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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 235 records · Page 13Linked to original sources
PubMed1997

Effects of whey protein on calcium and bone metabolism in ovariectomized rats.

We studied the effects of whey protein (WP) from cow's milk on calcium and bone metabolism in ovariectomized (OVX) rats. Six-week-old female Sprague-Dawley rats were ovariectomized and fed a low-calcium diet (0.03% Ca, 0.3% P) for 4 weeks. The OVX rats were divided into three groups and subjected to two experiments: Exp. 1, Cont group (20% casein, 0.3% Ca), WP (1%) group (19% casein, 1% whey protein, 0.3% Ca) and Low-Ca group (20% casein, 0.03% Ca); and Exp. 2, Cont group (20% casein, 0.3% Ca), WP (1%) group (19% casein, 1% whey protein, 0.3% Ca) and WP (2%) group (18% casein, 2% whey protein, 0.3% Ca). The rats were fed each experimental diet for 4 weeks. The final body weight, weight gain, food intake and food efficiency showed no significant difference between the Cont and WP (1%, 2%) groups in Exps. 1 and 2. There were no significant differences in the calcium balance, serum ALP or serum calcitonin levels between the Cont and WP groups in Exp. 1. But the breaking energies of the WP (1%, 2%) groups were higher than those of the Cont groups in Exps. 1 and 2. As for the amount of calcium, phosphorus and magnesium in the femur, there were no significant differences between the Cont and WP (1%, 2%) groups; however, the amounts of total amino acids in the femur of the WP (1%, 2%) groups were higher than those of the Cont groups in Exps. 1 and 2. The amounts of proline and hydroxyproline in the femur of the WP (1%, 2%) groups were also higher than those of the Cont groups in Exps. 1 and 2. These data indicate that the milk whey protein influence in OVX rats is an increase in bone proteins such as collagen and enhanced bone-breaking energy.

Animals↗
PubMed1997

[Two patients with mediastinal parathyroid cysts].

We encountered two patients with mediastinal parathyroid cysts. Patients 1 was a 44-year-old man with no complaints who had an abnormal shadow on a roentgenogram of the chest. An iperation was performed because a computed tomogram and a magnetic resonance image showed a cyst in the upper right part of the mediastinum, which was suspected to be a mediastinal thyroid cyst. Patient 2 was a 77-year-old woman with no complaints who had an abnormal shadow on a roentgenogram of the chest. Therapeutic thoracoscopy was performed because a mediastinal cyst was suspected based on the results of computed tomography and magnetic resonance image. Both patients had thin-walled that they were mediastinal parathyroid cysts. Mediastinal parathyroid cysts are very rare. We searched the medical literature but found previously published reports of only 39 cases.

Adult↗
PubMed1997

[Radiation therapy for adrenal metastases].

PURPOSE: To evaluate the role of radiation therapy for adrenal metastases. MATERIALS AND METHODS: Fourteen patients, 13 with primary lung carcinoma and one with primary unknown carcinoma, received radiation therapy for adrenal metastases from 1984 to 1995 at the Hyogo Medical Center for Adults. Total dose ranged from 16 Gy to 60 Gy, and fractional dose from 1.6 Gy/ Fr to 3 Gy/Fr. RESULTS: Partial response of the local tumor was recognized in 2 of 7 patients by CT imaging. Pain relief was obtained in 7 of 8 patients. Median survival was 3 months, and 6-month survival was 28.6% in all patients. Among patients in the symptomatic group, who had complaints of pain due to adrenal mass, survival was even worse (12.5% at 6 months). There were no severe complications, but 4 patients (29%) had gastrointestinal symptoms. CONCLUSION: Radiation therapy is useful for the purpose of pain relief in adrenal metastases.

Adrenal Gland Neoplasms↗
PubMed1997

[Analysis of in-field and marginal relapse in stage I/II non-Hodgkin's lymphoma treated with radiotherapy].

