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Biomedical subjects

K Masaki

Publications and source records attributed to K Masaki.

At least 37 records · Page 2Linked to original sources

Brain aging and midlife tofu consumption.

OBJECTIVE: To examine associations of midlife tofu consumption with brain function and structural changes in late life. METHODS: The design utilized surviving participants of a longitudinal study established in 1965 for research on heart disease, stroke, and cancer. Information on consumption of selected foods was available from standardized interviews conducted 1965-1967 and 1971-1974. A 4-level composite intake index defined "low-low" consumption as fewer than two servings of tofu per week in 1965 and no tofu in the prior week in 1971. Men who reported two or more servings per week at both interviews were defined as "high-high" consumers. Intermediate or less consistent "low" and "high" consumption levels were also defined. Cognitive functioning was tested at the 1991-1993 examination, when participants were aged 71 to 93 years (n = 3734). Brain atrophy was assessed using neuroimage (n = 574) and autopsy (n = 290) information. Cognitive function data were also analyzed for wives of a sample of study participants (n = 502) who had been living with the participants at the time of their dietary interviews. RESULTS: Poor cognitive test performance, enlargement of ventricles and low brain weight were each significantly and independently associated with higher midlife tofu consumption. A similar association of midlife tofu intake with poor late life cognitive test scores was also observed among wives of cohort members, using the husband's answers to food frequency questions as proxy for the wife's consumption. Statistically significant associations were consistently demonstrated in linear and logistic multivariate regression models. Odds ratios comparing endpoints among "high-high" with "low-low" consumers were mostly in the range of 1.6 to 2.0. CONCLUSIONS: In this population, higher midlife tofu consumption was independently associated with indicators of cognitive impairment and brain atrophy in late life.

Aged↗

Muscle strength and body mass index as long-term predictors of mortality in initially healthy men.

BACKGROUND: Muscle weakness, low body weight, and chronic diseases are often observed in the same people; however, the association of muscle strength with mortality, independent of disease status and body weight, has not been elucidated. The aim was to assess hand grip strength as a predictor of all-cause mortality within different levels of body mass index (BMI) in initially disease-free men. METHODS: Mortality was followed prospectively over 30 years. Maximal hand grip strength tests and BMI assessments were done at baseline in 1965 to 1970. The participants were 6040 healthy men aged 45 to 68 years at baseline living on Oahu, Hawaii. RESULTS: The death rates per 1000 person years were 24.6 in those with BMI <20, 18.5 in the middle BMI category, and 18.0 in those with BMI > or = 25. For grip strength tertiles, the mortality rates were 24.8 in the lowest, 18.5 in the middle, and 14.0 in the highest third. In Cox regression models, within each tertile of grip strength, BMI showed only minimal effect on mortality. In contrast, in each category of BMI there was a gradient of decreasing mortality risk with increasing grip strength. Among those with BMI <20, the adjusted relative risks (RRs) of mortality over 30 years were 1.36 (95% confidence interval 1.14-1.63) for those in the lowest third of strength at baseline, 1.27 (1.02-1.58) in the middle, and 0.92 (0.66-1.29) in the highest third. Correspondingly, for those with BMI 20-24.99, the RRs of death were 1.25 (1.08-1.45), 1.14 (1.00-1.32), and 1.0 (reference) in the lowest, middle, and highest third of grip strength, respectively. In those with BMI > or =25, the RRs were 1.39 (1.16-1.65) in the lowest, 1.27 (1.08-1.49) in the middle, and 1.14 (0.98-1.32) in the highest third of grip strength. Models were adjusted for age, education, occupation, smoking, physical activity, and body height. CONCLUSIONS: In healthy middle-aged men, long-term mortality risk was associated with grip strength at baseline, independent of BMI. The possible interpretation of the finding is that early life influences on muscle strength may have long-term implications for mortality. Additionally, higher strength itself may provide greater physiologic and functional reserve that protects against mortality.

Aged↗

Stability of the molten globule state of a domain-exchanged chimeric protein between human and bovine alpha-lactalbumins.

