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Biomedical subjects

R Olsen

Publications and source records attributed to R Olsen.

At least 19 recordsLinked to original sources
PubMed1992

Immunogenicity and safety of a recombinant vaccinia virus vaccine expressing the carcinoembryonic antigen gene in a nonhuman primate.

We have previously reported the development of a recombinant vaccinia virus vaccine expressing the human carcinoembryonic antigen (CEA) gene, designated rV(NYC)-CEA. This construct has been shown to elicit specific anti-CEA immune responses and an antitumor effect in a murine tumor model. In the studies reported here, the safety and immunogenicity of this recombinant vaccinia virus were evaluated in a rhesus monkey model. Human CEA is a M(r) 180,000 glycoprotein expressed in approximately 90% of gastrointestinal carcinomas and in some breast and non-small cell lung carcinomas. This family also includes normal cross-reacting antigen (NCA). Rhesus monkeys, like humans, have some NCA on the surface of their granulocytes. Eight monkeys were immunized 3 or 4 times by skin scarification with the recombinant CEA vaccine and four monkeys received wild-type vaccinia virus as control. After three vaccinations, all rV(NYC)-CEA-vaccinated animals exhibited a strong anti-CEA antibody response as measured by enzyme-linked immunosorbent assay. The functional ability of these antibodies to mediate lysis of a CEA-bearing tumor cell was demonstrated using human effector cells. This response could be enhanced by interleukin 2. Cellular immunity to CEA was measured by delayed-type hypersensitivity upon intradermal challenge with purified CEA. Only those animals receiving the recombinant vaccine displayed significant anti-CEA responses. Furthermore, peripheral blood mononuclear cells from immunized monkeys were found to proliferate in response to CEA stimulation. All vaccinated monkeys developed local skin irritation at the site of the vaccination, regional lymphadenopathy, and low-grade fevers after immunization. Following immunization with rV(NYC)-CEA, the response was consistent with the usual constitutional symptoms seen with human smallpox virus immunization. Blood counts, differentials, and hepatic and renal chemistries remained normal in all animals throughout the study and for up to 1 year following the primary vaccination. No evidence of immunological cross-reactivity to NCA was found by either a fall in the granulocyte count or analyses for anti-NCA antibodies. Thus, the rV(NYC)-CEA vaccine appears to be safe in rhesus monkeys. The administration of a CEA recombinant vaccine to rhesus monkeys induces both a humoral and a cell-mediated immune response directed against human CEA.

Animals↗
PubMed1991

Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days.

The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)-plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then 500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days, then 160/800 mg orally twice daily. Initially, all patients also received GM every 8 h iv (mean, 606 doses). Antimicrobial resistance necessitated modifying therapy of 14 (32%) of the Amp recipients but of none of the TMP/SMZ recipients (P less than .001). Both regimens produced a satisfactory bacteriologic and clinical response in all cases. Reinfection occurred in 11% of Amp and in 8% of TMP/SMZ recipients. No patient experienced relapsing infection. The TMP/SMZ regimen was less costly and less likely to require modification due to antimicrobial resistance.

Acute Disease↗
PubMed1991

Enhanced mobilization of intracellular Ca2+ induced by halothane in hepatocytes isolated from swine susceptible to malignant hyperthermia.

Halothane, in a dose-dependent manner, induced the release of intracellular Ca2+ in hepatocytes prepared from swine. The magnitude of the release induced by halothane was greater for hepatocytes prepared from animals susceptible to malignant hyperthermia (MH) than for those from normal swine. Two different methods were used to ascertain the release of Ca2+ induced by halothane: 1) the release of 45Ca2+ from nonmitochondrial stores of saponin-permeabilized hepatocytes was measured; and 2) changes in luminescence from intact hepatocytes loaded with the Ca2(+)-sensitive photoprotein aequorin were recorded. It was also observed that, although 1,4,5-inositol trisphosphate (IP3), guanosine-5-triphosphate, and arachidonic acid all induced a significant release of 45Ca2+ from permeabilized swine hepatocytes, only the quantities of 45Ca2+ released by IP3 were significantly greater for the hepatocytes prepared from the animals susceptible to MH. These data indicate an abnormal Ca2+ homeostasis in hepatocytes isolated from swine susceptible to MH, which supports the hypothesis that membrane systems from multiple organs may be affected in this genetic disorder.

Animals↗
PubMed1990

Amiodarone-mediated increase in intracellular free Ca2+ associated with cellular injury to human pulmonary artery endothelial cells.

