Biomedical subjects
Publications and source records attributed to M Wright.
Anterior fontanelles from 19 fetuses over a range of gestational ages (from 8 weeks to full term) were obtained to study the anatomy and development in relation to the application of the principles of fontanometry. The most important feature was the development of an elastic membrane by 23 weeks' gestation; a subcutaneous layer of fat had appeared by 28 weeks' gestation.
The regulation of the mitotic histone H1 kinase activity has been analyzed during the naturally synchronous cell cycle of Physarum polycephalum plasmodia. The universal binding property of the p13suc1 Schizosaccharomyces pombe gene product was used to precipitate and assay the cdc2 histone H1 kinase activity. The kinase activity peaks at the beginning of metaphase and its decline, which requires protein synthesis, appears to be an early event during the metaphase process. Microtubular poisons, temperature shifts and DNA synthesis inhibitors were used to perturb cell cycle regulatory pathways and characterize their effects on cdc2 kinase activation. Our results suggest that the full activation of the mitotic kinase requires at least two successive triggering signals involving microtubular components and DNA synthesis.
Explore the source record for details and available documents.
Chronic injection of iminodipropionitrile (IDPN) to rats causes persistent motor abnormalities such as hyperactivity, lateral and vertical dyskinesia of the neck, and random circling. These behavioral changes are very similar to those observed after the acute administration of serotonin (5-HT) agonists in rodents. Moreover, some aspects of this syndrome are reproduced by stimulation of 5-HT1A receptors. The present quantitative autoradiographic study revealed a number of changes in 8-hydroxy-2-[di-n-propylamino-3H]tetralin (8-OH[3H]DPAT)-labeled 5-HT1A receptors in the brains of IDPN-treated rats. There were significant increases of 8-OH[3H]DPAT binding in the frontal cortex and in the caudate-putamen. In contrast, there were significant decreases in the interpeduncular nucleus, the pyramidal layer of the CA3 field of hippocampus, the superior colliculus and the pars reticulata of the substantia nigra. These results provide further evidence for the involvement of the 5-HT system in the development of the IDPN-induced dyskinetic syndrome.
Chronic injection of iminodipropionitrile (IDPN) to rats causes a persistent set of abnormalities which includes hyperlocomotion, hyperexcitability, and dyskinetic movements of the neck. These behavioral changes are very similar to those observed after the acute administration of the dopamine (DA) agonist, amphetamine, in rodents. Because of the anatomical and functional evidence that neurotensin (NT) can modulate DA neurotransmission, the present receptor autoradiographic study investigated the binding of [3H]NT in the brains of IDPN-treated rats. There were significant decreases in binding in the frontal and cingulate cortices, the rhinal sulcus, the dorsolateral aspect of the caudate-putamen, and in the ventral tegmental area. These results provide the first evidence for the possible participation of the NT system in the manifestations of the IDPN-induced syndrome.
Barophilic bacteria inhabit the deep oceans, and the specific functional modifications and regulatory mechanisms which govern adaptation to hydrostatic pressure are beginning to be understood. For example, the rate of production of several proteins by some hydrothermal vent archaebacteria and the degree of saturation of membrane lipids in other deep-sea bacteria have been found to change as a result of cultivation at high pressure. We report here the cloning of gene, ompH, which encodes a major pressure-inducible protein of strain SS9, a gram-negative eubacterium isolated from a depth of 2.5 kilometres in the Sulu Sea. Messenger RNA encoded by ompH is expressed when cells are grown at 280 atm but not at 1 atm, indicating that transcription of the ompH gene is controlled by hydrostatic pressure. The function of the OmpH protein in adaptation to high pressure and the use of the ompH gene in studying how bacteria sense and respond to pressure is discussed.
Explore the source record for details and available documents.
