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Biomedical subjects

T Yamaji

Publications and source records attributed to T Yamaji.

At least 19 recordsLinked to original sources
PubMed2004

Coffee consumption and glucose tolerance status in middle-aged Japanese men.

AIMS/HYPOTHESIS: Several studies have reported that coffee has a protective effect against the development of type 2 diabetes. However, few of these studies used the standard glucose tolerance test to diagnose type 2 diabetes. The aim of this study was to investigate the relationship between coffee and green tea consumption and glucose tolerance status as determined using a 75-g OGTT. METHODS: We performed a cross-sectional study of 3224 male officials of the self-defence forces. Glucose tolerance status was determined in accordance with the 1998 World Health Organization criteria, and average intakes of coffee and green tea over the previous year were assessed by a self-administered questionnaire. The figures obtained were adjusted for BMI, physical activity and other factors. RESULTS: A total of 1130 men were identified as having glucose intolerance (IFG, IGT or type 2 diabetes). Compared with those who did not consume coffee on a daily basis, fasting and 2-h post-load plasma glucose levels were 1.5% and 4.3% lower in those who drank 5 cups of coffee or more per day respectively. The adjusted odds ratios of glucose intolerance for categories of <1, 1-2, 3-4 and >/=5 cups of coffee per day were 1.0 (referent), 0.8 (95% CI 0.6-1.0), 0.7 (95% CI 0.6-0.9) and 0.7 (95% CI 0.5-0.9) respectively (p=0.0001 for trend). No clear association was observed between green tea drinking and glucose tolerance status. CONCLUSIONS/INTERPRETATION: Coffee consumption may inhibit postprandial hyperglycaemia and thereby protect against the development of type 2 diabetes mellitus.

Alcohol Drinking↗
PubMed2001

The effect of micromovement on callus formation.

Micromovement at fracture sites is known to promote callus formation and bridging of the bony fragments. The present study was conducted to identify the suitable amount of micromovement, and to analyze the location and timing of callus proliferation. A standardized transverse osteotomy, in the right metatarsus of 32 sheep, was used as a fracture model. The osteotomy was externally fixed with a special ring fixator, which allowed axial micromovements of defined sizes. The animals were divided into four groups, with gaps of 2 mm and 6 mm, and micromovements of 0.3 mm and 0.7 mm, respectively. The labeling of new bone formation was performed by the intravenous injection of calcein green in the fourth week and tetracycline in the eighth week. Nine weeks postoperatively the sheep were killed. The explanted metatarsals were radiographed for the measurement of the periosteal callus area and were nondestructively loaded in a three-point bending test to determine their flexural rigidity. Histological analysis of undecalcified bone was performed in bone slices in the sagittal plane. Fluorescent green (callus formed in the fourth week) and yellow areas (callus formed in the eighth week) and the area of connective tissue were determined, using fluorescence microscopy. Bone formation was larger in the eighth week than that in the fourth week in all groups. In the fourth week, large micromovements in the small gap resulted in increased bone formation, whereas, for large gaps, the large micromovements diminished new bone formation. With large micromovement, the amount of newly formed bone within the gap decreased with increasing gap size, suggesting a delay of bone healing. Stimulation of new bone formation by micromovement was mainly effective in the early healing phase (4 weeks postoperatively). Large gaps showed the least new bone formation at the fracture site and the lowest flexural rigidity. From the histological analysis, it was found that the flexural rigidity correlated with the new bone area in the periosteal region.

Animals↗
PubMed2001

Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent.

In our previous study, the sphingosine-like immunosuppressant ISP-1 was shown to induce apoptosis in the mouse cytotoxic T cell line CTLL-2. In this study, we characterized the ISP-1-induced apoptotic pathway. Although caspase-3-like protease activity increases concomitantly with ISP-1-induced apoptosis in CTLL-2 cells, the apoptosis is not inhibited by caspase-3-like protease inhibitors, i.e. DEVD-cho and z-DEVD-fmk. In contrast, sphingosine-induced apoptosis in CTLL-2 cells is caspase-3-like protease-dependent. A caspase inhibitor with broad specificity, z-VAD-fmk, protects cells from apoptosis induced by ISP-1, indicating that ISP-1-induced apoptosis is dependent on caspase(s) other than caspase-3. Overexpression of Bcl-2 or Bcl-xL suppresses the apoptosis induced by ISP-1, although sphingosine-induced apoptosis is not efficiently inhibited by Bcl-2. Finally, ISP-1-induced mitochondrial depolarization, which is thought to be a checkpoint dividing the apoptotic pathway into upstream and downstream stages, is not inhibited by DEVD-cho, but is inhibited by z-VAD-fmk. These data suggest that a pathway dependent on caspase(s) other than caspase-3 is involved upstream of mitochondrial depolarization in ISP-1-induced apoptosis.

