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Biomedical subjects

K Young

Publications and source records attributed to K Young.

At least 163 records · Page 9Linked to original sources
PubMed1985

Abnormal globin gene structure and expression in beta-thalassemia.

Over the past five years, several new defects in the beta-thalassemias have been described from this laboratory using both restriction enzyme and sequencing analyses of cloned beta-thalassemia genes. The enzyme HphI has been shown to recognize a single nucleotide change at the 5' end of beta-IVS 2, and, using restriction enzyme analysis, demonstrated for the first time a specific defect associated with beta(0)-thalassemia. Cloning and sequencing of a beta-thalassemia gene have identified a single base change within IVS 2 at a position 705 nucleotides from the 5' end of IVS 2 that results in a beta(0)-thalassemia phenotype; no normal splicing occurs in this gene despite the fact that both the 5' and 3' ends of IVS 2 are unchanged. A unique and strong cryptic 3' acceptor splice site present in the normal gene at a position 580 nucleotides from the 5' end is used extensively in the mutant gene. Studies of this gene have indicated that there are sequences within IVS that are responsible for optimal expression of this gene; changes in these sequences can lead to markedly abnormal patterns of splicing. In addition, beta-globin gene expression has been evaluated in human erythroleukemia cells, K562 cells, and, although stable transformants with integrated beta-globin genes have been obtained, none of these transformants expressed the added beta-globin genes. This is presumably due to trans-acting factors or distal cis-acting effects that suppress the expression of these added beta-globin genes. In addition, a low epsilon-producing cell line, Bos cells, was used as a recipient for an exogenous epsilon-globin gene. A neomycin resistance gene was cotransfected into these cells, and a neomycin analogue (G418) was used to select cells containing both the neomycin resistance and epsilon-globin genes. Using Southern blotting, 10 of 11 stably transformed G418-resistant lines, which contain intact epsilon-globin genes, express epsilon-globin mRNA at much higher levels than the Bos cells into which they were transfected. Two of these lines express the epsilon-globin genes at a level comparable to that of wild-type K562 cells. These results indicate that the transfer and expression of human globin genes in human erythroid cells is feasible, and can occur at a high level.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Line↗
PubMed1985

Effect of heating on the contractile properties of triceps surae and maximal power output during jumping in elderly men.

The electrically evoked contractile properties of the triceps surae and short-term (less than 2 s) maximal power output during vertical jumping have been examined before and after heating (by water immersion) in 5 elderly men aged 70 +/- 5 years. Leg immersion in water at 44 degrees C for 30 min produced a 3.4 degrees C rise in muscle temperature (Tm) and was associated with a significant (p less than 0.001) reduction in maximal time to peak tension and half relaxation time of the twitch, but was without affect on maximal twitch, tetanic (20 and 50 Hz) and voluntary tensions. However, at 10 Hz maximal tetanic tension was reduced (p less than 0.05) from 604 +/- 104 to 422 +/- 142 N. During vertical jumping from a force platform, peak power output (W) was significantly (p less than 0.05) increased from 1,155 +/- 212 to 1,381 +/- 307 W after heating. The rise in W was due to a small increase in both take-off velocity and the exerted force, and was reflected in a 3-cm increase in the height jumped from the force platform. It is concluded that the contractile characteristics of elderly triceps surae can be modified by heating and a rise in Tm does effect a change in the capacity of the muscle to generate power.

Aged↗
PubMed1985

Structure and expression of two beta genes in a beta thalassemia homozygote.

Two beta globin gene alleles have been cloned and characterized from a patient with beta + thalassemia. Both beta genes have single base mutations in the small intervening sequence (IVS 1); one 6 nucleotides and the other 110 nucleotides from the 5' end of IVS 1. Both genes lead to abnormal splicing of beta globin mRNA precursors when expressed in HeLa cells. Despite the fact that both alleles produce some normal beta globin mRNA transcripts, the patient has clinically severe beta + thalassemia (Cooley's anemia).

