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Biomedical subjects

I Takeuchi

Publications and source records attributed to I Takeuchi.

At least 37 records · Page 2Linked to original sources

Studies on the reaction of benzo[x]quinoline N-oxides (X = f, h, and g) with methylsulfinyl carbanion using the semi-empirical molecular orbital method. Liberation of the N-oxide group.

The mechanism of the liberation reaction of the N-oxide group has been studied and compared with the methylation reaction using a semi-empirical molecular orbital PM3 method. By comparing the calculated values of Gibbs free energy of activation, we can determine whether a liberation reaction or methylation reaction occurs.

Cyclic N-Oxides↗

Studies on the 1,4-oxazepine ring formation reaction using the molecular orbital method.

1,4-Oxazepine formation reactions of 1,8-naphthyridine derivatives (1-4) with peroxy acid have been studied using a semiempirical MO method (AM1) and an ab initio molecular orbital method (Gaussian 94). The energies of molecules involved in the reaction paths were calculated and the transition states related to experimental products were obtained. For the reactions of 1-3, the calculated energies of the transition states predicted the previously obtained products. However, the calculated values for the reaction of 4 suggested a different type of oxazepine compound, which was verified in further experiments.

Chemical Phenomena↗

[Studies on the syntheses and reaction of nitrogen-containing heterocyclic compounds centered the naphthyridines].

1, X-Naphthyridines (X = 5, 6, and 8) (1-3) were synthesized in a high yield by the Skraup reactions of 4-, 3-, and 2-aminopyridines with glycerol, in the presence of ferrous sulfate and boric acid. The improved syntheses were applied to the syntheses of 1,5-, 1,6-, and 1,8-naphthyridines (4-28), pyridonaphthyridines (31, 32), benzonaphthyridines (38-42), naphthonaphthyridines (44, 48, 49, 59). New synthetic methods of naphtho[1,2-b or 2,1-b][1,8]naphthyridine (62, 63), benzo[b][1,8]naphthyridine (41) and benzo[g]quinoline (67) were developed and their compounds obtained conveniently. Reissert reaction of 1,6-naphthyridine (2) using triethylbenzylammonium chloride (TEBA) produced Reissert compounds and ring-opened compounds. Reissert reaction of 1,7-naphthyridine (29), 4,7- (87), 4,6-phenanthroline (38) gave the Reissert compounds, and the compounds (2, 38) gave their pseudo bases (79, 90). Reissert-type reactions of benzo[f]quinoline (68), and 1,7-phenanthroline (105) with acyl chloride and phosphite, gave alpha- and gamma-phosphonate, and 87 produced alpha,alpha'-(108a-c) and alpha,gamma'-diphosphonates (109a-c). The structure of 108c-1 was determined to be trans-type by an X-ray analysis. Compounds 1-3, 29, and benzo[f or h]quinoline were treated with dimetyl sulfoxide in the presence of sodium hydride to give mainly methylated compounds at the position para to the ring-nitrogen. When benzo[f or h]quinoline N-oxide was treated with methylsulfinylmethyl carbanion in the usual procedure, a new reaction took place to produce phenanthrene in an excellent yield. The same reaction of 1,10-, 1,7-, or 4,7-phenanthroline N-oxides (143-145) resulted in the liberation of the N-oxide group to form benzo[f or h]quinoline, but isoquinoline N-oxide afforded to benzazepine derivatives (161). Reaction of quinaldine with methylsulfinylmethyl carbanion gave novel tricyclic compound (121a). The oxidation of 41, 62, and 63 with peroxy acids afforded novel products such as seven-membered 1,4-oxazepine derivatives.

Chemistry, Organic↗

[A case of diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa effectively treated with sequential MTX.5-FU and 5'-DFUR].

A 37-year-old man was diagnosed as having a diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa. Sequential methotrexate (MTX).5-fluorouracil (5-FU) therapy with oral administration of doxifluoridine (5'-DFUR) was started. After 9 cycles of the MTX.5-FU therapy (total dose: MTX = 900 mg/body, 5-FU = 7,500 mg/body), radiographic examinations showed a partial response in the primary and pulmonary lesion, and paraaortic lymph nodes. Histological evaluation of the resected specimen by Hartmann's operation showed a grade 2 effect in the primary lesion and metastatic lymph nodes. This chemotherapy was repeated postoperatively. The patient died of pulmonary disease, deteriorating rapidly 60 days postoperatively. Diffusely infiltrating carcinoma of the large-bowel is generally far advanced at the time of diagnosis. The results suggest that sequential MTX.5-FU therapy and oral administration of 5'-DFUR are worth performing in clinical trials for patients with diffusely infiltrating carcinoma of the large-bowel.