Animals↗
PubMed2000

Inhibition by 9alpha-fluoromedoroxyprogesterone acetate (FMPA) against mammary carcinoma induced by dimethylbenz[a]anthracene in rats and angiogenesis in the rabbit cornea - comparison with medroxyprogesterone acetate (MPA).

Medroxyprogesterone acetate (MPA) is currently used therapeutically in the treatment of mammary and endometrial carcinomas. In order to develop a more potent and useful drug, we synthesized the novel compound, 9alpha-fluoromedoroxyprogesterone acetate (FMPA), by fluorinating MPA, and we also previously reported that FMPA displays more potent anti-angiogenic activity in the chorioallantoic membrane assay than MPA. In the present study, we investigated (1) the effects of FMPA on rat mammary carcinomas induced by dimethylbenz[a]anthracene (DMBA) to determine the anti-tumor activity, (2) the effect on angiogenesis in rabbit corneal assays, and (3) compared these results with those for MPA. FMPA inhibited the growth of mammary carcinomas in a dose-dependent manner (7.5, 30 and 120 mg/kg). Almost complete involution of the carcinomas was observed at doses of 30 and 120 mg/kg. MPA also inhibited the growth of carcinomas at doses of 30 and 120 mg/kg, but no involution of carcinomas was observed even at 120 mg/kg. FMPA significantly and MPA to a lesser degree inhibited carcinogenesis at 120 mg/kg within their treatments. In rabbit corneal assays, FMPA significantly inhibited angiogenesis (IC50 value=0.085 microg/pellet). MPA also significantly inhibited angiogenesis (IC50 value=0.60 microg/pellet). From these results, we conclude that FMPA is potentially more effective in the treatment of mammary carcinomas than MPA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Inhibition of cytokinesis by a lipid metabolite, psychosine.

Although a number of cellular components of cytokinesis have been identified, little is known about the detailed mechanisms underlying this process. Here, we report that the lipid metabolite psychosine (galactosylsphingosine), derived from galactosylceramide, induced formation of multinuclear cells from a variety of nonadherent and adherent cells due to inhibition of cytokinesis. When psychosine was added to the human myelomonocyte cell line U937, which was the most sensitive among the cell lines tested, cleavage furrow formed either incompletely or almost completely. However, abnormal contractile movement was detected in which the cellular contents of one of the hemispheres of the contracting cell were transferred into its counterpart. Finally, the cleavage furrow disappeared and cytokinesis was reversed. Psychosine treatment also induced giant clots of actin filaments in the cells that probably consisted of small vacuoles with filamentous structures, suggesting that psychosine affected actin reorganization. These observations could account for the formation of multinuclear globoid cells in the brains of patients with globoid cell leukodystrophy, a neurological disorder characterized by the accumulation of psychosine due to galactosylceramidase deficiency.

Actins↗
PubMed2000

Type V collagen is increased during rabbit medial collateral ligament healing.

To understand the reparative process of medial collateral ligament (MCL), fibrillar collagen and their relative ratios in healing MCL with anterior cruciate ligament (ACL) reconstruction were analyzed. Skeletally mature New Zealand white rabbits were subjected to a mop-end tear of MCL without repair with ACL reconstruction. Rabbits were killed 6 and 52 weeks after injury. Ligamentous tissues from the injury site and sham controls were soaked in 0.5 M acetic acid for 24 h, minced, and treated with pepsin to solubilize collagen. Pepsin solubilized about 80% of the total collagen as determined by hydroxyproline analysis of the pepsin residues. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the solubilized collagen revealed presence of fibrillar collagen types I, III, and V. Densitometric scanning of the protein bands corresponding to types I, III, and V collagen indicated that in sham controls types III and V collagen represented about 8% and 12%, respectively, of the type I collagen whereas the healed MCL ligaments at 6 weeks showed significant increase in type III and V collagen to about 19% and 24%, respectively. By 52 weeks type III collagen in the healed MCL had returned to that of sham controls while type V collagen remained elevated at approximately 18%. These data suggest that presence of type V collagen in high concentration in healing ligaments may have an influence on collagen fibril diameters seen in healed ligament and should be included in the analysis when evaluating ligament healing.

Animals↗
PubMed2000

The management of medial ligament tears in patients with combined anterior cruciate and medial ligament lesions.

