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Biomedical subjects

H Kaji

Publications and source records attributed to H Kaji.

At least 37 records · Page 2Linked to original sources
PubMed2001

Determinants of bone mineral density and spinal fracture risk in postmenopausal Japanese women.

The present study analyzed the factors that determine bone mineral density (BMD) and predict spinal fracture risk in postmenopausal Japanese women. Two hundred and five postmenopausal Japanese women aged 48-84 years (mean age 64 years) were enrolled in the cross-sectional study. BMD of the lumbar spine, femoral neck and total body as well as body composition were measured by dual-energy X-ray absorptiometry (DXA). Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-2, -3 and osteocalcin as well as urinary levels of pyridinoline (Pyr), deoxy-Pyr (D-Pyr) and growth hormone. Multiple regression analysis revealed that lean body mass (LBM) was positively correlated with BMD at all sites. In contrast, femoral neck BMD was highly related to fat mass as well as LBM, although fat mass was not an independent correlate of total body and mid-radial BMD. LBM and urinary D-Pyr were crucial determinants at all sites except the mid-radius in stepwise regression analysis. Fat mass and serum IGF-I were determinants of femoral neck and mid-radial BMD, respectively. In terms of reproductive history, parity affected lumbar BMD. Factors affecting BMD differed according to the site. On the other hand, lumbar BMD as well as serum levels of IGF-I and albumin were selected as predictors of spinal fracture risk in multiple logistic regression analysis. Lumbar BMD, serum IGF-I and LBM were selected in women with lumbar BMD above 0.727 g/cm2. In conclusion, the present study indicates that LBM is a more important determinant of BMD than fat mass at any site except the femoral neck. Age, serum IGF-I and urinary D-Pyr were also determinants of BMD, dependent on the regions measured. Lumbar BMD and LBM as well as serum levels of IGF-I and albumin were useful markers which predicted the risk of osteoporotic spinal fractures in postmenopausal Japanese women.

Absorptiometry, Photon↗
PubMed2001

Bone metabolism and body composition in Japanese patients with active acromegaly.

OBJECTIVE: Skeletal involvement is a common clinical feature in acromegalic patients. Although several recent reports are available concerning bone mineral density (BMD) in acromegaly, the controversy still exists as to whether BMD of acromegalic patients is increased or not. The present study was performed to examine biochemical bone metabolic indices and BMD as well as body composition in 26 Japanese patients with active acromegaly and 26 control subjects matched for age, sex, race and height in a cross-sectional study. MEASUREMENTS: BMD of the lumbar spine and femoral neck, as well as body composition, was measured by dual-energy X-ray absorptiometry. Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of IGF-I, IGFBP-3 and osteocalcin (OC) as well as urinary levels of deoxy-pyridinoline (D-Pyr) and CrossLaps. RESULTS: Percent lean body mass was increased and percent fat mass was decreased in the acromegalic patients compared to control subjects. Serum levels of OC, as well as urinary levels of D-Pyr and CrossLaps, were significantly higher in acromegalic patients compared to control subjects (9.8 +/- 1.2 vs. 5.7 +/- 0.77 for OC; 11.8 +/- 1.66 vs. 5.0 +/- 0.49 for D-Pyr; 437.6 +/- 68.4 vs. 156.5 +/- 39.6 for CrossLaps). Z scores of BMD at mid-radius as well as lumbar spine and femoral neck were significantly higher in acromegalic patients compared to control subjects (1.086 +/- 0.311 vs. -0.060 +/- 0.274 for mid-radius; 1.022 +/- 0.280 vs. 0.319 +/- 0.165 for lumbar spine; 1.292 +/- 0.347 vs. 0.232 +/- 0.264 for femoral neck). CONCLUSIONS: The present study revealed that a decrease in percent fat mass and an increase in percent lean body mass were observed in Japanese patients with active acromegaly. Bone mineral density at all sites and bone metabolic markers were also increased in acromegaly. The present findings provide additional evidence that the GH/IGF-I axis might play an important role in the maintenance of bone mass as well as the regulation of body composition in Japanese adults.

Absorptiometry, Photon↗
PubMed2001

Complete response of a stage IV mucinous cystadenocarcinoma of the ovary to systemic chemotherapy employing paclitaxel and carboplatin.

