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Biomedical subjects

Makoto Takagi

Publications and source records attributed to Makoto Takagi.

At least 19 recordsLinked to original sources

Metal ion-directed cooperative DNA binding of small molecules.

Compound (1), which consists of an oxine and a pyridinium group, was synthesized as a metal-responsive DNA binding ligand. Two 1s coordinate to a Cu(II) to form a stable dimer (1(2)-Cu), even in the presence of DNA. The binding of 1 with sonicated calf thymus DNA was enhanced by ca. 10(3) times after forming the dimer; the binding constants were estimated to be 3.2 x 10(4)M(-1) and 2.4 x 10(7)M(-1) in the absence and the presence, respectively, of a half mole of Cu(II). The enormous acceleration of the binding is partly attributed to the generation of a dicationic charge by the formation of the dimer. High cooperativity between dimers could be also responsible; dimers would gather along the duplex as a template to form 1D spiral aggregates.

Animals↗

Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6.

We investigated the diagnostic significance of IL-6 for lymph node metastasis and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1, ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL-6 expression in tumor tissue. From the receiver operating characteristic (ROC) curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to classify hepatic metastasis. These values indicated sensitivities of 55.0% and 71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1 were very useful for distinguishing among Dukes.s A/B group, C group, and D group. In all cases with high IL-6 values (more than 25.0 pg/ml), immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be useful diagnostically to estimate whether or not there is a high risk of lymph node and/or hepatic metastasis.

Adult↗

Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor.

BACKGROUND: It is becoming clear that various cytokines are associated with the spread of cancer cells. The purpose of this study was to compare interleukin (IL)-6 levels in patients with gastric cancer to elucidate the role of IL-6 in predicting the spread of tumors. METHODS: In 60 patients, we assessed the correlation of serum IL-6 (pg/ml) with stage, histological findings, hepatic metastasis, and related factors (hepatocyte growth factor [HGF], IL-1beta, tumor necrosis factor [TNF]-alpha, and transforming growth factor [TGF]-beta1). We also investigated the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, as well as the association between IL-6 elevation and outcome. Finally, we examined the expression of IL-6 in tumor tissue. RESULTS: Significant relationships were seen between serum IL-6 and stage, depth of tumor invasion (pT), lymphatic invasion (ly), venons invasion (v)*, lymph node metastasis (pN), hepatic metastasis (cH), and HGF (P < 0.01; *P < 0.05). With regard to the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, when the cutoff value of IL-6 was set at 1.97 pg/ml, the sensitivity was 81.8% and 87.5%; specificity was 66.7% and 58.3%; and accuracy was 77.1% and 72.9%, respectively. The 1- and 3-year cumulative survival rates for patients with an IL-6 value of more than 1.97 pg/ml (69.0% and 43.4%, respectively) were significantly lower than those for patients with an IL-6 value of 1.97 pg/ml or less (94.4% and 87.2%, respectively; P < 0.05). Immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. CONCLUSION: We suspect that IL-6 is involved in cancer invasion and lymph node and/or hepatic metastasis. Our results indicate that IL-6 could be used as a prognostic factor for survival.

Adult↗

Dependence of the timing system regulating the onset of gastrulation on cytoplasmic, but not nuclear, activities in the Xenopus embryo.

This study examines the properties of the timer that regulates the onset of gastrulation in the Xenopus embryo. Pre-gastrulation embryos were exposed to aphidicolin, vinblastine, 6-dimethylaminopurine (6-DMAP) or urethane. Embryos exposed to aphidicolin or vinblastine for 0.5-2 h before the presumptive onset of gastrulation, began gastrulation at the same time as control embryos. However, those exposed to 6-DMAP or urethane commenced gastrulation significantly later than controls. In 6-DMAP- and urethane-treated embryos, the onset of gastrulation was retarded by approximately 25% and 120%, respectively. 6-DMAP and urethane, but not vinblastine, also lowered the rate of nuclear doubling by 30% and 120%, respectively, in late-blastula to early-gastrula embryos. 6-DMAP and urethane also lowered the rate of cleavage and cleavage-relevant cytoplasmic cycling by 30% and 80%, respectively, in cleavage-stage embryos. We propose that cytoplasmic activities that can be retarded by 6-DMAP and urethane, but not aphidicolin or vinblastine, may be responsible for regulating the onset of gastrulation in Xenopus embryos.

Adenine↗

[Cerebral arterial dissection].