The management of patients with combined medial collateral (MCL) and anterior cruciate (ACL) rupture remains controversial. We studied 25 such patients who elected to have the ACL lesion treated conservatively; 14 underwent MCL repair with early mobilization and 11 were treated with immobilization for two weeks. The mean follow up was 5.9 years (2 to 11). There was no difference in the clinical assessment of ligamentous laxity, KT-1000 measurements or Tegner activity scores between the two groups but there were significantly higher Lysholm function scores in the operated group.

Adult↗
PubMed2000

Ender nailing for tibial shaft fractures.

During the period from December 1980, when we began using Ender nails for the treatment of tibial shaft fractures, to December 1995, 274 unions of 280 fractures in 275 patients treated by Ender nailing were successfully achieved. Ender nailing for tibial shaft fractures can be classified into three methods A, B, and C, according to the insertion points of the nails. In method A, which is used for the proximal one-third fractures of the tibia, the nails are inserted from the distal tibia medially and laterally towards the proximal tibia. In method B, which is for middle or distal one-third fractures of the tibia, the nails are inserted from the proximal tibia medially and laterally directed distally. In method C, which is for long oblique or double fractures, one nail is inserted from a proximal site, and the other is inserted distally; these two nails must form an X-shape. Ender nailing is an excellent semiconservative treatment for tibial shaft fractures, maintaining adequate elasticity at the fracture sites where much callus is formed, leading to a good union.

Adolescent↗
PubMed2000

Sli2 (Ypk1), a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast.

ISP-1 is a new type of immunosuppressant, the structure of which is homologous to that of sphingosine. In a previous study, ISP-1 was found to inhibit mammalian serine palmitoyltransferase, the primary enzyme involved in sphingolipid biosynthesis, and to reduce the intracellular pool of sphingolipids. ISP-1 induces the apoptosis of cytotoxic T cells, which is triggered by decreases in the intracellular levels of sphingolipids. In this study, the inhibition of yeast (Saccharomyces cerevisiae) proliferation by ISP-1 was observed. This ISP-1-induced growth inhibition was also triggered by decreases in the intracellular levels of sphingolipids. In addition, DNA duplication without cytokinesis was detected in ISP-1-treated yeast cells on flow cytometry analysis. We have cloned multicopy suppressor genes of yeast which overcome the lethal sphingolipid depletion induced by ISP-1. One of these genes, SLI2, is synonymous with YPK1, which encodes a serine/threonine kinase. Kinase-dead mutants of YPK1 did not show any resistance to ISP-1, leading us to predict that the kinase activity of the Ypk1 protein should be essential for this resistance to ISP-1. Ypk1 protein overexpression had no effect on sphingolipid biosynthesis by the yeast. Furthermore, both the phosphorylation and intracellular localization of the Ypk1 protein were regulated by the intracellular sphingolipid levels. These data suggest that the Ypk1 protein is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. The Ypk1 protein was reported to be a functional homologue of the mammalian protein kinase SGK, which is a downstream kinase of 3-phosphoinositide-dependent kinase 1 (PDK1). PDK1 phosphotidylinositol (PI) is regulated by PI-3,4,5-triphosphate and PI-3,4-bisphosphate through the pleckstrin homology (PH) domain. Overexpression of mammalian SGK also overcomes the sphingolipid depletion in yeast. Taking both the inability to produce PI-3,4, 5-triphosphate and PI-3,4-bisphosphate and the lack of a PH domain in the yeast homologue of PDK1, the Pkh1 protein, into account, these findings further suggest that yeast may use sphingolipids instead of inositol phospholipids as lipid mediators.

Fatty Acids, Monounsaturated↗
PubMed2000

A novel mutation of the MEN1 gene in a Japanese kindred with familial isolated primary hyperparathyroidism.

OBJECTIVE: To determine whether familial isolated hyperparathyroidism (FIHP) is a variant of multiple endocrine neoplasia type 1 (MEN1) we analyzed the MEN1 gene in such a kindred. DESIGN AND METHODS: The study included the 70-year-old proband and nine relatives. Blood was drawn for biochemical evaluation and germline mutation analysis by direct sequencing of the MEN1 gene amplified by PCR. A hyperplastic parathyroid gland obtained from a family member served for a loss of heterozygosity (LOH) study. RESULTS: Three members from two generations in this kindred were found to have primary hyperparathyroidism, while none had clinical or biochemical evidence of MEN1, MEN2 or hyperparathyroidism--jaw tumor syndrome. Analysis of germline DNA in the proband showed a missense mutation (GGC-->GAC) at codon 305 in exon 7 of the MEN1 gene that predicts an amino acid change from glycine to aspartic acid (G305D). This mutation segregated with primary hyperparathyroidism in the kindred, and, in addition, there were two asymptomatic mutant-gene carriers at relatively advanced ages. In contrast, the mutation was not detected in genomic DNA from five unaffected individuals and from 50 healthy subjects. The LOH study showed a loss of the wild-type allele, which confirmed that a functional defect of the MEN1 gene product, menin, is etiological for FIHP. CONCLUSIONS: FIHP is a genetically heterogeneous disease with a subset linked to MEN1, most likely representing a variant of MEN1. The late onset and the reduced penetrance of disease found in this kindred may be related to the site and the type of mutation, although the precise mechanism involved is unknown at present.

