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Biomedical subjects

M Olsen

Publications and source records attributed to M Olsen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Significantly improved oral uptake of amikacin in FVB mice in the presence of CRL-1605 copolymer.

Amikacin is an aminoglycoside which is used in the treatment of infection from gram negative bacteria. Amikacin is also used synergistically with penicillin against gram positive cocci. Amikacin cannot be delivered orally probably due to efflux of drug by P-glycoprotein pump in the brush border of intestine. We studied the possibility of delivering amikacin orally in mice using a copolymer (CRL-1605) as a vehicle. This copolymer inhibits P-glycoprotein pump. Two different doses of amikacin were used (500 mg/kg and 100 mg/kg). The concentration of polymer used was 132 mg/kg. The liquid formulation was fed to mice by gavage and serum amikacin concentrations were estimated after one hour and two hours using fluorescence polarization immunoassay. We observed a two fold increase in serum amikacin concentration when amikacin was orally delivered in the presence of CRL-1605 compared to controls (amikacin alone). We conclude that gastrointestinal absorption of amikacin is significantly increased in the presence of CRL-1605 in mice.

Administration, Oral↗
PubMed1999

Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides.

The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and learning. In this study, we identified a synthetic peptide-ligand of the NCAM Ig1 module by combinatorial chemistry and showed it could modulate NCAM-mediated cell adhesion and signal transduction with high potency. In cultures of dissociated neurons, this peptide, termed C3, stimulated neurite outgrowth by activating a signaling pathway identical to that activated by homophilic NCAM binding. A similar effect was shown for the NCAM Ig2 module, the endogenous ligand of NCAM Ig1. By nuclear magnetic resonance spectroscopy, the C3 binding site in the NCAM Ig1 module was mapped and shown to be different from the binding site of the NCAM Ig2 module. The C3 peptide may prove useful as a lead in development of therapies for neurodegenerative disorders, and the C3 binding site of NCAM Ig1 may represent a target for discovery of nonpeptide drugs.

Amino Acid Sequence↗
PubMed1999

Relationship of survival, organism containment, and granuloma formation in acute murine tuberculosis.

The relationship among organism growth, immunopathology, and survival was studied in C57BL/6 and A/J mice acutely infected with Mycobacterium tuberculosis (MTB) (Erdman). Although organisms grew at similar rates in the lungs of both mouse strains, A/J mice died prior to 14 days after infection, whereas C57BL/6 mice survived twice as long. The lungs of A/J mice exhibited necrotizing interstitial inflammation and widely distributed acid-fast bacilli without granuloma formation. In contrast, the lungs of C57BL/6 mice had relatively mild interstitial inflammation, which was replaced by focal granulomas, and acid-fast bacilli were primarily within granulomas. MTB induced similar granulomas for A/J and C57BL/6 mice in spleen and liver. In the lung, the A/J mice produced only transient messages for interferon-y (IFN-y), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-10, and inducible nitric oxide synthase (iNOS). The C57BL/6 mice, in contrast, produced a delayed but sustained response in the lung correlating with granuloma onset and characterized by high induction of IL-6, IFN-gamma, IL-1beta, IL-10, and TNF-alpha. Responses in the liver and spleen were also evaluated. These results demonstrate that histopathology and cytokine response to MTB infection varies among organs in mice. Increased survival during acute infection may, therefore, depend on the ability to contain organisms within granulomas in the lung.

Acute Disease↗
PubMed1999

Phase I trial of intravenous thymidine and carboplatin in patients with advanced cancer.

PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with a 24-hour infusion of thymidine 75 mg/m(2) in a phase I trial. PATIENTS AND METHODS: Thirty-two patients with cancer refractory to conventional therapy were treated. The first set of patients (n = 7) received thymidine alone 4 weeks before subsequent planned courses of thymidine combined with carboplatin followed (4 weeks) by carboplatin alone. Carboplatin was administered over 20 minutes at hour 20 of the 24-hour thymidine infusion. The carboplatin dose was escalated in patient groups: 200 mg/m(2) (n = 3); 300 mg/m(2) (n = 7); 350 mg/m(2) (n = 4); 400 mg/m(2) (n = 3); 480 mg/m(2) (n = 10); and 576 mg/m(2) (n = 5). At the maximum-tolerated dose (480 mg/m(2)), five patients received combined therapy first and carboplatin alone second, and five patients received carboplatin first and combined therapy second. Maintenance therapy for stable or responding patients was combined therapy. RESULTS: Evaluation demonstrated a trend toward thymidine protection of carboplatin-induced treatment-limiting thrombocytopenia. Neutropenia with carboplatin alone or in combination was negligible. Thymidine alone had no myelosuppressive effects and produced reversible grade 1 or 2 nausea and vomiting (57%), headache (25%), and grade 1 neurotoxicity (22%). Thymidine did not enhance expected carboplatin toxicities. There was no therapy-related infection or bleeding. Analysis of platinum in plasma ultrafiltrate and urine showed no effect by thymidine. Similarly, thymidine pharmacokinetics was not affected by carboplatin. As predicted, nicotinamide adenine dinucleotide levels in peripheral lymphocytes were increased during exposure to carboplatin and/or thymidine but were decreased by carboplatin alone. In three patients with high-grade glioma, responses included one complete remission (21 months) and one partial remission (14 months) at the 480-mg/m(2)-dose level, and disease stabilization (7 months) at the 400-mg/m(2-dose) level. A minor response was observed in a patient with metastatic colon cancer (5 months) at the 480-mg/m(2)-dose level. CONCLUSION: The combination of carboplatin and thymidine as described is well tolerated. The data presented have resulted in a phase II study by the North American Brain Tumor Consortium.

Adult↗
PubMed1998

Placental and lactational transfer of ochratoxin A in rats.

The placental and lactational transfer of ochratoxin A (OA) was investigated in a cross-fostering study in rats. Dams were given 50 microg OA(-1) kg body weight by gastric intubations 5 times a week for 2 weeks before mating, during gestation and then 7 days a week during lactation. Neonates from OA-treated dams were cross-fostered at birth to control dams treated with only vehicle. In the same way, neonates from control dams were cross-fostered to OA-treated dams. Treatment with OA did not result in any effects on birth weight or growth development of the pups during the first 21 days of life. There were no effects on milk quality as measured by milk lipids, protein or lactose concentrations, or on milk production, assessed by the mammary gland content of RNA and DNA. A mean milk:blood ratio of approximately 0.6 was found. The dose of OA from milk to the suckling pup at 14 days of age can be calculated to about 50 microg kg(-1) body weight(-1) day, which is similar to the dose given to the dams. Pups exposed to OA only via milk had blood and kidney levels of OA approximately 3 times higher than their dams, indicating a high absorption and/or a low excretion of OA in the sucklings. At 14 days of age the highest blood and kidney levels of OA were found in offspring exposed both via placenta and milk, with the highest contribution from milk. Offspring exposed only via milk had about 4-5 times higher levels of OA in blood and kidney compared to offspring exposed only via placenta. As milk could be a significant source of OA exposure in newborns, adverse health effects resulting from postnatal exposure should be studied and evaluated in the risk assessment of OA.

Animals↗
PubMed1998

Effects of mutations in residues near the active site of human immunodeficiency virus type 1 integrase on specific enzyme-substrate interactions.

The phylogenetically conserved catalytic core domain of human immunodeficiency virus type 1 (HIV-1) integrase contains elements necessary for specific recognition of viral and target DNA features. In order to identify specific amino acids that determine substrate specificity, we mutagenized phylogenetically conserved residues that were located in close proximity to the active-site residues in the crystal structure of the isolated catalytic core domain of HIV-1 integrase. Residues composing the phylogenetically conserved DD(35)E active-site motif were also mutagenized. Purified mutant proteins were evaluated for their ability to recognize the phylogenetically conserved CA/TG base pairs near the viral DNA ends and the unpaired dinucleotide at the 5' end of the viral DNA, using disintegration substrates. Our findings suggest that specificity for the conserved A/T base pair depends on the active-site residue E152. The phenotype of IN(Q148L) suggested that Q148 may be involved in interactions with the 5' dinucleotide of the viral DNA end. The activities of some of the proteins with mutations in residues in close proximity to the active-site aspartic and glutamic acids were salt sensitive, suggesting that these mutations disrupted interactions with DNA.