Base Sequence↗
PubMed1984

Identification of Mr variants of prolactin with monoclonal antibodies.

Monoclonal antibodies ( QB01 and 1200) prepared against human prolactin (hPRL) have helped define a variant form of the hormone. This variant is of apparently higher molecular mass (26 kDa) than the predominant form of the hormone (24 kDa) and its presence does not appear to be species-restricted. The demonstration of the 26 kDa form of hPRL in fresh pituitary tissue and amniotic fluid suggests it may retain some specific function.

Amniotic Fluid↗
PubMed1984

Effect of diet on human muscle weakness following prolonged exercise.

The effect of altering muscle glycogen on the ability of skeletal muscle to generate voluntary and electrically evoked isometric force following prolonged exercise has been investigated in five healthy male subjects. Measurements from the triceps surae were made at rest, and before and after prolonged exercise (uphill walking) at approximately 75% VO2 max in low muscle glycogen (low CHO) and high muscle glycogen (high CHO) conditions. The results showed that before exercise there was no change in maximal twitch tension (Pto), maximal tetanic tension at frequencies of 10 (Po10), 20 (Po20) and 50 HZ (Po50), and maximal voluntary contraction (MVC) in low and high CHO compared with normal. The loss of force during a 2 min electrically evoked "fatigue test" at rest was found to be higher (p less than 0.05) in low CHO and lower (p less than 0.05) in high CHO than normal. Following the prolonged exercise, muscle weakness was produced in both low and high CHO conditions, but was found to be significantly greater in the low CHO condition for the measurements of Po10 (P less than 0.01), Po20 (p less than 0.05) and MVC (p less than 0.05). It is concluded that changes in muscle glycogen alone do not alter the isometric force generating capacity of human muscle, but when combined with prolonged exercise low muscle glycogen enhances exercise-induced muscle weakness.

Adult↗
PubMed1984

Effects of external loading on short term power output in children and young male adults.

The effects of external loading, in the form of small weights distributed evenly over the limbs and torso, on physical performance and power output have been studied during vertical jumping in 10 children and four young adults and the results compared with maximal cycling. The results show under control (unloaded) conditions the absolute peak power output (W) achieved by children and adults was 572 W (45%) and 765 W (25%) respectively higher in cycling than jumping. The addition of weights during jumping served only to increase this difference. External loading produced a linear decrease of W in both groups of subjects. The reduction in W was entirely due to a decrease of take-off velocity (VT). The relationship between VT and added weights (delta wt) could be described by the equations: VT (ms-1) = 1.91 - 0.042 delta wt (kg); r = -0.96 (children); VT (ms-1) = 2.49 - 0.021 delta wt (kg); r = -0.99 (adults). Thus, contrary to the recent work of Caiozzo and Kyle (1980) which involved stair-climbing, body size and speed of movement in children and young adults would appear to be optimally matched for the production of lifting work during vertical jumping. External loading reduces the generation of power output immediately prior to take-off of a maximal jump from a force platform.

Adult↗
PubMed1984

Stable transfer and expression of exogenous human globin genes in human erythroleukemia (K562) cells.

To study the expression of globin genes in human cells, human epsilon-globin genes were transferred into a K562 cell line, Bos, which synthesizes very low amounts of epsilon-globin mRNA. A plasmid (pSV2neo-epsilon) containing a complete epsilon-globin gene and 2 kilobases (kb) of 5' flanking DNA as well as a neomycin-resistance gene and a simian virus 40 origin of replication was transfected into Bos cells; the compound G418, a neomycin analogue, was used to select transformed cells. The presence of unique bands by DNA restriction analysis shows that 11 of 14 of the G418-resistant clones have at least one copy of an integrated epsilon-globin gene. RNA expression measured by RNA blotting shows significantly more epsilon-globin mRNA sequences than in untransfected Bos cells in 10 of 11 lines; in most lines, epsilon-globin mRNA was additionally increased in the presence of hemin. In two lines, epsilon-globin mRNA expression with hemin was comparable to that of a high epsilon-globin producing cell line, K562 clone 2. The one G418-resistant line without epsilon-globin genes had no epsilon-mRNA expression. The high epsilon-mRNA expression in several of the lines suggests that exogenous epsilon-globin genes with only 2-kb 5' flanking DNA may be sufficient to be appropriately expressed in these homologous erythroid cells. These results have implications for the potential success of transfer of normal human genes to human bone marrow cells as an approach to the treatment of inherited anemias.