BACKGROUND: The survival rate of patients with advanced-stage mucinous cystadenocarcinoma of the ovary is dismal and no best treatment is known. We report a case of complete response of a stage IV mucinous cystadenocarcinoma of the ovary to systemic chemotherapy employing paclitaxel and carboplatin. CASE: A 51-year-old nullipara diagnosed with International Federation of Gynecology and Obstetrics stage IV mucinous cystadenocarcinoma of the ovary underwent cytoreductive surgery followed by systemic chemotherapy employing paclitaxel and carboplatin every 4 weeks for 3 courses. The patient tolerated chemotherapy well, demonstrated a remarkable response showing no evidence of malignancy at a second-look laparotomy. As a consolidation chemotherapy after negative second-look laparotomy, she underwent another three courses of chemotherapy of the same regimen, and is showing no evidence of disease. CONCLUSION: Paclitaxel and carboplatin may be effective in treating mucinous cystadenocarcinoma of the ovary.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Interleukin-1beta stimulates transendothelial mobilization of human peripheral blood mononuclear cells with a potential to differentiate into osteoclasts in the presence of osteoblasts.

There is accumulating evidence that interleukin-1 (IL-1) levels are increased locally at the site of active bone resorption in a variety of diseases including osteoporosis, periodontal disease and rheumatoid arthritis. However, the pathogenic role of IL-1 in bone loss remains to be fully elucidated. We present here additional evidence that IL-1beta enhances endothelial activation and thereby stimulates mobilization of peripheral blood mononuclear cells (PBMCs) from luminal to abluminal spaces across the endothelium. Furthermore, IL-1beta stimulates the differentiation of PBMCs into osteoclast-like cells with bone-resorbing activity in the presence of human osteoblastic SaOS-2 cells without systemic hormones. These findings provide circumstantial evidence for the hypothesis that IL-1beta generated in the bone microenviroment plays a stimulatory role in PBMC mobilization from the peripheral circulation and their subsequent differentiation into osteoclast-like cells in the bone tissue. In addition, the present study supports the notion that osteoclast progenitor cells might be derived from the peripheral circulating blood mononuclear cells in human.

Acid Phosphatase↗
PubMed2001

Skeletal responsiveness to parathyroid hormone in pseudohypoparathyroidism.

BACKGROUND: Although there have been some case reports suggesting that bone in patients with pseudohypoparathyroidism (PHP) might respond to parathyroid hormone (PTH), no information is available as to whether serum PTH concentration is related to bone metabolic markers or to bone mineral density (BMD) in PHP. OBJECTIVE: To address these relationships, by comparing intact serum PTH, bone metabolic markers and BMD in patients with PHP with those in patients with idiopathic hypoparathyroidism (IHP) and postoperative hypoparathyroidism (OHP). METHODS: Intact serum PTH, bone metabolic markers (osteocalcin, tartrate-resistant acid phosphatase, pyridinoline, deoxypyridinoline) and BMD by dual-energy X-ray absorptiometry or single-photon absorptiometry were measured in patients with PHP Ia (n=2) and PHP Ib (n=8). The results were compared with those in patients with IHP (n=5) and OHP (n=14). RESULTS: All bone metabolic markers measured were present in significantly greater amounts in patients with PHP Ib than in those with IHP+OHP. The Z score (standard deviation of average BMD at each age) of the BMD of femoral neck was significantly lower in patients with PHP Ib than in those with IHP+OHP. The Z scores of BMD of lumbar spine and radius were also lower in patients with PHP Ib than in those with IHP+OHP, but the difference was not significant. Moreover, the intact serum PTH concentrations were significantly and positively related to bone metabolic marker levels in all patients, and the intact serum PTH concentrations were significantly and negatively related to BMD of lumbar spine in PHP patients. CONCLUSIONS: These results suggest that PTH stimulates bone turnover in PHP Ib patients, resulting in a relatively lower BMD in PHP Ib patients than in IHP+OHP patients. The present study indicates that bones of most cases of PHP could respond to PTH.

Acid Phosphatase↗
PubMed2001

The V kappa III subgroup light chain proteins in AL amyloidosis & autoimmune diseases.

BACKGROUND & OBJECTIVES: Light chain associated amyloidosis (AL) is characterized by extracellular deposition of immunoglobulin light chain and its fragments. In vitro and in vivo studies have shown that some light chains are nonamyloidogenic and nonnephrotoxic, whereas others are potentially amyloidogenic. Some light chains are prone to be deposited as rheumatoid materials, and also as nodular amorphous aggregates (light chain deposition diseases). These findings suggest that specific sequence element(s) may control the various kinds of light chain associated diseases. In this study we tried to identify such sequence element(s). METHODS: Two Bence Jones proteins (BJPs), NIG93 and NIG2 of subgroup V kappa III, were characterized and compared with other members of the same subgroup whose sequences are available in the data base. RESULTS: Both NIG93 and NIG2 proteins had sequences characteristics of V kappa IIIa as distinguished from V kappa IIIb, subsubgroup proteins. They also contained several novel substitutions, such as Met-37, Leu-40, Val-58, and IIe-85 in NIG93, and Val-2, His-29, Arg-50, and Ile-72 in NIG2. The data accumulated at present indicate that all members of the V kappa IIIa subsubgroup are related to either AL amyloidosis or rheumatoid arthritis, whereas the V kappa IIIb proteins are related to autoimmune diseases. INTERPRETATION & CONCLUSION: These observations indicate that subgroup-specific residues might be critical for light chain pathogenesis, at least for the V kappa III proteins. Point mutations within these proteins may be another structural element controlling their conformation as well as their pathogenic aggregation.