Adult↗
PubMed2000

Malignant pheochromocytoma lacking clinical features of catecholamine excess until the late stage.

A malignant pheochromocytoma is described in a 71-year-old man. Osseous metastases became manifest 12 years after successful removal of the primary tumor which originated in paraganglionic tissue near the right adrenal gland. Although the patient had no symptoms of catecholamine excess initially, hypertension, tachycardia and excessive sweating appeared several months before his death, concomitantly with a sharp increase in noradrenaline secretion due to an accelerated growth of metastatic tumors. Since there is no histologic criterion of malignancy in this neoplasm, it would be prudent to consider every case of pheochromocytoma as potentially malignant and to follow-up carefully for a long time after removal of the primary tumor.

Adrenal Gland Neoplasms↗
PubMed1999

Anti-angiogenic activity of a novel synthetic agent, 9alpha-fluoromedroxyprogesterone acetate.

9Alpha-fluoromedroxyprogesterone acetate (FMPA) is a novel synthetic analog of medroxyprogesterone acetate (MPA), widely used as therapeutic agent for breast and endometrium cancers. FMPA showed almost the same binding affinities to the progesterone and glucocorticoid receptors as MPA. In the rabbit corneal assay, FMPA, MPA and fumagillin significantly inhibited the angiogenic response induced by rat mammary tumor at doses of 0. 1, 1 and 50 microg/pellet, respectively, so FMPA showed greater anti-angiogenic activity than MPA and fumagillin. In the mouse dorsal air sac method, FMPA inhibited the mouse sarcoma 180 cell-induced angiogenesis by oral administration at a dose of 200 mg/kg. FMPA inhibited the activity of plasminogen activator (PA) in bovine endothelial cells. These results suggest that FMPA may be useful for diseases associated with angiogenesis by oral administration.

Angiogenesis Inhibitors↗
PubMed1999

Cytokine-induced tendinitis: a preliminary study in rabbits.

This study was designed to determine the effects of a single injection of a species-specific preparation of cytokines into rabbit patellar tendons and to compare the results with a known model of tendinitis, the collagenase-injection model. New Zealand White rabbits were divided into two groups and two time periods (4 and 16 weeks) and injected in the midsubstance of the right patellar tendon with either cytokines or collagenase under ultrasound guidance to confirm intratendinous needle placement. The left patellar tendon was injected with 0.025 ml of saline solution and served as a control. The rabbits were returned to cage activity after injection. At death, two rabbits in each group underwent histological analysis; the remaining eight animals in each time frame were evaluated biomechanically and then biochemically with use of the patella/whole patellar tendon/tibia complex. Histologic results at 4 weeks in the tendons injected with cytokines demonstrated increased cellularity, which was resolving by 16 weeks. The matrix appeared unchanged. The tendons injected with collagenase demonstrated increased angiogenesis of the matrix, hypercellularity, and fibrosis around the tendon at 4 weeks. At 16 weeks, myxoid changes, focal fibrosis, and collagen-bundle disarray with persistent increase in cellularity were noted. Biomechanically, a significant decrease in ultimate load at 16 weeks was seen in the tendons injected with cytokines but no change was seen in cross-sectional area. The tendons injected with collagenase demonstrated a significant increase in cross-sectional area at 4 and 16 weeks compared with those injected with cytokines. Biochemically, there was no significant difference in collagen content between the two groups at 4 or 16 weeks but the tendons injected with collagenase demonstrated a significant increase in crosslinking at 16 weeks. Our conclusion is that the tendons injected with the cytokine preparation represent a model of mild, seemingly reversible tendon injury. The cytokine preparation produces no matrix damage or evidence of collagen degradation and is species specific.

Animals↗
PubMed1998

A heterogeneity in serum osteocalcin N-terminal fragments in Paget's disease: a comparison with other biochemical indices in pre- and postmenopause.

