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Biomedical subjects

K Olsen

Publications and source records attributed to K Olsen.

At least 55 records · Page 3Linked to original sources
PubMed1995

The limited role of pneumolysin in the pathogenesis of pneumococcal meningitis.

The aim of this study was to determine the role of pneumolysin, an intracellular toxin of Streptococcus pneumoniae, in the pathogenesis of pneumococcal meningitis. Recombinant pneumolysin (1 microgram), when injected intracisternally into rabbits, resulted in a brisk inflammatory response. However, a pneumolysin-deficient strain of S. pneumoniae caused meningeal inflammation in rabbits indistinguishable from that induced by the parent pneumolysin-producing strain. Furthermore, similar enhancement of meningeal inflammation occurred after ampicillin therapy in animals infected with either the parent strain or the pneumolysin-deficient mutant. These results suggest that although pneumolysin can stimulate the inflammatory cascade in the central nervous system, it is not necessary for the pathogenesis of meningeal inflammation nor does it play a role in postantibiotic enhancement of meningeal inflammation.

Ampicillin↗
PubMed1993

Reaction mechanisms of Trp120-->Phe and wild-type glucoamylases from Aspergillus niger. Interactions with maltooligodextrins and acarbose.

Interactions of wild-type and Trp120-->Phe glucoamylase with maltooligodextrin (Gx) substrates and the tight-binding inhibitor acarbose (A) were investigated here using stopped-flow fluorescence spectroscopy and steady-state kinetic measurements. All wild-type and Trp120-->Phe glucoamylase reactions followed the three-step model E + Gx(or A) (k1) <==> (k-1) EGx (or A) (k2) <==> (k-2) E*Gx(or A) (k3) --> E + P or E-A, previously shown to account for the glucoamylase-maltose system [Olsen, K., Svensson, B., & Christensen, U. (1992) Eur. J. Biochem. 209, 777-784]. K1 = k-1/k1, k2, and k-2, and the catalytic constant, k3, are determined. Binding of maltooligodextrins in the first reaction step is weak, with little difference between wild-type and Trp120-->Phe glucoamylase. The second step, involving a conformational change, in contrast, is strongly influenced by the mutation and by the substrate length. Here wild-type glucoamylase reacts faster and forms more stable intermediates the longer the substrate. In contrast, Trp120-->Phe reacts slower the longer the substrate. The effect of the mutation is thus smallest on maltose. The Trp120-->Phe substitution reduces the fluorescence signal only by 12-20%, indicating that other tryptophanyl residues are important in reporting the conformational change. Trp120 also strongly influences the actual catalytic step, since the mutation decreases the kc values 30-80-fold. Acarbose behaves similar to maltotetraose in the first and the second steps with wild-type but not the Trp120-->Phe glucoamylase. Also, a third step in the acarbose reaction which parallels the catalytic step is strongly affected by the mutation. The rate constant k3 increases 200-fold.

Acarbose↗
PubMed1993

Some occupational exposures as risk factors for malignant lymphomas.

BACKGROUND: Malignant lymphomas (Hodgkin disease [HD] and non-Hodgkin lymphoma [NHL]) have been subject to several epidemiologic studies and found to be associated with various environmental exposures, especially solvents, wood, and phenoxy herbicides. METHODS: Various determinants for HD and NHL were evaluated in a case-referent study encompassing 31 cases of HD, 93 cases of NHL, and 204 referents, all alive. Information on these determinants, mainly occupational exposures, was obtained by mailed questionnaires. RESULTS: Crude odds ratios were increased for various occupational exposures, i.e., exposures to solvents, pesticides, metal fumes, welding, and fresh wood, and nursing. Further analyses based on logistic regression indicated exposure to phenoxy herbicides and fresh wood among sawmill workers, lumberjacks, and paper pulp workers to be significant risk factors for HD. Welding, working as a lumberjack, nursing, and ex-smoking were associated with a significantly increased risk for NHL. Radiographic examinations were negatively associated with HD, as was office work for NHL. CONCLUSIONS: The results were mainly in agreement with the findings of earlier studies, but diverging associations also appeared.

