Search PubMed⌕ Search

Biomedical subjects

J M Olson

Publications and source records attributed to J M Olson.

At least 91 records · Page 5Linked to original sources

PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site.

Human gliomas were imaged in vivo using ligands for the peripheral-type benzodiazepine binding site (or omega 3 binding site) and positron emission tomography (PET). Although gliomas have a high density of the peripheral-type benzodiazepine binding site, PET scans with a selective ligand for this site, [11C] Ro5-4864, failed to demonstrate higher radioactivity levels in human gliomas than in brain. In vitro studies of surgically removed specimens of human glioma demonstrated little binding of Ro5-4864 but high levels of binding of another selective ligand, PK 11195. Scans with [11C]PK 11195 demonstrated increased radioactivity in glioma compared to brain in 8 of 10 patients. Radioactivity in tumor and the ratios of radioactivity in tumor to that in remote gray and in white matter correlated significantly with the specific activity of [11C]PK 11195, suggesting that accumulation represents saturable high-affinity binding. We conclude that the PK 11195 manifests greater binding than Ro5-4864 to the peripheral-type benzodiazepine binding site on human gliomas and that human gliomas can be successfully imaged using [11C]PK 11195 and PET.

Benzodiazepinones↗

Alternative genetic models for the inheritance of the phenylthiocarbamide taste deficiency.

Pedigree segregation analysis was used to examine several one- and two-locus models of the inheritance of phenylthiocarbamide (PTC) taste deficiency that extend the traditional one-locus recessive model by the addition of either another allele or another locus, and in some cases predict two types of nontasters. These models allow nontaster by nontaster matings to produce taster offspring, consistent with our data and several previous studies which use the Harris and Kalmus [Annals of Eugenics 15:24-32, 1949] dilution method. The models fit our data set of 1,152 individuals from 120 families significantly better than the one-locus recessive model. The best fit was obtained with a two-locus model in which one locus controls PTC tasting and the other locus controls a more general taste ability. This model is consistent with research on the physiology of PTC tasting and with results from genetic linkage studies. Further study is suggested to evaluate better the accuracy of the proposed model.

Alleles↗

Synthesis of a high specific activity 125I-labeled analog of PK 11195, potential agent for SPECT imaging of the peripheral benzodiazepine binding site.

The peripheral benzodiazepine binding site ligand PK 11195 has been 125I-labeled by direct displacement of aromatic chlorine under solid-state conditions in 50-76% radiochemical yield and greater than 94% radiochemical purity. Purification by high pressure liquid chromatography increased the specific activity of the product from an initial 15-17 Ci/mmol to a final activity of 260-910 Ci/mmol. To determine the affinity of this [125I]PK 11195 analog for human glioma cells, saturation experiments were performed on monolayers of U251 human glioblastoma cells. Scatchard analysis of saturation data demonstrated that the [125I]PK 11195 analog binds to a single class of sites with a KD of 8.0 +/- 1.7 nM and maximal binding of 3.8 +/- 0.1 pmol/mg protein. These values are similar to those obtained when [3H]PK 11195 was assayed in U251 cells (KD = 14 +/- 3.4, Bmax = 4.1 +/- 1.3) suggesting that iodination does not appreciably alter the binding of PK 11195 to human glioma cells. In vivo autoradiographic studies of brain in C6 glioma bearing rats demonstrate selective binding of the radioligand to the tumor. These results suggest that this [125I]PK 11195 analog may be a useful radiotracer for the study of peripheral benzodiazepine binding sites.

Animals↗

Tetanus: an uncommon cause of dysphagia.

A 53-year-old woman was examined at our medical center because of progressive dysphagia of 14 days' duration and a severe inability to open her mouth and swallow saliva. A barium esophagogram showed no obstruction, but pooling of barium in the hypopharynx suggested a neuromuscular disorder. The clinical diagnosis of tetanus was confirmed by electromyography. With appropriate therapy, the patient recovered during a period of 6 weeks. This case illustrates both an uncommon cause of dysphagia and an uncommon initial manifestation of tetanus.

Age Factors↗

Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for diagnostic imaging.