The cardiac antidysrrhythmic drug amiodarone can give rise to potentially fatal pulmonary toxicity in large numbers of patients. The effect of amiodarone on Ca2+ homeostasis and cell injury has been studied using human pulmonary artery endothelial (HPAE) cells in vitro. Amiodarone produced a concentration-dependent increase in intracellular free Ca2+ concentration ( [Ca2+]i) to micromolar levels that are similar to those seen with physiological stimuli that increase [Ca2+]i. Unlike physiological stimuli, the rise in [Ca2+]i produced by amiodarone developed slowly and was maintained over at least 30 min. Omitting Ca2+ from the external medium reversibly prevented the amiodarone-induced rise in [Ca2+]i. Amiodarone treatment increased the apparent first order rate constants for 45Ca2+ influx and efflux in intact HPAE cells. 45Ca2+ accumulation into the endoplasmic reticulum of saponin-permeabilized HPAE cells was decreased by amiodarone treatment. The release of 45Ca2+ from the endoplasmic reticulum stores by the putative intracellular second messengers inositol-1,4,5-trisphosphate, arachidonic acid, and Ca2+ was blocked by amiodarone treatment. The changes in Ca2+ homeostasis coincide with an increase in [3H]deoxyglucose release as a measure of early cell injury by amiodarone. It is concluded that amiodarone can produce an increase in [Ca2+]i by an action on the plasma membrane that allows the influx of external Ca2+. This increase in [Ca2+]i, together with other changes in Ca2+ homeostasis, may be responsible for the early cell injury associated with amiodarone toxicity.

Amiodarone↗
PubMed1989

Contribution of external and internal Ca2+ to changes in intracellular free Ca2+ produced by mitogens in Swiss 3T3 fibroblasts: the role of dihydropyridine sensitive Ca2+ channels.

Changes in intracellular free Ca2+ concentration [( Ca2+]i) produced by growth factors and mitogens have been studied using aequorin-loaded Swiss 3T3 cells. Decreasing free Ca2+ in the external medium by using EGTA had no significant effect on the increase in [Ca2+]i produced by vasopressin, bradykinin, bombesin or prostaglandin E2, but reduced the increase in [Ca2+]i produced by platelet derived growth factor (PDGF) by 58%, by prostaglandin E1 44% and by prostaglandin F2 alpha 47%. The dihydropyridine Ca2+-channel antagonist nifedipine at 10 microM inhibited the [Ca2+]i response to PDGF by 41% in both the presence of and in the absence of external Ca2+. Methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (BAY K8644), a Ca2+-channel agonist, at 10 microM produced an increase in [Ca2+]i and decreased the [Ca2+]i response to PDGF by 39%. Nifedipine did not block 45Ca2+ uptake or release by inositol 1,4,5-trisphosphate in saponin-permeabilized Swiss 3T3 fibroblasts but BAY K8644 inhibited 45Ca2+ release by inositol 1,4,5-trisphosphate. The results suggest that the increase in [Ca2+]i caused by PDGF in Swiss 3T3 fibroblasts is due to the influx of external Ca2+ through dihydropyridine sensitive Ca2+ channels, as well as release of internal Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Effect of scavengers of active oxygen species and pretreatment with acetyl-salicylic acid on the injury to cultured endothelial cells by thrombin-stimulated platelets.

Thrombin-stimulated human platelets adhere to and injure cultured human endothelial cells. We hypothesize that generation of active oxygen species by the stimulated platelets are involved in the injury. To confirm this, catalase [final concentration (8.25 micrograms/ml)], superoxide dismutase (SOD) (10 micrograms/ml), of D-mannitol (9 mg/ml) were added to the cell culture medium before the experiments. Platelet suspension (200,000/microliters) and thrombin (4 U/ml) were added and the culture dishes shaken for 15 min at room temperature. In separate experiments the endothelial cells were pretreated with acetylsalicylic acid (0.05, 0.1, or 0.5 mM) to test whether the arachidonic acid metabolism of the endothelial cells is involved in the injury process. In preliminary experiments we were able to confirm that platelets, when stimulated by thrombin, produce chemiluminescence which was suppressed by mannitol but not by catalase or SOD. The degree of injury to cultured endothelial cells by thrombin-stimulated platelets, as measured by release of 51Cr from prelabeled endothelial cells, was reduced significantly with the presence of mannitol, but only moderately when catalase or SOD had been added. Morphometric quantification based on scanning electron micrographs of the endothelial cells after exposure to thrombin-stimulated platelets in the presence of catalase or mannitol showed a reduced number of injured cells. Pretreatment of the endothelial cells with acetylsalicylic acid did not cause any significant change in the degree of endothelial cell injury as measured by the 51Cr release. It is concluded that active oxygen species, in particular hydroxyl radicals, may be generated during thrombin stimulation of platelets and cause injury to the endothelial cells.