Adult↗
PubMed1993

Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis.

In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria.

Animals↗
PubMed1993

Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.

The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 microgram/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.

Animals↗
PubMed1992

Stopped-flow fluorescence and steady-state kinetic studies of ligand-binding reactions of glucoamylase from Aspergillus niger.

The presteady-state and steady-state kinetics of the binding and hydrolysis of substrates, maltose and isomaltose, and the transition-state analogue, gluconolactone, by glucoamylase from Aspergillus niger were investigated using initial-rate, stopped-flow and steady-state methods. The change in the intrinsic fluorescence of the enzyme was monitored. Distinct mechanistic differences were observed in the interaction of the enzyme with maltose compared to isomaltose. Hydrolysis of maltose requires a three-step mechanism, whereas that of isomaltose involves at least one additional step. The rates of an observed conformational change, which is the second discernible step of the reactions, clearly show a tighter binding of maltose compared to isomaltose, probably because the reverse rate constants differ. Compared to the non-enzymic hydrolysis the transition-state stabilization energy of glucoamylase is approximately -66 kJ/mol with maltose and only -14 kJ/mol with isomaltose. Kinetic analysis of the binding of the inhibitor, gluconolactone, implies that independent interactions of two molecules occur. One of these, apparently, is a simple, fast association reaction in which gluconolactone is weakly bound. The other resembles binding of maltose, involving a fast association followed by a conformational change. Based on the results obtained, we propose new reaction mechanisms for Aspergillus glucoamylase.

Aspergillus niger↗
PubMed1991

Ocular injuries caused by elastic cords.

Five patients with ocular trauma due to elastic cords with attached metal or plastic hooks were evaluated over a 13-month period. Injuries included hyphema, angle recession, lens subluxation, choroidal rupture, vitreous hemorrhage, retinal detachment, and scleral rupture. Two patients suffered penetrating ocular injuries, and three patients had final visual acuities of 20/200 or less. This series emphasizes the potential severity of ocular injury due to these commonly used devices and reiterates a modification in design that might decrease the likelihood of accidental trauma from elastic cords.

Adult↗
PubMed1991

Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis.

Endotoxin concentrations were measured in paired samples of cerebrospinal fluid from 38 patients with Haemophilus influenzae type b meningitis. On admission, the median concentration of endotoxin in cerebrospinal fluid was 104 ng/mL and decreased rapidly in follow-up samples. From 17 to 48 hours after admission, 50% of the patients had concentrations of less than 1 ng/mL. Endotoxin concentrations correlated significantly with concentrations of interleukin 1 beta, protein, and glucose in cerebrospinal fluid, duration of secondary fever, and neurologic abnormalities during hospitalization and on follow-up examinations. Twenty-eight percent of patients with endotoxin concentrations of 100 ng/mL or more on admission had long-term complications, compared with none of those with lower endotoxin concentrations (relative risk, 2.31; 95% confidence interval, 1.53 to 3.48). These results indicate that quantitation of endotoxin in cerebrospinal fluid could be a valuable aid in identifying those children at increased risk of complications during Haemophilus influenzae type b meningitis and provide additional evidence that the Haemophilus influenzae type b meningitis lipo-oligosaccharide is important in the pathogenesis of meningitis.

Animals↗
PubMed1991

Choroidal detachment associated with malignant choroidal tumors.

The association of choroidal detachment with malignant choroidal tumors is not well recognized. The authors' experience with six cases suggests that choroidal detachment may be associated with both metastatic tumors and choroidal melanoma. In two of these cases, the choroidal or retinal detachment was so massive that echography was necessary to detect the underlying tumor. Three patients presented with painful visual loss, and three patients presented with painless visual loss or a visual field defect. In one patient, the correct diagnosis and appropriate treatment of the choroidal metastasis with external radiation relieved the patient's pain and improved visual acuity from 1/200 to 20/35. Metastatic and primary uveal malignant tumors should be added to the list of causes of choroidal detachment and can be excluded only after thorough clinical, and often echographic, examination.

