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Biomedical subjects

M Moss

Publications and source records attributed to M Moss.

At least 91 records · Page 5Linked to original sources

Effects of alterations of oxygen transport on the neonate.

In the foregoing discussion we have attempted to provide an overview of much of the information available on the effects of changes in systemic oxygen transport on the neonatal and young subject. Using data synthesized from both human and animal studies, we have described the normal developmental changes and the findings of studies in which oxygen transport has been acutely altered by experimental means. This was intended to highlight the potentially delicate balance that can occur between oxygen supply and utilization during the critical period of rapid growth after birth. Finally, using the left-to-right shunt as an example, we have tried to show how a common pathologic condition can impair oxygen transport at multiple sites, and how normal development can make matters worse. It is anticipated that from an understanding of both normal and abnormal physiology, we will be able to develop rational approaches to the management of infants in whom the oxygen transport system has been stressed beyond its reserve.

2,3-Diphosphoglycerate↗

Photoaffinity labeling of specific alpha-thrombin binding sites on Chinese hamster lung cells.

Binding sites for alpha-thrombin on cultured Chinese hamster lung cells were identified using photoactivatable cross-linking conjugates of diisopropylphosphorofluoridate-inactivated alpha-thrombin. A series of photoaffinity reagents was synthesized that permitted systematic variation of the extent of thrombin modification and of steric factors affecting the ability of the photoaffinity reagent to contact thrombin receptors. The reagents were synthesized with a tritium label to accurately determine the number of photoaffinity molecules linked to each thrombin. Also, they were synthesized with different length spacer arms between the photoreactive cross-linking group (a nitroarylazide) and the end which linked to alpha-thrombin (a succinimide ester). By calculating the percentage of the thrombin surface that would be accessed by modifying it with a fixed molar excess of each reagent, it was possible to select the photoaffinity reagents that would be most effective for cross-linking 125I-labeled diisopropylphosphorofluoridate-inactivated alpha-thrombin to its cellular binding sites. The validity of this selection procedure was confirmed in experiments in which an Mr = 150,000 cellular component was labeled. This component had the properties of a specific binding site for thrombin since labeling was readily competed for by nonlabeled alpha-thrombin. The cross-linking achieved was due to the photoactivatable reagent since no detectable cross-linked complex was formed in the absence of photoactivation or with 125I-labeled diisopropylphosphorofluoridate-inactivated alpha-thrombin that was not conjugated with the photoaffinity reagent.

Affinity Labels↗

Enhanced preference for perceptual novelty in the monkey after section of the fornix but not after ablation of the hippocampus.

Previously uncovered discrepancies between the behavioral effects of fornix sections and hippocampal ablations in the monkey suggested that damage to the fornix but not that to the hippocampus may result in a motivational post-operative change. To test this notion, control monkeys and those with damage to either hippocampus or fornix were given an opportunity to choose freely between presentations of novel or repetitive stimuli in two modalities. In the visual mode, the choice was between viewing color slides which changed on every trial or repeated presentations of a geometric pattern (experiments 1 and 1a). In the auditory mode, the choice was between trains of identical clicks and different sound patterns (experiments 2 and 2a). Monkeys with sections of the fornix, but not those with ablations of hippocampus, showed an abnormally marked preference for novel stimuli in both modalities, even when perceptual novelty was designed to compete unfavorably with food reward (experiments 1b and 2b). These findings (a) provide another instance of functional dissociation between the effects of fornix and hippocampal damage and caution against assuming safely that data obtained with sections of the fornix will always mirror the behavioral consequences of hippocampal ablations; and (b) suggest that the hippocampus of primates may participate in the mediation of cognitive-motivational aspects of behavior which should be taken into account when the role of the hippocampus in memory processes is considered.

Animals↗

Effects of calcium and verapamil on vesicourethral smooth muscle of rabbits.

Isolated smooth muscle strips from the rabbit bladder body, bladder base, and proximal urethra were contracted with ionic calcium (Ca2+) alone and with the calcium-selective ionophore A23187, acetylcholine, norepinephrine, adenosine triphosphate (ATP), and direct electrical stimulation. The effects of Ca2+ and the calcium entry blocker verapamil on spontaneous muscle activity and on contractions induced by these agonists were examined. Ca2+ -free Tyrode's solution and verapamil, 1 x 10(-7)M and above, relaxed all of the vesicourethral smooth muscle strips. In addition verapamil, 1 x 10(-8) to 1 x 10(-6) M depending on the particular stimulant employed, noncompetitively inhibited smooth muscle contractions elicited by Ca2+, acetylcholine, norepinephrine, ATP, and direct electrical stimulation. It was concluded that transmembrane Ca2+ influx was important not only in the maintenance of tone and spontaneous phasic muscle activity, but also for the activation of contractions induced by all of the stimulants tested. The data also suggest that intracellular Ca2+ fraction(s) participate in the contractile responses to acetylcholine and norepinephrine challenge, but not to contractions evoked by ATP or electricity.

