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Biomedical subjects

H Yabuki

Publications and source records attributed to H Yabuki.

17 recordsLinked to original sources

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: report of a case.

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutanenous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.

Carcinoma, Squamous Cell↗

Preparation of red blood cells containing exogenous hemoglobin.

A technique is described for opening the membrane of a red blood cell by electroporation in a manner which permits free exchange of the native hemoglobin with exogenous hemoglobin in the surrounding medium. After resealing the RBC's demonstrate near normal size and hemoglobin content and retain an effective methemoglobin reduction system. This method can be used to introduce natural or genetically engineered hemoglobins with altered oxygen binding characteristics. Allosteric effectors and other non-diffusible small molecules can be encapsulated during the same procedure. A fish Root effect hemoglobin exchanged into rat RBC's produced oxygen transport characteristics, unloading at high pressure at acidic pH, which should be useful to treat tissue hypoxia from a variety of causes.

Animals↗

Preparation of needle-like hydroxyapatite by homogeneous precipitation under hydrothermal conditions.

Preparation of hydroxyapatite was carried out by a homogeneous precipitation technique using hydrothermal reactions of Ca(EDTA)2- and PO4(3-) at 130-250 degrees C and pH 4-10. Hydroxyapatite and monetite were formed above pH 6 and below pH 4, respectively. Needle-like hydroxyapatite was formed at high temperatures above 130 degrees C. The length of the needle-like hydroxyapatite crystal increased with increasing working solution pH and temperature.

Calcium↗

Effects of hyperbaric oxygen and a perfluorooctylbromide emulsion on the radiation responses of tumors and normal tissues in rodents.

Perfluorochemical emulsions are being examined in many laboratory and clinical studies as possible adjuncts to radiotherapy and chemotherapy. The studies reported here examine the clinical potential of hyperbaric oxygen (HBO) in combination with a highly concentrated perfluorochemical emulsion (Oxygent) containing 100% w/v perfluorooctylbromide (PFOB). HBO alone produced only a small improvement in the radiation response of BA1112 tumors in WAG/rij rats, while regimens combining HBO with Oxygent produced much greater radiation sensitization. A sham emulsion, formulated without the O2-carrying PFOB, did not alter the radiation response of the tumors in comparison with that seen with HBO alone. Neither HBO nor Oxygent plus HBO altered the radiosensitivity of bone marrow progenitor cells in BALB/c mice. HBO alone augmented skin reactions in BALB/c mice, but addition of Oxygent did not alter the skin reactions in comparison to those seen with HBO alone. Regimens combining Oxygent with HBO selectively increased the radiation sensitivity of tumors relative to normal tissues, thereby enhancing the therapeutic ratio. These results support the potential usefulness of perfluorochemical emulsions and HBO in clinical radiation therapy.

Animals↗

Preclinical evaluation of Oxygent as an adjunct to radiotherapy.

These studies examine the potential value of a concentrated emulsion of perfluorooctylbromide (perflubron; Oxygent, Alliance Pharmaceutical Corp.) as an adjunct to radiotherapy. The effects of Oxygent on solid tumors were examined using EMT6 mammary tumors in BALB/c mice and BA1112 rhabdomyosarcomas in WAG/rij rats. Treatment with Oxygent plus O2, carbogen (95% O2/5% CO2), or hyperbaric oxygen (HBO) increased the effects of radiation on the tumors. Analyses of tumor cell survival curves and measurements of intratumor pO2 showed that this potentiation reflected an increase in the proportion of well-oxygenated tumor cells. Neither treatment of the animals with carbogen, O2, or HBO alone nor treatment of air-breathing rodents with Oxygent produced changes of similar magnitude. Treatment with a vehicle emulsion containing all the components of Oxygent except the perflubron did not alter tumor radiosensitivity, showing that tumor radiosensitization required the oxygen-transporting perfluorocarbon, and did not result from any biologic or physiologic effects of other components of the emulsion. These studies also examined the effects of Oxygent on the radiation responses of mouse skin and bone marrow. Oxygent selectively increased the radiation sensitivity of tumors relative to these normal tissues, thereby increasing the therapeutic ratio and producing therapeutic gain. Oxygent appears to warrant further testing as an adjunct to cancer therapy.

Animals↗

[A case of small cell undifferentiated carcinoma (SCUC) of the rectum treated with etoposide, cis-platinum and radiotherapy].

A 29-year-old-woman with recurrent cancer of rectum was treated with Etoposide, cis-platinum and external irradiation. Previous postoperative chemotherapies consisted of MMC, CPA, VCR and HCFU. Histologically, the tumor invaded in sheets and nests, and consisted of round to ovoid malignant cells with high nuclear/cytoplasmic and hyperchromatic nuclei with a coarse, clumped, or stippled chromatin pattern. Most cells demonstrated a positive reaction by Grimelius and NSE staining. Eight months after surgery, we switched to Etoposide cis-platinum and external irradiation, because of local recurrence. Etoposide (total 725 mg) and cis-platinum (total 100 mg) were injected into bilateral iliac artery and 60 Gy radiotherapy was performed. The patient showed a good response, and a complete response (CR) was evident for the following 42 months. Thus, Etoposide, Cis-platinum and radiotherapy are considered an effective combination therapy for a patient with small cell undifferentiated carcinoma.