Base Sequence↗
PubMed1984

Erythroleukemia (K562) cells contain a functional beta-globin gene.

K562 cells are human erythroid cells that synthesize embryonic and fetal globins but not adult beta-globin. A cloned beta-globin gene was isolated from K562 cells and transfected into HeLa cells. The RNA transcripts produced were comparable in both amount and size to those obtained with a normal beta-globin gene.

Cloning, Molecular↗
PubMed1984

Specific globin mRNAs in human erythroleukemia (K562) cells.

Specific globin mRNA accumulation was quantitated in several lines of K562 cells in the absence and the presence of hemin. Using specific cloned DNA probes, the amounts of zeta, alpha, epsilon and gamma mRNAs were shown to be increased 2-3-fold in the presence of 20 microM hemin. No delta- or beta-globin mRNAs were detectable in any of the lines. In one line, Bos, there was a marked decrease in epsilon-globin mRNA, which increased with hemin, although still to much lower levels than in the other lines. The decreased epsilon-globin mRNA accumulation in Bos is shown to be due to decreased epsilon-globin gene transcription.

Cell Line↗
PubMed1983

Muscle function in children.

Electrically evoked mechanical and contractile properties of the triceps surae have been measured in 52 children aged 11 and 14 years, and results compared with previously reported data for adults (Davies and White 1982). The results show that the time to peak tension (TPT), half relaxation time (1/2RT) and supramaximal tension (Pt) of the twitch were not significantly (P greater than 0.1) different in girls and boys and independent of age. The 14-year-old girls and boys were stronger in terms of their supramaximal 10, 20, and 50 Hz tetanic tensions and maximal voluntary contraction (MVC) than their younger counterparts, and both groups of children were significantly (P less than 0.001) weaker than the young adults. However, if standardisation was made for an anthropometric estimate of calf muscle (plus bone) cross-sectional area (CSA), the differences in strength disappeared. Electrically stimulated and voluntary maximal force per unit CSA measured at the knee were 17.1 and 20.5 N X cm2 respectively and independent of sex and age. The loss of force during a 2-min stimulated fatigue test was the same in the children as the adults. The average fatigue indices ranged from 0.52 to 0.72 in the children, compared with 0.68 in the adults. It is concluded that absolute differences in muscle strength in children are a function of muscle mass. The force generating capacity expressed in N X cm2, fatiguability, contraction and relaxation times of the triceps surae would appear to remain unchanged through adolescence and early adulthood.

Adolescent↗
PubMed1983

Electrically evoked and voluntary maximal isometric tension in relation to dynamic muscle performance in elderly male subjects, aged 69 years.

The dynamic performance and electrically evoked mechanical properties of elderly triceps surae muscle have been investigated in 9 men, aged 69 yr. Dynamic performance consisted of cycling on a force bicycle and a vertical jump off two feet from a force platform. The results showed that the time to peak tension (TPT) and half relaxation time (1/2 RT) were significantly greater (p less than 0.001) by 30 ms and 22 ms and the supramaximal twitch (Pt) and tetanic (20 Hz-P020) tensions and maximal voluntary contraction (MVC) were less by 45 N (-33%), 708 N (-49%), and 899 N (-43%) in the elderly compared with young male control subjects. On the force platform, the height jumped (Ht), maximal force exerted (P), take-off velocity (VT), net impulse (NI) and peak power output (W) were less by 18.6 cm, 173 N, 0.9 ms-1, 52 Ns and 1120 w respectively. Similar differences of power, force and velocity were observed on the force bicycle. The reduction of W in the elderly was associated with the contractile characteristics of the leg muscle. The loss of contractile speed and capacity to to generate force in old people was reflected in their inability to develop power during the performance of a maximal vertical jump and cycling.

