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Biomedical subjects

K Takamatsu

Publications and source records attributed to K Takamatsu.

At least 19 recordsLinked to original sources
PubMed2000

Isolation and characterization of the gene encoding mouse tax-responsive element-binding protein (TREB) 5.

TREB5/hXBP-1/HTF is a basic region leucine zipper protein which binds to a cyclic AMP responsive element (CRE)-like element in both human T-cell leukemia virus type 1 and human major histocompatibility complex (MHC) class II genes. To analyze the structure and transcription regulation of the TREB5 gene, we isolated the mouse TREB5 gene and cDNA. The mouse TREB5 gene contains five exons and four introns and spans approximately 5 kb. The deduced amino acid sequence of mouse TREB5 exhibited 77% and 94% homology to human and rat TREB5, respectively. The b-zip structure is completely conserved in mouse, rat and human. Southern blot analysis of the mouse genomic DNA demonstrated that positive bands exactly coincide with those expected from sequences of the cloned genes, indicating that the mouse TREB5 gene is present as a single copy. The transcription start site of the mouse TREB5 gene was mapped to -15 bp upstream from the ATG initiation codon. Promoter analysis of serial deletion mutants revealed that the -142 bp upstream region is the minimum sequence to promote mouse TREB5 gene expression and that the -1.0 kb upstream region is required for full promoter activity.

3T3 Cells↗
PubMed2000

Soy protein isolate and its hydrolysate reduce body fat of dietary obese rats and genetically obese mice (yellow KK)

This study examined in dietary obese and genetically obese rodents the effects of soy protein isolate (SPI) and its hydrolysate (SPI-H) on the rate of body-fat disappearance. Male Sprague-Dawley rats (4-16 wk old) and yellow KK mice (6-10 wk old) were made obese by feeding high-fat diets containing 30% fat. They were then fed energy-restricted, low-fat (5.0%), and high-protein (35% casein, SPI, or SPI-H) diets for 4 wk at 60% of the level of the energy intake of rodents on laboratory chow. The body-fat contents of rats and mice fed a high-fat diet were 27.3 and 33.6 g/100 g body weight, respectively, at the end of the obese period. For rats, the apparent absorbability of dietary energy and fat was significantly lower in the SPI and SPI-H groups than in the casein group, but vice-versa for nitrogen balance. Body-fat content in mice fed SPI and SPI-H diets was significantly lower than in those fed the casein diet. In rats, plasma total cholesterol level was lower with the SPI-H diet, and plasma glucose level was lower with the SPI and SPI-H diets than with the casein diet. These results indicate that SPI and SPI-H are suitable protein sources in energy-restricted diets for the treatment of obesity.

Adipose Tissue↗
PubMed2000

Absorption of calcium, magnesium, phosphorus, iron and zinc in growing male rats fed diets containing either phytate-free soybean protein or soybean protein isolate or casein.

The effect of dietary phytate-free soybean protein (PFS) on intestinal mineral absorption and retention was examined in growing male rats using a three-day mineral balance technique. The rats were fed diets containing PFS, soybean protein isolate (SPI) or casein at a 20% level for 5 wk. Total calcium (Ca), magnesium (Mg), phosphorus (P), iron (Fe) and zinc (Zn) contents in diets were adjusted to 0.35, 0.05, 0.7, 0.0035 and 0.003%, respectively, by supplementation of the diet with their salts. Mineral absorption and retention ratios in rats fed the PFS diet were significantly higher than those in rats fed either the SPI or casein diet. These results suggest that PFS may be a promising dietary protein source for improving the mineral bioavailability in humans.

Animals↗
PubMed1999

Site-directed mutagenesis of the response regulator DmsR for the dmsCBA operon expression in Rhodobacter sphaeroides f. sp. Denitrificans: An essential residue of proline-130 in the linker.

DmsR protein is a member of the OmpR response regulator subfamily that activates the transcription of the dmsCBA operon in Rhodobacter sphaeroides f. sp. denitrificans. By site-directed mutagenesis some functional amino acid residues were investigated in DmsR, which consists of the N-terminal regulatory and the C-terminal DNA-binding domains and the linker connecting the two domains. The substitution of P130S in the linker caused decreases of both DNA-binding and transcriptional activator activities. Introducing additional substitutions of R129P or D131P to the DmsR-P130S derivative recovered both activities, demonstrating necessity of proline residue at one of the positions 129-131 in the linker. Substitutions of D12A, D55A, and K104M, at residues conserved in the phosphorylation region, caused no production of DMSO reductase, but retained DNA-binding ability, suggesting that unphosphorylated DmsR also has high affinity to its target nucleotide sequence of DNA. Substitutions in the C-terminal domain suggested the presence of a winged helix-turn-helix structure observed in the DNA-binding domain of the Escherichia coli OmpR.

Bacterial Proteins↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

Physiological effects of water-soluble soybean fiber in rats.

Four-week-old rats were fed on diets containing either no dietary fiber (DF) or a DF source (WSSF, ISF or cellulose) for 4 weeks. The DF level was adjusted to 5%. The WSSF diet contained 3% and 2%, respectively, of WSSF and cellulose. No rat in any group experienced diarrhea, and none of the experimental diets suppressed the growth of rats, the apparent absorption of major nutrients being almost 100%. However, the rate of degradation of DF during the digestive process was significantly different (p < 0.05, cellulose, 23.6%; WSSF with cellulose, 64.5% (WSSF degradation only was 91.8%); and ISF, 77.6%). The plasma and liver lipid levels were within normal ranges, although the liver cholesterol level in those rats fed on WSSF and ISF was significantly lower (p < 0.05) than in those fed on cellulose. The cecal organic acid contents were in the order of WSSF > ISF > cellulose > DF-free. Furthermore, WSSF was effective in shortening the gastrointestinal transit time. The results indicate that WSSF seems to have favorable effects on the intestinal functions.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Isolation of two human cDNAs, HLP3 and HLP4, homologous to the neuron-specific calcium-binding protein genes.

We have cloned and sequenced two types of human cDNA, HLP3 and HLP4, encoding a protein of 191 amino acid residues with four EF-hand calcium-binding motifs. The HLP3 and HLP4 proteins are homologous to the neuron-specific calcium-binding proteins and are likely human counterparts of the neural visinin-like protein(NVP) 1 and NVP2 identified in the rat brain (Kajimoto et al. 1993), displaying 98% and 99% amino acid identities with these sequences, respectively. The human HLP3 and 4 mRNAs are detected only in the brain and found at high amount in the cerebral cortex and cerebellum by Northern blot analysis.

Amino Acid Sequence↗
PubMed1997

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↗
PubMed1997

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↗