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K Takeda

Publications and source records attributed to K Takeda.

At least 685 records · Page 38Linked to original sources

Portal vein embolization with steel coils and absolute ethanol: a comparative experimental study with canine liver.

Portal vein embolization (PVE) is expected to have an adjuvant effect on the treatment of human liver tumors with transcatheter hepatic arterial embolization (TAE). In this experimental study, PVE was tried using two kinds of embolic materials, steel coils (coils) and absolute ethanol (ethanol). The aim of this article is to compare the effectiveness between the two methods. Five dogs and 12 dogs were treated with coils and ethanol, respectively. The second order portal branches were embolized. Embolization effects of each embolic material on the hepatic vessels and the liver parenchyma were studied angiographically and histologically. PVE with coils achieved immediate occlusion of the embolized vessels in all dogs. Unexpectedly, unembolized vessels were also constricted and/or obstructed in 4 of 5 dogs during a 4-week follow-up period. Histological examination showed no hepatic necrosis in all dogs. By contrast, in the dogs treated with ethanol, venous occlusion was achieved immediately after embolization with ethanol of 0.4 mL/kg or more. The embolized vessels remained occluded and no obstruction of unembolized vessels was observed until 4 weeks after embolization. Hepatic necrosis was observed in the segments where portal veins were occluded. The degree of parenchymal damage was proportional to the injected ethanol dose. Judging from these results, ethanol is likely to be more suitable than coils as an embolic material for PVE. PVE with coils is often dangerous because unembolized vessels might be occluded unexpectedly. For the clinical use of PVE with ethanol, the appropriate dose of injection should be investigated.

Animals↗

Production of functional human bone morphogenetic protein-2 using a baculovirus/Sf-9 insect cell system.

A clone of a human Bone Morphogenetic Protein-2 (hBMP-2) cDNA was obtained from a cDNA library established from human dental pulp cells. After subcloning hBMP-2 cDNA into Autographa californica nuclear polyhedrosis virus, the recombinant baculovirus was transfected to Sf-9 cells. Immuno-reactive recombinant hBMP-2 (rhBMP-2) was detected by a polyclonal antibody against Xenopus BMP-2 in the transfected insect cells but not in the culture media. Three days after treatment with the lysate of the transfected Sf-9 cells, increase in alkaline phosphatase activity of a murine stromal cell line, ST2, was detected. Subcutaneous implantation of rhBMP-2 produced in the insect cells induced formation of cartilage, bone and bone marrow in the rats. The present data indicated that the rhBMP-2 preparation produced in the insect Sf-9 cells had a comparable activity to that produced in mammalian cells.

Alkaline Phosphatase↗

[Pharmacokinetics of SK & F 104864 in experimental animals. I. Plasma level].

A camptothecin derivative, SK & F 104864 (topotecan), was injected for 30 minutes into the rabbit ear vein at a dose of 2 mg/kg or 5 mg/kg, and the plasma concentration was assayed by a HPLC method. The plasma level of SK & F 104864 (lactone form) decreased bi-exponentially with mean alpha and beta half-lives of 0.101 h and 0.849 h at 2 mg/kg, respectively, and 0.518 h and 7.57 h at 5 mg/kg, respectively. The AUCs were 0.846 micrograms.h/ml at 2 mg/kg and 2.14 micrograms.h/ml at 5 mg/kg. The plasma level of total topotecan (SK & F 104864 plus SK & F 105992) decreased bi-exponentially with mean alpha and beta half-lives of 0.696 h and 9.07 h at 2 mg/kg, respectively, and 0.795 h and 8.97 h at 5 mg/kg, respectively. The AUCs were 2.15 micrograms.h/ml at 2 mg/kg and 5.73 micrograms.h/ml at 5 mg/kg. The AUCs of lactone form were 39.3% of total topotecan at the 2 mg/kg dose and 37.3% at the 5 mg/kg dose, respectively. After intravenous bolus injection of SK & F 104864 at 20 mg/kg into Sarcoma 180 bearing mice, the alpha and beta half-lives of SK & F 104864 were 0.401 h and 3.99 h, respectively, and the AUC was 5.49 micrograms.hr/ml. The alpha and beta half-lives of total topotecan were 0.517 h and 4.27 h, respectively, and the AUC was 9.88 micrograms.hr/ml. The ratio of lactone form to total topotecan was 55.6%.

