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Biomedical subjects

M H Pickett

Publications and source records attributed to M H Pickett.

7 recordsLinked to original sources

Control of red blood cell mass in spaceflight.

The effect of spaceflight on red blood cell mass (RBCM), plasma volume (PV), erythron iron turnover, serum erythropoietin, and red blood cell (RBC) production and survival and indexes were determined for six astronauts on two shuttle missions, 9 and 14 days in duration, respectively. PV decreased within the first day. RBCM decreased because of destruction of RBCs either newly released or scheduled to be released from the bone marrow. Older RBCs survived normally. On return to Earth, plasma volume increased, hemoglobin concentration and RBC count declined, and serum erythropoietin increased. We propose that entry into microgravity results in acute plethora as a result of a decrease in vascular space. PV decreases, causing an increase in hemoglobin concentration that effects a decrease in erythropoietin or other growth factors or cytokines. The RBCM decreases by destruction of recently formed RBCs to a level appropriate for the microgravity environment. Return to Earth results sequentially in acute hypovolemia as vascular space dependent on gravity is refilled, an increase in plasma volume, a decrease in hemoglobin concentration (anemia), and an increase in serum erythropoietin.

Adaptation, Physiological↗

Blood volume and erythropoiesis in the rat during spaceflight.

A decreased red blood cell mass (RBCM) and plasma volume (PV) have been consistently found in humans after return from spaceflight. Rats flown on the Spacelab Life Sciences-1 mission were studied to assess changes in RBCM, PV, erythropoiesis, and iron economy. The RBCM and PV increased in both ground control and flight animals as expected for growing rats. However on landing day, both the RBCM and PV, when normalized for body mass, were significantly decreased in the spaceflight animals. During an 8-d postflight observation period, iron incorporation into circulating red blood cells was diminished in the flight animals. During the first 4 d postflight, increases in reticulocyte counts were significantly smaller in the flight than the control animals. Fewer erythropoietin-responsive progenitor cells were recovered from the bone marrow of flight animals after landing than control rats. Serum erythropoietin (EPO) levels were the same in both groups. Thus, rats subjected to a 9-d spaceflight had less increase in RBCM than controls and diminished erythropoiesis during an 8-d post-spaceflight observation period. The rat, like humans, appears to require a smaller blood volume in microgravity.

Animals↗

Decreased production of red blood cells in human subjects exposed to microgravity.

The total-body red blood cell mass (RBCM) decreases during the first few days of spaceflight; however, the pathophysiology of "spaceflight anemia" noted on return to earth is poorly understood. In studies before, during, and after a 9-day mission we determined the rates of removal and replacement of RBCs by using chromium 51. The rate and efficiency of RBC production were assessed with iron 59. Serial measurements were made of plasma volume (PV), RBCM, serum ferritin level, and erythropoietin level. PV decreased within hours, resulting in an increased total body hematocrit during the first few days of the mission. Serum erythropoietin level decreased within 24 hours and remained low. Circulating RBCs disappeared at a normal rate during flight, but few new cells replaced those destroyed, resulting in a decrease in RBCM of 11% during the mission. After 22 hours in space, intramedullary formation of cells continued at near preflight levels as measured by erythron iron turnover. The coexistence of new cell formation in the bone marrow and failure of cells to be released into the blood is consistent with ineffective erythropoiesis. Microgravity causes blood located in gravity-dependent spaces to shift to a central volume. We conclude that the initial adaptation is a reduction in PV resulting in plethora. Increase in total body hematocrit causes a decrease in erythropoietin production. RBCM decreases because RBCs destroyed at a normal rate are not replaced.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗

Characteristic archaebacterial 16S rRNA oligonucleotides.

