Blood rheology and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in dyslipidaemic and normolipidaemic subjects.

The association between blood rheology and the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) was investigated in 142 dyslipidaemic and 253 normolipidaemic subjects. Blood rheology was examined by the microchannel method and fasting serum concentrations of LDL-C, triglyceride and HDL-C were measured. Passage time of whole blood correlated positively with LDL-C concentration, triglyceride concentration and LDL-C/HDL-C ratio, and negatively with HDL-C concentration. Passage time of whole blood was significantly higher in dyslipidaemic and normolipidaemic subjects with LDL-C/HDL-C ratio > 2.0 than in those with ratio < 1.5. Thus, dyslipidaemic subjects had impaired blood rheology, elevated LDL-C and triglyceride concentrations and elevated LDL-C/HDL-C ratio, and reduced HDL-C concentrations. Dyslipidaemic and normolipidaemic subjects with a more elevated LDL-C/HDL-C ratio had greater blood rheology impairment than those with a less elevated ratio. These data suggest that an elevated LDL-C/HDL-C ratio may be helpful in predicting impaired blood rheology.

Impaired blood rheology and elevated remnant-like lipoprotein particle cholesterol in hypercholesterolaemic subjects.

Blood rheology, fasting serum concentrations of remnant-like lipoprotein particle cholesterol (RLP-C) and concentrations of other lipids were compared in 23 hypercholesterolaemic and 69 normocholesterolaemic subjects, and the relationship between red blood cell (RBC) deformability and RLP-C concentrations were studied in a different set of six hypercholesterolaemic and six normocholesterolaemic subjects. Passage time of whole blood and concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and RLP-C were significantly higher in hypercholesterolaemic than in normocholesterolaemic subjects. Passage time of whole blood correlated positively with TC, TG, LDL-C and RLP-C and negatively with high-density lipoprotein cholesterol. Furthermore, the passage time of 10% haematocrit-adjusted RBCs in phosphate-buffered saline, which reflects RBC deformability, correlated positively with the passage time of whole blood and RLP-C. Thus, hypercholesterolaemic subjects had impaired blood rheology and elevated RLP-C concentrations, which may be associated with the pathophysiology of atherosclerosis in hypercholesterolaemic subjects. Impaired RBC deformability may contribute to impaired blood rheology associated with elevated RLP-C in hypercholesterolaemic subjects.

Paradoxical adaptation of mature radius to unilateral use in tennis playing.

The positive effects of physical activity on human bone mass have been well documented in many cross-sectional studies comparing athletes with sedentary controls as well as in longitudinal follow-up. By applying peripheral quantitative computed tomography (pQCT), which has the advantage of measuring volumetric bone mineral density (BMD) and the ability to distinguish among trabecular and cortical components, it was demonstrated that cortical BMD of the dominant arm was not greater than that of the nondominant arm. Cortical drift toward the periosteal direction and an increase in cortical thickness resulted in an improvement of mechanical characteristics of the playing arm's midradius. An improvement in the mechanical properties of young adult bone in response to long-term exercise was therefore related to geometric adaptation, but not to an increase in BMD. The manner in which the recruitment and function of bone cells are coordinated differs between the growing and the nongrowing skeleton. In the former, modeling is the dominant mode, and in the latter it is remodeling. In the present study, the side-to-side difference of 92 middle-aged female tennis players who initiated training after bone had matured was analyzed by pQCT. The side-to-side difference detected suggested a paradoxical adaptation of the mature radius to unilateral use during tennis playing, and that tennis playing after bone had matured did not stimulate cortical drift in the periosteal direction, unlike that seen in young subjects. Unexpectedly, the cross-sectional areas (periosteal and endocortical area) of the radius were smaller in the dominant arm than in the nondominant arm in the middle-aged female players. The findings suggest that unilateral use of the arm after the third decade of life suppresses age-related changes in bone geometry.

Effect of physical activity during teenage years, based on type of sport and duration of exercise, on bone mineral density of young, premenopausal Japanese women.

