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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 199 records · Page 11Linked to original sources
PubMed1999

Study on the distribution of radioactive trace elements in vitamin D-overloaded rats using the multitracer technique.

The uptake and distribution of radioisotopes of beryllium, calcium, scandium, vanadium, chromium, manganese, iron, cobalt, nickel, zinc, gallium, arsenic, strontium and barium in vitamin D (VD)-overloaded rats were investigated and compared with those in control rats, using the multitracer technique. Each element revealed its characteristic distribution among various organs in control and VD-overloaded rats. For some elements, such as cobalt and chromium, the distribution patterns in them were significantly different. These results are discussed in terms of the metabolism of the elements in rats.

Acid Phosphatase↗
PubMed1999

Labeling of phosphorothioate antisense oligonucleotides with yttrium-90.

Novel yttrium-90 (90Y)-labeled phosphorothioate antisense oligonucleotides were designed as a potential targeted radionuclide therapeutic agent for malignant tumors. A 15-mer phosphorothioate antisense oligonucleotide, which was complementary to the translation start region of the N-myc oncogene mRNA, was conjugated with isothiocyanobenzyl ethylenediamine tetraacetic acid (SCN-Bn-EDTA), via a C-5-substituted deoxyuridine that had replaced a thymine in the oligonucleotide, and was then labeled with 90Y-acetate. Following purification, the radiochemical purity of the 90-Y-Bn-EDTA-phosphorothioate antisense oligonucleotides was estimated by 2.0% agarose gel electrophoresis, and the specific hybridization of 90Y-Bn-EDTA-phosphorothioate antisense oligonucleotide to a phosphorodiester sense oligonucleotide was investigated by 20% polyacrylamide gel electrophoresis in a cell-free system. Radiochemical purity was 98.7 +/- 0.4% at 72 h after labeling and 90.3 +/- 0.9% after 72-h incubation with human normal serum. The 90Y-Bn-EDTA-phosphorothioate antisense oligonucleotide hybridized specifically to a complementary phosphorodiester sense oligonucleotide. In conclusion, phosphorothioate antisense oligonucleotides can be labeled stably with 90Y using SCN-Bn-EDTA without loss of hybridization properties.

Blood Physiological Phenomena↗
PubMed1999

Localization of indium-111 in human malignant tumor xenografts and control by chelators.

The kinetics of soluble indium-111 ((111)In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of (111)In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. (111)In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of (111)In-chloride. Secondly, the effect of edetate calcium disodium (CaNa2EDTA) on radioactivity in (111)In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa2EDTA significantly reduced (111)In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa2EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with (111)In-chloride was investigated. In one group of mice CaNa2EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of (111)In-chloride (postadministration), the localization of (111)In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa2EDTA administered intraperitoneally at 12 and 1 h before injection of (111)In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa3DTPA had a more powerful effect than CaNa2EDTA. In conclusion, (111)In-activity in tumors consists of intracellular and extracellular components, and the extracellular (111)In may be cleared by chelators. Pre- and postadministration of CaNa3DTPA could remove (111)In-nonspecific localization in tumors when (111)In is released from the radiolabeled agents.

Animals↗
PubMed1999

Yttrium-90-labeled human macroaggregated albumin for internal radiotherapy: combined use with DTPA.

The aim of this study was to investigate the possibility of yttrium-90-labeled human macroaggregated albumin (90Y-MAA) as an internal radiotherapeutic agent for whole-lung irradiation in combination with diethylenetriamine pentaacetic acid (DTPA). The influence of trisodium calcium DTPA (CaNa3DTPA) on the radioactivity of 90Y-MAA in serum was investigated in vitro. The effect of CaNa3DTPA on the biodistribution of radioactivity in normal mice intraveneously injected with 90Y-MAA was examined. CaNa3DTPA could deprive in vitro radioactivity of 90Y-MAA in 48-h incubation. Most of the radioactivity (>90% injected dose per lung) was observed at murine lung after injection of 90Y-MAA. Pulmonary radioactivity was cleared within 72 h postinjection, whereas the radioactivities in the bone, liver, kidneys, and spleen increased with a peak at 48 h. CaNa3DTPA-treatment reduced the in vivo radioactivities in bone, liver, and kidneys without influence on the radioactivity of lung. In conclusion, combined use of CaNa3DTPA enables 90Y-MAA to be used as a radiopharmaceutical for internal irradiation against whole lung.

