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Biomedical subjects

F Tajima

Publications and source records attributed to F Tajima.

At least 19 recordsLinked to original sources

Natural killer cell activity and cytokine production as prognostic factors in adult acute leukemia.

We studied the natural killer (NK) cell activity and in vitro production of the cytokines which can enhance NK activity (interleukin-1 beta (IL-1 beta), interferon gamma (IFN gamma), and interleukin-2 (IL-2)) after stimulation in 44 patients with acute leukemia (AL) and 14 normal controls. We also studied the influence of these parameters on relapse and the relapse-free survival (RFS) (after the date of assay) of the AL patients. The NK activity and the production of cytokines in the peripheral blood mononuclear cells (PBMNC) from 16 patients at the untreated or relapsed stage as well as from 12 patients after consolidation were significantly lower than those from controls (both P<0.01), and those from the 16 patients at maintenance or off treatment were also significantly lower than those from the controls (P<0.01 or P<0.05). RFS after the date of assay of the patients in remission with NK activity above the median value was significantly longer than that of the patients below the median (P<0.05). The production of cytokines in the PBMNC from patients who showed continuous complete remission for at least 6 months was higher than that from the patients who relapsed early. These findings suggest that impaired NK cell function and cytokine production are associated with early relapse of AL regardless of remission status.

Acute Disease

Effect of non-random sampling on the estimation of parameters in population genetics.

The amount and pattern of genetic variation in a population can be estimated from genes or DNA sequences sampled from the population. Although random sampling is assumed in almost all cases, we often do not know whether sampling is random or not. Using a simple non-random sampling model, the effects of non-random sampling on the estimation of parameters in population genetics were investigated. This non-random sampling model assumes that n genes are randomly sampled with replacement from m genes which were randomly sampled from a large random mating population, and various degrees of non-randomness can be generated by changing the value of m. The results obtained show that the effect of non-random sampling on the number of alleles and the number of segregating sites is substantially large whereas the effect of non-random sampling on heterozygosity and the average number of nucleotide differences is negligibly small unless non-randomness is extremely large. The effects of non-random sampling on the tests of neutrality were also investigated, and the results obtained indicate that the effect of non-random sampling is stronger on Fu and Li's tests than on Tajima's test.

Alleles

[Treatment of the porphyrias].

There are seven porphyrias which are caused by defective functions of the enzymes in the haem biosynthesis. The clinical classification of porphyrias are divided into three types which are neuroporphyria, neurocutaneous porphyria and cutaneous porphyria. For acute porphyric attack of neuroporphyria and neurocutaneous porphyria, the treatments of choice are administration of glucose and/or hematin, haem arginate and tinprotoporphyrin. Porphyria cutanea tarda in cutaneous porphyria is controlled by removal of iron by phrebotomies or low-dose chloriquine. A novel approach of intravenous administration of interferon may be useful to control the associated case of chronic hepatitis type C. Skin symptoms in erythropoietic protoporphyria can be alleviated with beta carotene. Hepatic failure due to protoporphyria may need a liver transplantation. Cimetidine, a H2-receptor antagonist, may be useful in the treatment of acute porphyric attack and in remission stage in neuroporphyrias, neurocutaneous porphyrias and cutaneous porphyrias such as porphyria cutanea tarda and protoporphyria.

Bloodletting

Use of an accelerometer in evaluating arm movement during wheelchair propulsion.

A piezoelectric accelerometer was attached to the arm of a wheelchair bound subject to obtain information on arm movement during wheelchair propulsion. Five physically fit normal subjects, seated on a suspended wheelchair in a laboratory setting, propelled a wheelchair 60, 90 and 120 times/min in succession for a total of 4 min each. With increased frequency of arm propulsion, arm acceleration also increased. A statistically significant (P < 0.05) relationship was found between arm acceleration and frequency of arm propulsion showing a linear regression correlation of Y = 0.118X-1.122. A clinical trial using the same recording system for a paraplegic athlete on a 160 m two way (80 m each way) track confirmed the system's practicality. Arm acceleration data may be extrapolated to frequency of arm propulsion or level of activity information. Complete computerization of the accelerometric data will facilitate its expansion to a variety of practical applications.

Acceleration

Anthropometric features of wheelchair marathon race competitors with spinal cord injuries.

The anthropometric data of the health check programme in the Oita Wheelchair Marathon Race were analysed. In the past 10 years, a total of 2677 competitors participated in this programme. Age, height, body weight, body fat, lung vital capacity, girth of chest, girth of upper arm, grasping force and power of upper arm were compared between 710 fine competitors and 99 poor competitors. Power of the upper arms and lung vital capacity played a major part in the result of the races. It was suggested that these two factors had major influences on the achievement of this type of sports activity.

Adult

Estimation of evolutionary distance for reconstructing molecular phylogenetic trees.