Binding of the isoquinoline PK 11195 and of the benzodiazepines Ro5-4864 and flunitrazepam was compared in glioma cells and tissues. In human and rat glioma cell cultures [3H]PK 11195 bound with higher affinity (Kd = 14.01 and 15.76 nM, respectively) than either Ro5-4864 (Ki = 1200 and 84.9 nM, respectively) or flunitrazepam (Ki greater than 10,000 and = 848 nM, respectively). Autoradiograms of postmortem human brain sections containing glioma revealed that [3H]PK 11195 bound specifically to intact tumor cells and not to cells of normal cerebral cortex or necrotic areas of the tumor. Total [3H]Ro5-4864 or [3H]flunitrazepam binding to these sections was indistinguishable from nonspecific binding, and regions of tumor and normal brain could not be delineated. These results support the use of radiolabeled PK 11195 for clinical trials of imaging human gliomas by positron emission tomography.

Benzodiazepines↗

Presence of peripheral-type benzodiazepine binding sites on human erythrocyte membranes.

A nanomolar affinity peripheral-type benzodiazepine binding site is described in human erythrocyte membranes. [3H]PK 11195 is displaced from this binding site by unlabeled drugs with the rank order PK 11195 greater than Ro 5-4864 greater than flunitrazepam much greater than clonazepam. Neither GABA nor a non-hydrolyzable analog of GTP have an effect on binding parameters. These data provide evidence that a peripheral-type benzodiazepine binding site, pharmacologically similar to the intracellular binding site described in other tissues, is present in the plasma membrane of human erythrocytes.

Benzodiazepinones↗

Thermogenic capabilities of the opossum Monodelphis domestica when warm and cold acclimated: similarities between American and Australian marsupials.

1. Monodelphis domestica is a small marsupial mammal from South America. Its thermogenic abilities in the cold were determined when the opossums were both warm (WA) and cold (CA) acclimated. Maximum heat production of M. domestica was obtained at low temperatures in helium-oxygen. 2. Basal metabolic rate (BMR) in the WA animals was 3.2 W/kg and mean body temperature was 32.6 degrees C at 30 degrees C. These values were lower than those generally reported for marsupials. Nevertheless, these M. domestica showed considerable metabolic expansibility in response to cold. Sustained (summit) metabolism was 8-9 times BMR, while peak metabolism was 11-13 times BMR. These maximum values were equal to, or above, those expected in small placentals. 3. Cold acclimation altered the thermal responses of M. domestica, particularly in warm TaS. However, summit metabolism was not significantly increased; nor did M. domestica show a significant thermogenic response to noradrenaline, which in many small placentals elicits non-shivering thermogenesis. The thermoregulatory responses of this American marsupial were, in most aspects, similar to those of Australian marsupials. This suggests that the considerable thermoregulatory abilities of marsupials are of some antiquity.

Acclimatization↗

Effects of stress and characteristic adaptability on semen quality in healthy men.

Semen from 28 healthy volunteers was assessed for basic semen measure and percent of abnormal morphologic forms every 2 weeks for 6 months. Concurrent self-reports were obtained on abstinence, frequency of ejaculation, health behavior and status, experienced stress, social support, and life events. A single assessment of characteristic adaptability (ego resiliency) also was obtained. Significant between-subject positive correlations were reported among selected semen measures, abstinence, and ego-resiliency. Stress was correlated negatively with semen measures of volume and percent normal morphologic forms.

Adult↗

Misattribution, preparatory information, and speech anxiety.

In two experiments with undergraduate subjects, I compared the effects of misattribution versus information manipulations on speech anxiety. In Experiment 1, some subjects were allegedly exposed to subliminal noise while reading a speech in front of a camera. These subjects were told that subliminal noise makes people feel either unpleasantly aroused or pleasantly relaxed or that it has no effect. Subjects in a fourth condition were given accurate information about how they would feel (unpleasantly aroused) but were not exposed to the subliminal noise misattribution source. In Experiment 2, I replicated the arousing noise and accurate information conditions from the first study and added two new groups incorporating a delay that should preclude misattribution. In both experiments, the alleged presence of arousing subliminal noise reduced subjects' speech dysfluencies during the speech task, whereas the presentation of accurate information alone did not have a comparable ameliorative effect. Thus, both experiments supported the misattribution interpretation of why neutral labels for arousal can reduce emotionality.

Anxiety↗

Autoradiographic localization of cerebellar excitatory amino acid binding sites in the mouse.