Amino Acid Sequence↗
PubMed2000

Structure-function study and anti-HIV activity of synthetic peptide analogues derived from viral chemokine vMIP-II.

The viral macrophage inflammatory protein II (vMIP-II) shows a broad spectrum interaction with both CC and CXC chemokine receptors including CCR5 and CXCR4, two principal coreceptors for the cellular entry of human immunodeficiency virus type 1 (HIV-1). Recently, we have shown that a synthetic peptide derived from the N-terminus of vMIP-II, designated as V1, is a potent antagonist of CXCR4 but not CCR5 [Zhou, N., et al. (2000) Biochemistry 39, 3782-3787]. In this study, we synthesized a series of new peptides derived from other regions of vMIP-II and characterized their binding activities with both CXCR4 and CCR5. The results provided further support for the notion that the N-terminus of vMIP-II is the major determinant for CXCR4 recognition and that vMIP-II probably interacts with other chemokine receptors such as CCR5 with different sequence and conformational determinants. To understand the structure-function relationship of V1 peptide, its solution conformation was studied using circular dichroism spectroscopy, which showed a random conformation similar to that of the corresponding N-terminus in native vMIP-II. In addition, we synthesized a series of mutant analogues of V1 containing alanine, glycine, or phenylalanine substitution at various positions. Residues Val-1, Arg-7, and Lys-9 of V1 peptide were found to be critical for receptor interaction, because single alanine replacement at these positions dramatically decreased peptide binding to CXCR4. In contrast, alanine or phenylalanine substitution at Cys-11 led to significant enhancement in peptide affinity for CXCR4. Finally, we showed that V1 peptide inhibits HIV-1 replication in CXCR4(+) T-cell lines. These studies provide new insights into the structure-function relationship of V1 peptide and demonstrate that this peptide may be a lead for the development of therapeutic agents.

Alanine↗
PubMed2000

Cloning and characterization of the 5'-flanking region of the human prolactin-releasing peptide receptor gene.

Recently a novel peptide which specifically stimulates the secretion of prolactin (PRL) was found and named PRL-releasing peptide (PrRP). To evaluate the regulation of human (h) PrRP-receptor (PrRP-R) gene expression, we cloned the 5'-flanking region of the hPrRP-R gene and determined the nucleotide sequence of 4.0 kilobase pairs (kb) upstream from the translation start site. Analysis of the hPrRP-R transcripts by means of 5'-rapid amplification of cDNA ends suggested that the hPrRP-R gene had multiple transcription start sites between -429 and -365 from the translation start site. There is no typical TATA or CAAT but a GC box and putative binding sites for several transcription factors including Pit-1 and pituitary homeobox 1 (Ptx1). However, transient transfection studies using a luciferase reporter gene demonstrated that 5'-flanking region exerts promoter activity in several non-pituitary cell lines as well as in GH(3) cells. The GC box located from -467 to -457 was identified as an important region for the basal expression of the hPrRP-R gene. Knowledge of the promoter region of the hPrRP-R gene, which was obtained in the present study, will facilitate the clarification of its transcriptional regulation.

Animals↗
PubMed2000

Methylglyoxal induces G:C to C:G and G:C to T:A transversions in the supF gene on a shuttle vector plasmid replicated in mammalian cells.

We previously reported that the majority of base-pair substitutions induced by an endogenous mutagen, methylglyoxal, were G:C-->T:A transversions and G:C-->A:T transitions in wild-type and nucleotide excision repair (NER)-deficient (uvrA or uvrC) Escherichia coli strains. To investigate the mutation spectrum of methylglyoxal in mammalian cells and to compare the spectrum with those detected in other experimental systems, we analyzed mutations in a bacterial suppressor tRNA (supF) gene in the shuttle vector plasmid pMY189. We treated pMY189 with methylglyoxal and immediately transfected it into simian COS-7 cells. The cytotoxicity and the mutation frequency (MF) increased according to the dose of methylglyoxal. In the mutants induced by methylglyoxal, multi-base deletions were predominant (50%), followed by base-pair substitutions (35%), in which 89% of the substitutions occurred at G:C sites. Among them, G:C-->C:G and G:C-->T:A transversions were predominant. The overall distribution of methylglyoxal-induced mutations detected in the supF gene was different from that for the spontaneous mutations. These results suggest that methylglyoxal may take part in causing G:C-->C:G and G:C-->T:A transversions in vivo.