Animals↗

Femoral artery thrombus complicating open reduction of congenital hip dislocation.

There are no reports in the literature of femoral artery thrombi occurring as a complication of open reduction of congenital hip displacement. In an 11-month-old female infant, a femoral artery thrombus most likely formed as a result of compression of the femoral artery with a muscle retractor hook used in performing Ludloff's procedure. Femoral artery thrombi should be considered as a possible complication of reduction of congenital hip dislocation with Ludloff's procedure.

Angiography↗

Cross-bridge activation rate constant determined from systolic time intervals in patients with systemic lupus erythematosus.

Cardiac adrenergic activity was investigated in 38 patients with systemic lupus erythematosus (SLE) who were not receiving cardiovascular agents using a new index of the adrenergic tone of the working left ventricular (LV) myocardium and using the heart rate to represent sinus node adrenergic tone. According to the active cross-bridge model employed in this study, the cross-bridge activation rate constant (Ka) of the LV myocardium, corresponding to the rate constant for the binding of Ca2+ to troponin C, can be approximately expressed as Ka = 3/electromechanical systole (sec-1). The Ka value corrected for heart rate (Kac) remains nearly constant in normal individuals, but is increased without change of the heart rate by dobutamine infusion. Fifty patients who fulfilled the American Rheumatism Association criteria for SLE underwent echocardiography, as well as simultaneous recording of the electrocardiogram, phonocardiogram, and carotid pulse wave tracing. Kac was calculated from the interval between the onset of the QRS complex to the second heart sound (QS2 interval) and the heart rate (HR) as follows: Kac = 3/QS2 + 0.0249 (66-HR). The 38 SLE patients were divided into a normal Kac group (n = 26, 6.9 < Kac < 8.3 sec-1) and a high Kac group (n = 12, Kac > or = 8.3 sec-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Valve replacement in an infant with congenital mitral stenosis--report of a case which showed hemodynamics similar to that of hypoplastic left heart syndrome in neonatal period].

In the neonatal period, the patient showed severely hypoplastic left ventricle, severe mitral stenosis, patent foramen ovale and patent ductus arteriosus with right-to-left shunting, which resulted in the hemodynamics similar to that of hypoplastic left heart syndrome. However, progressive left ventricular growth was recognized after spontaneous closure of the foramen ovale, and the cardiac catheterization at the age of 6 months revealed almost normal left ventricular volume and systolic forward flow from the left ventricle to the descending aorta. The operation was performed at the age of 7 months under cardiopulmonary bypass with moderate hypothermia and cardiac arrest. The mitral leaflets were thickened and dysplastic, two short papillary muscles were hypertrophic and very closely related, and the chordae were extremely short and fused each other making the interchordal space obstructed. Because the mitral annular diameter (13 mm) was too small for conventional valve replacement, the prosthetic valve (CarboMedics #16) was sewn to the left atrial wall 5 to 10 mm above the mitral annulus. The ductus arteriosus was ligated. The postoperative cardiac catheterization showed residual pulmonary hypertension, but pulmonary vascular response to oxygen-inhalation was recognized. We consider that there were two important hemodynamic factors which led to successful biventricular repair in this case. First, early spontaneous closure of the foramen ovale accerelated the left ventricular growth and prevented right ventricular failure resulting from increased pulmonary blood flow. Second, considerable part of the systemic output was supplied through a large ductus arteriosus, and thus over-systemic pulmonary hypertension was avoided.

Cardiopulmonary Bypass↗

[A case of hypertensive hypertrophy in which both regression of hypertrophy and improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG) myocardial imagings were observed after antihypertensive therapy].

