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T Saga

Publications and source records attributed to T Saga.

At least 55 records · Page 3Linked to original sources
PubMed1999

Avidin-biotin system for delivery of diagnostic agents.

Radiolabeled monoclonal antibodies specific for tumor-associated antigens are used for the diagnosis and therapy of malignant tumors. However, the blood clearance of antibodies is slow and tumor-to-nontumor ratios of radioactivity in the current system are not high. To increase tumor-to-nontumor ratios, the concept of pretargeting has been proposed. The strategy is based on the separate administration of the monoclonal antibody and the radiolabel. Because avidin and streptavidin bind to biotin selectively with extremely high affinity, the avidin-biotin system has been applied for pretargeting. With this method, high tumor-to-nontumor ratios are reported, not only in animal experiments, but also in clinical trials. The avidin-biotin system is also used to reduce the background radioactivity of the directly labeled antibody as well as radioimmunoguided surgery.

Journal Article↗
PubMed1999

Metaphyseal anadysplasia: evidence of genetic heterogeneity.

We report on two unrelated children, a girl and a boy, with regressive metaphyseal dysplasia. Both children had bow legs and a transient growth decline in early childhood. Metaphyseal modifications of the long bones in the children were most conspicuous at an early age and then subsided by age 2 to 3 years. The father of the boy may have had the same disorder, because he was shorter than his sibs and showed mild modifications of the vertebral end plates with mild narrowing of the interpediculate distance of the lumbar spine. The evolution of the metaphyseal dysplasia in the children closely resembled that of metaphyseal anadysplasia (MAD), which is X-linked recessive in inheritance. By contrast, the occurrence of an isolated, affected girl and possible father-to-son transmission reported here were consistent with autosomal dominant transmission, suggesting heterogeneity of MAD. Molecular studies of the type X collagen gene in the boy did not demonstrate any disease-causing mutation.

Adult↗
PubMed1999

Chronological study of the appearance of adenohypophysial cells in the ayu (Plecoglossus altivelis).

We previously reported the chronological appearance of adenohypophysial cells in freshwater teleosts using an immunocytochemical technique. The present study investigated the chronological appearance of adenohypophysial cells in the ayu, which is spawned and has its early development in brackish water, and the results were compared with those obtained in freshwater and seawater teleosts, as well as in other vertebrates. In the adult teleostean adenohypophysis, seven or eight types of secretory cells have been distinguished, each of which produce different hormones: prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), gonadotropic hormones (GTH I and GTH II), adrenocorticotropic hormone (ACTH), melanophore stimulating hormone (MSH) and somatolactin (SL). In the pituitary of adult ayu, seven distinct types of glandular cells (PRL, GH, TSH, GTH, ACTH, MSH and SL cells) were identified. Chronologically, a few immunoreactive (ir)-PRL and ir-GH cells appeared in the ventral side of the pituitary one day before hatching. Then, just after hatching, ir-GTH cells were observed in the central to dorsal portion; ir-ACTH cells were found distributed in the anterior portion and some ir-MSH and a few ir-SL cells were seen in the posterior portion of the pituitary. Finally, a small number of ir-TSH cells were identified 50 days after hatching. These results differed from those obtained in other fishes previously reported with regard to the times of appearance of the PRL and GH cells. PRL cells appeared first, followed by GH cells in the freshwater teleosts, PRL and GH cells appeared at the same time in the brackishwater teleosts, while GH cells appeared first and PRL cells appeared last in the seawater teleosts. These results reflect the fact that PRL plays a major role in osmoregulation among freshwater teleosts, as compared with GH, which plays a similar role in seawater teleosts. It seems that both PRL and GH may play important roles in osmoregulation in brackishwater fish.

Adrenocorticotropic Hormone↗
PubMed1999

Radioimmunotherapy of human glioma xenografts in nude mice by indium-111 labelled internalising monoclonal antibody.

The potential of 111Indium (111In)-labelled internalising anti-integrin alpha 3 antibody GA17 in the radioimmunotherapy of human glioblastoma xenografts in nude mice was investigated. A radioisotope retention assay showed a rapid release of radioiodine from the glioblastoma cells after the binding of 125I-GA17, whilst 111In-GA17 was retained in the cells for a longer time period. The glioblastoma xenografts showed a high and prolonged uptake of 111In-GA17, and tumour uptake of 125I-GA17 was lower and decreased with time. In the mice which received two injections of 18.5 MBq of 111In-GA17, the growth of the subcutaneous tumour was significantly suppressed compared with the untreated group and mice injected with an 111In-labelled control antibody. These results indicate that GA17 was internalized into the glioblastoma cells and that 111In was retained within the cancer cells. The injection of a high-dose of 111In-GA17 can suppress the growth of tumour xenografts in nude mice.