Acetylcholine↗

Nucleotide sequence of an external transcribed spacer in Xenopus laevis rDNA: sequences flanking the 5' and 3' ends of 18S rRNA are non-complementary.

We have sequenced the external transcribed spacer (ETS) of a ribosomal transcription unit from Xenopus laevis, together with sections of the preceding non-transcribed spacer. Our analysis was carried out on the same cloned transcription unit as that from which the internal transcribed spacers (ITS) were previously sequenced. The ETS is approximately 712 nucleotides long and, like the ITS regions, is generally very rich in C plus G. Features of the sequence include an excess of oligo-C tracts over oligo-G tracts and a tract of 37 nucleotides consisting almost entirely of G and A residues. Parts of the sequence can give rise to stable internal secondary structures. However, in contrast to Escherichia coli, there is no potential for major base-pairing between the 18S flanking regions of the ETS and ITS. Further findings are that there are no initiation (ATG) codons in the ETS and that, as in other X.laevis rDNA cloned units, the sequence preceding the ETS is duplicated, with a few changes, in the "Bam island" sequence of the non-transcribed spacer.

Animals↗

Platelet monoamine oxidase activity in relatives of alcoholics. Preliminary study with matched control subjects.

Platelet monoamine oxidase (MAO) activity levels were determined before and 180 minutes after ingestion of ethyl alcohol in 30 healthy men aged 21 to 25 years. The subjects included 15 men with alcoholic first-degree relatives who were matched by demography, height-weight ratio, and drinking history with 15 control subjects who had no family history of alcoholism. There was a nonsignificant trend toward lower platelet MAO activities at baseline and after ethyl alcohol ingestion in the group with alcoholic relatives when compared with the control subjects who had no family history of alcoholism. With an arbitrary MAO cutoff of 5.24 nmole/mg of protein per hour, eight of the 15 subjects with alcoholic relatives and 12 of the 15 without alcoholic relatives were correctly identified. However, because of the number of false-positive and false-negative findings, the results have limited clinical usefulness.

Adolescent↗

A research and service oriented multilevel assessment instrument.

An assessment instrument capable of measuring the wellbeing of the aged in a number of significant domains is described. This Philadelphia Geriatric Center Multilevel Assessment Instrument (MAI) systematically assesses behavioral competence in the domains of health, activities of daily living, cognition, time use, and social interaction and in the sectors of psychological wellbeing and perceived environmental quality. Determination of the psychometric qualities of measures of different length in each of these domains and sectors was made. The performance of 590 older people in groups composed of independent community residents, in-home services clients, and people awaiting admission to an institution was determined. The MAI is seen as useful for both research and for assessment in service-giving situations.

Activities of Daily Living↗

Hippocampal resections impair associative learning and recognition memory in the monkey.

Damage to the hippocampus has been implicated in the permanent loss of memory in patients with medial temporal lobe resections. In two previous studies, it was established that bilateral ablations of the hippocampus in the monkey impaired performance on an associative learning task and on an object discrimination retention task. The two objectives of the present study were to assess the long term effects of hippocampal resections in the monkey and to extend the analysis of the effects of these resections to recognition memory. Therefore, the performance of monkeys with either hippocampal ablations or fornix transections, sustained 5 years earlier, was compared (1) on a concurrent discrimination task--a previously unencountered associative learning task--and (2) on a nonmatching-to-sample recognition task with either delays interposed between the presentation of the sample object and the recognition trial or with lists of either 1-, 3-, 5-, or 10-object samples. Significant impairment on both tasks was found after hippocampal, but not after fornix, damage. Though monkeys in the hippocampal group were impaired on both delays and lists, the impairment was more severe on the lists, with abnormal sensitivity to pro- and retroactive interference as a possible source of difficulty. Thus, in parallel with clinical findings, ablations of the hippocampus in the nonhuman primate produce an enduring disruption of memory.

Animals↗

Cleavage of cell surface proteins by thrombin.

This study was based on our previous findings that the mitogenic action of thrombin on cultured fibroblasts can result from interaction of thrombin with the cell surface in the absence of internalization, and that the proteolytic activity of thrombin is required for stimulation of cell division. This prompted us to look for thrombin-mediated cleavages using 2-dimensional gel electrophoresis of labeled cell surface proteins. Surface membrane components were labeled by 3 procedures: 1) proteins were labeled by lactoperoxidase-catalyzed iodination using 125I-; 2) galactose and galactosamine residues of glycoproteins were oxidized with galactose oxidase and reduced with 3H-NaBH4; and 3) glycoproteins were metabolically labeled by incubating cells with 3H-fucose. labeling with the first 2 procedures was carried out after thrombin treatment; in contrast, cells metabolically labeled with 3H-fucose were subsequently treated with thrombin to look for proteolytic cleavages. Collectively, these studies indicated that only about 5 cell surface proteins were thrombin-sensitive, consistent with the high specificity of this protease. Each of the labeling procedures revealed a thrombin-sensitive cell surface glycoprotein which was identified as fibronectin by immunoprecipitation experiments. In addition, cell surface proteins of about 140K and 55K daltons were thrombin-sensitive. However, cell surface proteins of about 45K daltons and 130K to 150K daltons were increased after thrombin treatment. These experiments were conducted on an established line of Chinese hamster lung cells with the eventual goal of studying thrombin-mediated cleavages of cell surface proteins in a large number or in cloned populations derived from this line that are either responsive or unresponsive to the mitogenic action of thrombin. This approach should permit identification of proteolytic cleavages tha are necessary for thrombin-stimulated cell division.