A case of hypertensive hypertrophy is described in which both regression of hypertrophy and improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG) myocardial imagings were seen after 7 months of antihypertensive therapy. A 58-year-old man was diagnosed as having essential hypertension and hypertensive hypertrophy. The patient was treated with antihypertensive drugs and showed regression of left ventricular hypertrophy on electrocardiograms and echocardiograms. MIBG observations made before and after antihypertensive therapy showed increased heart-to-mediastinum activity ratio and decreased cardiac washout ratio. Despite the many theories addressing the mechanisms of regression of left ventricular hypertrophy, the process is still unclear. In the present case, the improvement of cardiac sympathetic nervous dysfunction might have been related to the regression of left ventricular hypertrophy because the abnormality in MIBG images improved. MIBG, therefore, may be helpful in clarifying the mechanisms of the regression of hypertensive hypertrophy.

3-Iodobenzylguanidine↗

[The function and role of extrathymic T cells].

Murine liver contains alpha beta T cells with intermediate TCR (TCRint) as well as alpha beta T cells with bright TCR. Liver TCRint cells express NK1.1 Ag (NK1+ TCRint) and IL-2 receptor beta chain, both of which are NK cell markers and are not expressed on conventional T cells. Liver NK1+ TCRint cells consist of CD4-8- double negative T cells and CD4+ T cells and have V beta 8+ T cell preponderance. They are dependent on class Ib or CD1 molecules of APC for their development. They can also develop thymus independent manner, because athymic nude mice have this population. These NK1+ TCRint cells in the livers of both euthymic and athymic mice were found to be activated by systemic administration of IL-12 and increased NK1 expression (NK1high TCRint) and cytotoxicity against various NK-sensitive and resistant tumors. Cytotoxicity assays after treatment of IL-12 stimulated hepatic MNC with respective Abs and C revealed that CD4+ NK1high TCRint cells are responsible for IL-12 induced cytotoxicity. Although NK1+ TCRint cells were normally few in the lungs, a significant proportion of NK1high TCRint cells with strong cytotoxicity was also induced in the lung by IL-12. Interestingly, adoptive transfer of IL-12 stimulated hepatic MNC into other mice, which were pre-injected with tumors, inhibits hepatic metastases of EL4 cells and pulmonary metastases of 3LL cells as similarly as IL-12 administration. Transfer experiments after treatment of IL-12 stimulated hepatic MNC with respective Ab and C revealed that depletion of either NK1+ cells, CD3+ cells or CD4+ cells but not CD8+ cells greatly impaired antimetastatic effect in both organs. Thus, CD4+ NK1high TCRint cells are a major antimetastatic population, especially, against hematogenous metastases.

Animals↗

Pharmacokinetics and pharmacodynamics of nisoldipine in hypertensive patients with normal and mild to moderate impaired renal function.

The pharmacokinetics and pharmacodynamics of nisoldipine (CAS 63675-72-9, isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, Bay k 5552), a calcium antagonist, were investigated after administration of a single oral 10 mg dose and after 7 same doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with mild to moderate renal dysfunction (impaired renal function, IRF). A significant decrease in blood pressure was observed after consecutive dosing of nisoldipine compared to baseline values over 24 h in both groups. There were no significant differences in plasma profiles of nisoldipine in both groups after either single or consecutive dosing. The plasma concentration-time profiles of the active metabolite, Bay r 9425, were similar to those of nisoldipine in both groups. The pharmacokinetic parameters of nisoldipine and its active metabolite in the NRF and IRF groups did not differ after the single and the consecutive dosing. In addition, there were neither prolongation of apparent elimination half-life (t1/2), nor increases in peak plasma levels (Cmax), or the area under the plasma concentration-time curve (AUC0-infinity) after consecutive dosing in both groups. Cumulative urinary excretion rates of the major metabolites, Bay s 4755 and Bay s 1869, did not differ significantly between the NRF and IRF groups in both single and consecutive studies. In the present study, mild flushing was observed in one patient with IRF. There was no deterioration in renal function during the study. These results suggest that nisoldipine may have a long-lasting antihypertensive effect during consecutive dosing and that it can be used in hypertensive patients regardless of presence of renal dysfunction.

Blood Pressure↗

Extrathymic T cells stand at an intermediate phylogenetic position between natural killer cells and thymus-derived T cells.

