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Biomedical subjects

J M Olson

Publications and source records attributed to J M Olson.

At least 19 recordsLinked to original sources

Mechanical performance of scallop adductor muscle during swimming.

Mechanical performance of skeletal muscle has long been the subject of intense interest, but the details of in vivo performance of individual skeletal muscles during normal locomotion remain largely unknown. Performance in vitro has been described with considerable precision under simplified loading conditions. The force production and shortening velocity of most muscles, however, probably change continuously during natural movements. Therefore, modelling in vivo performance on the basis of in vitro contractile properties is subject to large degrees of uncertainty. Designing in vitro experiments that effectively examine the limits of mechanical performance requires increasing knowledge of precisely how muscles are used during normal movements. We report here measurements of the mechanical performance of the adductor muscle in scallops during jet-propulsion swimming. Swimming in scallops is powered solely by the striated portion of the single adductor muscle. Exploiting this simple locomotor morphology with simultaneous high-resolution measurements of pressure and flow rate, we have recorded nearly instantaneous measurements of the performance of a single skeletal muscle during normal locomotion.

Animals

Localization of the peripheral-type benzodiazepine binding site to mitochondria of human glioma cells.

Subcellular fractionation was performed on human U251 glioblastoma cultures. In all subcellular fractions, the binding of the peripheral benzodiazepine ligand, [3H]PK 11195, correlated with the specific activity of monoamine oxidase (r = 0.95, p less than 0.001) and succinate dehydrogenase (r = 0.93, p less than 0.001), two mitochondrial enzymes. The specific activity of plasma membrane and nuclear markers correlated poorly with the presence of PK 11195 binding sites. These data support the mitochondrion as the primary location of peripheral-type benzodiazepine binding sites (PBBS) in human glioma cells. Mitochondria-rich preparations were then assayed for [3H]Ro5-4964 binding. Six nM [3H]Ro5-4964 failed to specifically bind to human U251 mitochondria, but bound vigorously to mitochondria from rat C6 glioma. These data indicate that the low affinity of Ro5-4864 for PBBS in human glioma cells compared to those in rat is due to interspecies receptor variation rather than impaired drug transport into human cells.

Alkaline Phosphatase

Dietary guar gum halts further renal enlargement in rats with established diabetes.

Guar gum, a dietary fiber known to improve glucose tolerance, was fed to rats with established diabetes to determine its effect on renal enlargement and microalbuminuria. Diabetic rats were fed a modified AIN-76A (basal) diet for 4 wk, at which time half the rats continued to receive the same basal diet (DB-BA group) and half were switched to a 5% guar gum diet (DB-GG group). Nondiabetic rats fed the basal diet served as controls (NRL group). After 8 additional weeks the animals were killed. Glycated hemoglobin, a measure of long-term blood glucose control, was 14.4% in the DB-BA group and 12.4% in the DB-GG group, a statistically significant difference (P < 0.05). Kidney weight of the DB-BA group (3.51 g) was significantly greater than that of the DB-GG group (2.76 g) (P < 0.05). Eight weeks after induction of diabetes, 24-h urinary albumin excretion was highest in the DB-BA group and lowest in the NRL group; excretion in the DB-GG group (4 wk of guar feeding) was intermediate. However, by 12 wk no differences in albumin excretion among the groups were apparent. These results suggest that guar gum may be useful for slowing the progression of diabetic nephropathy and that guar gum deserves further study in this regard.

Albuminuria

The amino acid sequence of a major protein component in the light harvesting complex of the green photosynthetic bacterium Chlorobium limicola f. thiosulfatophilum.

A 7.5-kDa protein has been isolated from chlorosomes of Chlorobium limicola f. thiosulfatophilum and the complete primary structure determined by a combination of automatic Edman degradation and plasma desorption mass spectrometry. The 74-residue protein shows great homology to a similar protein of unknown function which has been isolated from Pelodictyon luteolum but otherwise no significant homology to other proteins can be found. The possible role of the protein in the structure and function of the chlorosome is discussed.

Amino Acid Sequence

Regulation of glycolysis in the pectoralis muscles of seasonally acclimatized American goldfinches exposed to cold.

Regulation of glycolysis was assessed in winter- and summer-acclimatized goldfinches (Carduelis tristis). We exposed birds to a thermo-neutral temperature (30 degrees C), moderate cold (-15 degrees C), and severe cold (0 degrees C in an atmosphere of 21% O2-79% He), and then measured concentrations of glycogen, glycolytic intermediates, and citrate in the pectoralis muscles. Winter birds used less glycogen when exposed to moderate cold than did summer birds, confirming the carbohydrate sparing noted by Marsh and Dawson [Am. J. Physiol. 242 (Regulatory Integrative Comp. Physiol. 11): R563-R569, 1982]. However, depletion of muscle glycogen did not correlate with thermoregulatory failure in this study. Concentrations of glucose 6-phosphate and fructose 6-phosphate in the pectoralis muscles were approximately 1.9 and 0.3 mumol/g wet mass in birds exposed to thermoneutral temperatures. The levels of these intermediates fell 50-70% under conditions known to enhance flux through glycolysis as indicated by increased glucose turnover and glycogen depletion. This information identifies phosphofructokinase (PFK) as a major regulated step in glycolysis in these highly aerobic skeletal muscles. Winter birds maintained the inhibition of this step under conditions of moderate cold. However, concentrations of citrate, which have been hypothesized to be an important inhibitor of PFK, did not correlate with the observed pattern of inhibition. Therefore, if the enhanced beta-oxidative capacity of winter birds is important in the regulation of glycolysis, a mechanism other than the accumulation of citrate may be involved.

Acclimatization

Monte Carlo comparison of preliminary methods for ordering multiple genetic loci.

We carried out a simulation study to compare the power of eight methods for preliminary ordering of multiple genetic loci. Using linkage groups of six loci and a simple pedigree structure, we considered the effects on method performance of locus informativity, interlocus spacing, total distance along the chromosome, and sample size. Method performance was assessed using the mean rank of the true order, the proportion of replicates in which the true order was the best order, and the number of orders that needed to be considered for subsequent multipoint linkage analysis in order to include the true order with high probability. A new method which maximizes the sum of adjacent two-point maximum lod scores divided by the equivalent number of informative meioses and the previously described method which minimizes the sum of adjacent recombination fraction estimates were found to be the best overall locus-ordering methods for the situations considered, although several other methods also performed well.

Chromosome Mapping

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