Aged↗
PubMed1991

Suicide in later life: psychological autopsy findings.

The authors report preliminary data from a psychological autopsy study of completed suicide in late life. Sixteen of 18 victims had diagnosable psychopathology, most commonly major depression of late onset. Symptoms manifest prior to death are described and directions for future investigation discussed. The psychological autopsy is shown to be a viable method for studying suicide in the elderly.

Aged↗
PubMed1991

Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1 beta and tumor necrosis factor alpha expression in cultured human astroglial cells by dexamethasone and indomethacin.

In bacterial meningitis, LPS induces production in cerebrospinal fluid of the cytokines IL-1 beta and tumor necrosis factor alpha (TNF alpha), which are the principle mediators of meningeal inflammation. IL-1 beta and TNF alpha induce fever, and elevated temperature may affect cytokine expression. Dexamethasone treatment improves outcome in bacterial meningitis possibly by inhibiting IL-1 beta and TNF alpha. In this report, the effects of elevated temperature and dexamethasone on LPS-stimulated IL-1 beta and TNF alpha mRNA gene expression and protein synthesis were studied in human astrocytoma cell lines and primary cultures of human fetal astrocytes. Cells cultured at 40 degrees C exhibited smaller peaks of IL-1 beta and TNF alpha transcription and protein synthesis compared with cells cultured at 37 degrees C. The addition of dexamethasone before, during, or after exposure of the cells to LPS resulted in temperature-dependent inhibition of IL-1 beta transcription and protein synthesis. The most extensive inhibition occurred in pretreated cells cultured at 37 degrees C. Cotreatment with LPS and dexamethasone also inhibited TNF alpha mRNA transcription at both temperatures. The effects of another antiinflammatory agent, indomethacin, on LPS induction of IL-1 beta and TNF alpha mRNA were temperature and cell line dependent. These findings provide a possible explanation for the efficacy of dexamethasone treatment of bacterial meningitis and support the proposal that fever may be beneficial to the host in this disease.

Astrocytes↗
PubMed1990

Encircling photothrombotic therapy for choroidal Greene melanoma using rose bengal.

The photosensitizing dye rose bengal in combination with an argon green laser (514.5 nm) operated at low power was evaluated in 49 rabbit eyes for treatment of experimental choroidal Greene melanoma by circumferential occlusion of the choroidal vasculature. The effects of no treatment, laser alone, and rose bengal alone were observed in 16 control eyes, all of which showed rapid tumor growth. Immediately following rose bengal injection, 3 minutes of continuous irradiation at 20.4 W/cm2 (500-microns spot, 40 mW) applied in three to four circumferential revolutions around the base of tumor nodules, without direct tumor irradiation, produced peripheral vascular occlusion and consequent tumor inhibition. Similar therapy at higher laser intensity (30.6 W/cm2) and with multiple retreatment sessions (28.0 to 30.6 W/cm2) resulted in increased tumor-inhibiting effect. Low-dose rose bengal phototherapy did not appear to directly damage ocular tissues adjacent to treatment areas; however, when multiple irradiation sessions were given within a short interval, an increased incidence of retinal detachment was observed.

Animals↗
PubMed1990

Suicide and cancer in late life.

In a controlled psychological autopsy study of suicide in late life, eight cases in which the victim's belief that he had cancer played a major role in the decision to end his life were examined. All victims were men. The majority had diagnosable major affective disorders, but none had been seen in mental health care settings. Other common characteristics were an active relationship with a primary physician, numerous losses, prior experience with cancer or debilitating disease, and a rigid, self-sufficient personality style. The cases illustrate the complex determinants of suicidal behavior in the elderly and suggest preventive strategies for the primary care setting.