A series of recent studies have revealed that extrathymic pathways of T cell differentiation exist at multiple sites in mice and humans. In terms of their properties, extrathymic T cells may stand at an intermediate position between natural killer (NK) cells and thymus-derived T cells in phylogenetic development. It is speculated that primitive lymphocytes such as NK cells and extrathymic T cells develop from primordial macrophages in intraepithelial regions of e.g., the intestine, skin and liver. In this regard, the immune system of the bone marrow and thymus is relatively recent, developing after the emergence of living beings onto the land (i.e., amphibia). A complete elimination of self-reactive T cell clones occurs in mainstream intrathymic T cell differentiation and a consistent generation of such clones occurs through the extrathymic pathways. Therefore, thymus-derived T cells are efficient for processing foreign antigens, whereas extrathymic T cells recognize abnormal self-cells. Although thymus-derived T cells play the major role in youth, extrathymic T cells may play rather a pivotal role with aging and under conditions of malignancy, intracellular infections, pregnancy, and autoimmune diseases.

Animals↗

Expression of (Na, K) ATPase/Ca-ATPase chimeric proteins in Xenopus oocytes revealed that the COOH-terminal one-third of the (Na, K) ATPase alpha-subunit is involved in assembly with the beta-subunit.

Chimeric proteins consisting of parts from the alpha-subunit of Torpedo californica (Na, K) ATPase (N) and the rabbit sarcoplasmic reticulum Ca-ATPase (C) were expressed in Xenopus oocytes by injecting the respective chimeric cRNA in combination with cRNA for the beta-subunit of Torpedo (Na, K) ATPase. The chimeric protein (NCN) that consisted of the NH2-terminal and COOH-terminal one-thirds of the alpha-subunit of the (Na, K) ATPase and the central one-third of the Ca-ATPase was able to assemble with the beta-subunit in the same fashion as the wild-type alpha-subunit of the (Na, K) ATPase (NNN). On the other hand, chimeric proteins in which the COOH-terminal one-third was derived from the Ca-ATPase (NNC and NCC) were unable to form stable complexes with the beta-subunit. These results suggest that the COOH-terminal one-third of the (Na, K) ATPase alpha-subunit is required for the assembly with the beta-subunit.

Animals↗

Spontaneous regression of lung metastases from osteosarcoma.

BACKGROUND: Spontaneous regression of malignancy is infrequent, but in osteosarcoma, such occurrence is extremely rare. Through a survey of many university hospitals and cancer centers in Japan, two patients with such regression were found. METHODS: In both patients, radiograms of the primary sites and histologic specimens were studied carefully for accurate diagnosis. The clinical records, serum alkaline phosphatase values, and changes in the pulmonary metastasis on chest radiograms were followed for 26 years and 13 years, respectively. In the second patient, metastatic lesions were studied histologically. RESULTS: The patients, a 19-year-old man and an 11-year-old boy each with osteosarcoma in the distal femur. Each was treated by amputation. Pulmonary metastases were found on routine checkup 5 months and 12 months after the surgery, respectively, despite adjuvant chemotherapy. The metastatic nodules of both patients became denser and smaller 12 and 5 months, respectively, after detection, and the alkaline phosphatase concentration returned to normal, without special treatment. To date, the patients are alive and well. In the second patient, histologic examination of the metastatic nodules showed no remarkable infiltration of lymphocytes that would suggest an immunologic response; however there was florid bone formation indicating maturation of the tumor cells. CONCLUSION: Cases that have been reported as spontaneous regression of pulmonary metastases from osteosarcoma often show equivocal pathologic or clinical signs, and some have shown only temporary regression of the lesions. The two patients presented here are unique, however, because they had a definite diagnosis of osteosarcoma and showed extraordinarily long-lasting regression, which presumably occurred spontaneously, not as a direct effect of chemotherapy.

Adult↗

Modulation of responses to TGF-beta by 1, 25 dihydroxyvitamin D3 in MG-63 osteoblastic cells: possible involvement of regulation of TGF-beta type II receptor.