The effects of fluorodeoxyuridine were investigated during three events of the cell cycle: S-phase, mitosis, and the cyclic synthesis of thymidine kinase in the synchronous plasmodium of the myxomycete Physarum. DNA synthesis was inhibited, and there was limited action on other macromolecular syntheses. When DNA synthesis was slowed down, onset of the following increase of thymidine kinase synthesis occurred at approximately the same time as in the control, but mitosis was blocked in a very early prophase stage and metaphase was never observed. These effects were suppressed when the action of fluorodeoxyuridine was prevented by the addition of thymidine to the medium. In agreement with the action of aphidicolin and hydroxyurea, these observations show that: 1) perturbation of the S-phase does not prevent the nuclei from entering a very early prophase stage, but it does prevent them from proceeding through metaphase; 2) blockage of DNA synthesis does not perturb the normal timing of the triggering of thymidine kinase synthesis; and 3) the signal that triggers the arrest of thymidine kinase synthesis is postmitotic and does not require extensive DNA synthesis. In contrast with hydroxyurea and aphidicolin, in the presence of fluorodeoxyuridine metaphase was not observed. Thus, the triggering of thymidine kinase synthesis is unambiguously dissociated from metaphase and postmitotic events. Because synthesis of thymidine kinase remains under the control of temperature shifts from 22 to 32 degrees C, a simple model of the cell cycle involving two regulatory pathways could account for the triggering of thymidine kinase synthesis, early prophase stage, and metaphase.
Survival of infants with greater than 80 per cent body surface area burns has not been well documented. Survival of a 4-month-old infant with 80 per cent full skin thickness flame injury is reported. Data from the National Burn Information Exchange showed that there were 2266 infants under 8 months of age treated for burns in reporting hospitals. Only four children of the 2266 were treated for full skin thickness thermal injury covering more than 80 per cent TBSA and none survived except for the child reported here. It was felt that early aggressive excision of the burn eschar was an important factor leading to the survival of this infant. Complex rehabilitation issues related to developmental issues as well as physical and psychosocial needs were identified and addressed throughout her time in hospital by a multidisciplinary team to ensure the best possible quality of life.
Explore the source record for details and available documents.
The half-life of tubulin has been studied during the cell cycle of the myxomycete Physarum, using a specific quantitative immunological method. In asynchronous microplasmodial and amoebal cultures the apparent half-life of tubulin was greater than 15 h. In contrast, in the naturally synchronous plasmodia, in which tubulin exhibits a cyclic synthesis, we have shown for the first time that tubulin half-life was not constant through the cell cycle. There was no tubulin degradation before mitosis, while tubulin half-life was reduced to about 1 h during the postmitotic period. Such a variation of stability through the cell cycle has not been observed in the case of thymidine kinase, another protein showing a cyclic synthesis in Physarum plasmodia. The decrease of tubulin half-life that occurred during the S-phase immediately following mitosis (no G1-phase in Physarum) was independent of the increase of growth temperature between 22 and 32 degrees C, in contrast with the half-life of thymidine kinase which decreased in the same conditions. Tubulin did not completely disappear after mitosis. A 20% residual amount of tubulin persisted from late S-phase to early G2-phase. We have shown that tubulin degradation was not modified by actinomycin D or cycloheximide but was prevented when DNA synthesis was inhibited by fluorodeoxyuridine and hydroxyurea. In contrast, inhibition of S-phase did not modify the half-life of thymidine kinase. These results indicate that: 1) during the cell cycle, the pool of tubulin is regulated not only at the transcriptional and translational levels but also by a cell cycle-dependent degradative process.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
This paper describes the implementation and evaluation of the Coke Oven Intervention Program developed jointly by the United Steel Workers of America and the University of Pittsburgh. The program was offered on four occasions at each of seven coke oven plants over a 2-year period. Participants were compared with nonparticipating co-workers and controls from matched plants on knowledge of the Coke Oven Standard and workplace behaviors. Few baseline differences were found among participants, nonparticipants, and controls. Participants improved significantly as a result of the program, with those attending multiple programs accruing the greatest benefits. Panel controls interviewed on six occasions throughout the 2-year period showed little improvement. Reasons for and implications of the effectiveness of the program are discussed.
A thyrotropin-releasing hormone (TRH) binding protein of 64 kDa has been identified by covalently crosslinking [3H]TRH to GH4C1 cells by ultraviolet illumination. The crosslinkage of [3H]TRH is UV-dose dependent and is inhibited by an excess of unlabeled TRH. A 64 kDa protein is also detected on immunoblots using an antiserum raised against GH4C1 cell surface epitopes. In a closely related cell line (GH12C1) which does not bind [3H]TRH, the 64 kDa protein cannot be demonstrated by [3H]TRH crosslinking nor by immunoblotting. These findings indicate that the 64 kDa protein is a candidate for a TRH-receptor protein in GH4C1 cells.