Aged↗
PubMed1989

Structure of a second crystal form of Bence-Jones protein Loc: strikingly different domain associations in two crystal forms of a single protein.

We have determined the structure of the immunoglobulin light-chain dimer Loc in a second crystal form that was grown from distilled water. The crystal structure was determined to 2.8-A resolution; the R factor is 0.22. The two variable domains are related by local 2-fold axes and form an antigen binding "pocket". The variable domain-variable domain interaction observed in this crystal form differs from the one exhibited by the protein when crystallized from ammonium sulfate in which the two variable domains formed a protrusion (Chang et al., 1985). The structure attained in the distilled water crystals is similar to, but not identical with, the one observed for the Mcg light-chain dimer in crystals grown from ammonium sulfate. Thus, two strikingly different structures were attained by this multisubunit protein in crystals grown under two different, commonly used, crystallization techniques. The quaternary interactions exhibited by the protein in the two crystal forms are sufficiently different to suggest fundamentally different interpretations of the structural basis for the function of this protein. This observation may have general implications regarding the use of single crystallographic determinations for detailed identification of structural and functional relationships. On the other hand, proteins whose structures can be altered by manipulation of crystallization conditions may provide useful systems for study of fundamental structural chemistry.

Bence Jones Protein↗
PubMed1989

Cloning, analysis, and expression of murine perforin 1 cDNA, a component of cytolytic T-cell granules with homology to complement component C9.

The nucleotide sequence coding for the cytotoxic T-lymphocyte (CTL) protein perforin 1 (P1) has been determined and the corresponding protein sequence has been derived. Murine CTL cDNA libraries contained in the vector lambda gt11 were screened by using a monospecific antiserum to purified P1. Three recombinant phages were isolated and their cDNA inserts were sequenced. The derived protein sequence contains 554 amino acids and displays, as expected, considerable homology with certain functional domains in the complement components C9, C8 alpha, C8 beta, and C7. The identity of P1 cDNA clones was verified by prokaryotic expression and the reactivities of antisera produced to the expressed proteins. In addition, antisera were produced to two synthetic peptides located in the center and C-terminal portions of P1. All antisera reacted with purified P1. In Northern blot analyses, P1 cDNA probes recognized a 2.9-kilobase mRNA only in CTL. Perforin mRNA was found in all cloned CTL and in all mixed lymphocyte reactions that gave rise to cytotoxic cells. Perforin mRNA was also detected in virus-specific CTL that had been generated in vivo and isolated from liver tissue of mice infected with lymphocytic choriomeningitis virus. The cell-specific expression of perforin is consistent with its postulated role in cytolysis.

Amino Acid Sequence↗
PubMed1989

Molecular analysis of the fetal IgM response to Treponema pallidum antigens: implications for improved serodiagnosis of congenital syphilis.

Western blot analysis of the fetal IgM response to Treponema pallidum antigens was examined among 39 pairs of maternal/infant sera; this included 12 mothers and infants with active syphilis (group I), 9 mothers with active syphilis and their infants with uncertain infection (group II), and 18 mothers treated for syphilis before delivery and their asymptomatic infants (group III). A fetal IgM response to T. pallidum antigens with apparent molecular masses of 72, 47, 45, 42, 37, 17, and 15 kDa was observed among sera of infants with congenital syphilis. Fractionation of sera into IgM and IgG components by high performance liquid chromatography confirmed that fetal IgM antibodies in every case were directed specifically against a 47-kDa antigen. Two asymptomatic infants from group II also showed serum IgM reactivities with the 47-kDa antigen, thereby appearing to confirm in utero infection. The combined data suggest that fetal serum IgM reactivity with the 47-kDa antigen of T. pallidum can be used as an important molecular marker for the diagnosis of congenital syphilis.

Antibodies, Bacterial↗