One hundred sixty-three patients with previously untreated stage I/II non-Hodgkin's lymphoma were analyzed as to their in-field and marginal relapse of the irradiated field following treatment with more than 30 Gy of radiotherapy between 1981 and 1995 at Hyogo Medical Center for Adults. Local regrowth in case of partial response was counted as in-field relapse. Complete response was obtained in 94.5% of the cases at the termination of radiotherapy and in 98.8% finally. The ten-year cumulative in-field relapse and marginal relapse rates were 5% and 8.7%, respectively. The cumulative in-field relapse rate (CIFRR) in cases of bulky disease (more than 5 cm in largest diameter of the tumor) was significantly higher than in those of non-bulky disease (26.1% in 8 years vs 2.4% in 10 years, P < 0.01). The radiation dosage delivered (40 Gy = < and 50 Gy > vs 50 Gy < =) a great much difference in cases of bulky disease (23.8% for 8-year CIFRR vs 0% for 1-year CIFRR, respectively), but less difference with non-bulky disease (2.6% vs 2.2%). High LDH and suboptimal dose chemotherapy (three courses and less chemotherapy containing ADM or its derivatives, chemotherapy without ADM or no chemotherapy) had a negative impact on marginal control in aggressive lymphoma. Extended field setting in aggressive lymphoma was not proven to be beneficial in comparison with involved field setting as to marginal field relapse. Thus, it is concluded that (1) higher doses should be given to bulky disease, (2) careful field coverage with enough margin is recommended for aggressive lymphoma with high LDH or treated without optimal dose chemotherapy, and (3) extended field setting is not necessary.

Adolescent↗
PubMed1997

[Radiotherapy for adenocarcinoma of the uterine cervix].

One hundred three patients with adenocarcinoma of the uterine cervix treated with radiotherapy between 1975 and 1992 were evaluated. The results for 24 patients treated with radiotherapy alone were as follows: The overall 5-year survival rates for Stages I + II (N = 12) and III + IV (N = 12) were 52% and 16%, respectively, lower than those for squamous cell carcinoma (stage I: 89%, II: 54%, III: 44%, IV: 19%). The overall response rate was 79.1%, and the recurrence rate was 54.2% (local recurrence: 29.2%, distant metastasis: 33.3%). In Stage I + II patients with an intracavitary irradiation dose of 40 Gy (LDR) or more, there was no local recurrence. In stage III + IV patients, local recurrence was recognized in spite of the high dosage of intracavitary irradiation. The results for 79 patients treated with combined irradiation and operation were as follows: The overall 5-year survival rates for Stages I, II, III and IV were 76%, 60%, 57%, and 0%, respectively. The incidence of lymph node metastasis was 30.4%, and for Stages I, II, III and IV was 26.7%, 34.6%, 28.6%, and 100%, respectively. This showed that adenocarcinoma had a higher incidence of lymph node metastasis after the early stage. The recurrence rate for patients with lymph node metastasis was 75.0%, significantly higher than 25.4% for patients without lymph node metastasis (p < 0.001). To improve prognosis, 40 Gy or more of intracavitary irradiation dose (LDR) and systemic chemotherapy to prevent distant metastasis are recommended for stage I and II cases. For stage III and IV cases, it was thought to be difficult to control local disease with radiation alone. Additional treatment should be used for these cases, i.e. intraarterial infusion, chemotherapy, hyperthermia and so on.

Adenocarcinoma↗
PubMed1996

The effect of a 5HT2 receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function in Buerger's disease.

The effect of a new, specific 5-HT2 receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function and serotonin levels in both plasma and whole blood in Buerger's disease, was assessed in a pilot study. We investigated 10 patients suffering from Buerger's disease. Sarpogrelate in a dose of 3 x 100 mg a day was given p.o. for a period of 8 weeks. It was well tolerated and no major side effects were noted. It was judged to be effective in some patients as assessed by its effect on both subjective complaints and objective evaluation of ankle pressure index (API). Sarpogrelate induced a significant decrease in plasma serotonin (5-HT) concentration starting after the 4th week which lasted through to the 8th week of the study, whereas plasma tryptophan concentration increased significantly after 2 and 4 weeks. There were no changes in plasma 5-HIAA concentration. On the other hand whole blood 5-HT concentration increased significantly after 2 weeks, and there was also a tendency to increase in whole blood tryptophan concentration (p = 0.052). Platelet aggregation induced by ADP and collagen did not show any statistically significant changes. Surprisingly, platelet aggregation induced by serotonin increased significantly after 2 weeks and even more so after 4 weeks of treatment, and then it returned to baseline values after 8 weeks. There was no effect on platelet count, APTT, TT and fibrinogen concentration.