Aspirin↗
PubMed1989

Effect of reduced training volume on cardiac function, VO2 max, and running performance.

This study examined the physiological effects of reducing training mileage in a veteran long distance runner while increasing exercise intensity. Variables measured included stroke volume, cardiac output, maximum oxygen uptake, ventilation threshold and performance time in a 10,000 m run. For 8 weeks, training mileage was reduced from 75.8 miles per week to 42.5 miles per week including interval training twice weekly. Following the specialized training, performance time was 10 seconds faster although VO2max and heart contractility had decreased. It was concluded that distance running performance can be maintained while considerably reducing training mileage and increasing exercise intensity twice a week.

Adult↗
PubMed1988

An increase in intracellular free Ca2+ associated with serum-free growth stimulation of Swiss 3T3 fibroblasts by epidermal growth factor in the presence of bradykinin.

Bradykinin gave a biphasic increase in intracellular free Ca2+ concentration ([Ca2+]i) in serum-deprived Swiss 3T3 fibroblasts loaded with the photoprotein aequorin. Epidermal growth factor (EGF) alone did not increase [Ca2+]i, but when added after bradykinin there was an increase in [Ca2+]i. The EGF-dependent increase in [Ca2+]i was maximal at 3 min and disappeared with a half-life of 6 min after bradykinin. Removing Ca2+ from the external medium did not abolish either the bradykinin or the EGF-induced [Ca2+]i responses. Although prostaglandins E2 and F2 alpha also gave [Ca2+]i responses and permitted an EGF-dependent [Ca2+]i response, the effect of bradykinin did not appear to be mediated by prostaglandins since it was not blocked by indomethacin. Vasopressin and phorbol 12-myristate 13-acetate both gave a [Ca2+]i response but did not facilitate a [Ca2+]i response by EGF. Bradykinin or EGF alone did not increase DNA synthesis in growth-arrested Swiss 3T3 fibroblasts, but EGF added together with, or after, bradykinin increased DNA synthesis. The effect disappeared with a half-life of 180 min after the addition of bradykinin. It is concluded that stimulation of receptor protein tyrosine kinase is unlikely, by itself, to explain the increase in DNA synthesis produced by EGF. The observed increase in [Ca2+]i caused by EGF after bradykinin probably reflects the interaction of intracellular second messenger pathways leading to facilitation of DNA synthesis.

Aequorin↗
PubMed1988

Effects of endotoxin on the pancreatic ultrastructure.

Intravenous administration of Escherichia coli endotoxin caused a state of shock with increased serum cationic trypsin-like immunoreactivity (CTLI) in a porcine model. The pancreatic acinar cells revealed focal changes, including intracellular oedema, appearance of membrane-bound vacuoles and breaks in the plasma membrane. In the micro circulatory vessels, there was swelling of endothelial cells. Similar changes have been observed in hemorrhagic and cardiogenic shock. This study demonstrates severe ultrastructural changes in the pancreas during E. coli endotoxin shock.

Acute Disease↗
PubMed1987

Ultrastructural changes induced in the isolated rat heart by enzymatically generated oxygen radicals.

This study describes the effect of oxygen radicals on the ultrastructure of the isolated Langendorff-perfused rat heart. Oxygen radicals were enzymatically generated by xanthine oxidase (0.025 U/ml) and hypoxanthine (0.96 mM). Hearts were perfusion-fixed for electron microscopy and stereological technique was performed to obtain estimates of volume fractions (Vv) of different tissue components. Perfusion with oxygen radicals resulted in areas with severely damaged myocardial cells. These changes included swelling and cristolysis of mitochondria, disruption of filaments, development of intracellular edema and focal disruption of the sarcolemma. Stereological examination revealed few alterations after 5 min perfusion with oxygen radicals. After 10 min perfusion with oxygen radicals, however, the Vv (myocyte/myocardium) increased from 0.542 +/- 0.042 (mean +/- S.D.) to 0.663 +/- 0.144, and this paralleled the development of Vv (cellular edema/myocyte) being 0.047 +/- 0.028. Vv (capillary wall/capillary) increased from 0.215 +/- 0.046 to 0.411 +/- 0.123 indicating endothelial swelling. Although the mitochondria appeared swollen, Vv (mitochondria/myocyte) remained constant. The effect of a 35 min recovery period on the ultrastructure was minor. The application of SOD and catalase together with xanthine oxidase and hypoxanthine reduced the observed changes significantly, thus proving the participation of oxygen radicals. This study confirms that oxygen radicals can induce major alterations in myocardial ultrastructure.