The most commonly used measure of evolutionary distance in molecular phylogenetics is the number of nucleotide substitutions per site. However, this number is not necessarily most efficient for reconstructing a phylogenetic tree. In order to evaluate the accuracy of evolutionary distance, D(t), for obtaining the correct tree topology, an accuracy index, A(t), was proposed. This index is defined as D'(t)/square root of[D(t)], where D'(t) is the first derivative of D(t) with respect to evolutionary time and V[D(t)] is the sampling variance of evolutionary distance. Using A(t), namely, finding the condition under which A(t) gives the maximum value, we can obtain an evolutionary distance which is efficient for obtaining the correct topology. Under the assumption that the transversional changes do not occur as frequently as the transitional changes, we obtained the evolutionary distances which are expected to give the correct topology more often than are the other distances.

Computer Simulation

Statistical methods for estimating the effective number of alleles, expected heterozygosity and genetic distance in self-incompatibility locus.

In order to understand the evolutionary process of self-incompatibility, we must know the genetic variability of the self-incompatibility genes within and between populations. Statistical methods for estimating the effective number of alleles, expected heterozygosity and genetic distance from pollination experiments were developed, which can be applied to both gametophytic and sporophytic self-incompatibility systems. In these methods, bud-pollination, which is necessary for obtaining homozygotes, is not required. Since bud-pollination, which is time-consuming, is not required in the present methods, they might be useful.

Alleles

Chronic exposure to simulated altitude does not increase angiogenic activity in skeletal muscle of rats.

In order to examine whether the hypoxia of high altitude increases angiogenic activity in skeletal muscle, six male Wistar rats were subjected to a simulated altitude of about 5,500 m (ambient pressure 380 mmHg) for 3 weeks, and the whole soleus, gastrocnemius, and extensor digitorum longus muscles were collected. As a result, any muscle extracts from high altitude rats did not significantly enhance the capillary growth in an in vitro angiogenesis model compared with those from sea-level rats. This appeared to confirm previous morphological studies that hypobaric-hypoxic environment did not cause the formation of new capillaries in skeletal muscles.

Altitude

Simple methods for testing the molecular evolutionary clock hypothesis.

Simple statistical methods for testing the molecular evolutionary clock hypothesis are developed which can be applied to both nucleotide and amino acid sequences. These methods are based on the chi-square test and are applicable even when the pattern of substitution rates is unknown and/or the substitution rate varies among different sites. Furthermore, some of the methods can be applied even when the outgroup is unknown. Using computer simulations, these methods were compared with the likelihood ratio test and the relative rate test. The results indicate that the powers of the present methods are similar to those of the likelihood ratio test and the relative rate test, in spite of the fact that the latter two tests assume that the pattern of substitution rates follows a certain model and that the substitution rate is the same among different sites, while such assumptions are not necessary to apply the present methods. Therefore, the present methods might be useful.

Amino Acid Sequence

Unbiased estimation of evolutionary distance between nucleotide sequences.

A new algorithm for estimating the number of nucleotide substitutions per site (i.e., the evolutionary distance) between two nucleotide sequences is presented. This algorithm can be applied to many estimation methods, such as Jukes and Cantor's method, Kimura's transition/transversion method, and Tajima and Nei's method. Unlike ordinary methods, this algorithm is always applicable. Numerical computations and computer simulations indicate that this algorithm gives an almost unbiased estimate of the evolutionary distance, unless the evolutionary distance is very large. This algorithm should be useful especially when we analyze short nucleotide sequences. It can also be applied to amino acid sequences, for estimating the number of amino acid replacements.

Algorithms

Statistical analysis of DNA polymorphism.

A large amount of genetic variation can be maintained in natural populations. In order to understand the mechanism maintaining genetic variation, we must first estimate the amount of genetic variation. There are two measures for estimating the amount of DNA polymorphism, i.e., the average number of pairwise nucleotide differences and the number of segregating sites among a sample of DNA sequences. Using these two measures, we can test the neutral mutation-random drift hypothesis (the neutral theory). The expectation of the amount of DNA polymorphism has been studied under several models, including population subdivision, change in population size, and natural selection. When a population is subdivided, a large amount of DNA polymorphism can be maintained in the population if the migration rates among subpopulations are small. In this case the amount of DNA polymorphism in the subpopulation with lower migration rate is expected to be smaller than that of higher migration rate. When the population size changes, the number of segregating sites changes more rapidly than does the average number of nucleotide differences. When purifying selection is operating, the number of segregating sites is more strongly affected by the existence of deleterious mutants than is the average number of nucleotide differences. On the other hand, when balancing selection is operating, the effect of the selection on the average number of nucleotide differences is larger than that on the number of segregating sites. A mutant under natural selection affects the amount of DNA polymorphism at linked sites (hitchhiking effect). DNA sequences are not random sequences and there may be conservative and variable regions in them. A statistical method for determining the window size and for finding nonrandom regions in the sequence is also presented.

Animals

Cardiovascular responses to upright tilt at a simulated altitude of 3,700 m in men.

