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Biomedical subjects

K Takamatsu

Publications and source records attributed to K Takamatsu.

At least 19 recordsLinked to original sources

Age-related changes in expression of hippocalcin and NVP2 in rat brain.

Expression of hippocalcin and neural visinin-like calcium-binding protein 2 (NVP2) in aging rat brain was investigated by immunoblot and immunohistochemical analyses. In 3-month old rats, hippocalcin and NVP2 were present at high concentrations in hippocampal and cerebral pyramidal cells and dentate granule cells, with hippocalcin protein levels being five to ten times higher than NVP2 levels. Hippocalcin levels in hippocampus and cerebral cortex decreased by approximately 20% at 24 months. While the number of hippocalcin-positive cells in CA3, dentate gyrus and cerebral cortex were preserved, staining intensity decreased. In contrast, the number and staining intensity of hippocalcin-positive cells in CA1 were maintained. NVP2 levels in hippocampus and cerebral cortex decreased by approximately 30% at 24 months. In cerebral cortex, the number and intensity of NVP2-positive cells decreased. In CA1 through CA3 and in dentate gyrus, NVP2-positive cell numbers were preserved, but staining intensity decreased. In summary, the loss of hippocalcin and NVP2 in aging rat brain may be associated with age-related impairment of postsynaptic functions.

Aging

Periodically fluctuating protein kinases phosphorylate CLOCK, the putative target in the suprachiasmatic nucleus.

We studied nuclear protein phosphorylation in the rat suprachiasmatic nucleus (SCN) and found that a nuclear fraction of the SCN contained histone H1 kinase activity that periodically fluctuated with a diurnal rhythm, reaching a maximum at the midpoint of the light phase and a minimum at the midpoint of the dark phase. A p13suc1-bound fraction from the SCN nuclear fraction also exhibited diurnally fluctuating histone H1 kinase activity. Using in situ kinase assay, three histone H1 kinases, p45PFK, p100PFK, and p200PFK (termed periodically fluctuating protein kinases, or PFKs) were found in the p13suc1-bound fractions. p45PFK exhibited the highest level of light/dark cycle phosphorylation activity fluctuation. p45PFK highly phosphorylated the Ser-Pro-rich region of CLOCK, the putative physiological target. These results suggest that PFKs, especially p45PFK, are involved in circadian clock-related signal transduction and gene expression, through the phosphorylation of target proteins such as CLOCK.

Animals

Genomic structure and chromosomal mapping of the human and mouse hippocalcin genes.

In an attempt to elucidate the possible relationship of hippocalcin to neurological disorders, we isolated and analyzed the human and mouse hippocalcin genes. The human and mouse hippocalcin genes contain three exons and two introns, and span approximately 7 and 8kb, respectively. The exon/intron splice junctions of the human and mouse genes are all situated in exactly the same position and are not consistently placed with respect to the coding regions of the tandemly repeated EF-hand motifs. The amino acid sequences of human and mouse hippocalcins deduced from the genes are 100% identical. Within the 2-kb 3'-flanking sequences of the human and mouse genes, one conserved polyadenylation signal was identified at positions 762 and 823bp downstream from TAG, respectively. Within the 2.6-kb 5'-flanking sequences of the human and mouse genes, neither a canonical 'TATA' box nor a 'CAAT' box was found. Southern blot analysis of the human and mouse genomic DNAs demonstrated that the positive bands coincide exactly with those expected from the sequence of the cloned genes, indicating that the human and mouse hippocalcin genes are present as a single-copy gene. Fluorescence in-situ hybridization revealed that the human hippocalcin gene is located at chromosome 1 p34.2-35 and the mouse hippocalcin gene at chromosome 4 D2-D3.

Animals

Purification and molecular cloning of a novel calcium-binding protein, p26olf, in the frog olfactory epithelium.