Administration, Oral↗
PubMed1996

The inhibition of human factor Xa by plasminogen activator inhibitor type 1 in the presence of calcium ion, and its enhancement by heparin and vitronectin.

Plasminogen activator inhibitor type 1 (PAI-1), a member of serine proteinase inhibitor superfamily, is known to inhibit thrombin in the presence of either heparin or vitronectin. We analyzed possible inhibitory activity of PAI-1 on human factor Xa. PAI-1 inhibited factor Xa in the presence of calcium ion (Ca2+), whereas no inhibition was observed in the absence of Ca2+. Half maximal enhancement by Ca2+ was obtained at 0.8 mM. An equimolar complex formation between factor Xa and PAI-1 in the presence of Ca2+ was observed by SDS polyacrylamide gel electrophoresis. Both unfractionated heparin and vitronectin enhanced the inhibition only in the presence of Ca2+. Apparent second-order rate constant (ki) for the inhibition of factor Xa by PAI-1 at 5 mM Ca2+ was 1.6 x 10(4) M-1 s-1, and was enhanced 3-fold by 2 u/ml of heparin (4.6 x 10(4) M-1 s-1) and 10-fold by 100 nM vitronectin (1.6 x 10(5) M-1 s-1), respectively. The interaction between Ca(2+)-bound factor Xa and PAI-1 could be important from the view of PAI-1 neutralization and enhancement of fibrinolysis.

Calcium↗
PubMed1996

A novel activating anti-beta1 integrin monoclonal antibody binds to the cysteine-rich repeats in the beta1 chain.

The functional status of an integrin depends on the conformation of its extracellular domain, which is controlled by the cell expressing that receptor. The transmission of regulatory signals from within the cell is considered to be via propagated conformational changes from the receptor's cytoplasmic tails to the extracellular ligand binding "pocket." The end result is increased accessibility of the ligand binding pocket in the high affinity ("active") form of integrins. We report a novel monoclonal antibody (QE.2E5) that binds within the cysteine-rich repeats in the integrin beta1 chain and induces high affinity binding of fibronectin to the integrin alpha5beta1. The QE.2E5 epitope is located approximately 200 residues both from the predicted binding site for fibronectin and from the epitopes recognized by other activating anti-beta1 monoclonal antibodies. It is also expressed on beta1 integrins from a number of nonhuman species. Although they have the same functional effects, the binding of QE.2E5 and another activating antibody (8A2) to the receptor have contrasting effects on the expression of an activation-dependent epitope in the beta1 chain. We propose that the cysteine-rich repeats contain a regulatory region that is distinct from those previously described in the integrin beta1 chain.

Amino Acid Sequence↗
PubMed1996

Critical residues for ligand binding in an I domain-like structure of the integrin beta1 subunit.

Several integrin alpha subunits have an inserted sequence of about 200 residues (the I or A domain) that is critical for ligand interactions. The presence of an I domain-like structure within the integrin beta subunit has been proposed based on the similarity of the hydropathy profiles and the homology of sequences between the alpha and beta subunits. This study was designed to determine whether the region of the beta1 subunit that includes residues 101-335 has the characteristics of an I domain. We found novel critical residues for ligand binding (Ser-132, Asn-224, Asp-226, Glu-229, Asp-233, Asp-267, and Asp-295, in addition to the previously reported Asp-130) using site-directed mutagenesis. The critical residues for ligand binding are located in several of loop structures of the region (or in a potential loop between an alpha helix and a beta strand), which have been predicted using multiple secondary structure prediction methods. The data suggest that the beta subunit has multiple disrupted critical oxygenated residues for ligand binding similar to those found in the alpha I domain.

Amino Acid Sequence↗
PubMed1996

Differential display and cloning of shear stress-responsive messenger RNAs in human endothelial cells.

