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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 343 records · Page 19Linked to original sources

Complete response of esophageal cancer achieved by combination therapy with 5-fluorouracil, low-dose cisplatin, and radiation: report of a case.

To improve the survival rate of patients with esophageal cancer, several protocols of a preoperative combination of chemotherapy and radiotherapy, known as chemoradiation therapy, have been developed, recently characterized by the combination of 5-fluorouracil (5-FU), cisplatin, and radiation. Although some of these combinations have been demonstrated to be effective, the optimal chemoradiation dose and schedule are not yet precisely established. Recent investigations have elucidated that the radiosensitizing effects of cisplatin are able to be achieved more effectively by the daily administration of cisplatin before each fraction of radiation. Based on these investigations, we report herein the case of a patient with esophageal cancer with direct invasion to the trachea, in whom a complete response was achieved by the continuous administration of 5-FU, 600 mg/m2 per day, from days 1-5 combined with the daily administration of low-dose cisplatin, 10 mg/m2 per day before each fraction of radiation, given as 2Gy each time, throughout the entire treatment period of 3 weeks beginning on day 1. The benefits of our preoperative chemoradiation therapy included no severe side effects, down-staging and resectability of the tumor, as well as a pathological complete response, which could prolong the survival time. Our experience of this case prompts us to recommend the concurrent daily preoperative chemoradiation therapy for patients with locally advanced esophageal cancer.

Antimetabolites, Antineoplastic↗

Primary meningeal malignant fibrous histiocytoma with cerebrospinal dissemination and pulmonary metastasis.

Primary intracranial malignant fibrous histiocytoma (MFH) is very rare, and not much is known about its clinical features. The authors report a case of left temporal leptomeningeal MFH, with consequent cerebrospinal fluid (CSF) dissemination and pulmonary metastasis. The clinical features of this case and the therapeutic prognosis of 17 cases reported previously in the literature were reviewed.

Cerebrospinal Fluid↗

Examination of number-average degree of polymerization and molar-based distribution of amylose by fluorescent labeling with 2-aminopyridine.

Suitable conditions for the fluorescent labeling of the reducing residue of amylose with 2-aminopyridine were examined. Amylose of up to 38.5 nmol was labeled with a constant labeling efficiency. The same efficiencies were obtained for amyloses having a number-average degree of polymerization (dpn) of 521-4400. The analysis of labeled amylose on size-exclusion HPLC with refractive index and fluorescence detection enabled the determination of dpn and dp distribution on a molar basis. The analysis of eight amylose specimens from seven botanical sources (potato, sweet potato, barley, wheat, indica rice, japonica rice, and maize) gave dpn values in good agreement with those determined by a conventional colorimetric method. The molar-based distributions of these amyloses were characteristic of botanical source and revealed the presence of several molecular species with different dp not detectable in the distribution on a weight basis. Small amyloses with a dp less than 10(3) were predominant in the cereals while amyloses with a dp over 10(3) were predominant in the tubers, suggesting a difference in the biosynthetic process determining the dp distribution of amylose between cereals and tubers.

Aminopyridines↗

Advances in perinatal medical care--from our experience.

In the last 30 years, maternal and perinatal mortality rates have markedly improved in Japan. These results are supported by the advanced technologies and newly developed treatments in obstetric and neonatal medicine, the evidence of which will be described through the authors' experiences. Ultrasound-guided treatments for fetuses and pediatric surgery for extremely tiny infants have been performed with cooperation among cardiac surgeons, anesthesiologists and perinatologists. The remarkable achievements in neonatal medicine are surfactant replacement therapy, application of high frequency oscillation (HFO) respirator, nitric oxide and extracorporeal membrane oxygenation (ECMO) systems and transcutaneous blood gas monitoring. The possibility to have a safe pregnancy and delivery arose for women with severe medical complications such as diabetes mellitus (DM), heart diseases, and hemo-dialysis, factors formerly regarded as contraindications to pregnancy. The accumulative data of these high-risk pregnancies treated in our center are introduced. It is noted that molecular mechanisms in fetal growth have been elucidated to some extent. The insulin-like growth factor I (IGF-I) and IGF-binding protein 1 (IGFBP1) system, and cytokines, are involved in the fetal growth. Newly developed treatments such as urinary trypsin inhibitor (Urinastatin) for prevention of preterm delivery and amnioinfusion to cases of preterm premature rupture of the membrane are summarized. Finally, the reference to advanced medicine and its side effects lead to broad discussions regarding the future development of perinatal medicine.

Adolescent↗

Diagnostic and biological significance of sideroblastic erythropoiesis in the myelodysplastic syndromes.