Olfactory adaptation requires the change of intracellular calcium concentration during stimuli. To contribute in the study of the molecular mechanism of calcium-dependent regulations in olfactory receptor cells, we isolated a novel 26-kDa Ca2+-binding protein named p26olf from the frog olfactory epithelium after four chromatographical steps. Based on the partial amino acid sequences of the proteolysed fragments of p26olf, we obtained a cDNA clone that encodes p26olf. The analysis of its amino acid sequence revealed that p26olf consists of two S-100-like regions aligned sequentially with a calculated molecular mass of 24,493. Northern blot analysis showed that p26olf is expressed in the frog olfactory epithelium and also in other tissues. Immunoreactivity against p26olf was detected in the cilia layer of the olfactory epithelium. These results suggest that p26olf is a dimeric form of S-100 proteins and is involved in the olfactory transduction or adaptation.

Adaptation, Physiological

Influence of bilateral oophorectomy upon lipid metabolism.

OBJECTIVES: Reduction in serum level of estrogen has been thought to result in hyperlipidemia which triggers atherosclerosis, and even to lead to cardiovascular diseases, in postmenopausal women. The present study was designed to investigate the influence of bilateral oophorectomy (OPX), which induces as much reduction in serum estrogen level as menopause, upon lipid metabolism, especially the serum levels of total cholesterol. METHODS: In 31 OPX subjects and 31 age- and body size-matched premenopausal controls, the serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C), apoprotein-A1 (Apo-A1), apoprotein-B (Apo-B), lipoprotein lipase (LPL) and lipoprotein-a [LP(a)] were measured as indices of lipid metabolism and the index of arteriosclerosis was calculated. RESULTS: TC level was significantly higher in the OPX group than in the premenopausal control group, being 8995 +/- 244 (mean +/- S.E.) mmol/l and 7757 +/- 228 mmol/l, respectively. LDL-C and Apo-B levels and the index of arteriosclerosis were all significantly higher in the OPX group than in the premenopausal control groups. However, there were no significant intergroup differences with regard to HDL-C, Apo-A1, LPL and LP(a). CONCLUSIONS: The above results demonstrated that, in spite of no reduction in HDL-C, the blood levels of Apo-B, LDL-C and TC change due to OPX. These changes suggest OPX induces cardiovascular diseases and, therefore, follow-up of the changes in lipid metabolism is required, paying special attention to Apo-B and LDL-C.

Apoproteins

Effect of a HMG-CoA reductase inhibitor combined with hormone replacement therapy on lipid metabolism in Japanese women with hypoestrogenic lipidemia: a multicenter double-blind controlled prospective study.

OBJECTIVES: Menopause is associated with a rise in serum lipid concentrations. We compared a regimen of pravastatin alone with pravastatin and hormone therapy in postmenopausal women with hyperlipidemia. METHODS: We performed a double-blind, randomized, multicenter controlled study in postmenopausal women with hyperlipidemia. The women were randomly assigned to receive pravastatin alone (M group; n = 25) or pravastatin and hormone replacement therapy (HRT) (MC group; n = 32) for 12 weeks. Serum lipid and estrogen concentrations were measured at baseline and after 4 weeks and 12 weeks of treatment. RESULTS: The two groups were similar with respect to baseline demographic characteristics such as age, height, and body weight. As compared with baseline, the total cholesterol (TC) concentration was 15.0% lower at 4 weeks and 17.7% lower at 12 weeks in the M group and 15.1% lower at 4 weeks and 18.3% lower at 12 weeks in the MC group. The low-density-lipoprotein cholesterol (LDL-C) concentration decreased by 25.0% at both 4 weeks and 12 weeks in the M group and by 26.8% at 4 weeks and 30.0% at 12 weeks in the MC group. Serum TC and LDL-C concentrations were significantly lower in the MC group than in the M group after 4 weeks of treatment, but there was no significant difference between the groups in serum lipid concentrations after 12 weeks. Pravastatin combined with HRT was therefore suggested to lower serum lipid concentrations earlier than pravastatin alone. There were no significant differences between the treatment groups in serum high-density-lipoprotein cholesterol concentrations or triglyceride concentrations after the initiation of therapy. In the MC group, there was a significant positive correlation between the percentage change in serum lipid concentrations and that in estrogen concentrations, suggesting that the HRT-induced rise in estrone (E1) as well as that in estradiol (E2) contributed an improved serum lipid profile. TC and E2, and LDL-C and serum E1 had significant negative correlation at 12 weeks and 4 weeks, respectively. Pravastatin had no apparent effect on endogenous estrogen levels and was not associated with any side effects, which confirmed that pravastatin is safe, either alone or in combination with HRT. CONCLUSIONS: The combination of pravastatin and HRT in the management of hyperlipidemia in postmenopausal women is very useful therapeutically, because it additionally provides the broad benefits of HRT, without compromising the lipid lowering effects of either treatment.