In this cross-sectional study, 91 healthy premenopausal women aged 20-39 years were investigated to determine the effect of physical activities during their teenage years on their current bone mineral densities (BMD). We measured whole-body BMD (WBMD), lumbar BMD (LBMD), and radial BMD (RBMD) with dual energy X-ray absorptiometry (DXA). Using a questionnaire, we asked the women about their physical activities during junior and senior high school and at present. We also asked about their current nutritional status and past and current milk intake. After adjusting for age, body mass index (BMI), current total calorie and calcium (Ca) intake, and milk intake when they were teenagers and at present, we determined that subjects who exercised during extracurricular activities at each of the three periods (during junior and senior high school and at present) had significantly higher WBMD and LBMD (P <0.01, respectively) than did those who did not exercise at those times. Subjects who played high-impact sports at each period had significantly higher WBMD and LBMD than did subjects who played low-impact sports (P <0.05, respectively). Subjects who had exercised regularly from their teenage years to the present had significantly higher BMD at all sites than BMD in other subjects after adjusting for the potential confounders described above (P <0.05, respectively). Our data suggest that continuous exercise beginning in junior high school, especially high-impact sports, may be associated with greater current bone mass. It is important to incorporate adequate exercise beginning in the teenage years to lower one's future risk for osteoporosis.

Occlusal function associated with body composition in premenopausal Japanese women.

OBJECTIVES: The goal of the present study was to investigate the relationship between occlusal function and body composition in 108 premenopausal healthy Japanese women aged 20-45 years. METHODS: Pressure-sensitive sheets were used to measure occlusal function. Whole fat mass and lean mass, fat-free mass, and whole-bone mineral content were measured by dual-energy X-ray absorptiometry (DXA). RESULTS: After being adjusted for age and the square of height, the whole lean mass and grip strength of the large occlusal contact-area group were found to be significantly higher than those of the small occlusal area groups (p<0.05, respectively). In the 1-year follow-up study, changes in weight in the small-occlusal contact-area group and the low-occlusal force group were significantly larger than other occlusal-contact area or occlusal-force groups. The mean occlusal-contact area and occlusal force were both significantly smaller in subjects with partial dentures than in those without (p<0.05). CONCLUSION: Large occlusal contact-area, high occlusal force, and no dentures may be associated with some good health conditions in premenopausal Japanese women.

Genetic and environmental factors affecting peak bone mass in premenopausal Japanese women.

The purpose of this study was to examine the relationships between peak bone mass and genetic and environmental factors. We measured whole-body bone mineral density (BMD), lumbar spine BMD, and radius BMD with dual-energy X-ray absorptiometry (DXA) and analyzed eight genetic factors: vitamin D receptor (VDR)-3', VDR-5', estrogen receptor (ER), calcitonin receptor (CTR), parathyroid hormone (PTH), osteocalcin (OC), apolipoprotein E (ApoE), and fatty acid binding protein 2 (FABP2) allelic polymorphisms using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). We also surveyed menstrual history, food intake, and history of physical activity using questionnaires.After adjusting for age, body mass index (BMI), current smoking status, current Ca intake, alcohol intake, menoxenia, and physical activity, the mean BMD in subjects with the HH/Hh genotype was significantly higher than that of subjects with the hh genotype for whole-body BMD (mean±SD, 1.20±0.10 vs. 1.18±0.09 g/cm(2); HH/Hh vs. hh, p=0.04) and at lumbar spine BMD (mean±SD, 1.18±0.14 vs. 1.14±0.12 g/cm(2); HH/Hh vs. hh, p=0.02) in OC allelic polymorphism. Furthermore, the results of multiple regression analyses taking the 8 genetic factors plus the 7 environmental factors listed above into account showed that the strongest factor contributing to BMD was BMI at any site (whole-body and lumbar BMD p<0.0001, radius BMD p=0.0029). In addition, OC polymorphism (p=0.0099), physical activity (p=0.0245), menoxenia (p=0.0384), and PTH polymorphism (p=0.0425) were independent determinants for whole-body BMD, and OC polymorphism (p=0.0137) and physical activity (p=0.0421) were independent determinants for lumbar BMD and radius BMD, respectively.

[Studies on circulating interleukin-6 and thyroid functions in acute myocardial infarction].