To investigate the effect of shear stress on endothelial gene expression, we performed differential display of mRNAs from cultured human umbilical vein endothelial cells either incubated under static conditions or exposed to shear stress (15 dynes/cm2) for 6 h in a flow-chamber. Around 4% of the total number of mRNAs detected were either up- or down-regulated by shear stress. DNA sequencing of some of these shear stress-responsive mRNAs revealed homology of several clones to known gene sequences and many other clones for unknown genes. Known genes, including those for human laminin B1 chain, H(+)-ATP synthase coupling factor 6, lysyl oxidase, myosin light chain kinase, and interleukin-8 receptor, were upregulated by shear stress, while the gene encoding NADH dehydrogenase was down-regulated. The present results suggest that shear stress can change the expression of numerous genes in endothelial cells, far more than reported to date, and that mRNA differential display is quite useful for cloning known and unknown shear stress-responsive genes.

Antigens, CD↗
PubMed1996

Critical residues of integrin alphaIIb subunit for binding of alphaIIbbeta3 (glycoprotein IIb-IIIa) to fibrinogen and ligand-mimetic antibodies (PAC-1, OP-G2, and LJ-CP3).

Integrin alphaIIbbeta3 plays a critical role in platelet aggregation through its interaction with fibrinogen. Elucidation of the mechanisms of alphaIIbbeta3-fibrinogen interaction is critical to understanding hemostasis and thrombosis. Here we report that mutations of Gly-184, Tyr-189, Tyr-190, Phe-191, and Gly-193 within the predicted turn structure of the third amino-terminal repeat of alphaIIb significantly block binding of alphaIIbbeta3 to soluble fibrinogen. These mutations also block binding of alphaIIbbeta3 to ligand-mimetic monoclonal antibodies PAC-1, OP-G2, LJ-CP3, which have an RGD-related RYD sequence in their antigen-binding sites. These mutations do not significantly affect the expression of alphaIIbbeta3, in contrast to most of the natural alphaIIb mutations occurring in Glanzmann's thrombasthenic patients. The data suggest that these residues are critically involved in alphaIIbbeta3-ligand interactions.

Amino Acid Sequence↗
PubMed1996

Effect of glimepiride (HOE 490) on insulin receptors of skeletal muscles from genetically diabetic KK-Ay mouse.

A new sulfonylurea, glimepiride (HOE 490), has been developed for the glycemic control in non-insulin-dependent diabetes mellitus. We examined the effect of glimepiride on glucose and insulin levels in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus, which is characterized by hyperglycemia and hyperinsulinemia. Administration of glimepiride (0.5 mg/kg/day) for 8 weeks to KK-Ay mice resulted in decrease in glucose (297 +/- 36 to 250 +/- 51 mg/dl) and insulin (76 +/- 14 to 41 +/- 14 microU/ml) levels. To clarify the mechanism of the agent, we examined the effect of this new drug on insulin receptors in the skeletal muscles. There was no difference in insulin binding to the receptors from both glimepiride-treated and -untreated KK-Ay mice muscles. The insulin-stimulated autophosphorylation of insulin receptors from KK-Ay mice was decreased compared to that from normal mice (5 +/- 1 vs. 39 +/- 13% over basal). Glimepiride did not ameliorate impaired insulin-stimulated insulin receptor autophosphorylation. To determine the effect of glimepiride on post-insulin receptor signaling pathway, we measured 2-[3H]glycerol incorporation into diacylglycerol in the cultured rat fibroblast cell line overexpressing human insulin receptors. Glimepiride (100 microM) as well as insulin (10 nM) significantly stimulated diacylglycerol production. These results suggest that glimepiride has a potent extrapancreatic effect on glucose metabolism and may directly stimulate glucose transport activity through phospholipid signaling pathway, but not through insulin receptor kinase signaling pathway.

Animals↗
PubMed1996

Regulation of conformation and ligand binding function of integrin alpha5beta1 by the beta1 cytoplasmic domain.