Adenocarcinoma↗

[Combination chemotherapy with irinotecan hydrochloride plus carboplatin for patients with advanced or recurrent colorectal cancer--a pilot study].

A pilot study was performed to evaluate the feasibility and efficacy of irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks followed by a one-week rest. This treatment was repeated until disease progression or severe toxic effects were found. The total dose of CPT-11 ranged from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022 (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%) diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%), thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7; PD,5). The median survival time of all patients was 405 days from the start of chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to be longer than that of those with PD (n = 5) (p = 0.06). The median time to disease progression was 105 days. These results suggest that this combination chemotherapy is feasible and effective in the treatment of advanced or recurrent colorectal cancer.

Adult↗

[Clinical significance of determinations of dihydropyrimidine dehydrogenase levels in primary and hepatic lesions of colorectal cancer patients].

Dihydropyrimidine dehydrogenase (DPD) levels were determined by enzyme-linked immunosorbent assay in primary tumors and adjacent normal mucosa from 114 colorectal cancer patients, including 9 with synchronous liver metastases. The level of intratumoral DPD was 55.0 +/- 38.7 unit/mg protein (n = 114) and that of mucosal DPD was 55.0 +/- 38.7 unit/mg protein (n = 114). The ratio of intratumoral DPD to mucosal DPD was 1.8 +/- 0.8 in patients developing metachronous liver metastases (n = 7), 1.0 +/- 0.5 in patients without recurrence (n = 61), and 1.0 +/- 1.1 in patients with synchronous liver metastases (n = 31) (p = 0.01, metachronous liver metastasis group versus recurrence-free and synchronous liver metastasis groups). The levels of DPD were higher in primary lesions than in synchronous liver metastasis (n = 9, p < 0.05). These results indicate that: (1) degradation of 5-fluorouracil (5-FU) is enhanced in hepatic lesions more than in primary lesions, which is consistent with previous findings showing the therapeutic advantage of hepatic arterial infusion over intravenous infusion in relation to the treatment of 5-FU for liver metastases of colorectal cancer patients; and (2) predicting the effectiveness of hepatic arterial infusion of 5-FU for patients with metachronous liver metastases is difficult based on DPD determination of primary lesions alone.

Colorectal Neoplasms↗

[Hepatic arterial injection of degradable starch microspheres (DSM) combined with adriamycin (ADM) and mitomycin C (MMC) in patients with liver metastasis of colorectal cancer].

We evaluated the adverse effects, response rates, and changes in CEA-doubling time before and during DSM.ADM.MMC therapy (DSM therapy) in 8 patients with liver metastases of colorectal cancer. In principle, 600 mg/body DSM, 30 mg/body ADM, and 10 mg/body MMC were injected into the hepatic artery, and this treatment was repeated as often as possible. A total of 26 injections revealed no severe adverse effects. In 5 patients who received 3 or more injections of DSM, the response rate was 20% (partial response, one) and an improvement of CEA-doubling time was confirmed in 3 patients (60%). Two patients who demonstrated the shortening of CEA-doubling time after this therapy had shorter survival. It is suggested that to compare CEA-doubling times before and during DSM therapy is useful for selecting candidates for this treatment.

Aged↗

Distribution and specific bioaccumulation of butyltin compounds in a marine ecosystem

Butyltin compounds (BTs), including tributyltin (TBT) and its breakdown products, di- (DBT) and monobutyltin (MBT), were determined in sea water, sediment, and biota at various trophic levels in the food chain collected from Otsuchi Bay, Japan, for understanding distribution and bioaccumulation of BTs in natural marine ecosystems. BT residues were detected in all the compartments analyzed, although their concentrations appeared to be less than those in polluted areas. Concentrations of BTs in sea water were higher in locations near Otsuchi Port, indicating that maritime activities in the harbor has been a major source of BTs in this bay. A specific peak in BT residue levels was found in sediment cores at an estimated depth that dated to be from the 1980s. Lack of significant variation in the composition of BTs at different depths of cores suggests slow degradation rate of these compounds in sediments. BTs were accumulated in plankton and other organisms up to approximately 70,000 times higher than in sea water. However, no considerable biomagnification was observed for BTs through the food chain. Relatively high concentrations were found in caprellids and smaller fish, such as gunnels. These organisms accumulated TBT as the predominant compound among BT derivatives and showed higher bioconcentration factors for TBT than in other species reported so far. Our results suggest that certain organisms in the food chain may have a less capacity to degrade TBT, and therefore may accumulate BTs at elevated levels.http://link.springer-ny. com/link/service/journals/00244/bibs/37n1p50.html

Journal Article↗

[Clinical trial of prophylactic hepatic arterial chemotherapy for liver metastases in patients with Dukes' C colorectal cancer].