We have investigated the cellular localization of cerebellar excitatory amino acid binding sites in normal mice, in mice deficient in granule cells and, perhaps, stellate, basket and Golgi cells (granuloprival mice) and in mice lacking Purkinje cells. In the molecular layer of normal mouse cerebellum, the quisqualate-sensitive binding sites were the predominant type of excitatory amino acid receptor and there were relatively few N-methyl-D-aspartate or kainate-sensitive binding sites. The granule cell layer of normal mice contained a mixture of all 3 types, the N-methyl-D-aspartate-sensitive binding sites being predominant. In the molecular layer of granuloprival mice, the number of quisqualate-sensitive binding sites was increased to 214% of control (P less than 0.01), whereas N-methyl-D-aspartate-sensitive binding sites were decreased to 62% of control (P less than 0.001) and kainate-sensitive binding sites were unchanged. In the granule cell layer of these mice, quisqualate-sensitive binding sites were increased to 200% (P less than 0.01), N-methyl-D-aspartate-sensitive binding sites were decreased to 47% (P less than 0.001) and kainate-sensitive binding sites were decreased to 49% (P less than 0.01 of their respective control values. In the molecular layer of mice lacking Purkinje cells, quisqualate-sensitive binding sites were reduced to 29% (P less than 0.001) of control and N-methyl-D-aspartate-sensitive binding sites were unchanged. In the granule cell layer of these mice, neither quisqualate nor N-methyl-D-aspartate-sensitive binding sites were changed. These results suggest that (1) quisqualate-sensitive binding sites are located principally on dendrites of Purkinje cells and that they up-regulate after deafferentation; (2) N-methyl-D-aspartate-sensitive binding sites are located on granule cells and, perhaps, stellate, basket and Golgi cells, and (3) kainate binding sites are located on cell bodies of granule and, perhaps, Golgi cells.

Animals↗

Barriers to receiving adequate prenatal care.

One hundred eleven postpartum patients who received varying amounts of prenatal care (no care, inadequate care, intermediate care, and adequate care) were assessed for demographic, medical and sociocultural factors by interview and review of the medical chart. Six sociocultural factors identified by stepwise multiple regression contributed to 49% of the variance for amount of prenatal care: amount of insurance, attitudes toward health professionals, delays in suspecting pregnancy, delay in telling others about the pregnancy, perception of the importance of prenatal care, and initial attitudes about being pregnant. Results are discussed in terms of developing outreach programs altered to the patient's needs and life-styles.

Adult↗

A new bacteriochlorophyll a-protein complex associated with chlorosomes of green sulfur bacteria.

Chlorosomes were prepared from Chlorobium limicola f. thiosulfatophilum by sucrose density gradient centrifugation. Cells broken in the presence of 2 M NaSCN yielded three chlorosome fractions in the gradient: low density (no sucrose), medium density (approx. 18% sucrose), and high density (approx. 26% sucrose). All fractions were stable at any chlorosome concentration. Cells broken in the absence of 2 M NaSCN also yielded three fractions, but only the high-density fraction contained stable chlorosomes. The medium-density chlorosomes were stable only when highly concentrated. Upon dilution, bacteriochlorophyll (BChl) c was degraded to bacteriopheophytin c and concomitantly a band at 794 nm (BChl a) was revealed. Two 794-nm fractions were observed with the same densities as low- and medium-density chlorosomes. The protein composition of the 794-nm fractions was similar to that of the stable chlorosome fractions. All showed a 4-5 kDa (Mr) protein as a major component, but no trace of the 40-kDa protein characteristic of the water-soluble BChl a-protein of green sulfur bacteria. BChl a was present in all types of chlorosomes, in stable chlorosomes the BChl c/BChl a ratio was approx. 90. A special BChl a-protein (794 nm) inside the chlorosome is postulated to mediate energy transfer from BChl c to the water-soluble BChl a-protein in the baseplate.

Bacteria↗

Correlation of serum estradiol levels and ultrasound monitoring to assess follicular maturation.