Aged↗
PubMed1983

Investigation of biorhythms in female athletic performance.

Implications for sports performance and athletic injury occurrence have been forcefully insinuated by proponents of a biorhythm theory based on date of birth. The theory postulates that variations in human abilities are governed by three consistently recurring cycles of 23, 28 and 33 day lengths. This study assessed the validity of biorhythms by analysing best performances in 610 top ranked European female track and field specialists over a single competitive season. Chi-square analysis of data found no significant influence of the computed physical, emotional or intellectual cycles on peak performances. It concluded that 'biorhythms' theory has no basis to justify its application to strenuous exercise.

Journal Article↗
PubMed1983

Effect of temperature on the contractile properties and muscle power of triceps surae in humans.

The effects of heating and cooling on the electrically evoked mechanical and contractile properties of the triceps surae in relation to the maximal dynamic performance of the leg muscles during cycling and vertical jumping have been examined in five healthy male subjects. A mean rise of 3.1 degrees C in muscle temperature (Tm) was associated with a decrease in time to peak tension (TPT) and half-relaxation time (1/2RT) but was without effect on twitch (Pto) and tetanic tension at 20 Hz (Po20) and 40 Hz (Po40) and maximal voluntary contraction (MVC). Reducing Tm by 8.4 degrees C had the opposite effect on TPT and 1/2RT and produced a fall in Pto, Po40, and MVC. The peak power output during cycling (W1) and jumping (W) was linearly related to Tm as well as negatively associated with TPT. The best single guide to W and W1 was given by a ratio of MVC to TPT: W (W) = 626.5 + 79.04 (MVC/TPT)(N/ms; r = +0.82) and W1 (W) = 1,342 + 84.9 (MVC/TPT)(N/ms; r = +0.87). The results underline the importance of the contractile and force generating capacity of human muscle in determining maximal power output and performance during exercise of a few seconds duration.

Adult↗
PubMed1983

Aflatoxicol and aflatoxins B1 and M1 in eggs and tissues of laying hens consuming aflatoxin-contaminated feed.

This study was undertaken to relate quantitatively the aflatoxin residue found in eggs and tissues to the aflatoxin intake via feed. Eighteen hens were fed an aflatoxin B1 (B1)-contaminated feed (8 micrograms/g) for 7 days, after which half the group was sacrificed; the remainder were sacrificed after an additional 7 days on an aflatoxin-free diet. Eggs were collected over the entire 14-day period. Aflatoxicol (R0), B1, or both were found in eggs and tissues (kidneys, liver, muscle, blood, and ova). Aflatoxin M1 (M1) (.04 to .1 ng/g) was found only in the kidneys. Levels of R0 and B1 were approximately the same in eggs, ova, kidneys, and liver. In eggs, the levels of R0 and B1 (.02 to .2 ng/g) increased steadily for 4 or 5 days, after which time the levels plateaued and then decreased after B1 withdrawal at the same rate as they had increased. At 7 days after withdrawal, only trace amounts of R0 (.01 ng/g) remained in eggs. All tissues, except blood, from hens sacrificed immediately before aflatoxin withdrawal contained R0 (.04 to .4 ng/g) or R0 and B1 (.04 to .8 ng/g). The R0 (.03 to .11 ng/g) was the only aflatoxin detected in muscle, and B1 (.05 to .07 ng/g) was the only aflatoxin in blood. Seven days after aflatoxin withdrawal, B1 (.08 ng/g) was found in one of nine livers and R0 (.01 to .04 ng/g) in eight of nine muscles analyzed, but no aflatoxins were found in any other tissues.

Aflatoxin B1↗