A domain-exchanged chimeric alpha-lactalbumin (alpha-LA), which consisted of the alpha-domain of human alpha-LA and the beta-domain of bovine alpha-LA, was constructed. Like native alpha-LA, the chimeric protein was in a molten globule state in the absence of Ca(2+) at neutral pH and low salt concentration. The stability of the molten globule state of the constructed chimeric protein was identical to that of the recombinant human protein and was higher than that of the recombinant bovine protein. The stability of the molten globule state of alpha-LA is defined by the stability of the alpha-domain.

Amino Acid Sequence↗

Depressed mood and body mass index as predictors of muscle strength decline in old men.

OBJECTIVE: To study depressed mood as a predictor of strength decline within body weight categories over a 3-year follow-up period. DESIGN: A prospective cohort study over 3 years. SETTING: Honolulu, Hawaii. PARTICIPANTS: The subjects were 2275 men participating in the Honolulu Heart Program with an average age of 77.1 years (range 71-92 years), who were not cognitively impaired at baseline (Exam 4), and who participated in maximal hand grip strength measurements at baseline and 3 years later (Exam 5). MEASUREMENTS: Hand grip strength was measured using a dynamometer. Depressive symptoms were studied using an 11-item version of Center for Epidemiologic Studies Depression Scale with 9 as a cutoff. Body weight categories were formed on the basis of body mass index (BMI) (BMI = weight/height2; underweight: BMI < 20; normal weight: BMI 20-24.99, overweight: BMI > or = 25). MAIN RESULTS: At baseline, 9.4% of the participants were rated as having depressed mood. The mean individual strength change over 3 years was - 6.9% (standard deviation 14.0). Steep strength decline was determined as losing > or = 14% (lowest quartile). The proportions of those with steep strength decline in the groups based on combined distributions of BMI and depressed mood were: underweight/ depressed (n = 22) 41%, underweight/not depressed (n = 200) 28%, normal weight/depressed (n = 127) 30%, normal weight/not depressed (n = 1181) 25%, overweight/depressed (n = 55) 31%, overweight/not depressed (n = 675, referent) 21%. After adjusting for baseline strength, age, height, sociodemographic variables and diseases, the odds ratio for steep strength decline was more than four times greater among those who were depressed and underweight, and twice as great among people who were depressed and normal weight compared with those who were nondepressed and overweight. The risks of nondepressed under- and normal weight people and depressed overweight people did not differ from the reference group. CONCLUSIONS: Depressed mood was associated with increased risk of steep strength decline, in particular in older men with low body weight. Low body weight in combination with depressed mood may be an indicator of frailty or severe disease status that leads to accelerated strength loss and disability.

Aged↗

Postural hypertension in elderly men--the Honolulu Heart Program.

Postural hypertension is a condition in which the blood pressure rises abnormally during standing. The aim of this study is to determine the prevalence of postural hypertension and its association with morbidity and subsequent mortality. At the fourth examination (1991-1993) of the Honolulu Heart Program longitudinal cohort, 3741 Japanese-American men aged 71-93 were examined. Prevalence of postural hypertension in this cohort was 39%. Although there was a high prevalence of postural hypertension in this cohort, its clinical significance is questionable as there were no significant correlations with morbidity and subsequent mortality.

Age Factors↗

The molten globule state of a chimera of human alpha-lactalbumin and equine lysozyme.

The molten globule state of equine lysozyme is more stable than that of alpha-lactalbumin and is stabilized by non-specific hydrophobic interactions and native-like hydrophobic interactions. We constructed a chimeric protein which is produced by replacing the flexible loop (residues 105-110) in human alpha-lactalbumin with the helix D (residues 109-114) in equine lysozyme to investigate the possible role of the helix D for the high stability and native-like packing interaction in the molten globule state of equine lysozyme. The stability of the molten globule state formed by the chimeric protein to guanidine hydrochloride-induced unfolding is the same as that of equine lysozyme and is substantially greater than that of human alpha-lactalbumin, although only six residues come from equine lysozyme. Our results also suggest that the non-native interaction in the molten globule state of alpha-lactalbumin changes to the native-like packing interaction due to helix substitution. The solvent-accessibility of the Trp residues in the molten globule state of the chimeric protein is similar to that in the molten globule state of equine lysozyme in which packing interaction around the Trp residues in the native state is partially preserved. Therefore, the helix D in equine lysozyme is one of the contributing factors to the high stability and native-like packing interaction in the molten globule state of equine lysozyme. Our results indicate that the native-like packing interaction can stabilize the rudimentary intermediate which is stabilized by the non-specific hydrophobic interactions.