We retrospectively reviewed clinical and hematologic features of nine patients with acquired idiopathic sideroblastic anemia (AISA). Seven of them had ringed sideroblasts (RS) more than 15% of marrow nucleated cells. RS persisted in the marrow even in the remaining two patients who had a relatively low marrow erythroblasts despite RS ranging from 1/4 to half of the marrow erythroid series. However, RS declined in proportion in another two patients of the nine whose disease progressed to refractory anemia with excess of blasts (RAEB), although a high proportion of RS reappeared in one patient at the time of relapse following allogeneic marrow transplantation. A similar decline of RS concomitant with disease progression was also seen in seven additional patients with RAEB or RAEB in transformation (RAEB-t) with sideroblastic erythropoiesis. Cytogenetic abnormalities, although rare initially, became detectable either at the time of disease progression or at the worsening of anemia in AISA. These observations suggest that the majority of AISA fall in the category of myelodysplasia, and that a progressive decline in RS is part of the natural history of myelodysplasia. Closer follow-up of the proportion of RS in patients with AISA is warranted to better understand its biologic significance.

Adolescent↗

Sequence-dependent antitumour efficacy of combination chemotherapy of nedaplatin, a novel platinum complex, with 5-fluorouracil in an in vivo murine tumour model.

The antitumour efficacy of a sequential combination of nedaplatin (NDP) and 5-fluorouracil (5-FU) was evaluated using Lewis lung carcinoma in vivo. NDP was developed as a second generation platinum complex. Because it has greater antitumour activity and lower nephrotoxicity than cisplatin (CDDP), we also compared the antitumour activity of NDP plus 5-FU with that of CDDP plus 5-FU. A fixed 5-FU dose was injected daily for 5 days and increasing doses of either NDP or CDDP were injected once via the tail vein into the Lewis lung carcinoma-implanted mice. The sequential administration of either NDP or CDDP prior to 5-FU (NF or CF therapy) resulted in severe body weight loss followed by the death of the tumour-bearing mice when the high-dose of NDP or CDDP was administered. In contrast, the sequential administration of 5-FU prior to NDP or CDDP (FN or FC therapy) resulted in synergistically enhanced inhibition of tumour growth and prolonged survival in comparison with NDP, CDDP or 5-FU monotherapy. At the high-dose of NDP in FN therapy, a reduction of tumour size and long-term tumour-free survival were frequently observed. The survival effect of the combinations of NDP with 5-FU was superior to those of the combination of CDDP with 5-FU. In conclusion, the sequence-dependent antitumour efficacy and toxicity of the combination of NDP or CDDP with 5-FU was demonstrated in this study, and FN therapy appeared to be the most efficient regimen as a clinical therapy.

Animals↗

Phosphoisoforms of insulin-like growth factor binding protein-1 in appropriate-for-gestational-age and small-for-gestational-age fetuses.

We analysed phosphoisoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in maternal and cord sera from preterm and term fetus with different growth status. Phosphoisoforms were separated by non-SDS-polyacrylamide gel electrophoresis and detected by immunoblot. Phosphoisoforms were also analysed by anion exchange chromatography on HPLC. The proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was significantly higher in preterm fetus than in their mothers, however, the relative amounts of each IGFBP-1 isoforms were similar between preterm and term fetus. The levels of non-phosphorylated IGFBP-1 were similar between appropriate for gestational age (AGA) and small for gestational age (SGA) fetus at term, however, phosphorylated isoforms of IGFBP-1 were increased in SGA fetus compared to those of AGA fetus and the proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was lower in SGA fetus than those in AGA fetus. Thus, the profiles of non-phosphorylated and phosphorylated IGFBP-1 in the fetus varies corresponding to fetal growth suggesting that not only total amounts of IGFBP-1 but also the proportion of phosphoisoforms of IGFBP-1 is important for fetal growth.

Biomarkers↗

Phosphorylated insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) inhibits while non-phosphorylated IGFBP-1 stimulates IGF-I-induced amino acid uptake by cultured trophoblast cells.

The effects of phosphorylated insulin-like growth factor-binding protein (pIGFBP-1) and non-phosphorylated (npIGFBP-1) IGFBP-1 on amino acid uptake induced by IGF-I were studied using cultured trophoblast cells. Trophoblast cells obtained from term pregnancy were incubated with indicated concentrations of pIGFBP-1 or npIGFBP-1 for 24 h and further incubated with 10 nM IGF-I for 3 h. Cells were then incubated with 3H-alpha-amino isobutyric acid (3H-AIB) for 30 min. Both pIGFBP-1 and npIGFBP-1 alone had no effect on 3H-AIB uptake; however, pIGFBP-1 inhibited IGF-I-stimulated 3H-AIB uptake with an ED50 of 0.26 nM while npIGFBP-1 potentiated 3H-AIB uptake with an ED50 of 0.27 nM. Maternal IGF-I promotes fetal growth by stimulating nutrient transport in the placenta. As shown in this study, pIGFBP-1 inhibits while npIGFBP-1 stimulates this IGF-I action in the placenta. Thus, it is suggested that IGFBP-1 phosphoisoforms are also involved in fetal growth by modulating IGF-I action in the placenta.