Animals↗

Regulation of tropomyosin gene expression during myogenesis.

In skeletal muscle, tropomyosin has a critical role in transduction of calcium-induced contraction. Presently, little is known about the regulation of tropomyosin gene expression during myogenesis. In the present study, qualitative and quantitative changes in the nucleic acid populations of differentiating chicken embryo muscle cells in culture have been examined. Total nucleic acid content per nucleus increased about fivefold in fully developed myotubes as compared to mononucleated myoblasts. The contribution of deoxyribonucleic acid to the total nucleic acid population decreased from 24% in myoblasts to 5% of total nucleic acid in myotubes. Concomitant with the decrement in deoxyribonucleic acid contribution to total nucleic acid was an increase in polyadenylated ribonucleic acid (RNA) content per cell which reached levels in myotubes that were 17-fold higher than those of myoblasts. Specific changes in the RNA population during myogenesis were further investigated by quantitation of the synthetic capacity (messenger RNA levels) per cell for alpha- and beta-tropomyosin. Cell-free translation and immunoprecipitation demonstrated an approximately 40-fold increase in messenger RNA levels per nucleus for alpha- and beta-tropomyosin after fusion in the terminally differentiated myotubes. Indirect immunofluorescence with affinity-purified tropomyosin antibodies demonstrated the presence of tropomyosin-containing filaments in cells throughout myogenesis. Thus, the tropomyosin genes are constitutively expressed during muscle differentiation through the production of tropomyosin messenger RNA and translation into tropomyosin protein.

Animals↗

Concurrent discrimination learning of monkeys after hippocampal, entorhinal, or fornix lesions.

Ablations of anterior inferotemporal cortex in monkeys are known to impair learning when discriminations between members of several pairs of objects are taught concurrently. This deficit has been attributed to a loss of visual mnemonic functions. But ablations of hippocampus have also been shown to impair retention, and this impairment transcends the visual modality. Therefore, in the first of two experiments, we compared the behavioral effects of inferotemporal cortical lesions with those of either hippocampus, entorhinal area, or fornix, using a visual concurrent discrimination task. Monkeys with either hippocampal or entorhinal ablations were impaired, while those with fornix sections were not. However, ablations of hippocampus included inadvertent damage of the inferotemporal cortex. Therefore, in the second experiment, behavioral effects of inferotemporal lesions were compared with those of hippocampus (without additional inferotemporal damage) on the concurrent task in both visual and tactual modalities. In the visual mode, monkeys with hippocampal removals were as impaired as those with inferotemporal ablations. In the tactual mode, however, hippocampal, but no inferotemporal, ablations were followed by a deficit. Our results, taken together with other existing evidence, emphasize the role of the hippocampus in mediating associative learning in more than one modality. These results, obtained with non-human primates, are in line with clinical findings.

Animals↗

Dopamine-beta-hydroxylase activity levels in men at high risk for alcoholism and controls.

Plasma DBH activity levels were determined for 22 nonalcoholic young men with alcoholic close relatives (the FHP or family history positive group) and results compared to family history negative (FHN) controls matched on demography, height/weight ratio, and drinking history. These enzyme levels were then correlated with the usual drinking history over the prior 6 months and with the intensity of intoxication achieved after drinking 0.75 ml of ethanol/kg body weight. The FHP men demonstrated a 20% lower level of DBH (p greater than 0.1) indicating no significant difference between the groups. Base-line DBH activities correlated significantly with the level of intoxication for the FHN group (r = 0.44, p less than 0.025) with a trend for an inverse correlation with the average drinking history. FHP men, on the other hand, demonstrated only a nonsignificant association between peak intoxication level and base-line DBH and a positive correlation (r = 0.37, p less than 0.05) with the average number of drinks/drinking day. These results are not consistent with the probability that a premorbid DBH assay could be used as one indicator of propensity towards alcoholism. The differences between FHP and FHN groups on correlations between DBH and peak intoxication or usual drinking history raise speculations that the "normal" (FHN) relationship between alcohol intake and plasma DBH activity may be impaired in individuals at high risk (FHP) for the future development of alcoholism.

Adult↗