Acrylamide↗

Cisplatin-induced toxicity in LLC-PK1 kidney epithelial cells: role of basolateral membrane transport.

Cytotoxicity of cisplatin was evaluated after apical and/or basolateral treatment of LLC-PK1 cell monolayers grown on porous membrane filters with 300 microM cisplatin. When LLC-PK1 cells were exposed from basolateral side for 0.5-4 h, lactate dehydrogenase (LDH) release into culture medium was markedly stimulated. However, apical treatment of the cells with cisplatin for 0.5 h did not stimulate LDH release. gamma-Glutamyltransferase activity and amount of protein in the cell homogenate were markedly decreased by basolateral treatment with cisplatin. However, in the apical treatment with cisplatin, these changes were relatively small, suggesting that degrees of the toxicities were different between basolateral and apical treatment with cisplatin. Cellular platinum level after basolateral treatment with cisplatin was higher compared to that following apical treatment. Furthermore, both accumulation and toxicity of cisplatin in LLC-PK1 cells were decreased by treatment with cisplatin at 4 degrees C. These results suggested that there were specific mechanisms mediating cisplatin uptake at the basolateral membranes of LLC-PK1 cells.

Animals↗

Midlife hand grip strength as a predictor of old age disability.

CONTEXT: Poor muscle strength, functional limitations, and disability often coexist, but whether muscle strength during midlife predicts old age functional ability is not known. OBJECTIVE: To determine whether hand grip strength measured during midlife predicts old age functional limitations and disability in initially healthy men. DESIGN AND SETTING: A 25-year prospective cohort study, the Honolulu Heart Program, which began in 1965 among Japanese-American men living on Oahu, Hawaii. PARTICIPANTS: A total of 608945- to 68-year-old men who were healthy at baseline and whose maximal hand grip strength was measured from 1965 through 1970. Altogether, 2259 men died over the follow-up period and 3218 survivors participated in the disability assessment in 1991 through 1993. MAIN OUTCOME MEASURES: Functional limitations including slow customary walking speed (< or =0.4 m/s) and inability to rise from a seated position without using the arms, and multiple self-reported upper extremity, mobility, and self-care disability outcomes. RESULTS: After adjustment for multiple potential confounders, risk of functional limitations and disability 25 years later increased as baseline hand grip strength, divided into tertiles, declined. The odds ratio (OR) of walking speed of 0.4 m/s or slower was 2.87 (95% confidence interval [CI], 1.76-4.67) in those in the lowest third and 1.79 (95% CI, 1.14-2.81) in the middle third of grip strength vs those in the highest third. The risk of self-care disability was more than 2 times greater in the lowest vs the highest grip strength tertile. Adding chronic conditions identified at follow-up to the models predicting disability reduced the ORs related to grip strength only minimally. CONCLUSIONS: Among healthy 45- to 68-year-old men, hand grip strength was highly predictive of functional limitations and disability 25 years later. Good muscle strength in midlife may protect people from old age disability by providing a greater safety margin above the threshold of disability.

Activities of Daily Living↗

Two cases of focal nodular hyperplasia of the liver: value of scintigraphy with Tc-99m GSA and positron emission tomography with FDG.

Focal nodular hyperplasia (FNH) of the liver is relatively rare, and can be difficult to differentiate from other benign tumors arising in the liver. We describe a 23-year-old woman and a 25-year-old man with FNH. They were hospitalized for further evaluation of a space-occupying lesion in the liver. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) revealed increased radioactivity in the tumor in one patient and radioactivity similar to that in the normal part of liver in the other. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed uptake similar to that of the normal liver in both patients. FNH was diagnosed on the basis of angiographic findings and histological findings in liver biopsy specimens. Our results show that scintigraphy with Tc-99m GSA and FDG-PET may provide information helpful in the diagnosis of FNH.

Adult↗

Calcitriol for bone loss in patients with primary biliary cirrhosis.