Animals↗
PubMed1986

Characteristics of psychiatric patients who engage in assaultive or other fear-inducing behaviors.

The hospital records of 1687 psychiatric patients were rated for the presence of assaultive or other fear-inducing behaviors associated with the reasons for their hospital admissions. Data analyses indicated that significant associations existed between these behaviors and sex, race/ethnicity, diagnosis, previous admissions, referral source for hospitalization, legal status at admission, and legal status at discharge. No associations were found for age, education, marital status, employment status, number of days hospitalized during the index hospitalization, and referral at discharge. A comparison of these results with the results of studies by other investigators led to the conclusion that clinical variables appear to have a more consistent relation to violent behavior than demographic variables. Future research examining for the correlates of violent behavior in psychiatric patients may be more productive by focusing on the type and degree of patients' psychopathologies rather than on patients' demographic characteristics.

Adolescent↗
PubMed1986

Multiple-angle, variable-interval, nonorthogonal MRI.

Multiple-angle, variable-interval, nonorthogonal (MAVIN) MRI is a new, time-saving technique that allows for the independent choice of slice angle and position for each slice in a multiangle pulse sequence. By appropriate adjustment of the slice-select radiofrequency pulse and the slice-select and readout magnetic-field gradients, the interval and angle of each slice may be individually chosen. MAVIN can reduce examination time in studies of the lumbar spine, orbits, knees, and heart, where nonparallel oblique scanning may be necessary and would otherwise require the use of additional pulse sequences. Loss of signal in the region of intersection of multiple planes due to local changes in effective repetition time is a practical limitation. For this reason, scan planes are chosen so that the intersection does not overlie the region of interest.

Humans↗
PubMed1985

Violent or fear-inducing behavior associated with hospital admission.

Recent studies indicate that the incidence of violent or fear-inducing behavior among the mentally ill may be higher than once thought. In this study, medical record admission notes for 1,687 psychiatric patients over a four-year period were examined for indications that the patients had engaged in violent or fear-inducing behavior just prior to hospital admission. This and other studies suggest that the frequency of violent or fear-inducing behavior associated with psychiatric admissions may have stabilized in recent years. The authors also found a significantly higher level of hospital readmissions for violent patients than for other patients. As a result, they caution against assuming that the rate of violent behavior among hospital admissions accurately reflects the prevalence of violent behavior among the general population of the mentally ill.

California↗
PubMed1979

Photoaffinity labeling of three renal cyclic 3',5'-adenosine monophosphate-binding proteins.

Evidence is presented for the presence of multiple cyclic AMP binding components in the plasma membrane and cytosol fractions of porcine renal cortex and medulla. N6-(Ethyl-2-diazomalonyl)-3',5'-adenosine monophosphate, a photoaffinity label for cyclic AMP binding sites, exhibits non-covalent binding characteristics similar to cyclic AMP in membrane and soluble fractions. Binding data for either compound to the plasma membrane fraction yields biphasic Scatchard plots while triphasic plots are obtained with the dialyzed cytosol. When covalently labeled fractions are separated on SDS-polyacrylamide gel electrophoresis, the cyclic AMP photoaffinity label is found on 49 000 and 130 000 dalton components in each kidney fraction. DEAE-cellulose and gel filtration chromatography of the labeled cortical cytosol fraction establishes that the three components suggested by the binding data correspond to two 49 000 dalton species and a 130 000 component. The 49 000 species have higher affinities for cyclic AMP than the 130 000 component (Ka(1) = 2.0 . 10(9), Ka(2) = 1.7 . 10(8), Ka(3) = 1.0 . 10(7)). The 49 000 components are associated with protein kinase activity while the 130 000 component does not exhibit protein kinase, adenosine deaminase, or cyclic nucleotide phosphodiesterase activity. Immunologic results and effects of phosphorylation and cyclic GMP on cyclic AMP binding further suggest that the 49 000 components are regulatory subunits of cyclic AMP-dependent protein kinases. Cyclic AMP binding to the 130 000 component is markedly inhibited by adenosine and adenine nucleotides, but not cyclic GMP. Thus, this component may reflect an aspect of adenosine control or metabolism which may or may not be a cyclic AMP-related cellular function.

Animals↗