Albumins↗
PubMed1999

The portal component of hepatic perfusion measured by dynamic CT: an indicator of hepatic parenchymal damage.

CT can measure absolute hepatic arterial and portal venous perfusion; pilot data suggests these are raised and lowered, respectively, in cirrhosis. This study examined the value of functional CT in assessing cirrhosis, using the prothrombin ratio (PTR) as a marker for hepatic parenchymal damage. Twenty subjects with viral-induced cirrhosis (11 men and 9 women; 55.41 +/- 7.86 years) and 14 controls (8 men and 6 women; 48.36 +/- 17.67 years) were studied. A single section through the liver was scanned after bolus intravenous injection of 40 ml ioversol 320 mgI/ml. Hepatic arterial and portal perfusion was measured using a previously described technique. Hepatic portal perfusion was decreased in patients (0.66 +/- 0.21 ml/min/ml) compared with controls (1.11 +/- 0.23 ml/min/ml; P < 0.0001). A strong correlation was seen between PTR and portal perfusion (r = 0.662, P = 0.0038) in cirrhotics. Hepatic arterial perfusion did not differ between patients (0.088 +/- 0.082 ml/min/ml) and controls (0.091 +/- 0.067), and did not correlate with PTR. In conclusion, portal perfusion is reduced in cirrhosis, and this reduction correlates with PTR. It could thus be used as a marker of hepatic parenchymal damage. This technique may be useful in the follow-up of chronic liver disease, potentially reducing the need for serial liver biopsy.

Adult↗
PubMed1999

Marked histiocytosis in the portal tract in a patient with reactive hemophagocytic syndrome: An autopsy case.

We report an autopsy case of reactive hemophagocytic syndrome with peculiar liver histology. A 71-year-old female was diagnosed as having acute myelogenous leukemia and treated with chemotherapy. During her course, methicillin-resistant Staphylococcus aureus (MRSA) was noted in blood culture and she was diagnosed as having MRSA sepsis. She died of respiratory failure 5 months after the onset of leukemia and 10 days after the MRSA sepsis. Ante-mortem liver function tests were within normal ranges. At autopsy, myeloblastic leukemia cells positive for CD13 were present in the bone marrow and, to a much lesser extent, in the spleen and liver. Numerous histiocytes of a bland appearance with erythrophagocytosis were noted in the bone marrow and spleen. The histiocytes were positive for CD68, but negative for S-100 and lysozymes. In the liver, many histiocytes of bland appearance with erythrophagocytosis and CD68 positivity were present in the portal tracts with no Kupffer cell hyperplasia. There were no hepatocellular degeneration, fatty changes or sinusoidal dilations. We consider that this histiocytosis was associated with MRSA infection and diagnosed this as infection-associated hemophagocytic syndrome. In previously reported cases, hemophagocytosis in hyperplastic Kupffer cells was the main liver change of reactive hemophagocytic syndrome. The present case suggests that marked histiocytosis in portal tracts only may be a main feature of liver changes in reactive hemophagocytic syndrome and that such cases may not show abnormal liver function tests.

Aged↗
PubMed1999

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis.

UNLABELLED: 22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.

Animals↗
PubMed1999

Evaluation of an implantable motor-driven left ventricular assist device.