An osteocalcin (OC) nitrogen (N)-terminal sandwich enzyme immunoassay that employs anit-N-20 (amino acids 1-20) polyclonal and monoclonal antibodies has been developed. This assay has demonstrated the existence of a heterogeneity in the OC N-terminal fragments observed in the serum of a patient with Paget's disease and a normal child. The elevation of the serum OC N-terminal value that occurs in Paget's disease was considered to be comparable to the serum alkaline phosphatase (ALP) elevations that also occur. The size of the peaks corresponding to N-terminal OC fragments in Paget's serum decreased 3 months after bisphosphonate treatment. Serum levels of OC N-terminals, and other biochemical indices, were determined for 67 premenopausal and 181 postmenopausal Japanese women. Serum OC N-terminal levels increased significantly (41.2%) in postmenopausal women compared with age-matched premenopausal women. These results strongly suggest that serum OC N-terminal levels reflect bone turnover rates when bone resorption is dominant.

Adolescent↗
PubMed1997

Neutral glycosphingolipids induce cell-cell aggregation of a variety of hematopoietic cell lines.

Exogenous neutral glycosphingolipids induced homotypic cell-cell aggregation of a variety of hematopoietic cell lines. A mouse cytotoxic T cell line, CTLL-2, was chosen to study the neutral glycosphingolipid-induced aggregation. Among neutral glycosphingolipids tested, galactosylceramide (GalCer) and glucosylceramide (GlcCer) were potent inducers, followed by lactosylceramide (LacCer); globotriaosylceramide (Gb3Cer) and neolactotetraosylceramide (nLc4Cer) were less effective. GalCer that contained a non-hydroxy fatty acid was more efficient than GalCer containing an alpha-hydroxy fatty acid. The minimum concentration of GalCer containing a non-hydroxy fatty acid that induced aggregation was 1 microM, and maximum aggregation occurred at 10-20 microM within 24 h. Cytochalasin B and a mixture of sodium azide and 2-deoxyglucose inhibited the aggregation, whereas cycloheximide, actinomycin D, and colchicine did not. Aggregated and dispersed cells, which were designated as competent cells, re-aggregated in the absence of neutral glycosphingolipids. Anti-GalCer polyclonal antibody inhibited GalCer-induced reaggregation. Furthermore, competent cells bound and aggregated non-competent cells in the absence of neutral glycosphingolipids. Cell-cell aggregatign was similar for CTLL-2 cells and the other hematopoietic cells that were tested. These findings suggest that the neutral glycosphingolipid-induced cell-cell aggregation of CTLL-2 cells was mediated by heterophilic interaction(s) between glycosphingolipids and other cell surface components. These properties are shared by a variety of hematopoietic cell lines.

Animals↗
PubMed1997

Biomechanics of knee ligament healing, repair and reconstruction.

Injuries of the anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) are common, accounting for 90% of all knee ligament injuries in young and active individuals. During the last decade, our research center has focused on MCL healing and ACL reconstruction. We have found that the MCL heals without intervention after an isolated injury, and that primary repair offers no apparent advantage. After a combined injury of the ACL and MCL, the ACL requires reconstruction, whereas primary repair again contributes little or nothing toward MCL healing. Midsubstance ACL injuries have limited healing ability. Hence, the treatment of choice for a torn ACL in a young, active patient is generally reconstruction with an autograft or allograft. However, the appropriate replacement graft and reconstruction technique to use are still debated. Current research efforts have been placed on investigating the magnitude and direction of in situ forces in the human ACL. We use a six-component universal force moment sensor combined with a six-degree-of-freedom (DOF) robotic manipulator to learn as well as to reproduce the six-DOF motion of the knee before and after ACL injury. This way, the in situ force in the ACL under an anterior posterior tibial load of 110 N was obtained. This methodology should make it possible to obtain the needed data to aid in better understanding of ACL reconstruction and possible development of improved clinical management.

Animals↗
PubMed1997

Chronic treatment with antidepressants, verapamil, or lithium inhibits the serotonin-induced intracellular calcium response in individual C6 rat glioma cells.

The effects of chronic treatment with antidepressants, verapamil, or lithium on serotonin (5-HT)-induced Ca2+ increase were investigated in single C6BU-1 glioma cells with digital imaging microscopy. Clomipramine and citalopram, at a concentration of 100 nM, decreased the peak values of 5-HT-induced [Ca2+]i changes. Verapamil (100 nM), a calcium antagonist, and lithium (1 mM) also inhibited the peak amplitudes in the same way. The present findings suggest that chronic treatment with antidepressants, verapamil, or lithium, at therapeutic concentrations, have the common action of inhibiting 5-HT-mediated [Ca2+]i increase.

Animals↗