Cholesterol

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.

Age Factors

Increase or decrease of HDL-cholesterol concentrations during pravastatin treatment depending on the pre-treatment HDL cholesterol levels.

OBJECTIVE: The effect of pravastatin was evaluated using patient data accumulated in the data base of a hospital information system (HIS). METHODS: We selected 130 patients treated with pravastatin 10 mg per day, for a minimum period of 4 weeks. RESULTS: In the t test analysis, the reduction rates of total cholesterol (TC) and low-density lipoprotein (LDL) levels for pravastatin administration were 18%, and 27%, respectively. These values were similar to previous reports. The high-density lipoprotein (HDL) level, however, did not change significantly, although previous reports have shown an elevation of HDL levels. In an attempt to explain the origin of this difference, we studied the pretreatment value dependence of the cholesterol change using regression analysis. We found that pravastatin raised the HDL level in those cases where pretreatment values were lower than 58 mg.dl-1 and reduced it for higher values. We also showed that the reductions of TC, LDL and triglyceride (TG) levels correlated positively with their pretreatment values.

Anticholesteremic Agents

Effect of smoking on the prevalence of albuminuria in Japanese men with non-insulin-dependent diabetes mellitus.

Smoking is a risk factor for diabetic nephropathy in patients with IDDM and potentially those with NIDDM. We investigated the relationship between renal involvement and cigarette smoking in 148 men with NIDDM. The presence of renal involvement was assessed by determining the overnight urinary albumin/creatinine ratio (mg/g, ACR). The patients were divided into three groups, normo-, micro-, and macroalbuminuria, based on the ACR (< 30, 30-300, and 300 < or = mg/g, respectively). The incidence of micro-/macroalbuminuria in 81 smokers was significantly higher than that in 21 ex-smokers (stopped smoking at least 10 years prior to the study) or 40 non-smokers (53.1, 33.3, and 20.0%, respectively). The prevalence of smoking in the groups of patients with normo-, micro-, and macroalbuminuria were 45, 73, and 76%, respectively. The relative risk (odds ratio) for the prevalence of micro-/macroalbuminuria associated with smoking was 4.5 (95% CI, 1.9-11.6, P < 0.001) in smokers and was 2.0 (not significant) in ex-smokers. Our results indicate that stricter counselling about the importance of quitting smoking will be necessary in patients with NIDDM to protect against the development of diabetic nephropathy.

Aged

Changes in CA602 and CA546 concentrations in patients during in-vitro fertilization and embryo transfer, and ovarian hyperstimulation syndrome.

Changes in CA602 and CA546, two carbohydrate-related antigens newly established in our institute, were evaluated during the course of in-vitro fertilization and embryo transfer. The concentration of CA602, an antigen with characteristics similar to those of CA125, did not change substantially until embryo transfer. In patients with clinical evidence of ovarian hyperstimulation syndrome (OHSS), a significant increase in serum concentrations of CA602 was observed 10 days after embryo transfer (P < 0.01). There were no significant changes in the patients without OHSS. A significant elevation of oestradiol concentration in OHSS patients was also observed, with the variation before oocyte retrieval being greater than that seen with CA602. The concentration of CA546, which had lower false-positive rates in benign disease, did not differ significantly in the OHSS and non-OHSS patients. Our data demonstrate that serum concentrations of CA602 are increased even in early stages of OHSS, and suggest a possible role for this antigen as a marker for OHSS.

Adult

Diffuse lipomatosis: imaging features.

A case of diffuse lipomatosis is reported. A 54-year-old man presented with a large mass in the left gluteal region. Plain radiographs showed hyperostosis of the phalanx of the left third toe. The diagnosis was aided by magnetic resonance imaging and computed tomography which clearly demonstrated a diffuse overgrowth of fatty tissue in the left buttock and the extremity involving the subcutaneous and gluteal muscular tissue.