Amino Acids↗

Association of a disease approximating cholera caused by Vibrio cholerae of serogroups other than O1 and O139.

One hundred and six patients suffering from severe dehydrating diarrhoea were studied of whom 36 patients were positive for Vibrio cholerae. Out of 36, 15 were positive for V. cholerae O1, 10 for V. cholerae O139 and 11 for V. cholerae non-O1 non-O139. O1 and O139 were positive for the 301-bp ctxA amplicon and 471-bp tcpA amplicon indicating that the strains possessed toxigenic capability whereas no non-O1 non-O139 strain possessed ctxA or tcpA genes. Post-admission severity of purging and amount of ORS required were less in the V. cholerae non-O1 non-O139 group (P < 0.05) compared to the V. cholerae O1 and O139 groups. It appears from this study that a cholera-like clinical condition can be caused in the absence of CT as exemplified by strains of non-O1 non-O139.

Adolescent↗

Rapid spread of the new clone of Vibrio cholerae O1 biotype El Tor in cholera endemic areas in India.

Using molecular techniques, we investigated whether the clone of Vibrio cholerae O1 biotype El Tor which appeared in Calcutta, India, in 1994 has spread to other cholera endemic areas in the country. The ribotype of 31 of the 33 strains isolated from different parts of India during 1996 and 1997 was identical to the ribotype displayed by the new clone of V. cholerae O1 which emerged in Calcutta in 1994. Likewise, 12 of the 15 strains examined by pulsed-field gel electrophoresis (PFGE) showed identical profile to that exhibited by the new clone of O1. The restriction fragment length polymorphism (RFLP) of CTX genetic element of these strains also matched with the new clone of O1 which emerged after the outbreak of V. cholerae 0139 in Calcutta. However, two strains (AH042 and AH046) isolated from an outbreak in Ahmedabad (western India) showed different CTX RFLP but had the same ribotype and PFGE profile as the new clone, whereas one strain from Goa (G2) showed distinct ribotype and PFGE profile and the CTX RFLP was identical to the O1 strains which prevailed before the genesis of 0139 in Calcutta. The drug resistance pattern of most of the O1 strains examined in this study, except strain G2, was similar to that of the new clone of V. cholerae O1. None of the strains in this study carried plasmids. Molecular studies clearly show that the new expanded drug resistant clone of V. cholerae O1 has spread to all cholera endemic areas in India and also provide evidence for the evolution of new clones of the O1 serogroup.

Cholera↗

Synthesis of (+/-)-cassumunins A and B, new curcuminoid antioxidants having protective activity of the living cell against oxidative damage.

A chemical synthesis of cassumunins A (1) and B (2), natural curcuminoid antioxidants, was developed. The synthesis was started from o-vanillin and after nine reaction steps resulted in 20% and 26% overall yields of 1 and 2, respectively. The synthetic cassumunins showed stronger protective activity than curcumin against oxidative cell death induced by hydrogen peroxide in a rat thymocyte system.

Animals↗

Nuclear magnetic resonance and biosynthetic studies of neoantimycin and structure elucidation of isoneoantimycin, a minor metabolite related to neoantimycin.

In preparation for biosynthetic studies on the 3,4-dihydroxy-2, 6-dimethyl-5-phenylvaleric acid portion of neoantimycin (1), the 1H and 13C NMR signals of 1 were assigned unambiguously by means of 2D correlation spectroscopy and NOE experiments. The previously undetermined absolute stereochemistry at C-15 and C-16 was deduced as (S) and (S). The structure of isoneoantimycin (2) was also elucidated. The methyl groups of methionine and propionate were incorporated stereospecifically into C-13 and C-12 of 1, respectively, and the configuration of the methyl group of methionine is inverted in the process. The results also suggest the intervention of phenylpyruvate as an actual precursor.

Anti-Bacterial Agents↗

TATA sequence requirements for the initiation of transcription for an RNA polymerase II in vitro transcription system from Nicotiana tabacum.