The euthyroid sick syndrome is reported to exist in acute myocardial infarction(AMI). Previous reports showed serum levels of triiodothyronine(T3) are low and thyroid stimulating hormone(TSH) is normal or subnormal levels in patients with AMI. However, the mechanism of altered thyroid hormone metabolism is unknown. Interleukin-6(IL-6) is reported to be a key role in the pathogenesis of AMI and euthyroid sick syndrome. We measured circulating TSH, free T3(FT3), free thyroxine (FT4), IL-6, soluble IL-6 receptor, soluble transducing 130-kD glycoprotein, atrial natriuretic peptide(ANP) and brain natriuretic peptide in 25 patients and 32 healthy subjects. Circulating FT3 levels in patients with AMI became lower than in control group(p < 0.05). IL-6 levels were significantly(p < 0.05) higher than those of healthy subjects. The peak levels of IL-6 was 30.5 +/- 46.9 pg/ml at 25-27 hours(the first peak) and 64.4 +/- 24.6 pg/ml at 70-72 hours(the second peak). FT3 was negatively related to IL-6(p < 0.05) and hANP(p < 0.05) in patients with AMI. These results indicate that the lower levels of FT3 show the greater severity of AMI. We conclude that euthyroid sick syndrome occurs in patients with AMI and euthyroid sick syndrome may regulated by IL-6 through suppressed of thyroid function.

Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism.

Bone metabolism is strongly influenced by heredity and environmental factors. To investigate interaction of the effects between vitamin D receptor polymorphism by Fok I and resistance exercise training on bone metabolism, young male subjects with FF genotype (F, n = 10) and Ff or ff genotypes (f, n = 10) followed 1 mo of weight training, and changes in bone metabolism were compared. An additional 14 subjects served as a sedentary control. Biomarkers of bone formation, bone-specific alkaline phosphatase, and osteocalcin were significantly increased by training in both F and f groups. 1, 25-Dihydroxyvitamin D(3), known to upregulate bone formation, was also increased by the training in the f but not in the F group. Bone resorption assessed by cross-linked NH(2)-terminal telopeptide of type I collagen was significantly suppressed by the training, and the decrease in F was greater and longer lasting than that in f group. In conclusion, stimulation of bone formation and suppression of bone resorption occurred within 1 mo in young men. Despite a significant increase in 1,25-dihydroxyvitamin D(3) in the f group but not in the F group, the response of bone metabolism to the training in the F was similar to or greater than that in f group, suggesting a functional difference between vitamin D receptor genotypes f and F.

Ratio of factor V activities in PT and APTT assays as a new diagnostic marker of lupus anticoagulant.

Lupus anticoagulant (LA) is an antibody that interferes with phospholipid-dependent coagulation tests. We investigated the usefulness of the ratio of factor V activity determined by the Simplastin auto test (PT assay) to factor V activity determined by the Platelin Excel LS test (APTT assay) for detection of LA in plasma samples obtained from 276 patients with haematological and non-haematological disorders and 73 healthy subjects. This ratio was significantly higher in the 15 LA-positive (4.82 +/- 3.34) than in samples from healthy subjects (1.09 +/- 0.10) and was > 1.4 in 10 of the remaining 261 patient samples. The ratio was particularly low in the 54 samples from warfarin-treated patients. These findings suggest that determination of this ratio may be useful as a routine laboratory test for detection of LA. This test requires no specific antigens and can be applied in patients receiving anticoagulants such as warfarin and heparin.

Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.

Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD.

Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, sex steroids, osteocalcin and bone mineral density in male and female rats.