Humans

Cholecystoparesis with diabetic autonomic neuropathy.

A 69-year-old male diabetic patient was hospitalized with pneumonia in February 1996. Abdominal ultrasonography performed as a routine examination on admission revealed marked dilatation of gallbladder with a fasting maximal size of 25.7 cm2 compared with 8.8 +/- 2.9 cm2 evaluated in 30 male healthy controls aged 67 +/- 8 years old. Four months after recovery from pneumonia, abnormal gallbladder dilatation remained unchanged (25.0 cm2), while dilatation had not been observed on an examination performed 6 years earlier (9.8 cm2). Because of accompanying neurological defects, we suppose that cholecystoparesis may be caused by progression of autonomic neuropathy in this patient with diabetes mellitus.

Aged

Trypsin inhibitor activity in commercial soybean products in Japan.

The effect of trypsin inhibitor (TI) in soybean on the prevention of cancer has been reported in animal studies. However, the actual intake of active TI in daily life is not known. In this experiment we measured TI activity in various soybean products and the effects of some factors of processing on the TI activity. Average TI activity in whole soybean was 4,819 U/100 g, and the average percentages of remaining activity in products against that of whole soybean were momen-tofu 2.5%, yose-tofu 3.4%, kinugoshi-tofu 4.3%, jyuten-tofu 7.9%, soymilk 13.0%, natto 0.7%, soy sauce 0.8% and miso 0.3%. By heating soymilk at 100 degrees C, TI activity decreased to 11% at 10 min and 5% at 20 min. After heating soymilk in a water-bath for 15 min at 75 and 100 degrees C, TI activity decreased to 35 and 12%, respectively. The TI activity of tofu was proportional to the remaining whey. The effects of chemicals used for the coagulation of soy protein and foam-removal on TI activity were little. The results suggest that soybean products retain 2.5-12.5% TI activity of the whole soybean and that humans are consuming some active TI in their daily lives.

Food Handling

Functional evaluation of flail hip joint after periacetabular resection of the pelvis.

Five patients subjected to flail hip joint after resection of primary bone tumor of the pelvis involving acetabular region were examined with respect to function. When a thick portion of the supraacetabular pelvic neck was left in place, the operated legs functioned well regardless of whether the head of the femur was placed anterior or posterior to the iliac wing. In a patient who had only a thin portion of the iliac wing left in place and in those who underwent total excision of the ilium or hemiresection of the pelvis, the function of operated legs was poorer than with a thick portion of the supraacetabular pelvic neck left in place, but still more than 50% of leg function remained. Although flail hip joint results in a larger leg-length discrepancy than do other techniques, it enables favorable healing of the operative wound. Therefore, this method should be considered for women or sedentary patients with primary bone tumor of the pelvis involving acetabular region.

Acetabulum

Decreased bone mineral density associated with early menopause progresses for at least ten years: cross-sectional comparisons between early and normal menopausal women.

To establish whether early onset of menopause carries an increased risk of osteoporosis, we compared the bone mineral density (BMD) of the second to fourth lumbar vertebrae (L2-4) between 18 women who had menopause before 43 years of age (early menopause group) and 19 women who had menopause after reaching 43 years of age (normal menopause group). Serum levels of calcium, phosphorus, calcitonin, intact parathyroid hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and alkaline phosphatase activity were measured, and urine samples were analyzed to derive calcium/creatinine, hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine (D-Pyr/Cr) ratios. Mean BMD was significantly lower in the early menopause group than in the normal menopause group, and individual BMD values in about half of the subjects in the former group were below the fracture threshold for Japanese women. Serum concentrations of LH, FSH, and E2 were slightly, but not significantly, lower in the early menopause group than in the normal menopause group. The D-Pyr/Cr ratio was significantly higher in the early menopause group than in the normal menopause group. There was no correlation between L2-4 BMD and age or the number of years after menopause in the normal menopause group, but both age and the number of years after menopause were negatively correlated with L2-4 BMD in the early menopause group. These results indicate that BMD in women who have early menopause continues to decline for up to 10 years, and that menopause and aging increase the risk of osteoporosis.

Adult