Animals↗
PubMed1999

A novel 111In-labeled antisense DNA probe with multi-chelating sites (MCS-probe) showing high specific radioactivity and labeling efficiency.

A multi-aminolinked oligodeoxynucleotide (ODN) was synthesized by substitution of dT with aminolinked dU in the sequence, following conjugation with isothiocyanobenzyl-EDTA (IBE) for 111In labeling. As a model target gene, the c-erbB-2 protooncogene was used. The probability of the number of aminolinked dU in the 20mer ODN was 5, but there were actually 3 and 4 in the selected antisense and sense ODNs, respectively. The IBE/ODN conjugation levels of probes with multi-chelating sites (MCS-probe) were 1.6 (antisense) and 2.4 (sense), more than 50 times higher than those of our previous studies using 5'-end aminolinked ODNs (IBE/ODN = 0.03). Labeling studies using the MCS-probe and 111In indicated that specific radioactivity as high as 48 MBq/nmol could be obtained with a labeling efficiency of over 90%. The 111In-antisense-MCS-probe could bound to sense ODN under physiological conditions, but the 111In-sense-MCA-probe could not. Thus, side-chain modification of ODN for metal labeling is considered to be useful for antisense techniques.

Antisense Elements (Genetics)↗
PubMed1999

A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment.

Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3'-iodohippuryl N-epsilon-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine.

Angiotensin II↗
PubMed1999

Autoimmune pancreatitis with F-18 fluoro-2-deoxy-D-glucose PET findings

Two cases of pancreatitis induced by autoimmunity with PET images using F-18 fluoro-2-deoxy-D-glucose (FDG) are reported. The patients had abdominal pain and were thought to have possible pancreatic neoplasms. In one patient, PET showed intense uptake of the entire pancreas, but a Ga-67 scan yielded a negative result. Because the serum immunoglobulin G level was high, autoimmune pancreatitis was diagnosed in this patient. He underwent steroid therapy and fully recovered. In another patient with positive antinuclear antibodies and hyperglobulinemia, focal intense uptake was found in the head of the pancreas on the FDG PET. She also recovered with steroid therapy. Autoimmune pancreatitis is a relatively new form of chronic pancreatitis and should be kept in mind when making a differential diagnosis of pancreatic cancer with the assistance of FDG PET.

Journal Article↗
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↗
PubMed1999

Residual cardiomyocytes and scintigraphic findings in advanced coronary artery disease: correlation with technetium-99m-tetrofosmin and thallium-201 single photon emission computed tomography.

A 68-year-old man suffering from chronic heart failure due to coronary artery disease (CAD) underwent rest technetium-99m (99mTc)-tetrofosmin and thallium-201 (201Tl) with reinjection studies, but died thereafter. The heart was removed and sectioned into short-axis slices and examined by gross and microscopic pathologic methods. A close correlation between the amount of residual cardiomyocytes and the level of regional tracer activity in the left ventricular wall was obtained for redistribution 201Tl, reinjection 201Tl and rest 99mTc tetrofosmin images. The correlation coefficients were r=0.901 for the 201Tl redistribution images, r=0.913 for the 201Tl reinjection images and r=0.917 for the rest 99mTc-tetrofosmin images. This case report provides further evidence of the validity of SPECT tetrofosmin imaging for the determination of myocardial viability in CAD.

Aged↗
PubMed1999

Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in experimental liver metastases model of nude mouse.

UNLABELLED: The biodistribution and intratumoral distribution of radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver metastases and the therapeutic effect of 131I-labeled anti-CEA antibody on the metastases were studied. METHODS: Three weeks after an intrasplenic injection of human colon cancer cells, mice received an intravenous injection of 125I- or 111In-labeled anti-CEA antibody F33-104. The biodistribution and tumor penetration of radiolabeled antibody were examined by using quantitative autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150, 250 or 300 microCi) 131I-labeled F33-104 were injected into groups of mice that had micrometastases smaller than 1 mm. Control groups were injected with phosphate-buffered saline or 131I-labeled control antibody. Mice were killed 3 wk later to determine the size of liver metastases. RESULTS: 1251-labeled F33-104 showed a high accumulation in the liver metastases (percentage of injected dose per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis-to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral in the nodules more than 1 mm in diameter. When the antibody dose was increased, antibody penetration was improved, but tumor uptake of radioactivity and specificity ratios decreased. In mice with large metastases, radioactivity in the normal tissue was lower than that in mice with small metastases, resulting in higher metastasis-to-background ratios. 111In-labeled antibody showed even higher tumor uptake than 125I-labeled antibody (>51 %ID/g). Metastases formation was suppressed in a dose-dependent manner by 131I-labeled F33-104 injection (5 of 8 mice had no macroscopic tumor after an injection of 5.55 MBq (150 microCi), and all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or 300 microCi]), whereas tumor progression was seen in the control groups. CONCLUSION: Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with 131I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In-labeled antibody suggest that the use of a radiometal with high beta-energy, such as 90Y or 188Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.