Binding Sites↗
PubMed1997

Magnetic properties experiments on the Mars Pathfinder lander: preliminary results.

Many of the particles currently suspended in the martian atmosphere are magnetic, with an average saturation magnetization of about 4 A. m2/kg (amperes times square meters per kilogram). The particles appear to consist of claylike aggregates stained or cemented with ferric oxide (Fe2O3); at least some of the stain and cement is probably maghemite (gamma-Fe2O3). The presence of the gamma phase would imply that Fe2+ ions leached from the bedrock, passing through a state as free Fe2+ ions dissolved in liquid water. These particles could be a freeze-dried precipitate from ground water poured out on the surface. An alternative is that the magnetic particles are titanomagnetite occurring in palagonite and inherited directly from a basaltic precursor.

Atmosphere↗
PubMed1997

Quality control of two rose bengal and modified DRBC and DG18 media.

The effect of storage on the performance of four mycological media, DG18, DRBC and two Rose Bengal agars, one from Difco, the other recommended by the Swedish Standard Institution, was investigated. The autoclaved media were stored (+4 degrees C) in the dark for up to 26 weeks. Following each storage period, the media were remelted and poured and the plates stored (+4 degrees C) in the dark for a maximum of 8 weeks before inoculation with test microorganisms. All media contained antibiotics. Both rapidly and slowly growing moulds, and also yeasts and bacteria were used as test microorganisms. No distinct effect of storage time on colony appearance could be shown for any of the four media. If the loss of restricted growth of Rhizopus stolonifer is used as a measure of the performance of the media, DRBC plates should not be stored for longer than 2 weeks after being poured from fresh medium. Storage of DRBC in flasks should not exceed 4 weeks and plates prepared from this medium should not be kept for more than 1 week. DG18 plates should only be poured from fresh medium and kept for a maximum of 1 week. The inhibitory effect of the antibiotic supplement on bacteria lasted for at least 4 weeks in DG18 and the two rose bengal media.

Agar↗
PubMed1997

Comparisons of shear bond strength of precoated and uncoated brackets.

In an attempt to save chairside time during bonding, orthodontists are using ceramic and metal brackets that have been precoated with the adhesive material. The adhesive used on the precoated brackets is similar in composition to that used for bonding uncoated brackets; the difference is essentially in the percentages of the various ingredients incorporated in the material. The purpose of this study is to determine whether these changes in composition affect the shear bond strength and the site of bond failure when precoated and uncoated ceramic and metal brackets are used. Eighty-five recently extracted human molars were bonded according to the manufacturer's instructions and mounted in phenolic rings. An occlusogingival load was applied to the bracket, producing a shear force at the bracket-tooth interface with a Zwick Universal Test Machine. After debonding, all teeth and brackets were examined under 10x magnification. Any adhesive remaining after bracket removal was assessed with the Adhesive Remnant Index (ARI). The current findings indicated that: (1) Precoated ceramic brackets that used a slightly modified adhesive have similar shear bond strengths as that provided by Transbond XT adhesive on uncoated brackets; (2) precoated metal brackets that used the same adhesive have significantly lower shear bond strength than those obtained with Transbond XT on uncoated brackets. The differences in the bond strength between the ceramic and metal brackets were attributed to the combined effects of the changes in the composition of the adhesives used and in the retention mechanisms incorporated in the bracket bases of the different types of brackets; (3) all bracket/adhesive combinations tested provided clinically acceptable shear bond forces.

Acid Etching, Dental↗
PubMed1996

Changes in the dental arches and dentition between 25 and 45 years of age.