We have studied the role of the cytoplasmic domain in the conformation and affinity modulation of the integrin beta1. Expression of a conformation-dependent anti-beta1 antibody 15/7 correlates with activation in wild-type beta1. Truncation of 16 carboxyl-terminal residues in the cytoplasmic domain (the 762t beta1 mutant) induces constitutive expression of the 15/7 epitope at a high level (which probably reflects a major conformational change of the extracellular domain) but does not activate ligand binding. The dissociation of epitope expression and affinity suggests that the epitope expression reflects the conformation of nonligand binding sites of the extracellular domain of beta1 but does not necessarily reflect that of the ligand binding sites. Indeed we discovered that the 15/7 epitope is in fact located in the nonligand binding region of beta1 (within residues 354-425). The 762t mutant has apparently normal alpha/beta association, suggesting that the overexpression of the 15/7 epitope is not due to alpha/beta dissociation. The data suggest that the carboxyl-terminal 16 residues of the beta1 cytoplasmic domain are critical for properly modulating conformation and affinity of beta1 integrins.

Amino Acid Sequence↗
PubMed1996

Whey protein stimulated the proliferation and differentiation of osteoblastic MC3T3-E1 cells.

We examined the effects of whey protein on osteoblastic MC3T3-E1 cells. This protein caused dose-dependent increases in [3H]thymidine incorporation and DNA content in the cells. It also increased the total protein and hydroxyproline contents in the cells. These activities were heat resistant when the protein was heated at 75 degrees C to 90 degrees C for 10 min. Heat-treated whey protein was first fractionated on a Mono S column, and the active fraction (basic protein fraction) was then applied to Superose 12. The molecular weights of the active components were approximately 10,000 and 14,000 Da, as determined with gel filtration. The inner solution of an everted gut-sac incubated in a solution of intact BP (basic protein), pepsin-digested BP or pepsin/pancreatin-digested BP also stimulated the [3H]thymidine incorporation. Thus these active components can possibly permeate or be absorbed by the intestines. We propose the possibility that the active component in the whey protein plays an important role in bone formation by activating osteoblasts.

3T3 Cells↗
PubMed1996

Characterization of a novel variant of apolipoprotein E, E2 Fukuoka (Arg-224 --> Gln) in a hyperlipidemic patient with xanthomatosis.

A new variant of apolipoprotein (apo) E, designated apo E2 Fukuoka, was identified in a 54-year-old Japanese woman who suffered from hyperlipoproteinemia (total cholesterol 29.7 mmol/l, triglyceride 12.0 mmol/l, when she was 48-year-old) with the presence of xanthoma in the palms, bones, and ocular fundi, and other sites. Foam-cell macrophages were observed in bone marrow specimens. Analysis of apo E phenotype showed the E3/E2 isoform on isoelectric focusing performed on plasma, but the E3/E3 isoform on restriction-fragment-length polymorphism of the apo E gene. This discrepancy indicated that the apo E had an amino-acid substitution outside of amino-acid residues at 112 and 158. Sequence analysis of the patient's DNA, which was amplified by PCR and subcloned, revealed a single substitution from arginine (CGG) to glutamine (CAG) at residue 224, thereby adding one negatively charged unit to apo E3. Recombinant apo E2 Fukuoka produced in COS-1 cells showed almost the same binding activity to the LDL receptor on human skin fibroblasts as compared with recombinant apo E3. Recombinant apo E2 Fukuoka showed the same heparin binding ability than recombinant apo E3. Findings indicated that apo E2 Fukuoka was not the primary cause of the hyperlipoproteinemia observed in this case.

Apolipoprotein E2↗
PubMed1996

Pioglitazone attenuates the inhibitory effect of phorbol ester on epidermal growth factor receptor autophosphorylation and tyrosine kinase activity.

A new anti-diabetic drug, pioglitazone, was tested as to whether it could ameliorate the decreased kinase activity of epidermal growth factor (EGF) receptor induced by phorbol ester (PMA) in A431 cells. The treatment of A431 cells with PMA decreased the tyrosine kinase activity of EGF receptors to 37% of normal in autophosphorylation and to 24% in tyrosine kinase activity toward Glu/Tyre synthetic polymers. Co-incubation of the cells with pioglitazone and PMA improved the receptor tyrosine kinase activity to 81% of control. Pioglitazone treatment alone did not change the kinase activity of EGF receptors. Pioglitazone did not decrease the PMA-activated protein kinase C activity and did not affect the protein tyrosine phosphatases activity in A431 cells. These results suggest that pioglitazone may act as a specific antagonist to the inhibitory effect by protein kinase C on the EGF receptor tyrosine kinase.

Carcinoma, Squamous Cell↗