We investigated a total of 98 cases with stroke caused by cerebral arterial dissection recruited in Strategies against Stroke Study for Young Adults in Japan (SASSY-Japan). The most frequent site of dissection was the intracranial vertebrobasilar artery. The stroke subtype was divided into ischemic (TIA and cerebral infarction) and hemorrhagic types (subarachnoid hemorrhage). The ischemic type was predominant (69%) and patients with the ischemic type were younger than those with the hemorrhagic type (P < 0.01). In the intracranial arterial dissection, nearly all cases were of the ischemic type. In contrast, in the extracranial arterial dissection, 60% of cases were ischemic and 40% were hemorrhagic. Cerebral angiography was the most important diagnostic procedure in the hemorrhagic type. In the ischemic type, MRI and MRA were more frequently used to show the findings specific to the dissection such as an intimal flap or double lumen and intramural hematoma. The outcome at discharge is generally good such that the modified Rankin Score was among 0-II in 69% of cases. However, in the hemorrhagic type, recurrence during an acute stage was frequent, and the outcome was poor with a mortalit rate of 19%. The establishment of an effective intervention to prevent the recurrence of subarachnoid hemorrhage is urgently required.

Adult↗

[A case of gastric cancer with a synchronous hepatic metastasis responding to postoperative oral administration of UFT and intermittent intrahepatic arterial chemotherapy of 5-FU].

A 65-year-old male was admitted to our hospital because of sudden onset of upper abdominal pain due to the perforation of gastric cancer with synchronous hepatic metastasis. He underwent total gastrectomy with lymphatic dissection of D1 + alpha. Pathological diagnosis of the surgical specimen was moderately differentiated tubular adenocarcinoma. The cancer progression was fStage IV (T1, N0, H1, P0). Since 50 days after surgery, he had received oral administration of UFT (300-600 mg/day) and intermittent intrahepatic arterial infusion of 5-FU (one injection, 500 mg/2 weeks). Seven months after the start of chemotherapy, the size of hepatic lesion was reduced. Thirteen months later, the tumor became necrotic with cystic change. Furthermore, 22 months later, abdominal CT scan showed complete response. He has been well without recurrence for 38 months following the start of chemotherapy.

Adenocarcinoma↗

[Micro-tourniquet method: a substitute or supporting technique for aneurysm clipping].

The micro-tourniquet method is designed as a substitute and/or supporting technique for obliterating aneurysms that are difficult to operate on using the conventional clipping technique. This method is useful for squeezing the aneurysm neck and making a detour around the neck to spare the branching vessels. These micro-tourniquet instruments are a ligature with both ends attached to a ligature guide, a guide holder, a silastic sheath, and a hemostatic clip or a small aneurysm clip set. The ligature is a 20cm long GORE-TEX suture CV-3, and is attached on both ends to a ligature guide. These ligature guides are made of 7mm wire, and are malleable enough to be bent intentionally during surgery. However, they are also rigid enough to be used as a micro dissector. The silastic sheath is made of a 20G infusion needle, and is cut to a length of 2cm. After branching vessels and perforators are dissected and spared with the aid of the ligature guide, the ligature is passed around the aneurysm neck, both ends of the ligature are passed through the sheath, the aneurysm neck is squeezed, and a clip is applied as a stopper on the ligatures adjacent to the distal end of the sheath. By gently displacing the distal end of the sheath, a conventional aneurysm clip is applied on the aneurysm neck just distal or proximal to the ligature on the neck. Then, the ligature is removed. Two demonstrable cases are presented and the usefulness of the micro-tourniquet method is discussed.

Humans↗

[Spinal cord infarction due to cholesterol emboli complicating intra-aortic balloon pumping (case report and review of the literature)].

A 62-year-old man with diabetes mellitus, hypertension, and hyperlipidemia was admitted to our hospital because of sudden onset of left chest pain. He was diagnosed with unstable angina with left heart failure and underwent intra-aortic balloon pumping (IABP) immediately. On the 3rd day after removal of the IABP (7th hospital day), he developed sudden paraplegia with pain. Spinal MRI on the 12th hospital day revealed a spinal swelling (Th11-L2). He was died of cardiac shock on the 19th hospital day. Autopsy examination of the spinal cord revealed a large infarct from the lower thoracic segment to the sacral segment. Microscopic examination of these areas disclosed occlusive emboli most frequently of the anterior spinal arteries including posterior spinal arteries. These emboli were found in two different forms, one consisting of new cholesterol emboli and the other of old atheromatous emboli. On autopsy, the aorta exhibited severe atherosclerosis with multiple ulcerative plaques, and there was infarction of the spleen. In our case, spinal cord infarction was caused by a massive amount of cholesterol crystals from the aorta related to IABP.