Although it has been reported that the rate of weight gain and linear growth increases markedly during puberty in rats, little is known about the relationship between endocrine changes and bone mineral density (BMD) changes upon sexual maturation in these animals. The aim of this study was to examine the levels of serum insulin-like growth factor-I (IGF-I), IGF binding protein (IGFBP)-3, sex steroids and osteocalcin, and the changes in BMD in normal aging male and female rats. Male rats exhibited increases in serum IGF-I and IGFBP-3 concentrations before increases in serum testosterone levels. IGF-I and testosterone peaked at 9 weeks of age, and thereafter remained in a steady state, whereas IGFBP-3 reached a peak at 7 weeks of age, and then gradually declined. A strong correlation between serum IGF-I and IGFBP-3 levels was found in subjects 3-9 weeks old. A highly significant correlation between serum IGF-I and testosterone levels was also found. In females, serum 17 beta-estradiol, IGF-I and IGFBP-3 levels increased gradually from 3 to 5 weeks old, peaked at 9 weeks, and then decreased slowly thereafter. The correlation coefficient between serum IGF-I and IGFBP-3 was highly significant. The correlation coefficient between serum IGF-I and 17 beta-estradiol levels was weak, although it was strongest when the subjects were 3-9 weeks old. Serum osteocalcin is a marker of bone formation; its level remained relatively high from 3 to 9 and from 3 to 7 weeks of age in males and females, respectively, although osteocalcin in both sexes declined gradually with age. As for bone mass, sharp increases in BMD in the tibia, femur and lumbar vertebrae appeared earlier in female than in male rats, and the BMD in females tended to be higher than in males between 5 and 9 weeks old. After 9 weeks of age, BMD in males was higher than that in females, as BMD in males continued to increase whereas females tended to remain in a steady state after this stage. The correlation coefficients between tibial BMD and serum IGF-I or IGFBP-3 levels were highly significant when the subjects were from 3 to 9 weeks old. Taken together, these results suggest that BMD development occurs earlier in female than in male rats. This sex-related difference in changes in the BMD pattern may result from the earlier onset of puberty in females, and from sex-specific differences in concentrations of IGF-I, IGFBP-3 and sex steroids during maturation.

Histomorphometric study of iliac bones in cervical myelopathy with ossification of the posterior longitudinal ligament.

To investigate whether there was any abnormal systemic bone metabolism in patients with ossification of the posterior longitudinal ligament (OPLL), we measured various histomorphometric indices of the iliac trabecular bones in 19 patients with OPLL (14 men, 5 women). For each index, the Z-score for each patient was calculated, using the SD and mean value for non-OPLL control group (n = 159) who underwent orthopaedic surgeries and had no systemic disease, age-matched for each decade. A Z-score of 1.0 meant that the observed data deviated 1 SD from the normal average, and a distribution from -2 to +2 was considered normal. All the averaged Z-scores were within +/-1.0 and there were no significant differences between the OPLL and the control groups. There was also no difference in Z-score among three types of OPLL (segmental, continuous, and mixed). From these results, we concluded that there was no common abnormal bone metabolism affecting the bone histomorphometry of the iliac bone in OPLL patients. However, in two patients, the Z-score for bone volume (BV/TV) was more than 2.0, with increased osteoid volume (OV/TV) and increased trabecular thickness, suggesting that there was some abnormal bone metabolism in these two patients with OPLL.

Effect of resistance exercise training on bone formation and resorption in young male subjects assessed by biomarkers of bone metabolism.

We studied the effects of high intensity resistance exercise training on bone metabolism in 17 young adult Oriental males (23-31 years) by measuring sensitive biomarkers of bone formation and resorption. The subjects were assigned to a training group and a sedentary group. The training group followed a weight training program three times per week for 4 months. In the training group, serum osteocalcin concentration and serum bone-specific alkaline phosphatase activity were significantly increased within the first month after the beginning of resistance exercise training, and the elevated levels remained throughout the training period, while there was no significant change in plasma procollagen type-I C-terminal concentration. Urinary deoxypyridinoline excretion was transiently suppressed and returned to the initial value but was never stimulated during the 4 months. These results suggest that the resistance exercise training enhanced bone formation without prior bone resorption. In the sedentary group, there was no significant difference in bone metabolic markers except plasma procollagen type-I C-terminal, which continuously decreased during the experimental period. There were no significant changes in total and regional bone mineral density in either group. In conclusion, (1) resistance exercise training increased markers of bone formation, while it transiently suppressed a marker of bone resorption, and (2) such adaptive changes of bone metabolism to resistance exercise training occurred during the early period of the training, before changes in bone density were observable through densitometry.

Activated protein C resistance assay as a screening test for thromboembolic disposition.