Because osteoporosis is a common complication of primary biliary cirrhosis, we evaluated the effects of calcitriol (1alpha, 25-dihydroxyvitamin D3) on bone mineral density in 34 women with primary biliary cirrhosis (stage I disease in 16 patients, stage II in 9, stage III in 4, and stage IV in 5). Patients were assigned randomly to receive calcitriol (0.5mg twice a day) or not. Bone mineral density of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at least twice during a period of 12-43 months. The mean annual change in bone mineral density was 0.1% in the treatment group and -3.1% in the control group. The median annual change (with 25th and 75th percentiles) in bone mineral density was 0.3% (-0.5%, 1.9%) in the treated group and -3.1% (-4.1%, -2.1%) in the control group. This difference between the two groups was significant (P = 0.0007, Mann-Whitney U-test). Our findings suggest that calcitriol prevents bone loss and may be an effective treatment for osteoporosis in patients with primary biliary cirrhosis.

Absorptiometry, Photon↗

Calcitriol for bone disease in patients with cirrhosis of the liver.

BACKGROUND: Osteoporosis is associated with cirrhosis of the liver, but the effects of therapy for osteoporosis associated with cirrhosis are still controversial. METHODS: We evaluated the effects of calcitriol (1alpha,25-dihydroxyvitamin D3) on bone mineral density (BMD) in 76 patients (26 men and 50 women) with cirrhosis who were assigned randomly to receive calcitriol (0.5 mg twice per day) or not. The BMD of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at least twice, 12-57 months apart. RESULTS: For men, the mean annual change in BMD was 1.1% in the treated group and -0.4% in the control group. The median (25th and 75th percentiles) annual change in BMD was 0.6 (-0.1, 2.1%) in the treated group and -1.4 (-1.9, 1.6%) in the control group. The difference in the median annual change between the two groups was significant (P = 0.013). For women, the mean annual change in BMD was -0.5% in the treated group and -2.3% in the control group. The median (25th and 75th percentiles) annual change in BMD was -0.5 (-1.8, 1.3%) in the treated group and -1.5 (-3.8, -0.7%) in the control group. This difference was significant (P = 0.011). CONCLUSIONS: Our results suggest that calcitriol can prevent bone loss and, therefore, may be useful for the treatment of bone disease in patients with cirrhosis of the liver.

Absorptiometry, Photon↗

Adsorption of human lysozyme onto hydroxyapatite. Identification of its adsorbing site using site-directed mutagenesis.

To elucidate hydroxyapatite-protein interaction, mutant human lysozymes in which the surface charge was modified by site-directed mutagenesis were used. Five mutant human lysozymes (K1A, K13A, K33A, R10A, R14A) were expressed in yeast. The chromatographic behavior of these lysozymes was studied with a HPLC hydroxyapatite column. Elution molarities of K1A and R14A mutants were greatly lowered. While Lys-13 and Arg-10 are located around Lys-1 and Arg-14, K13A and R10A mutants bound onto hydroxyapatite stronger than K1A and R14A mutants. In combination with an X-ray crystal structure of human lysozyme, it is concluded that the adsorbing site of human lysozyme is at the back of the active site and that Arg-14, Lys-1, Arg-10 and Lys-13 play important roles in binding.

Adsorption↗

Longitudinal changes of bone mineral content with age in patients with cirrhosis of the liver.

Bone disorders are associated with cirrhosis. Knowledge of the natural course of bone changes in cirrhosis could help in decision-making about medical treatment. We carried out one measurement of bone mineral density (BMD) in 184 Japanese patients (98 men and 86 women) with cirrhosis by dual-energy X-ray absorptiometry. Differences in BMD values means +/- SD between the 98 cirrhotic men and 283 healthy men of the same age reported in another study were not significant. In the 86 cirrhotic women, BMD tended to show a greater decrease with age than in healthy controls reported elsewhere. Differences in BMD values (means +/- SD) between 622 healthy women reported elsewhere and our patients were not significant for women up to age 60 years, but at 60 years or more, the mean BMD in cirrhotic women (0.692 +/- 0.100) was lower than that in healthy women (0.749 +/- 0.101; P < 0.01). In 61 of the 184 patients (31 men and 30 women), the bone mineral content (BMC) of lumbar vertebrae was measured at least twice, at intervals of 10-72 months. In this longitudinal part of the study, the group mean of estimated annual change for cirrhotic men was -0.4%, close to that of healthy men (-0.2%). This mean in cirrhotic women was -2.8%, significantly different from that of healthy women (-1.1%; P < 0.05). As expected, cirrhotic women were the most likely to lose BMC, and many needed prompt treatment.