A method of analyzing 16S rRNA catalog data has been developed in which groupings at various taxonomic levels can be characterized in terms of specific "signature" oligonucleotides. This approach provides an alternative means for evaluating higher order branching possibilities and can be used to assess the phylogenetic position of isolates that are poorly placed by the usual clustering procedures. This signature approach has been applied to forty archaebacterial catalogs and every oligonucleotide with significant signature value has been identified. Sets of specific oligonucleotides were identified for every major group on a dendrogram produced by cluster analysis procedures. Signatures that would establish between group relationships were also sought and found. In the case of the Methanobacteriaceae the clustering methods suggest a specific relationship to the Methanococcaceae. This inclusion is in fact supported by six strong signature oligonucleotides. However there are also significant numbers of signature oligonucleotides supporting a specific relationship of the Methanobacteriaceae to either the Halobacteriaceae or the Methanomicrobiaceae. Thus the placement of the Methanobacteriaceae is less certain than the usual dendrograms imply. The signature approach also was used to assess the phylogenetic position of Thermoplasma acidophilum which is found to be more closely related to the methanogen/halophile Division than to the sulfur dependent Division of the archaebacteria. This does not imply however that Thermoplasma acidophilum is properly regarded as being in the methanogen/halophile Division.

Archaea↗

16S rRNA oligonucleotide catalog data base.

We have developed a package of programs to create, maintain and manipulate a data base of 16S rRNA oligonucleotide catalog data. For the first time all the published catalog data is brought together in one place in a readily usable form. The package allows generation of dendrograms, facilitates searches for related oligonucleotides between catalogs, and allows construction of global and local dictionaries. Interactive capabilities allow for searches of the dictionary as well as an associated file of likely oligonucleotide families.

Base Sequence↗

Evidence that translational control mechanisms operate to optimize antifreeze protein production in the winter flounder.

In fall and winter, the liver of the winter flounder produces large amounts of alanine-rich (60 mol %) antifreeze proteins for export to the circulation. We have examined the tRNA in the liver to see if the seasonal production of antifreeze protein is accompanied by changes in tRNAAla isoacceptors. Total tRNA from the liver of winter fish showed an approximate 40% increase in alanine acceptor capacity over tRNA from summer fish. In contrast, the acceptor capacities for other amino acids showed no seasonal difference. When labeled alanyl-tRNAs were separated by reverse phase chromatography-5 chromatography, a large proportion of the increase in alanine acceptor capacity was in one of three main peaks. Measurements of the optimum temperatures for various flounder amino-acyl-tRNA synthetases suggest that alanyl-tRNA synthetase functions best between 0 and 5 degrees C, which is the sea water temperature when antifreeze protein synthesis occurs, while prolyl- and valyl-tRNA synthetases are most active between 20 and 30 degrees C. These differences in temperature optima and the seasonal variation in tRNAAla levels and isoaccepting species may both serve to optimize antifreeze protein production by increasing the translational efficiency of its mRNA.

Alanine-tRNA Ligase↗

Seasonal variation in the level of antifreeze protein mRNA from the winter flounder.

Livers from winter flounder collected at monthly intervals throughout the year were analyzed for their content of antifreeze protein mRNA. Putative mRNA was detected in liver RNAs from summer fish by liquid hybridization to kinetically purified antifreeze protein cDNA. These mRNA sequences were shown by Northern blot analysis to be of the same length as mature antifreeze protein mRNA isolated from winter fish, and were able to direct the incorporation of alanine into a translation product which comigrated with antifreeze preproprotein. The build-up of antifreeze protein mRNA levels in the autumn and their decline in the spring to summer levels were measured by liquid hybridization. These seasonal fluctuations match closely, but slightly precede, the rise and fall in plasma osmolality due to the presence of antifreeze protein. In mid-winter 0.5% of the total liver RNA is antifreeze protein mRNA, and although by late August the level of this mRNA has declined to 0.0007% of the total RNA, at no time during the summer is the mRNA undetectable. These results suggest that antifreeze protein production is more likely to be regulated by changing the rate of transcription of their genes than by switching them between active and inactive states.

Acclimatization↗