Preliminary results of a prospective non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from colorectal cancer are presented. Twenty-two colorectal cancer patients (infusion group) in Dukes' C stage were given hepatic arterial infusion of 5-FU (500 mg/body for 1 hr per week, repeated 50 times) and peroral UFT-E (2.0 g/body, daily). Informed consent was obtained from all patients. Adverse effects and postoperative recurrence in the infusion group were compared with those of patients with UFT-E alone (control group). Complications related to hepatic arterial infusion in the infusion group were also demonstrated. There was no adverse effect in the control group, while diarrhea (grade 1) developed in one patient (5%) and pigmentation in five (24%) in the infusion group. Complications related to infusion were found in five patients (5%). Three patients in the infusion group presented with metachronous hepatic lesions, two of which were resected successfully. In the control group, one patient died of marked hepatic metastases, and one developed ovarian metastasis with lymph node involvement. Our regimen appears hematologically safe, however, the high frequency of pigmentation should be kept in mind. The oncological benefit of this chemotherapy would be clarified by a larger series of cases and longer follow-up.

Administration, Oral↗

[A case of liver metastases of rectal carcinoid successfully treated with hepatic arterial infusion of methotrexate and 5-fluorouracil].

Standard therapy for liver metastasis from colorectal carcinoid remains controversial because of the rarity of the disease. We report herein a case of rectal carcinoid with multiple liver metastasis successfully treated with hepatic arterial infusion of methotrexate (MTX) and 5-fluorouracil (5-FU). A 65-year-old woman underwent posterior pelvic exenteration and hepatic arterial catheterization for rectal carcinoid involving the vagina associated with multiple liver metastases. Hepatic arterial infusion of MTX (50 mg/body) and 5-FU (500 mg/body) was started and repeated with a frequency of twice a week postoperatively. After 40 cycles of this chemotherapy, all but the largest metastatic lesion disappeared, and the largest decreased in size by 53%. The partial response was maintained for 7 months. Her performance status did not deteriorate throughout the period of the chemotherapy. These results suggest that hepatic arterial MTX/5-FU is safe and worth trying in patients with liver metastases from colorectal carcinoid.

Aged↗

The Dictyostelium developmental cDNA project: generation and analysis of expressed sequence tags from the first-finger stage of development.

In an effort to identify and characterize genes expressed during multicellular development ill Dictyostelium, we have undertaken a cDNA sequencing project. Using size-fractionated subsets of cDNA from the first finger stage, two sets of gridded libraries were constructed for cDNA sequencing. One, library S, consisting of 9984 clones, carries relatively short inserts, and the other, library L, which consists of 8448 clones, has longer inserts. We sequenced all the selected clones in library S from their 3'-ends, and this generated 3093 non-redundant, expressed sequence tags (ESTs). Among them, 246 ESTs hit known Dictyostelium genes and 910 showed significant similarity to genes of Dictyostelium and other organisms. For library L, 1132 clones were randomly sequenced and 471 non-redundant ESTs were obtained. In combination, the ESTs from the two libraries represent approximately 40% of genes expressed in late development, assuming that the non-redundant ESTs correspond to independent genes. They will provide a useful resource for investigating the genetic networks that regulate multicellular development of this organism.

Animals↗

Identification of a blue photoluminescent composite material from a combinatorial library

A quaternary combinatorial masking strategy was used in conjunction with photolithography to generate compositionally diverse thin-film phosphor libraries containing 1024 different compositions on substrates 2.5 centimeters square. A parallel imaging system and scanning spectrophotometer were used to identify and characterize compositions in the library with interesting luminescent behavior. Optimal compositions were identified with the use of gradient libraries, in which the stoichiometry of a material was varied continuously. This process led to the identification of an efficient blue photoluminescent composite material, Gd3Ga5O12/SiO2. Experimental evidence suggests that luminescence in this material may arise from interfacial effects between SiO2 and Gd3Ga5O12.

Journal Article↗

Experience with kidney transplantation in children and adolescents.