Angina, Unstable↗

Comparison of potassium ion preference of potassium-sensing oligonucleotides, PSO-1 and PSO-2, carrying the human and Oxytricha telomeric sequence, respectively.

Human [G(3)(TTAG(3))(3)] and Oxytricha [G(4)(T(4)G(4))(3)] telomere model oligonucleotides, PSO-1 and PSO-2, bearing two fluorophores, 6-carboxyfluorescein (6-FAM) and 6-carboxytetramethylrhodamine (6-TAMRA) at their 5'- and 3'-termini, respectively, were synthesized. Both of them can form an intramolecular antiparallel tetraplex upon addition of K(+), and an enhanced fluorescence resonance energy transfer (FRET) was observed. PSO-1 showed a 43,000 times higher selectivity for K(+) against Na(+). Fluorometric and circular dichroism spectrophotometric studies revealed that this system is useful for the evaluation of the interaction of different telomeric repeat oligonucleotide sequences with metal ions.

Animals↗

Correlation between clinicopathologic factors and kinetics of metabolic enzymes for 5-fluorouracil given to patients with colon carcinoma by two different dosage regimens.

PURPOSE: Using tumor tissue specimens from colon carcinoma patients given 5-fluorouracil (5-FU) by two different administration methods, we investigated the degree of correlation between clinicopathologic factors and the kinetics of metabolic enzymes for 5-FU. METHODS: Group A patients received 500 mg/day of 5-FU as a rapid infusion over 2 h for 3 days preoperatively, and group B patients received 500 mg/day of 5-FU as a continuous infusion for 3 days preoperatively. The activities of orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), uridine phosphorylase (UP), and dihydropyrimidine dehydrogenase (DPD) were measured by separation on ion-exchange filter paper, by high-performance liquid chromatography (HPLC) with UV detection and by HPLC with radioactive flow monitoring, respectively, and the [(3)H]-5-fluorodeoxyuridine monophosphate binding site in thymidylate synthetase (TS) was determined as an index of the amount of TS using a radiobinding assay. The TS inhibition rate (TSIR) was calculated from the formula: 1-(TS(free)/TS(total))x100. Finally, 5-FU incorporation into RNA (FRNA) was measured by capillary gas chromatography-mass spectrometry. RESULTS: In group A patients, FRNA showed a positive correlation only with OPRT, and TSIR showed positive correlations with OPRT and TP, but a negative correlation with TS. In group B patients, FRNA showed a negative correlation with DPD, and TSIR showed a negative correlation with TS. No difference in TSIR levels was seen between groups A and B. FRNA was higher in group A than in group B, but the difference was not statistically significant. CONCLUSION: The method of administration may influence 5-FU metabolism in colon carcinoma patients.

Aged↗

Liver metastasis of pancreatic cancer managed by intra-arterial infusion chemotherapy combined with degradable starch microspheres.

A patient with liver metastasis of pancreatic cancer received chemotherapy using mitomycin C and degradable starch microspheres. The patient was a 52-year-old woman who had undergone surgery for cancer of the head of the pancreas in October 1996. She had stage III disease and was followed up as an outpatient on oral therapy with a combined uracil and tegafur preparation. In October 2000, abdominal computed tomography (CT) scans detected multiple liver metastases. Three courses of intra-arterial infusion of mitomycin C and microspheres (1000 mg) resulted in regression of her tumor and a decrease of tumor marker levels. After three more courses of this therapy, the patient developed bile duct necrosis and died of disseminated intravascular coagulation. As her metastases were controlled for about 7 months, hepatic arterial infusion of mitomycin C and degradable starch microspheres appears to be useful for treating liver metastasis of pancreatic cancer, but careful attention should be paid to the risk of severe complications such as bile duct necrosis.

Antineoplastic Combined Chemotherapy Protocols↗

Metal ion-directed outside binding of small DNA ligand.

DNA binding of the ligand bearing an oxine and a pyridinium group was regulated by coexisting Cu2+ over the binding constant range of three orders of magnitude. The ligands coordinated to Cu2+ to form a dimer and then cooperatively bound outside of DNA duplex to give the well-regulated 1-D structure along the DNA backbone.

DNA↗