Thirty-eight patients underwent 38 cycles of induction of ovulation using stepwise human menopausal gonadotropin and human chorionic gonadotropin (hCG) administration. Ultrasonography was performed on the day of hCG injection. The mean age +/- standard error of the mean (SEM) of the patients was 32.9 +/- 0.8 years, and the duration of infertility ranged from 1 to 14 years (median, 2.8). Ultrasonographic measurements were obtained of the largest diameter and the volume of the dominant follicles as well as all other follicles in both ovaries. Data were analyzed by Student's t-test, regression analysis, and analysis of variance. The mean +/- SEM diameter of dominant follicles was 1.8 +/- 0.1 cm, and the volume of dominant follicles was 3.5 +/- 0.8 cm. The mean +/- SEM serum estradiol (E2) level before hCG administration was 659 +/- 62 pg/ml. Significant correlations were found between preovulatory serum E2 levels and the total follicular volume of both ovaries (r = 0.41, P less than 0.05) and follicular volume of the ovary containing the dominant follicle (r = 0.42, P less than 0.01). No significant correlation was observed between the diameter of the dominant follicle and serum E2 levels. These results suggest that ultrasound findings reflect growth, whereas serum E2 levels primarily detect functional activity of follicles.

Adult↗

Variation of semen measures within normal men.

Variation in semen measures was assessed bimonthly in 15 healthy men over a 6-month period. Average within-subject coefficients of variation for sperm count, morphologic features, motility, and semen volume demonstrate considerable variation. Each day of abstinence increased the volume by an increment of 0.62 ml, the count by 17.6 X 10(6)/ml, and motility by 1.2%. Sperm count and semen volume correlated positively within subjects. Intraclass and serial correlations of semen measures provided an empirical clinical guide to the number and spacing of specimens. Three specimens spaced no more than 2 weeks apart established a reliable semen profile. Findings can be applied to basic research and clinical practice.

Adult↗

Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate- and kainate-sensitive glutamate binding sites.

Quantitative autoradiography was used to characterize the pharmacological specificity and anatomical distributions of subtypes of L-[3H]glutamate binding sites in rat brain. One population of sites was sensitive to N-methyl-D-aspartate (NMDA) and other compounds thought to be specific for the NMDA receptor. This site was enriched in stratum radiatum of hippocampus (CA1) where it constituted about 80% of glutamate binding sites and it represented a variable portion of glutamate binding sites throughout the brain. A second population of sites had a high affinity for quisqualate. Approximately 80% of glutamate binding sites in cerebellar molecular layer were of the high affinity quisqualate type. The number of these sites was greatly increased in the presence of Cl- and Ca++ ions. A subset of the high affinity quisqualate sites was sensitive to competition by kainate, particularly in stratum lucidum of hippocampus; the density of these high affinity kainate-sensitive sites was decreased in the presence of Ca++ but not Cl- ions. At high concentrations quisqualate competes for all glutamate binding sites, as reported previously. There was a good correspondence between the density and distribution of low affinity quisqualate sites and NMDA-sensitive sites. Pharmacological analysis suggested that the low affinity quisqualate site and the NMDA site are equivalent. Anatomical and pharmacological evidence suggests that the NMDA-, (high affinity) quisqualate- and kainate-sensitive glutamate binding sites may correspond to the physiologically defined NMDA, quisqualate and kainate receptors.

Animals↗

Depression, psychopathology, and self-serving attributions.

Depressed and non-depressed psychiatric in-patients and non-depressed non-psychiatric controls classified their performance on a verbal recognition task as either a success or a failure, and made attributions about the causes of their perceived success or failure. In all three groups, subjects who classified their performance as a success attributed their outcome more to internal and less to external factors than did subjects who classified their performance as a failure. These results suggest that depression and attributional style may not necessarily be related. Discussion centres on the idea that individuals' expectations of success can affect their subsequent attributions.

Depressive Disorder↗

Protein carboxymethylation during in vitro culture of human peripheral blood monocytes and pulmonary alveolar macrophages.

Protein carboxymethylase (PCM) activity was evaluated for long-term in vitro cultures of human peripheral blood monocytes and pulmonary alveolar macrophages. Both cell types exhibited increases in endogenous (without addition of the exogenous substrate, gelatin) and total (with gelatin) enzyme activity with increased time in culture. Monocytes developed increased activity after a 5-day lag period; three-to four-fold increases over day 1 values in both total and endogenous specific activity occurred. In contrast, PCM activity increased for pulmonary alveolar macrophage (PAM) without a detectable lag period. Although the increase in endogenous activity of 10--14-day PAM culture was similar to comparable age monocyte cultures, total enzyme activity increased only two-fold above day 1 values. The observation of changes in PCM endogenous specific activity in monocyte cultures may reflect alterations in enzyme activity and/or levels of endogenous methyl-acceptor proteins.

Cells, Cultured↗