Absorptiometry, Photon↗

Prolonged QTc interval, impaired pulmonary function, and a very lean body mass jointly predict all-cause mortality in elderly men.

PURPOSE: Assess the joint impact of prolonged QTc interval (QT interval corrected for heart rate), impaired lung function, and low body weight on all-cause mortality. METHODS: This is a population-based, prospective study of the Honolulu Heart Program cohort, performed in Oahu Island, Hawaii, during the 1991-1993 fourth examination of cohort survivors. The participants were 3056 Japanese-American men, 71 to 93 years of age. The measurement consisted of: 1) instrument calculated, heart rate corrected QT interval; 2) one second forced expiratory volume (FEV1) as a percentage of age- and height-predicted FEV1; and 3) body mass index (BMI, kg/m2). Relations of subsequent 3 1/2 year, on average, mortality rates with high risk states of these variables are determined. High risk states are QTc > 440 msec, percent predicted FEV1 < or = 80%, and BMI < or = 21 kg/m2. RESULTS: Mortality rates synergistically increase among groups with one, two, or three high risk states. Men having all three high risk states are seven times more likely to die in the follow-up period than men with no high risk conditions. Very thin men having one other high risk state, pulmonary impairment or prolonged QTc, are four times more likely to die. Excluding diabetics, active smokers, or men taking drugs affecting QT interval does not alter findings. Excluding prevalent coronary heart disease decreases mortality rates among joint high risk groups. CONCLUSION: Results are consistent with clinical studies identifying an autonomic neuropathy associated with wasting chronic lung disease, prolonged QTc, and mortality. Aging populations in developed nations will increase the prevalence of diseases associated with these conditions in decades to come.

Aged↗

Calorimetric study of mutant human lysozymes with partially introduced Ca2+ binding sites and its efficient refolding system from inclusion bodies.

During the process of evolution, ancestral lysozymes evolved into calcium-binding lysozymes by acquiring three critical aspartate residues at positions 86, 91 and 92. To investigate the process of the acquisition of calcium-binding ability, two of the aspartates were partially introduced into human lysozyme at positions 86, 91 and 92. These mutants (HLQ86D, HLA92D and HLQ86D/D91Q/A92D), having two critical aspartates in calcium-binding sites, were expressed in Escherichia coli as non-active inclusion bodies. For the preparation of lysozyme samples, a refolding system using thioredoxin was established. This system allowed for effective refolding of wild-type and mutant lysozymes, and 100% of activity was recovered within 4 days. The calcium ion dependence of the melting temperature (Tm) of wild-type and mutant lysozymes was investigated by differential scanning calorimetry at pH 4.5. The Tm values of wild-type, HLQ86D and HLA92D mutants were not dependent on calcium ion concentration. However, the Tm of HLQ86D/D91Q/A92D was 4 degrees higher in the presence of 50 mM CaCl2 than in its absence, and the calcium-binding constant of this mutant was estimated to be 2.25(+/-0.25)x10(2) M(-1) at pH 4.5. Moreover, the calcium-binding ability of this mutant was confirmed by the result using Sephadex G-25 gel chromatography. These results indicate that it is indispensable to have at least two aspartates at positions 86 and 92 for acquisition of calcium-binding ability. The process of the acquisition of calcium-binding site during evolution of calcium-binding lysozyme is discussed.

Aspartic Acid↗

Grip strength changes over 27 yr in Japanese-American men.