Animals↗
PubMed2000

Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro.

Recent evidence indicates that both leptin and eicosapentaenoic acids (EPA) improve insulin sensitivity. In the present study, we examined the effect of EPA on endogenous leptin expression in 3T3-L1 adipocytes to clarify whether the EPA's effect is exerted through leptin expression. EPA caused a time- and dose-dependent increase of leptin mRNA levels in 3T3-L1 adipocytes. Leptin mRNA expression was significantly increased up to 309.4 +/- 17.0% of the control by 24 h (P < 0.01; n = 6). Leptin secretion was also significantly increased up to 193.3 +/- 12.1% of the control by 24 h (P < 0.01; n = 6). EPA is a ligand for peroxisome proliferator-activated receptors (PPARs) with the highest affinity to PPARalpha. We examined the effect on leptin expression of clofibrate, a ligand for PPARalpha, bezafibrate, for PPARbeta, or troglitazone, for PPARgamma, to clarify whether these ligands for PPARs could mimic EPA-induced stimulation of leptin expression. Neither clofibrate nor bezafibrate affected leptin mRNA expression, whereas troglitazone significantly suppressed leptin mRNA expression. On the other hand, inhibition by 6-diazo-5-oxo-l-norleucine of the rate-limiting enzyme in hexosamine biosynthesis blunted EPA-induced stimulation of leptin mRNA expression and its secretion. These data suggest that EPA up-regulates leptin gene expression and its secretion probably through a hexosamine biosynthetic pathway.

3T3 Cells↗
PubMed2000

Profiling of Caenorhabditis elegans proteins using two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry.

The nematode Caenorhabditis elegans (C. elegans) is the first animal whose whole 97 Mb genome sequence, encoding ca. 19000 open reading frames (ORF's), has been essentially determined. We tried to establish a 2-DE map of the nematode proteome by means of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). A soluble protein fraction of mixed stages of the worm, wild-type strain N2, was applied to 2-D PAGE. After Coomassie Brilliant Blue (CBB) staining, 1200 spots were detected and 140 major spots were excised from the gel and subjected to in-gel digestion with Achromobacter protease I (lysyl endopeptidase). Resulting peptides were analyzed by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) followed by peptide mass fingerprinting for protein identification. With this approach we have obtained a two-dimensional electrophoresis (2-DE) protein map in which 69 spots were localized as landmarks for comparison of expression profiles to elucidate the basis of various biological events.

Animals↗
PubMed2000

Structural comparison between wild-type and P25S human cystatin A by NMR spectroscopy. Does this mutation affect the alpha-helix conformation?

The effect of substituting Pro25, located in the alpha-helical region of the cystatin A structure, with Ser has been studied. The structures of wild type and P25S cystatin A were determined by multidimensional NMR spectroscopy under comparable conditions. These two structures were virtually identical, and the alpha-helix between Glu15-Lys30 exists with uninterrupted continuity, with a slight bend at residue 25. In order to characterize the possible substitution effects of Pro25 with Ser on the alpha-helix, the chemical shifts of the amide nitrogens and protons, the generalized order parameters obtained by the analyses of the 15N-1H relaxation data, the amide proton exchange rates, and the NOE networks among the alpha-helical and surrounding residues were carefully compared. None of these parameters indicated any significant static or dynamic structural differences between the alpha-helical regions of the wild-type and P25S cystatin A proteins. We therefore conclude that our previous structure of the wild-type cystatin A, in which the alpha-helix exhibited a sharp kink at Pro25, must be revised. The asymmetric distribution of hydrophobic interactions between the side-chain residues of the alpha-helix and the rolled beta-sheet surface, as revealed by NOEs, may be responsible for the slight bend of the alpha-helix in both variants and for the destabilized hydrogen bonding of the alpha-helical residues that follow Pro25/Ser25, as evidenced by increased amide exchange rates.

Amino Acid Sequence↗
PubMed2000

Mutations induced by glyoxal and methylglyoxal in mammalian cells.

