↗
PubMed2001

Receptor for advanced glycation end products mediates inflammation and enhanced expression of tissue factor in vasculature of diabetic apolipoprotein E-null mice.

Advanced glycation end products (AGEs) and their cell surface receptor, RAGE, have been implicated in the pathogenesis of diabetic complications. Here, we studied the role of RAGE and expression of its proinflammatory ligands, EN-RAGEs (S100/calgranulins), in inflammatory events mediating cellular activation in diabetic tissue. Apolipoprotein E-null mice were rendered diabetic with streptozotocin at 6 weeks of age. Compared with nondiabetic aortas and kidneys, diabetic aortas and kidneys displayed increased expression of RAGE, EN-RAGEs, and 2 key markers of vascular inflammation, vascular cell adhesion molecule (VCAM)-1 and tissue factor. Administration of soluble RAGE, the extracellular domain of the receptor, or vehicle to diabetic mice for 6 weeks suppressed levels of VCAM-1 and tissue factor in the aorta, in parallel with decreased expression of RAGE and EN-RAGEs. Diabetic kidney demonstrated increased numbers of EN-RAGE-expressing inflammatory cells infiltrating the glomerulus and enhanced mRNA for transforming growth factor-beta, fibronectin, and alpha(1) (IV) collagen. In mice treated with soluble RAGE, the numbers of infiltrating inflammatory cells and mRNA levels for these glomerular cytokines and components of extracellular matrix were decreased. These data suggest that activation of RAGE primes cells targeted for perturbation in diabetic tissues by the induction of proinflammatory mediators.

Animals↗
PubMed2001

Gene expression in a pure population of odontoblasts isolated by laser-capture microdissection.

Studies of odontoblast differentiation and function have been limited due to difficulties in obtaining sufficient numbers of intact cells. We describe a novel approach of laser-capture microdissection to obtain homogenous populations of pre-odontoblasts and odontoblasts from tissue sections of mouse molar cusp tips. Fixation, processing, and staining conditions were assessed for the optimal retrieval of total RNA from microdissected odontoblasts. Fluorometric assays and RT-PCR analysis of alpha1(I) collagen, dentin sialophosphoprotein (Dspp), and osteocalcin (OC) confirmed that the total RNA from three-day-old captured odontoblasts was sufficient in quantity and quality. Odontoblast-specific gene expression was studied by RT-PCR analysis performed in a single streptavidin-coated tube. At E15.5, Days 0 and 3, gene expression in laser-captured odontoblasts resembled that seen in vivo by in situ hybridization. The use of LCM is thus a valuable means of retrieving quality RNA from discrete populations of odontoblasts at different stages of dentinogenesis.

Animals↗
PubMed2001

The care crisis.

Explore the source record for details and available documents.

Forecasting↗
PubMed1999

American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee.

Fomepizole (4-methylpyrazole, 4-MP, Antizol) is a potent inhibitor of alcohol dehydrogenase that was approved recently by the US Food and Drug Administration (FDA) for the treatment of ethylene glycol poisoning. Although ethanol is the traditional antidote for ethylene glycol poisoning, it has not been studied prospectively. Furthermore, the FDA has not approved the use of ethanol for this purpose. Case reports and a prospective case series indicate that the intravenous (i.v.) administration of fomepizole every 12 hours prevents renal damage and metabolic abnormalities associated with the conversion of ethylene glycol to toxic metabolites. Currently, there are insufficient data to define the relative role of fomepizole and ethanol in the treatment of ethylene glycol poisoning. Fomepizole has clear advantages over ethanol in terms of validated efficacy, predictable pharmacokinetics, ease of administration, and lack of adverse effects, whereas ethanol has clear advantages over fomepizole in terms of long-term clinical experience and acquisition cost. The overall comparative cost of medical treatment using each antidote requires further study.

Antidotes↗
PubMed1998

Reliability of the hip distraction index in two-month-old German shepherd dogs.

OBJECTIVE: To determine whether distraction index (DI), a measure of passive hip joint laxity, at 2 months of age was predictive of DI at 4 or 12 months of age in German Shepherd Dogs. DESIGN: Prospective cohort study. ANIMALS: 45 German Shepherd Dogs. PROCEDURE: DI was measured at 2, 4, and 12 months of age. At the same times, a standard ventrodorsal radiographic projection of the pelvis with the hip joints extended was obtained and examined for evidence of degenerative joint disease (DJD). To facilitate radiographic positioning, dogs were sedated or anesthetized. RESULTS: DI at 2 months of age was not significantly correlated with DI at 4 or 12 months of age. However, DI at 4 months of age was correlated with DI at 12 months of age. The proportion of dogs with DI > or = 0.3 at 12 months of age that had radiographic evidence of DJD by 12 months of age (13/22; 59%) was significantly greater than the proportion of dogs with DI < 0.3 at 12 months of age that had radiographic evidence of DJD by 12 months of age (1/9; 11%). CLINICAL IMPLICATIONS: For German Shepherd Dogs, DI at 2 months of age was not sufficiently reliable to predict DI at 4 and 12 months of age; however, DI at 4 and 12 months of age were comparable. We recommend that, for German Shepherd Dogs, DI not be measured before 4 months of age and that particularly for breeding dogs, DI be remeasured after maturity to confirm DI obtained at earlier ages. Studies including other breeds of dogs should be done to determine the youngest reliable age to initiate hip joint screening.

Age Factors↗
PubMed1998

From the laboratory to the hospital, adults to adolescents, and disorders to personality: the case of psychological reactance.