Equilibrium microdialysis of [3H]acetyltaxol against different tubulin assemblies showed that: (i) the binding capacity of tubulin does not depend on the temperature; (ii) two classes of 'polymers' exist, with respect to Ac-taxol binding. Some of them (plaques, complex cylinders induced with some polycations and spirals made with rhazinilam) bound Ac-taxol, as do normal microtubules. In contrast, spirals formed with vinblastine and griseofulvin, rings made with polycations and complex cylinders induced with spermine do not bind Ac-taxol as is the case with free tubulin.
The effect of taxol on microtubule proteins at 0 degrees C is controversial. In order to determine if taxol is unable to bind to unassembled tubulin, as has been hypothesized, the binding of [3H]acetyl taxol has been studied using equilibrium microdialysis. Ac-taxol bound to microtubules at 37 degrees C and the binding remained stable when the temperature was lowered to 0 degrees C. Ac-taxol bound also at 0 degrees C to microtubules stabilized with rhazinilam. In contrast, there was no binding of Ac-taxol to unassembled tubulin, either free tubulin at 0 degrees C or tubulin, complexed with several microtubule poisons, at 0 and 37 degrees C.
The effects of hydroxyurea have been investigated on three events of the cell cycle, S-phase, mitosis, and the cyclic synthesis of thymidine kinase, in the synchronous plasmodium of the myxomycete Physarum. DNA synthesis was slowed down with limited action on other macromolecular syntheses and any increase of thymidine kinase that had already been triggered was indistinguishable from that of the control. When DNA synthesis was inhibited, the onset of the following cyclic increase of thymidine kinase synthesis occurred at the same time as in the control, but mitosis was delayed in a very early prophase stage. The arrest of thymidine kinase synthesis occurred after completion of the delayed mitosis. All these effects were suppressed when the action of hydroxyurea was prevented by the addition, to the medium, of the four deoxyribonucleosides. These observations show that (1). The blockage of S-phase does not prevent the nuclei from entering a very early prophase stage but does prevent them from proceeding through metaphase. (2) The transient blockage of DNA synthesis does not perturb the normal timing of the triggering of thymidine kinase synthesis. (3) The signal which triggers the arrest of thymidine kinase synthesis is postmitotic but does not require extensive DNA synthesis. The effect of hydroxyurea is not limited to an inhibition of S-phase. The blockage of DNA replication also led to the dissociation of the normal coordination between two other events of the cell cycle, mitosis and thymidine kinase synthesis. This observation could have strong implications in cell synchronization with chemical agents.
The amoebae of the myxomycete Physarum polycephalum are of interest in order to analyze the morphogenesis of the microtubule and microfilament cytoskeleton during cell cycle and flagellation. The amoebal interphase microtubule cytoskeleton consists of 2 distinct levels of organization, which correspond to different physiological roles. The first level is composed of the 2 kinetosomes or centrioles and their associated structures. The anterior kinetosomes forming the anterior and posterior flagella are morphologically distinguishable. Each centriole plays a role in the morphogenesis of its associated satellites and specific microtubule arrays. The 2 distinct centrioles correspond to the 2 successive maturation stages of the pro-centrioles which are built during prophase. The second level of organization consists of a prominent microtubule organizing center (mtoc 1) to which the anterior centriole is attached at least during interphase. The mtoc plays a role in the formation of the mitotic pole. These observations based on ultrastructural and physiological analyses of the amoebal cytoskeleton are now being extended to the biochemical level. The complex formed by the 2 centrioles and the mtoc 1 has been purified without modifying the microtubule-nucleating activity of the mtoc 1. Several microtubule-associated proteins have been characterized by their ability to bind taxol-stabilized microtubules. Their functions (e.g., microtubule assembly, protection of microtubules against dilution or cold treatment, phosphorylating and ATPase activities) are under investigation. These biochemical approaches could allow in vitro analysis of the morphogenesis of the amoebal microtubule cytoskeleton.