The aim of this study was to describe changes in grip strength over a follow-up period of approximately 27 yr and to study the associations of rate of strength decline with weight change and chronic conditions. The data are from the Honolulu Heart Program, a prospective population-based study established in 1965. Participants at exam 1 were 8,006 men (ages 45-68 yr) who were of Japanese ancestry and living in Hawaii. At follow-up, 3,741 men (age range, 71-96 yr) participated. Those who died before the follow-up showed significantly lower grip-strength values at baseline than did the survivors. The average annualized strength change among the survivors was -1.0%. Steeper decline (>1.5%/yr) was associated with older age at baseline, greater weight decrease, and chronic conditions such as stroke, diabetes, arthritis, coronary heart disease, and chronic obstructive pulmonary disease. The risk factors for having very low hand-grip strength at follow-up, here termed grip-strength disability (</=21 kg, the lowest 10th percentile), were largely same as those for steep strength decline. However, the age-adjusted correlation between baseline and follow-up strength was strong (r = 0.557, P < 0.001); i.e., those who showed greater grip strength at baseline were also likely to do so 27 yr later. Consequently, those in the lowest grip-strength tertile at baseline had about eight times greater risk of grip-strength disability than those in the highest tertile because of their lower reserve of strength. In old age, maintenance of optimal body mass may help prevent steep strength decrease and poor absolute strength.

Aged↗

Predictors of healthy aging in men with high life expectancies.

OBJECTIVE: The purpose of this study was to identify risk factors that consistently predict staying healthy in contrast to developing clinical illness and/or physical and mental impairments. METHODS: More than 8000 men of Japanese ancestry were followed for 28 years with repeat examinations and surveillance for deaths and incident clinical illness. Physical and cognitive functions were measured in 1993. Measures of healthy aging included surviving and remaining free of major chronic illnesses and physical and cognitive impairments. RESULTS: Of 6505 healthy men at baseline, 2524 (39%) died prior to the final exam. Of the 3263 available survivors, 41% remained free of major clinical illnesses, 40% remained free of both physical and cognitive impairment, and 19% remained free of both illness and impairment. The most consistent predictors of healthy aging were low blood pressure, low serum glucose, not smoking cigarettes, and not being obese. CONCLUSIONS: Beyond the biological effects of aging, much of the illness and disability in the elderly is related to risk factors present at midlife.

Aged↗

[Palmaz-Schatz stent implantation for aorto-ostial stenoses of native coronary arteries and saphenous vein grafts].

Conventional balloon angioplasty treatment of aorto-ostial stenoses in native coronary arteries and saphenous vein grafts is associated with a low primary success rate, a high complication rate and a high incidence of restenosis. The short-term outcome of Palmaz-Schatz stent implantation in aorto-ostial lesions was compared with that of balloon angioplasty. Thirteen patients underwent stent implantation for 13 de novo lesions (four in the left main coronary trunk, two in the right coronary artery, seven in the vein graft) between January 1994 and December 1995. Fourteen patients underwent balloon angioplasty for 14 de novo lesions (five in the left main coronary trunk, four in the right coronary artery, five in the vein graft between January 1986 and April 1992. Both groups had similar clinical characteristics. Initial success was obtained in all patients in the stent group, compared with 71% of the balloon angioplasty group. Insufficient dilation was the main cause for such failure in the balloon angioplasty group. Baseline reference diameters were similar (3.40 +/- 0.65 mm in the stent group vs 3.36 +/- 0.42 mm in the balloon angioplasty group) and there was no difference in baseline minimal luminal diameter (1.41 +/- 0.74 vs 1.08 +/- 0.56 mm). Minimal luminal diameter was significantly greater in the stent group than in the balloon angioplasty group at both post-procedure and follow-up examinations (post: 3.36 +/- 0.58 vs 2.69 +/- 0.45 mm, p < 0.01; follow-up: 2.33 +/- 0.96 vs 1.52 +/- 0.68 mm, p < 0.05). There was no subacute occlusion in either group. The overall angiographic restenosis rate (> 50% stenosis) was lower in the stent group (17%) than in the balloon angioplasty group: the restenosis rates of native lesions were 0% in the stent group and 40% in the balloon angioplasty group; those of saphenous vein graft lesions were 33% in the stent group and 50% in the balloon angioplasty group. Although the number of patients was limited, these results suggest that Palmaz-Schatz stent implantation may be a safe and effective strategy for treating aorto-ostial lesions in both native coronary arteries and saphenous vein grafts.

Angioplasty, Balloon, Coronary↗