Study 1 assessed whether trait reactance in disturbed adolescents (ages 12 to 17) is part of the same constellation of personality variables associated with reactance in adults, and Study 2 examined whether reactance predicts inpatient treatment duration and outcomes. Correlations between reactance and MMPI-A variables among 76 inpatients (41 girls) showed that reactance is associated with oppositional, nonaffiliative, and narcissistic traits in disturbed adolescents as well as adults. Reactance predicted longer hospital stays among 176 adolescents (90 girls), and also changes in aggression, mood problems, and substance abuse among those in middle (n=89) but not early (n=87) adolescence. Additional analyses identified "typically male" and "typically female" patterns of reactance-change relationships. The clinical significance and utility of these findings are discussed.

Adolescent↗
PubMed1998

Preventing pressure sores in oncology patients.

This project addresses staff nurses' concerns about the development of hospital-acquired pressure sores in cancer patients. The Braden Scale and the National Pressure Sore Advisory Panel Staging System were pilot tested. The incidence of hospital-acquired pressure sores was 8% and a mean Braden score of 16 was sufficiently sensitive (82%) and specific (84%) for use with our patient population. Eighty-two percent (9/11) of the patients with a score of 16 on the Braden Scale developed a pressure sore that day. The model of pressure sore development constructed by Braden and Bergstrom (1987) was used to guide the development of a pressure sore prevention protocol. The pilot test of this protocol over 6 months showed no decline in the incidence of hospital-acquired pressure sores and a reduction in the sensitivity and specificity of the Braden Scale. Possible explanations for this finding and revisions to the protocol are suggested.

Humans↗
PubMed1998

Tissue and whole-body extracellular, red blood cell and albumin spaces in the rainbow trout as a function of time: a reappraisal of the volume of the secondary circulation

[58Co]EDTA, [51Cr]RBC and [125I]albumin spaces in the whole body and 28 tissue samples were examined at timed intervals over 16 h in rainbow trout Oncorhynchus mykiss. [58Co]EDTA space (which approximates extracellular fluid volume; ECF) in fins, skin, gallbladder and eye are reported for the first time. After a 16 h equilibration, ECF volume was large (376-726 microl g-1 wet tissue mass) in kidney, swimbladder, skin and fins, moderate (219-313 microl g-1 wet tissue mass) in stomach, skull, spleen, liver, intestine, gills, eye and cecum, and small (53-181 microl g-1 wet tissue mass) in red muscle, fat, brain, gallbladder and white muscle. Whole-body ECF was 387+/-10.6 microl g-1 (mean +/- s.e.m.; N=11). [51Cr]RBC space relative to [58Co]EDTA space was large in spleen, liver, intestine and gill, and low in skin, fins, stomach and skull. Whole-body [51Cr]RBC space was 9.9+/-0.6 microl g-1 body mass (N=17). Blood volume calculated from [51Cr]RBC space at 16 h and a dorsal aortic hematocrit of 24.5 % was 40.4 microl g-1 body mass. Whole-body [125I]albumin space at 16 h was 118.0+/-7.4 microl g-1 body mass (N=6), which resulted in an estimated blood volume of 156. 6 microl g-1 body mass, nearly four times that estimated from the [51Cr]RBC space. Tissue hematocrits, calculated from [125I]albumin and [51Cr]RBC spaces, were significantly lower than dorsal aortic hematocrit in all tissues except spleen, kidney and liver. [58Co]EDTA and [51Cr]RBC spaces reached equilibrium in nearly all tissues within 1 h, whereas [125I]albumin continued to accumulate in many tissues up 24 h. The disparity between [125I]albumin distribution kinetics compared with the kinetics of [58Co]EDTA and [51Cr]RBC distribution, as well as the accumulation of [125I]albumin in tissues not known to have a secondary circulation, indicates that [125I]albumin is a poor marker of plasma volume in trout and that previous studies based on [125I]albumin clearance from the plasma have overestimated both the volume and the turnover rate of the secondary system. Revised estimates of secondary circulation volume, based on [58Co]EDTA distribution rate, indicate that it is no more than 10-20 % of the volume of the primary circulation.

Journal Article↗
PubMed1997

Clinical realities and economic considerations: patient selection in intrathecal therapy.

Chronic nonmalignant pain, persisting more than 6 months, affects 15%-30% of the United States population. The majority of chronic pain patients respond to a combination of physical modalities and non-opioid analgesics. However, approximately 20% do not derive sufficient pain relief from traditional measures (back surgery, oral drugs, etc.). An additional percentage of patients do not achieve a favorable balance between analgesia and side effects with systemic opioid therapy. For these patients, intraspinal delivery of opioids may improve pain relief, reduce suffering, and enhance quality of life and functional ability. Patient selection is a significant determinant of the success of this approach. Because pain is a biopsychosocial phenomenon, psychological and social assessment are essential along with adequate trials of opioid responsiveness. There are several valid approaches to conducting trials of intraspinal pain therapy including epidural and intrathecal trials. Other important issues concern trial length, the utility of placebo trials, and drug selection in cases where morphine alone provides insufficient analgesia.

Analgesics, Opioid↗
PubMed1997

Simultaneous presence of a large coronary aneurysm and ectasia in a young patient with myocardial infarction--a case report.

Idiopathic or congenital coronary artery ectasias and aneurysms are uncommon forms of coronary artery disease. The prognosis and optimal management of such patients remains unknown. The authors describe the case of an otherwise healthy 30-year-old man with concomitant severe right coronary artery ectasia and left main coronary artery aneurysm who sustained a mild anterior myocardial infarction. There was no obstructive coronary artery disease, and no cause for the lesions could be identified. Chronic anticoagulation and antiplatelet therapy were initiated with resolution of symptoms.

Adult↗