Animals↗
PubMed1999

[Frequent convulsions in the post-eruptive stage of exanthem subitum].

We report here three infants with frequent convulsions in the post-eruptive stage of exanthem subitum (ES) due to human herpesvirus 6 (HHV-6) infection. Postictal electroencephalogram (EEG) showed in all the patients abnormal epileptic discharges, which disappeared in the following by three to eighteen months. In one case, brain magnetic resonance imaging (MRI) revealed focal gliosis. SPECT demonstrated hypoperfusion of the lesion. In the cerebro spinal fluid (CSF) of all the patients, HHV-6 DNA was negative on polymerase chain reaction (PCR) and HHV-6 antibodies were not significantly increased. Although encephalitis has been reported to complicate primary HHV-6 infection, our patients were not diagnosed as having encephalitis because of the clinical, CSF, EEG and CT findings. However, they had frequent convulsions. Not only virus invasion but also a secondary reaction including vasculitis may cause the central nervous system complications of HHV-6 infection. Frequent convulsions may occur in the post-eruptic stage after HHV-6 infection.

Electroencephalography↗
PubMed1999

[Progressive mitral regurgitation which is necessitated the mitral valve replacement after partial left ventriculectomy (Batista procedure): a case report].

The patient is 61-year-old woman who underwent partial left ventriculectomy, (Batista procedure) due to dilated cardiomyopathy and multiple thromboembolism. Although postoperative course was uneventful, she has had clinical symptoms of the left heart failure due to the increased mitral valve regurgitation at the early postoperative period, gradually. Even though mitral valve regurgitation was severe, it was not apt to re-dilatate the left ventricular capacity evaluated by echocardiography. She underwent the mitral valve replacement on the 92nd postoperative day, and was once possible for weaning from cardiopulmonary bypass under the support of IABP. However, she died on the 19th postoperative day caused by sepsis. It is important to evaluate the accurate mitral valve regurgitation preoperatively for Batista procedure. Although there was the mild mitral valve regurgitation, it is essential to repair or replace the mitral valve for Batista procedure.

Cardiac Surgical Procedures↗
PubMed1999

Asialoglycoprotein receptor scintigraphy in evaluation of auxiliary partial orthotopic liver transplantation.

UNLABELLED: The purpose of this study was to evaluate asialoglycoprotein receptor scintigraphy in the post-transplant monitoring of liver graft and native liver functions in recipients of auxiliary partial orthotopic liver transplantation (APOLT) from living donors. METHODS: We performed 36 asialoglycoprotein receptor scintigraphies on 13 patients who had undergone APOLT for noncirrhotic metabolic liver diseases or for small-for-size grafts. The portal vein of the native liver was separated in 12 patients. Anterior dynamic images including the heart and both livers were obtained for 16 min after intravenous injection of 99mTc-diethylenetriamine pentaacetic acid-galactosyl human serum albumin (GSA), and thereafter static SPECT images of both livers were obtained. Uptake rates from the blood to the graft and to the native liver were determined separately by Patlak plot graphical analysis. Relative uptake of GSA by the graft was calculated from transverse SPECT images. The relative volume of the graft liver was determined by CT. RESULTS: The relative uptake of GSA by the graft was higher or increased more rapidly than the relative volume of the graft in 8 of 11 patients with no severe complications concerning the graft. The relative uptake by severely damaged graft liver in 2 patients was much lower than the relative volume. The uptake rate of GSA by the graft was low in these 2 patients. The uptake rate by the native liver decreased when the portal vein was separated. CONCLUSION: The relative uptake of GSA was a better indicator of graft liver function than was anatomic volume. The uptake rate provided additional independent information of each liver. Asialoglycoprotein receptor scintigraphy is useful for distinguishing and monitoring the graft and native liver functions in patients who had undergone APOLT.

Adolescent↗
PubMed1998

Reactions of 7- and 9-aminoadenines with 2,4-pentanedione. Formation of new ring systems, pyridazino[6,1-f]purine and pyridazino[1,6-e]purine.