An activated partial thromboplastin time (APTT) based method was developed to determine the anticoagulant response in patient plasma to added purified activated protein C (APC). On the other hand, Bertina et al. (1994) reported that one point mutation of amino acid 506 in the factor V was observed in such APC resistance patients. APC resistance for blood samples with known abnormal findings on the coagulation test also may be determined. Coagmaster II for the APTT assay system (Sankyo, Tokyo, Japan) was employed. The APC resistance assay system was a useful reagent as a screening test for lupus anticoagulant (LA), in addition to APC resistance.

[Relationship between dietary life style in youth and osteoporosis].

The relationship between the dietary life style and osteoporosis was examined by comparing 71 osteoporotic women [age--65.5 +/- 8.9 (mean +/- SD)] with 76 women age-matched as controls. All subjects lived in and around Tsukuba City. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The frequencies of drinking milk and eating meat, fish, or potatoes, etc. both in their youth (about 18-25 years old) and at the present were investigated. The results were as follows: 1) The frequency of having unbalanced diets in their youth was significantly higher in osteoporotic patients than in controls. 2) During their youth, osteoporotic patients had significantly lower frequency of drinking milk, and significantly higher frequency of eating meat, dried fish or eggs, compared with controls. 3) High milk-consumers during their youth (milk-drinking: > or = 3 times per week) were significantly less frequent in osteoporotic patients than that in controls. 4) In the controls, the frequencies of drinking milk and eating meat during their youth were significantly positively correlated with lumbar BMD. The frequency of eating potatoes was significantly negatively correlated with the BMD in controls. 5) No strong relationships between present dietary life and osteoporosis or BMD were found. These findings suggest that drinking milk in their youth may influence BMD and associate with osteoporosis in women.

Sulfated colominic acid: an antiviral agent that inhibits the human immunodeficiency virus type 1 in vitro.

Colominic acid is a homopolymer of N-acetylneuraminic acid (NANA), which has an alpha-2,8 ketosidic linkage between its polymer units. In this study, colominic acids were sulfated under different conditions and their antiviral activities against human immunodeficiency virus type 1 (HIV-1) were examined. Sulfated colominic acids, containing 6-12% sulfur, blocked the expression of HIV-1 antigen in MT-4 cells or C8166 cells following exposure to MOLT-4/HTLV-IIIB or HIV-1[GUN-1]. The compounds inhibited syncytium formation upon co-cultivation of MOLT-4 cells (clone 8) with MOLT-4/HTLV-IIIB cells and abolished the production of HIV-1 p24 antigen in culture medium of peripheral blood lymphocytes (PBLs). HIV-1 reverse transcriptase (RT) activity was not directly affected by the drugs. The compounds did not prolong activated partial thromboplastin time (APTT) at 10 and 1.0 microgram/ml, suggesting that they may not have appreciable side effects in vivo. These agents were still able to block the expression of HIV-1 antigen even when the cells were infected with HIV-1 in RPMI-1640 medium containing high percentages of fetal calf serum (FCS). These properties may be therapeutically advantageous if these compounds were considered for possible clinical use.

Selection of somaclonal variants with low-temperature germinability in melon (Cucumis melo L.).

Plants were regenerated from adventitious buds and somatic embryos (R0) of melon (Cucumis melo L.), the cultivar Andes. Somaclonal variants of melon with low temperature germinability were selected from the progenies (R1) of R0 plants. Among 5,618 R1 seeds harvested from 23 R0 plants that were regenerated from adventitious buds 4 seeds germinated after 5 days of culture at 15 °C (selection rate; 0.07%). However, among 374 R2 seeds harvested from 2 R1 plants no seed germinated after 7 days of culture at 14 °C. Among 9,181 R1 seeds harvested from 50 R0 plants regenerated from somatic embryos 110 seeds germinated after 5 days of culture at 15 °C (selection rate; 1.20%). Among 3,717 R2 seeds harvested from 17 R1 plants 113 seeds germinated after 7 days of culture at 14 °C (selection rate; 3.04%). R3 seeds were collected from these R2 plants following self-pollination. Forty-five of the 47 lines (R3) originated from 10 R0 plants showed higher germination rates than that of the original cultivar. Selected lines with low-temperature germinability showed greater fruit growth rate than the original cultivar during the middle stage when they were cultivated in a greenhouse under low-temperature conditions. Of fruits harvested from 31 lines, 15 lines showed greater fruit volume than the original cultivar.