BACKGROUND: Paediatric kidney transplantation has different aspects in adults in terms of underlying primary renal disease, surgical technique, perioperative care and graft prognosis. Significant urological problems are present in a high percentage of paediatric recipients. This study was undertaken to characterize paediatric kidney transplantation as performed at our institutes. METHODS: Twenty-eight patients (age range 4-17 years, 10 girls, 18 boys) were included in this study. We analyzed (1) urologic procedures performed prior to or simultaneously with transplantation, (2) intraoperative changes in haemodynamics, (3) postoperative complications and (4) acute allograft rejection and graft prognosis. RESULTS: Of 4 patients with lower urinary tract abnormalities (neurogenic bladder in 3, posterior urethral valve in 1), 2 underwent augmentation ileocystoplasty prior to transplantation. The Mitrofanoff procedure as a diversion for neourethra was also performed in 2 of the 4 patients. All these 4 patients were managed with clean intermittent catheterization. Central venous pressure changes before and after graft vessel declamping were much greater in patients with body weight below 25 kg than in those above 25 kg. Five surgical complications and 6 infections were encountered postoperatively and hypertension was lasting in 6. Thirteen patients experienced 19 periods of acute allograft rejection. All of the 24 patients in the cyclosporin era (1986-) overcame rejections and they are all alive with good graft function. CONCLUSIONS: As long as proper pretransplant patient evaluation and management, and intensive perioperative care are undertaken, good prognosis of renal allograft can be achieved in young patients.

Adolescent↗

Rapid patterning of Dictyostelium discoideum cells under confined geometry and its relation to differentiation.

The following was recently reported by Bonner et al. (1995): (1) Rapid differentiation occurred into two zones in Dictyostelium discoideum cells confined in a fine glass capillary. The cells in the anterior zone exposed to the air appear similar to prestalk cells, while the posterior zone isolated from the air mimics prespore cells. (2) The volumes of the two zones are proportional to each other for different sized cell masses, and the proportion is the same as that in normal migrating slugs. We investigated the nature of this newly discovered rapid differentiation in a slightly modified geometry. Exponentially growing cells were harvested, washed to remove external nutrients, and pelleted by centrifugation. Subsequently, a small drop of the pelleted (starved) cells was placed on a slide glass and then confined in a two-dimensional space between the slide glass and a coverslip, with help of spacers whose thickness varied from 25 to 100 microm. As a result, a dark zone, which looked optically different, emerged within several minutes in the periphery of the disc of the confined cells, corresponding to the zonation in a capillary as previously reported. When the width of the peripheral zone was measured for more than 30 samples of different diameters for each thickness of the spacers, the width was found to be always about 100 microm, irrespective of the size difference of the cell mass placed. This seems to be contradictory to the previous observation made by Bonner et al. (1995). We also examined oxygen concentration dependence on the zone width. The zone width was found to be independent of the oxygen concentration at low concentrations, but increased rapidly at high concentrations. A reaction-diffusion mechanism for formation of the zone and possible involvement of atmospheric oxygen (O2) in the initial steps of cell differentiation and pattern formation is discussed.

Animals↗

Kidney transplantation in patients with neurovesical dysfunction.

BACKGROUND: Five renal recipients with neurovesical dysfunction (NVD) were retrospectively reviewed focusing on anatomical and urodynamic abnormalities of the lower urinary tract and their management prior to kidney transplantation. METHODS: The underlying anomalies in these 5 patients were a posterior urethral valve (1 with an imperforate anus; n = 2), meningomyelocele (n = 2) and a congenital short urethra with an imperforate anus (n = 1). Their urinary tracts were evaluated prior to transplantation with voiding cystourethrography, urethrocystoscopy, cystometrography and electromyography of the external urethral sphincter to identify a possible focus of urinary tract infection, urine storage and voiding function. RESULTS: All 5 patients had NVD proven by urodynamic studies or by documentation of urinary retention in the absence of mechanical outlet obstruction. Bilateral high grade vesicoureteral reflux was noted in all patients, requiring ureteroneocystostomy. Clean intermittent catheterization (CIC) was ultimately employed for bladder emptying in all patients. Two patients with poor bladder compliance underwent augmentation cystoplasty before transplantation. The Mitrofanoff procedure was used in 2 patients with structural urethral abnormalities to access the bladder for catheterization. After eradication of possible sources of infection and establishment of a low-pressure urine storage system with bladder emptying by CIC, kidney transplantation was performed. Following kidney transplantation, all of the recipients were asymptomatic for urinary tract infections using CIC. Although 1 patient lost his graft due to chronic rejection, the other 4 other patients have good renal function. CONCLUSION: Kidney transplantation in patients with NVD can be performed provided that their urinary tract problems are properly resolved.

Adolescent↗