Adult↗

Modulation of tumor oxygenation and radiosensitivity by a perfluorooctylbromide emulsion.

The effect of a concentrated perfluorooctylbromide emulsion (Oxygent) on the radiosensitivity and oxygenation of solid tumors was examined using EMT6 mammary tumors in BALB/c mice and BA1112 rhabdomyosarcomas in WAG/rij rats. Treatment with Oxygent plus carbogen or oxygen breathing increased the radiosensitivity of both tumors. Analysis of tumor cell survival data and polarographic measurements of intratumoral pO2 indicated that this potentiation reflected an increase in the proportion of well-oxygenated tumor cells. Treatments with carbogen breathing alone, with Oxygent plus air-breathing, or with a vehicle emulsion containing all the components except the perfluorocarbon did not produce comparable improvements in tumor radiosensitivity. Concentrated perfluorooctylbromide emulsions appear to warrant further development and preclinical testing as adjuncts to cancer therapy.

Animals↗

A method for determination of iododeoxyuridine substitution of thymidine using reversed-phase high-performance liquid chromatography.

An assay for thymidine substitution by iododeoxyuridine (IdUrd) using reversed-phase high-performance liquid chromatography (HPLC) has been developed. Three principal steps in this procedure are: extraction of DNA from cell or tissues, hydrolysis of DNA into deoxynucleosides and separation using HPLC. Approximately 1 microgram of DNA was recovered from 10(5) cells by phenol extraction, and subjected to hydrolysis into deoxynucleosides which required a three-stage DNA digestion using enzymes DNAse I. phosphodiesterase I and alkaline phosphatase. The deoxynucleosides were separated on the Microsorb C18 column with isocratic elution; 90-100% of the DNA was recovered as deoxynucleosides on the column. The method was used to determine quantitatively the percent IdUrd substitution of thymidine in Chinese hamster lung cells in vitro and BA1112 rhabdomyosarcoma in WAG/Rij rats perfused with IdUrd. It was possible to determine the thymidine substitution by IdUrd as small as 1% using a few micrograms of DNA. The close correspondence between the percent substitutions determined by HPLC and those determined by radioactive assay using [125I]-labelled IdUrd, confirmed the accuracy of our HPLC method. The HPLC analysis is especially suitable for the determination of percent IdUrd substitution of thymidine in tissue biopsies from animals used in in vivo experiments or humans undergoing radiation treatment.

Animals↗

Effects of a perfluorochemical emulsion on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation.

The effects of the combination of a perfluorochemical emulsion (Fluosol DA, 20%) and carbogen (95% O2, 5% CO2) on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation were examined. Tumors were irradiated locally in unrestrained, unanesthetized rats at a dose rate of 0.98 Gy/h, using a specially designed 241Am irradiator system. Cell survival was measured using a colony formation assay. The tumor cell survival curves were fitted to linear relationships of the form ln S = - alpha D, where alpha for air-breathing rats was 0.104 +/- 0.005 Gy-1, as compared to 0.137 +/- 0.009 Gy-1 for rats treated with Fluosol plus carbogen. The increase in the slope of the survival curve produced by the treatment with Fluosol and carbogen was highly significant with a P value of 0.0015. The radiosensitization factor for the combination of Fluosol/carbogen plus continuous low-dose-rate irradiation was 1.32 +/- 0.11. Slightly less radiosensitization was observed with continuous low-dose-rate irradiation than in previous experiments using acute high-dose-rate irradiation. The diminished sensitization with Fluosol/carbogen during continuous low-dose-rate irradiation probably reflects the intrinsically lower oxygen enhancement ratio (OER) of low-dose/low-dose-rate irradiation, reoxygenation of the tumors during the prolonged treatment times used for continuous low-dose-rate irradiation, and the decrease in the levels of circulating perfluorochemicals during the 30-h irradiations. More importantly, the significant level of radiosensitization observed in the experiments with continuous low-dose-rate irradiation suggests that hypoxic cells persist in BA1112 tumors during continuous low-dose-rate irradiations and that the response of these tumors to continuous low-dose-rate irradiation can be improved by adjunctive treatments which oxygenate these radioresistant hypoxic tumor cells.

Americium↗

Relative biological effectiveness of 241Am relative to 192Ir for continuous low-dose-rate irradiation of BA1112 rat sarcomas.