The effect of TGF-beta 1 on the expression of alkaline phosphatase (ALPase) activity was examined during osteoblastic cell line (MG-63) differentiation induced by 1,25-dihydroxyvitamin D3 (1,25D3). TGF-beta 1 and 1,25D3 were found to enhance ALPase activity. However, preincubation of the cells with 1,25D3 transiently abolished the effects of TGF- beta 1. Kinetics of the complex responses to TGF- beta 1 and 1,25D3 were found to correlate well with that of the expression level of type II receptor for TGF- beta. These results suggest that 1,25D3 may regulate the cellular responses to TGF- beta 1 in part via regulation of functional receptor for TGF- beta.

Alkaline Phosphatase↗

Molecular cloning of rat bone morphogenetic protein (BMP) type IA receptor and its expression during ectopic bone formation induced by BMP.

A cDNA for the rat bone morphogenetic protein (BMP) type IA receptor (BMPR-IA) was isolated from a dental pulp cell cDNA library. The rat BMPR-IA cDNA encodes a protein of 532 amino acids with a single transmembrane domain and a putative serine/threonine kinase domain. The overall amino acid sequence identity between the rat and human BMPR-IA was 97%. Reverse transcriptase-polymerase chain reaction analysis revealed that BMPR-IA mRNA was highly expressed in the BMP-induced bone forming tissues throughout the stages tested.

Amino Acid Sequence↗

Identification of a cis-acting element that is responsible for cadmium-mediated induction of the human heme oxygenase gene.

Heme oxygenase is an essential enzyme in heme catabolism and is inducible by various environmental derangements such as cadmium. The activity and mRNA levels of heme oxygenase were remarkably increased in HeLa cells by the treatment with cadmium. As a first step in studying the molecular mechanisms of this induction, we performed transient expression assays in four human cell lines including HeLa to analyze the cadmium-mediated inducibility of the fusion genes, containing the firefly luciferase gene as a reporter under the human heme oxygenase gene promoter. By determining the luciferase activity expressed in the transfected cells, we found the region between about 4.5 and 4 kilobase pairs upstream from the transcriptional initiation site of the heme oxygenase gene which confers cadmium-mediated inducibility on the fusion gene. The region was then subjected to further functional analysis in HeLa cells, which allowed us to localize the cadmium-responsive element to 20 base pairs. Gel mobility shift assays demonstrated that this 20-base pair element is specifically bound by nuclear protein(s) of HeLa cells, the binding activities of which were however unchanged by the treatment with cadmium. Using the synthetic cadmium-responsive elements containing various base changes, we have identified a 10-base pair sequence, TGCTAGATTT, required for the cadmium-mediated inducibility and in vitro protein binding. We thus suggest that this binding protein(s) is involved in the cadmium-mediated activation of the heme oxygenase gene. Incidentally, the consensus sequence of AP-1 binding site, TGAGTCA, is present downstream of this cadmium-responsive element. However, we provide evidence that AP-1 is not directly involved in the cadmium-mediated induction of the human heme oxygenase gene.

Animals↗

Demonstration of MHC class I-specific cytolytic activity in IL-2-activated NK1+CD3+ cells and evidence of usage of T and NK cell receptors.

Lethally irradiated F1 hybrid mice are able to reject allogeneic or parental marrow within hours of transplantation. It has been shown in several mouse strains that the effector cells responsible for this rejection are NK1+ CD3+, leading to the postulate that NK1 CD3 cells express specific cytolytic activity. Previous attempts to demonstrate this were unsuccessful, however. Here we report that the majority of splenic NK1 CD3 cells is in a nonactivated state and that culture in IL-2 induces specific cytolytic activity. Using unseparated as well as purified cells, we demonstrate that NK1 CD3 cells use the TCR alpha/beta for recognition of MHC class I domains alpha 1 and alpha 2. Cytotoxic specificity matches that of specificity of marrow graft rejection when lymphoblast targets are used. Assay of effector cells on L or tumor cell targets results in nonspecific lysis. The possibility that these targets are recognized via receptors other than TCR is supported by the observation that lysis is inhibited by anti-NK1 antibody. We also show that anti-NK1 is able to induce target lysis in a redirected lysis assay not only in NK1+ CD3- but also NK1+ CD3+ effector cells. The conclusion is drawn that, NK1+ CD3+ cells may utilize two receptors--i.e., NK1 and TCR/CD3.

Animals↗