The purpose of this longitudinal investigation was to study changes in the dental arches and dentition that occur in midadulthood in an untreated, normal sample. The subjects had Class I molar and canine relationships with less than 4.0 mm of overjet and less than 50% overbite. None had undergone previous orthodontic treatment. Evaluations and measurements were made from dental casts and periapical radiographic surveys of 15 females and 15 males from approximately 25 years to 46 years. The findings indicate that over the span of the study, significant changes occur in the maxillary and mandibular dental arches and dentition in both males and females, including a clinically significant increase in tooth size-arch length (circumference) discrepancy. These changes should be considered part of the normal maturational process and should be taken into consideration when planning treatment and retention options for adolescent and adult patients.

Adult↗
PubMed1995

Lactate and H+ uptake in inactive muscles during intense exercise in man.

1. The present study examined how uptake of lactate and H+ in resting muscle is affected by blood flow, arterial lactate concentration and muscle metabolism. 2. Six males subjects performed intermittent arm exercise in two separate 32 min periods (Part I and Part II) and in one subsequent 20 min period in which one leg knee-extensor exercise was also performed (Part III). The exercise was performed at various intensities in order to obtain different steady-state arterial blood lactate concentrations. In the inactive leg, femoral venous blood flow (draining about 7.7 kg of muscles) was measured and femoral arterial and venous blood was collected frequently. Biopsies were taken from m. vastus lateralis of the inactive leg at rest and 10 and 30 min into both Part I and Part II as well as 10 min into recovery from Part II. 3. The arterial plasma lactate concentrations were 7, 9 and 16 mmol l-1 after 10 min of Parts I, II and III, respectively, and the corresponding arterial-venous difference (a-vdiff) for lactate in the resting leg was 1.3, 1.4 and 2.0 mmol l-1. The muscle lactate concentration was 2.8 mmol (kg wet wt)-1 after 10 min of Part I and remained constant throughout the experiment. During Parts I and II, a-vdiff lactate decreased although the arterial lactate concentration and plasma-muscle lactate gradient were unaltered throughout each period. Thus, membrane transport of lactate decreased during each period. 4. Blood flow in the inactive leg was about 2-fold higher during arm exercise compared to the rest periods, resulting in a 2-fold higher lactate uptake. Thus, lactate uptake by inactive muscles was closely related to blood flow. 5. Throughout the experiment a-vdiff for actual base excess and for lactate were of similar magnitude. Thus, in inactive muscles lactate uptake appears to be coupled to the transport of H+.

Acid-Base Equilibrium↗
PubMed1995

Novel avidin and streptavidin binding sequences found in synthetic peptide libraries.

Synthetic resin-bound peptide libraries made of protein L-amino acids have been synthesized. During screening of the libraries, peptides that bind to avidin have been identified containing a novel motif with two histidines separated by one residue. A sub-library was synthesized and screened, and new critical residues appeared surrounding the two histidines. Additionally peptide libraries made of D-amino acids have been screened with avidin and streptavidin and novel motifs have been found.

Amino Acid Sequence↗
PubMed1995

Effects of ochratoxin A on the mouse immune system after subchronic exposure.

The effects on the immune system of oral, subchronic exposure to ochratoxin A (OA) at 6, 250 or 2600 micrograms/kg diet were studied in female Balb/c mice. After 28 days of exposure, antibody production plague-forming cells/spleen, was suppressed in a dose-dependent manner which was significant in the two highest exposure groups. In addition, a decrease in thymocyte cell counts was seen in the 250-micrograms/kg group. After 90 days exposure, flow cytometry analysis of thymic lymphocyte subpopulations revealed a decreased proportion of mature (CD4+ or CD8+) cells. Furthermore, the mitogenic responsiveness of thymocytes and splenocytes to concanavalin A (Con A) was significantly decreased. This effect was observed in all three treatment groups. Interleukin-2 production of Con A-stimulated lymphocytes, natural killer cell activity, and humoral antibody titres to a viral antigen were not affected by OA treatment. The present results indicate that subchronic, oral exposure to OA affects certain immune functions in mice at exposure levels that may be found in contaminated food products.

Administration, Oral↗