Reactions of 7-aminoadenines with 2,4-pentanedione yielded pyridazino[6,1-f]purines and 5-pyrazolylpyrimidines. The structure of the latter was identified by X-ray analysis. Reaction of 9-amino-N6-methyladenine with 2,4-pentanedione gave pyridazino[1,6-e]purine and Schiff base products. Possible reaction mechanisms are discussed.

Crystallography, X-Ray↗
PubMed1998

Avidin targeting of intraperitoneal tumor xenografts.

BACKGROUND: Lectins (proteins that bind specific sugar molecules on glycoproteins and glycolipids) are expressed at various levels on the surface of tumor cells. Conjugation of cytotoxic agents to glycoproteins recognized by lectins could be useful in the treatment of tumors. Avidin (a highly glycosylated, positively charged protein found in egg white) contains terminal N-acetylglucosamine and mannose residues that bind to some lectins. In this study, we tested the ability of avidin, labeled through conjugation to radioactive biotin (a B vitamin), to target intraperitoneal tumors. METHODS: Biotin was radioactively labeled with 111In. Four tumor models (one ovarian, one lung, and two colon) were established in nude mice by intraperitoneal injection of cultured cancer cells. The following two approaches were used in the intraperitoneal administration of avidin: 1) radioactive biotin-avidin conjugates were injected and 2) avidin was injected 1-24 hours before the injection of radioactive biotin (avidin pretargeting; avidin-biotin conjugates formed in vivo). The distribution of injected radioactivity in the tissues of treated animals was assessed. RESULTS: Radiolabeled avidin localized highly and rapidly in the tumors. More than 50% of the administered dose of avidin-biotin conjugate accumulated per gram of tumor tissue 2 hours after injection; high tumor uptake of radioactivity was observed up to 24 hours after conjugate injection. In contrast, accumulation of radioactivity in normal tissues was low, yielding high tumor to nontumor ratios. With avidin pretargeting, accumulation of radioactivity in the liver, kidney, and spleen was reduced to a greater extent than that in the tumor, and tumor to nontumor ratios were increased. CONCLUSIONS: Avidin may be a promising vehicle for the delivery of radioisotopes, drugs, toxins, or therapeutic genes to intraperitoneal tumors.

Animals↗
PubMed1998

Imaging of intraperitoneal tumors with technetium-99m GSA.

99mTc labeled galactosyl serum albumin (GSA) has been used clinically as a receptor-binding agent for the assessment of liver function. The aim of this study was to investigate the usefulness of 99mTc-GSA in intraperitoneal (i.p.) tumor imaging. A tumor model was established by i.p. inoculating nude mice with human ovarian cancer cell SHIN-3, or colon cancer cell LS 180. Radiolabels were i.p. injected into the tumor-bearing mice and the biodistribution of radioactivity was examined. After administration, 99mTc-GSA rapidly accumulated in the tumor. The tumor uptake was 5.82-8.46 %ID/g from 30 min to 6 h after the injection. Radioactivity in the blood was very low, less than 0.3 %ID/g, resulting in high tumor-to-blood ratio. Tumors could be clearly seen by scintigraphic imaging. Accumulation of i.p.-injected 99mTc labeled human serum albumin (HSA) in i.p. tumors was similar to that of 99mTc-GSA, but radioactivity of 99mTc-HSA in the circulation was high, resulting in a significantly lower tumor-to-blood ratio. In conclusion, 99mTc-GSA, when i.p. injected, accumulated in i.p. tumors and cleared from circulation rapidly, which would make it useful for the imaging of i.p. tumors.

Animals↗
PubMed1998

Three-step tumor imaging with biotinylated monoclonal antibody, streptavidin and 111In-DTPA-biotin.

The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin. Nude mice bearing subcutaneous LS180 human colon cancer xenografts were intravenously administered with 200 microg of the biotinylated anti-Tn monoclonal antibody MLS128, and 2 days later they got intravenous injection of 50 microg of streptavidin. They were intravenously injected 1, 4 or 7 days later with 0.5 microg of 111In-diethylenetriamine pentaacetic acid (DTPA)-biotin. The tumor uptake, determined 2 h later, was 1.4, 0.5 and 0.6% injected dose/gram of tissue (ID/g), respectively, and the blood radioactivity was 1.0, 0.2 and 0.2% ID/g, respectively. When the interval between the streptavidin and radiolabeled biotin injections was prolonged from 1 day to 7 days, the tumor-to-blood ratio 2 h after injection of 111In-labeled biotin increased from 1.5 to 4.0. Clear tumor images were obtained as early as 2 h after injection of radiolabeled biotin. In conclusion, these preliminary data suggested that the three-step method using the streptavidin-biotin system would be applicable in an experimental mouse tumor model and provides images of tumors rapidly and clearly after injection of radiolabeled biotin.

Animals↗