This is the first report to describe the detailed analysis of TATA sequence requirements for the initiation of transcription for RNA polymerase II in a plant in vitro transcription system. We examined the transcriptional activities associated with 24 promoters, including wild-type (TATATATA), and the 21 point and two multiple mutations in tobacco, Drosophila, and HeLa in vitro systems. Although the relative transcriptional activities varied among these promoters, all three systems gave similar results. These results suggest the functional conservation of TATA sequence requirements for in vitro transcription systems among plants, insects, and human.

Animals↗

IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W F1 mice.

In the present study, we examined the preventive effect of anti-mouse IL-6 receptor (IL-6R) antibody, MR16-1, on the development of autoimmune kidney disease in female NZB/W F1 (BWF1) mice. Immunological tolerance to MR16-1 or isotype-matched control antibody, KH-5, was induced by the simultaneous administration of anti-CD4 MoAb in mice. Thereafter, mice were intraperitoneally given 0.5 mg of MR16-1, 0.5 mg of KH-5 or saline once a week from 13 to 64 weeks of age. MR16-1 treatment dramatically suppressed proteinuria and prolonged the survival time of BWF1 mice. Only one out of 10 mice died with high levels of proteinuria throughout the experiment. MR16-1 almost completely suppressed the production of IgG forms of anti-DNA and anti-TNP antibodies, but not the IgM forms of these antibodies. In particular, all IgG subclasses (IgG1, IgG2a, IgG2b and IgG3) of anti-DNA antibody production were significantly suppressed. Moreover, serum IgG1, IgG2a and IgG3 levels in MR16-1-treated mice were lower than those in saline- and KH-5-treated mice, whereas serum IgM and IgA levels were not influenced. In conclusion, MR16-1 potently suppressed the development of autoimmune disease in BWF1 mice, and this was attributed to its effect of specific suppression of IgG class antibody production.

Animals↗

Management of venous thrombosis and pulmonary embolism after gynecological surgery.

We experienced 23 cases of venous thrombosis after gynecological surgery for the past 12 years at Tokyo Women's Medical University Hospital, representing 0.345 % of all patients. Eighteen of the 23 cases had deep venous thrombosis (DVT) including five cases followed by pulmonary embolism (PE), and five cases had PE without any symptoms of DVT. The main risk factors for thrombosis in these 23 patients were (1) obesity, DM, hyperlipidemia; (2) huge abdominal tumor, severe adhesion; and (3) hemoconcentration, post-treatment of severe anemia. The onset of PE varied from 1 to 3 postoperative days, when the patients started to walk. Five cases had dyspnea, chest pain, and decreased PaO2 levels without leg pain, while five cases showed only calf pain and tenderness with decreased PaO2 levels. PE was confirmed by immediate diagnostic images such as RI venography with ventilation and perfusion lung scan, pulmonary arterial CT, or pulmonary arteriography. Two patients died and eight patients recovered. The best way of managing venous thrombosis might be as follows: (1) identify the risk factors of thrombosis before surgery; (2) perform prophylactic leg exercises in bed and/or active anticoagulant therapy depending on the degree of risk factors; (3) rapid diagnosis with the images; and (4) proper treatment.

Adult↗

Effect of follicle stimulating hormone and insulin-like growth factors on proteolysis of insulin-like growth factor binding protein-4 in human granulosa cells.

Follicular fluid from dominant follicles, but not atretic follicles, contains insulin-like growth factor binding protein-4 (IGFBP-4) proteolytic activity. The effect of follicle stimulating hormone (FSH) and insulin-like growth factors (IGFs) on IGFBP-4 proteolytic activity was studied using granulosa cell cultures. Proteolytic activity was assessed by the incubation of [1251]-IGFBP-4 with medium and cleaved products which were analysed by autoradiography. The iodinated IGFBP-4 was cleaved into an 18 kDa fragment when cells were incubated with FSH or IGFs while IGFBP-4 remained intact in the control culture. Inhibition of IGFBP-4 degradation by several protease inhibitors suggests that IGFBP-4 degradation was induced by a metalloserine protease. The degradation of IGFBP-4 was not stimulated when cells were incubated with the IGF-I analogue, LR3-IGF-I, and insulin which binds to IGF-I receptor but has little or no affinity for IGFBPs. Addition of IGFs, but not FSH, to medium from untreated granulosa cell cultures stimulated proteolysis of [1251]-IGFBP-4. Similarly, exogenously added covalently cross-linked [125I]-IGF-II-IGFBP-4 complexes were proteolyzed; however, IGFs did not enhance the degradation of these complexes. These results suggest that human granulosa cells produce IGFBP-4 protease and that the increased susceptibility of IGFBP-4 to proteolysis is induced by the binding of IGFs to IGFBP-4. These novel mechanisms may be important in modulating IGF-mediated folliculogenesis in the ovary.

Autoradiography↗