A console based implantable motor-driven left ventricular assist device (LVAD) was developed and tested. Ten sheep weighing 42-73 kg (mean, 54.4 kg) were used as the experimental animals. Four animals survived 5-12 h (mean, 9.5 h). The mean pump flow was 1.63 L/min, ranging from 0.8 to 2.5 L/min. The cause of termination was respiratory failure in 3 animals, bleeding in 2, ventricular fibrillation in 2, vent tube obstruction in 1, thrombus formation in 1, and mechanical failure of the driving console in 1. Following the in vivo studies, the computer regulated controller was tested in a mock circulatory system. The LVAD provided 5.34 L/min of maximum output against a mean afterload of 80 mm Hg with a filling pressure of 15 mm Hg when the pump rate was 80 bpm in the fixed rate mode. With an increase in the pump afterload from 80 to 140 mm Hg, the total system efficiency varied from 7.81 to 8.34% when the pump preload was 15 mm Hg. An ultracompact, completely implantable electromechanical VAD has been under development. This device should fit in a 60 kg adult. As the next step, we are preparing to implant this ultracompact implantable VAD with an electronic controller in an animal model with better results being expected.

Animals↗
PubMed1999

Facial nerve repair using a collagen conduit in cats.

We evaluated facial nerve regeneration using a collagen tube as a nerve conduit in five cats. In three 5 mm of the facial nerve were resected, a collagen tube was implanted, and a 5 mm segment of the opposite facial nerve was resected, reversed 180 degrees, and sutured back as an autologous nerve graft. In one a collagen tube was implanted on one side, and in the remaining one a 5 mm nerve segment was reversed. Histological, electrophysiological, and horseradish peroxidase labelling examinations were carried out 4-24 weeks postoperatively. Histological study showed that the nerve was well vascularised and regenerated. Electrophysiological examination confirmed the recovery of evoked electromyograms through to the regenerated axons. Horseradish peroxidase examination also confirmed restoration of the whole facial nerve. The collagen tube is an efficient nerve conduit.

Animals↗
PubMed1999

Two subfamilies of olfactory receptor genes in medaka fish, Oryzias latipes: genomic organization and differential expression in olfactory epithelium.

We cloned and characterized two subfamilies of olfatory receptor (OR) genes from medaka fish (Oryzias latipes). Southern blot analysis showed that each of the two subfamilies, designated as subfamilies Y and E, consists of about five members, as usually observed for other vertebrate ORs. Analyses of the genomic clones encoding these members revealed that two members of subfamily Y and four members of subfamily E are tandemly reiterated in 15 and 22 kbp regions of the medaka genome, respectively. The members of each subfamily show very similar amino acid sequences, with similarities greater than 70%. However, the similarities to the sequences of other vertebrate ORs are lower. Members of subfamily Y show amino acid sequence similarities of ca. 30% to other fish ORs, including subfamily E members, as well as to mammalian ORs. On the other hand, members of subfamily E show sequence similarities of ca. 50% to other fish ORs and ca. 30% to mammalian ORs. Phylogenic analyses of various fish ORs, including medaka, catfish, and zebrafish ORs, indicate that the primary structures of fish ORs are diverse compared with those of mammalian ORs, which consist of much larger numbers of members. The expression patterns of subfamilies Y and E genes in the olfactory epithelium of adult medaka fish were examined by in situ hybridization, showing that the frequency of positive signals is different between the two subfamilies: about 2% of the olfactory neurons are positive to probes for members of subfamily Y, while less than 1% are positive to probes for members of subfamily E. These results indicate that each subfamily is under different transcriptional control.

Amino Acid Sequence↗
PubMed1999

Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats.

The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40-50%). An in vitro cell culture study was performed using cells from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with 13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/- 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.

Animals↗
PubMed1999

Metabolic studies of [18F-alpha-methyl]tyrosine in mice bearing colorectal carcinoma LS-180.