To investigate the mutation spectra of glyoxal and methylglyoxal in mammalian cells, we analyzed mutations in a bacterial suppressor tRNA (supF) gene in the shuttle vector plasmid pMY189. The cytotoxicity and the mutation frequency increased according to the doses of glyoxal and methylglyoxal. The majority of glyoxal-induced mutations (65%) were base-pair substitutions, in which G:C-->C:G transversions were predominant. In the mutants induced by methylglyoxal, multi-base deletions were predominant (50%), followed by base-pair substitutions (35%), in which G:C-->C:G and G:C-->T:A transversions were predominant.

Animals↗
PubMed2000

Multifocal fibrosclerosis as a possible cause of panhypopituitarism with central diabetes insipidus.

Multifocal fibrosclerosis denotes a combination of similar fibrous disorders occurring at different anatomical sites. We encountered a 53-year-old male patient with orbital pseudotumor, chronic paranasal sinusitis, fibrous nodules of the lungs, intracranial pachymeningitis, and panhypopituitarism with central diabetes insipidus (DI) as a possible manifestation of multifocal fibrosclerosis. It has been reported that intracranial pachymeningitis or orbital pseudotumor associated with multifocal fibrosclerosis could invade the sella turcica causing a variety of anterior and/or posterior pituitary dysfunctions. In our case, intracranial pachymeningitis apparently involved the pituitary stalk and gland. Isolated gonadotropin deficiency, in addition to central DI, preceded panhypopituitarism. Although panhypopituitarism with central DI due to multifocal fibrosclerosis is quite rare and only one case has ever been reported, this systemic fibrotic disorder can be a possible cause of panhypopituitarism with central DI.

Diabetes Insipidus↗
PubMed2000

[Relationship between fatty liver and coronary risk factors].

Fatty liver is a common finding in abdominal ultrasonographic examination in health check-ups, but the relationship between fatty liver and so-called coronary risk factors has rarely been investigated from the viewpoint of prevention of coronary heart disease. The purpose of the present study was to elucidate such a relationship by comparing the coronary risk factors with and without fatty liver by using data from health check-ups for the mid-management and management staff of a manufacturing company. The majority (77.1%) of those with fatty liver in the present study were categorized as "normal" or "marginally obese" and only a small portion (22.9%) were categorized as "obese" according to the classification of the body mass index. The group of subjects with fatty liver had significantly lower mean HDL-cholesterol and higher levels of fasting blood sugar, HDL/total cholesterol ratio, triglyceride, uric acid and transaminases, than those parameters in subjects without fatty liver, even after adjustment for age and body-mass index. The blood pressure (both systolic and diastolic) and total cholesterol level did not show any significant difference after controlling the covariates. Our results indicated that fatty liver has a close correlation with the majority of coronary risk factors causing atheroscleotic diseases, and most of these relationships are independent of total body mass. Our results regarding fatty liver are a help to occupational health personnel when advising workers to reduce their own risk of atherogeic diseases.

Adult↗
PubMed2000

Estrogen modulates osteoblast proliferation and function regulated by parathyroid hormone in osteoblastic SaOS-2 cells: role of insulin-like growth factor (IGF)-I and IGF-binding protein-5.

Although there is clinical evidence showing that combined therapy with parathyroid hormone (PTH) and estrogen is additively effective in increasing the bone mass of patients with osteoporosis, the mechanism of the interaction between these hormones remains unclear. The present study was performed to determine whether estrogen would affect osteoblast proliferation and function modulated by PTH in human osteoblastic SaOS-2 cells. Human PTH-(1-34) significantly inhibited [(3)H]thymidine (TdR) incorporation, which was attenuated by 24 h pretreatment with 10(-10) to 10(-7) M 17 beta-estradiol (17 beta-E(2)) in a concentration-dependent manner. PTH significantly stimulated alkaline phosphatase (ALP) activity, collagen synthesis and type-1 procollagen mRNA expression after pretreatment with 17 beta-E(2 )in these cells. Tamoxifen, an anti-estrogen, antagonized these 17 beta-E(2)-induced effects. Pretreatment with insulin-like growth factor-I (IGF-I) mimicked estrogen action, and coincubation of 3 microg/ml anti-IGF-I antibody antagonized the effects of 17 beta-E(2 )as well as those of IGF-I. In the presence of 17 beta-E(2 )pretreatment, PTH strongly stimulated IGF-binding protein (IGFBP)-5 mRNA expression in these cells, and recombinant IGFBP-5 increased type-1 procollagen mRNA expression and ALP activity. In conclusion, estrogen attenuates PTH-induced inhibition of osteoblast proliferation and PTH stimulates osteoblast function in the presence of estrogen pretreatment. IGF-I and/or IGFBP-5 seemed to be involved in the estrogen-induced modulation of PTH action on osteoblast proliferation and function.

Alkaline Phosphatase↗