Sealed sources of 241Am have been developed for intracavitary irradiation of gynecological cancers. Relative to conventional isotopes (that is, 226Ra, 137Cs, 192Ir), 241Am allows for better shielding of dose-limiting normal tissues in the patient. In addition, the long half-life of 241Am (432 years) makes it an attractive isotope both for clinical use and for long-term radiobiology studies. Using a previously developed in vivo applicator system, BA1112 sarcomas on WAG/Rij Y rats were irradiated using 241Am or 192Ir at three different dose rates. Following in vivo treatment of the sarcomas with graded doses of radiation, cell survival curves were determined using an in vitro colony formation assay. The slopes of the resulting cell survival curves were observed to increase significantly as the dose rate increased from 0.30 to 0.60 Gy/h, then to decrease slightly as the dose rate increased from 0.60 to 0.95 Gy/h. The relative biological effectiveness (RBE) of 241Am relative to 192Ir was observed to increase linearly with increasing dose rate; the RBEs were 0.96 +/- 0.009, 1.09 +/- 0.12, and 1.17 +/- 0.11 at dose rates of 0.30, 0.60, and 0.95 Gy/h, respectively.

Americium↗

16 Alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol: a radiochemical probe for estrogen-sensitive tissues.

We have synthesized an analog of 16 alpha-iodoestradiol, 11 beta-methoxy-16 alpha-iodo-estra-1,3,5-(10)triene-3,17 beta-diol (16 alpha-iodo-11 beta-methoxyestradiol), as a potential radiopharmaceutical for the in vivo imaging of estrogen-sensitive tissues. This steroid was synthesized labeled with 125I by halogen exchange of the stable intermediate 11 beta-methoxy-16 beta-bromo-17 beta-estradiol with Na125I. The halogen exchange reaction produces the radioiodinated steroid with a 65-80% yield in 3 h. This rapid synthesis and purification of the 125I-labeled estrogen permits a similar synthesis with 123I, a radioisotope with excellent properties for imaging. The 11-methoxy analog is a highly potent estrogen that binds to the estrogen receptor with an affinity equal to that of estradiol. In vivo, 11 beta-methoxy-16 alpha-[125I]iodoestradiol concentrates in an estrogen receptor-dependent manner in the uterus, producing remarkably sustained and much higher uterus to blood ratios than 16 alpha-[125I]iodoestradiol. Thus, this radiosteroid shows great promise, both as a research probe of the estrogen receptor and as a clinical tool for the imaging of estrogen-responsive tumors.

Animals↗

Orientation of nucleosomes in the thirty-nanometer chromatin fiber.

We have measured the linear dichroism of Mg2+-stabilized and dimethylsuberimidate cross-linked 30-nm chromatin fibers, using electric fields to produce orientation. The limiting dichroism of Mg2+-stabilized fibers at low monovalent ion concentration is -0.09, with indistinguishable results for avian erythrocyte and calf thymus chromatin. Correction of the apparent dichroism signal for an absorbance change that becomes significant at high electric field yields the dichroism of -0.09 and reveals that the fibers reach saturation of their orientation by about 15 kV/cm. Calf thymus chromatin fibers cross-linked at 100 mM NaCl concentration have a dichroism of +0.05, with a dependence of orientation on field similar to that observed for Mg2+-stabilized fibers. Comparative sedimentation studies of Mg2+-stabilized fibers and fibers in 100 mM cross-linking buffer revealed a 25% sedimentation coefficient increase accompanying the dichroism increase from -0.09 to +0.05. We interpret the results to mean that the nucleosomal disk diameters form an angle of about 30 degrees to the chromatin fiber axis in Mg2+-stabilized fibers at low monovalent ion concentration. When 100 mM NaCl is added, the fiber becomes more compact, and the disk diameter angles increase by 8 degrees, to about 38 degrees. Cross-linking itself may also contribute slightly to fiber compaction. The results are consistent with a large longitudinal compressibility of the 30-nm fiber, a feature required for the bendability necessary when the fiber is further coiled to form structures such as chromosomes. Our results indicate that compression is accommodated by small changes in the angular orientation of the nucleosomal disks.

Animals↗

Isolation of nonhistone-protein-rich chromatin fragments differing in composition and recovery between transcriptionally active and inactive sources.

Soluble chromatin was fragmented by deoxyribonuclease I[EC 3.1.4.5] or II[EC 3.1.4.6] digestion or sonication, followed by 0.7 m NaCl treatment, which preferentially removed DNA fragments and histones from the fragmented chromatin, but not from intact chromatin, leaving an insoluble fraction of DNA-histone-nonhistone protein complex without appreciable redistribution of the chromatin components. Fragmentation of DNA and concentration of nonhistone proteins in the fraction were most effective with deoxyribonuclease I under the conditions used. Thus, only 1% of the DNA in transcriptionally inactive chicken erythrocyte chromatin was recovered, together with 2% of the total histone and 50-100% of the total nonhistone protein. Separate experiments showed that this DNA fraction was among the double-stranded segments having in average size of 210 base pairs and was associated with histone components responsible for the nucleosome conformation as well as most of the nonhistone protein components in the original chromatin. From transcriptionally active chicken liver or calf thymus chromatin, however, 5-10% of the total DNA, 20-40% of the histone, and 80-100% of the nonhistone protein were recovered in the corresponding fraction. These results may reflect the native states and template activities in situ of various chromatins.

Animals↗