To examine the effects of high altitude on cardiovascular responses to orthostasis, 11 healthy males were tested at a 10-min passive 70 degrees head-up tilt at sea level and at a simulated high altitude of 3,700 m. During the control period in the supine position, heart rate and forearm blood flow were higher at high altitude (p < 0.05). Mean arterial pressure remained unchanged during head-up tilt at sea level, but it reduced from 82 mm Hg to 72 mm Hg (p < 0.05) during head-up tilt at high altitude. There were no altitude-related changes in the magnitude of the increase in forearm vascular resistance and the reduction in cardiac output and laser-Doppler skin blood flow in response to head-up tilt. The total peripheral resistance increased from 14.4 to 20.5 mm Hg.L-1 x min-1 (p < 0.05) during head-up tilt at sea level, but the change was not significant at high altitude. The lack of altitude-related changes in forearm vascular resistance and laser-Doppler skin blood flow during head-up tilt in the presence of attenuated total peripheral resistance response at high altitude may suggest that the orthostatic hypotension at high altitude is associated with a lower magnitude of vasoconstrictor response in the regions other than the limbs and the skin.

Adult

Statistical method for estimating the standard errors of branch lengths in a phylogenetic tree reconstructed without assuming equal rates of nucleotide substitution among different lineages.

A statistical method is developed for estimating the standard errors of branch lengths in a phylogenetic tree reconstructed without assuming equal rates of nucleotide substitution among different lineages. This method can be easily used for testing whether the length of an interior branch in a reconstructed tree is positive, i.e., whether the topology of the tree is correct. Computer simulations indicate that this method is appropriate for a statistical test. As an example, this method is applied to phylogenetic trees reconstructed for the four hominoid species: human, chimpanzee, gorilla, and orangutan. The results obtained show that the present method provides a powerful statistical test.

Animals

Effect of dehydration on thirst and drinking during immersion in men.

The mechanism for reduced voluntary water intake during water immersion was studied in eight men (19-25 yr of age) immersed to the neck while sitting for 3 h at 34.5 degrees C or in air at 28 degrees C when euhydrated (Eu-H2O and Eu-air, respectively) and hypohydrated (Hypo-H2O and Hypo-air) by 3.6% body weight loss. Thirst sensations (degree of thirst, mouth dryness and taste, drinking desirability, and stomach fullness) were similar at the beginning of Hypo-air and Hypo-H2O test periods. Initial drinking of tap water (15 degrees C) was 216 +/- 30 ml/7 min (P less than 0.05) with Hypo-air, decreased to 108 +/- 28 ml/7 min (P less than 0.05) with Hypo-H2O, and was 10-50 ml/10-30 min thereafter. Intake was less than 10 ml/10-30 min in Eu-air, and there was no drinking in Eu-H2O. Within the first 10 min of immersion, compared with Hypo-air findings, the significant reduction in drinking in the Hypo-H2O experiment was associated with unchanged plasma Na+, plasma osmolality, heart rates, and mean arterial pressures; the different responses were increased cardiac output, plasma volume, and atrial natriuretic peptides and decreased plasma renin activity and arginine vasopressin. Thus the extracellular pathway, as opposed to the osmotic pathway, appears to be the major mechanism for immersion-induced suppression of drinking.

Adult

Cardiovascular responses to upright tilt in man during acute exposure to 3 atm abs air.

To examine the effect of acute hyperbaric exposure on cardiovascular response to orthostasis, a passive 70 degrees head-up tilt (HUT) test was performed for 15 min in a simulated compressed-air hyperbaric environment of 3 atm abs at ambient temperature of 31 degrees C (thermoneutral) on 8 male subjects. Heart rate (HR), blood pressure, cardiac output (CO) by impedance cardiography, forearm blood flow (FBF) by the occlusion plethysmography, and laser-Doppler skin blood flow (BFLD) on the thigh were measured for 15 min before, during, and after HUT. Esophageal temperature and HR data were recorded continuously. An identical test was performed in a 29 degrees C (thermoneutral) normal atmospheric condition. None of the subjects showed signs of syncope during HUT in either environment. Baseline HR was significantly lower (P less than 0.05) at 3 atm abs, and the increase in HR (delta HR) during HUT was of the same magnitude (15 beats/min) at both atmospheric pressures. The reduction of systolic blood pressure (delta SBP) was identical in both environments. Thus, the chronotropic response to HUT (delta HR/delta SBP) was the same. A marked reduction in CO (P less than 0.05) was attributed to a reduction of stroke volume during HUT, and the reduction was greater (P less than 0.05) at 3 atm abs. There were no pressure-dependent changes during HUT in FBF, forearm vascular resistance, and BFLD except for a greater increase (P less than 0.05) in total peripheral resistance at 3 atm abs. These observations suggest that orthostatic tolerance was maintained in the presence of lower CO at 3 atm abs, probably by a greater vasoconstrictor response in the splanchnic areas. We conclude that the substantial bradycardia which occurred at 3 atm abs did not interfere with a normal response to orthostasis in humans because of a peripheral vasoconstriction caused by the elevated oxygen pressure and an enhanced increase in total peripheral resistance which occurred during HUT in 3 atm abs.

Adult