Brain and tumor uptake of [18F-alpha-methyl]tyrosine (18F-AMT) and the incorporation into each of four fractions (lipid, RNA, DNA and protein) were investigated in mice bearing LS180 colorectal carcinoma. Homogenized tissues were analyzed by the fractionation method into an acid-soluble fraction (ASF) and an acid-precipitable fraction (APF). The APF was further investigated to assess the incorporation of 18F-AMT into each fraction. Incorporation into four fractions of brain and tumor at 60 min post-injection was 20 and 12%, respectively; 10% of the activity was incorporated to lipid in brain and 5% in tumor. There was 5, 2 and 2% incorporation with RNA, DNA and protein, respectively. Metabolites in ASF were analyzed by high-performance liquid chromatography and thin-layer chromatography. There was only one radioactive peak, which corresponded to 18F-AMT. The incorporation of 18F-AMT into lipid was twice that of 18F-AMT in tumor. The uptake of 18F-AMT in tissues was rapid and accomplished before 30 min, and then slowly diffused in blood. These results implied that 18F-AMT was metabolized to protein to only a small extent and trapped as intact 18F-AMT in cells up to 60 min. We conclude that 18F-AMT is a promising tracer for tumor imaging and quantification of the transport rate using two-compartment models.

Animals↗
PubMed1999

Biodistribution studies of the 186Re complex of 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid in mice.

Preliminary studies of 186Re-labelled 3-amino-1-hydroxypropylidene-1, 1-bisphosphonic acid (APD) were performed to determine its potential for bone pain palliation, and as a treatment for increased bone resorption. The synthesis of 186Re-APD was carried out by reduction of 186Re-perrhenate in the presence of SnCl2. The APD kit, comprising 2.5 mg of APD, 2.5 mg of gentisic acid and 1 mg of Sn++ as SnCl2 2H2O, was prepared in-house. The APD was labelled with 186Re and injected intravenously into normal mice. Mice were subsequently sacrificed at 1, 3, 24, 48, 72, 168 and 240 h post-injection. The greatest accumulation of 186Re-labelled APD was found in bone, resulting in bone-to-blood ratios of 25, 35, 65, 100, 151, 181 and 189, respectively. 186Re-APD showed high uptake in bone, and relatively low uptake in soft tissue, suggesting that 186Re-APD is a potential agent for bone therapy.

Animals↗
PubMed1999

Accuracy of standardized uptake value measured by simultaneous emission and transmission scanning in PET oncology.

We assessed the accuracy of the standardized uptake value (SUV) measured by simultaneous emission and transmission scanning in cancer patients using FDG positron emission tomography (PET). Conventional, independent emission (E)/transmission (T) scans and simultaneous E/T scans were conducted consecutively in 30 patients who underwent FDG PET examinations. The SUVs of 35 mass lesions and 34 selected normal tissues were derived from the independent E/T scan and simultaneous E/T scan. Experimental studies using a cylindrical phantom were also conducted to evaluate the accuracy and reproducibility of the SUV derived from a simultaneous E/T scan. The SUVs of 18F solution in the phantom were estimated to be approximately 1, with high reproducibility in the range of total counts observed in the clinical examinations. There were no significant differences in the SUVs in 35 tumours derived from simultaneous E/T scans and those derived from independent scans, and there was a strong positive correlation between the two (r = 0.99, P < 0.01). There were also no significant differences in the SUVs in 34 normal tissue regions derived from simultaneous E/T scans and those derived from independent scans. In conclusion, simultaneous E/T scanning with FDG in patients with malignant tumours is a valid method, since the SUV derived from the simultaneous scan is accurate and reproducible.

Algorithms↗
PubMed1999

Radioimmunotherapy for liver micrometastases in mice: pharmacokinetics, dose estimation, and long-term effect.

The pharmacokinetics of a therapeutic dose of 131I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/ 40 microg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 microm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0 % injected dose (ID)/g on day 1 to 17.8 %ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-microm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions.

Animals↗