Biomedical subjects

T Saga

Publications and source records attributed to T Saga.

At least 127 records · Page 7Linked to original sources

PubMed1993

Changes in CA125 release and surface expression caused by drugs in uterine cervix adenocarcinoma cells.

The effect of drugs on the release of CA125 antigen and the binding of anti-CA125 monoclonal antibody (MoAb) to malignant cells was evaluated in vitro. TMCC-1, uterine cervical adenocarcinoma cells, were exposed to dexamethasone (DEX), sodium n-butyrate (NaB), dibutyryl cyclic AMP (dbcAMP), retinoic acid (RA), calcitriol (VD3), and interferon-gamma (IFN-gamma). NaB, RA and VD3 increased CA125 release per cell and 125I-labeled anti-CA125 MoAb binding to the cells. DEX also increased the 125I-labeled anti-CA125 MoAb binding to the cells, and CA125 antigen release per cell was also slightly increased. IFN-gamma suppressed both CA125 release and 125I-labeled MoAb binding. A combination of DEX, VD3 and RA and increased the binding of MoAb to TMCC-1 cells, but the amount of bound MoAb was not significantly different from that obtained by single drug treatment. DbcAMP had no significant effect on enhancing MoAb binding. Drugs can increase the binding of anti-CA125 MoAb to malignant cells and they may be applied to increase the tumor uptake of radiolabeled MoAbs in vivo.

Adenocarcinoma↗

PubMed1993

Monomelic muscle atrophy.

Two patients with slowly progressive muscle atrophy limited to only one leg are reported. They had pes equinovarus deformity and muscle weakness in the affected leg but no symptom in the other limbs. Muscle biopsies from the affected leg showed dystrophic changes consisting of variation in muscle fiber size, endomysial fibrosis, and necrotic and regenerating fibers. Dystrophin was normally expressed at the surface membrane of the muscle fibers. These two patients possibly had a variant of distal muscular dystrophy, though a neural influence could not be completely excluded.

Biopsy↗

PubMed1993

In vivo instability of reduction-mediated 99mTc-labeled monoclonal antibody.

A murine monoclonal antibody that reacts with human osteogenic sarcoma (OST7) was reduced and directly labeled with 99mTc without any loss of immunoreactivity. No fragmentation of the antibody was detected by high performance liquid chromatography after the labeling. However, SDS-PAGE analysis of the labeled antibody demonstrated the presence of low molecular weight species. Although more than 95% of the radioactivity remained bound at the antibody after incubation with human serum for 24 h, 99mTc-labeled OST7 was cleared faster from the circulation than 125I-labeled OST7 or 111In-labeled OST7 in mice. Urinary and fecal excretion of 99mTc were higher than those of 125I. When the 125I-labeled antibody was dual-labeled with 99mTc, the blood clearance of 99mTc was faster than that of 125I, suggesting release of 99mTc from the antibody in vivo. 99mTc-labeled OST7, however, gave a higher tumor-to-blood ratio than 125I- or 111In-labeled OST7 in mice bearing human osteogenic sarcoma. The 99mTc-labeled antibody prepared by the direct method was unstable in vivo, but retained a good tumor targeting ability.

Animals↗

PubMed1993

An improved synthesis of [125I]N-(diethylaminoethyl)-4-iodobenzamide: a potential ligand for imaging malignant melanoma.

To improve the radiolabeling yield and the specific activity of [125I]N-(2-diethylaminoethyl)-4-iodobenzamide (DAB), the aryltributyltin precursor was synthesized from the N-(2-diethylaminoethyl)-4-bromobenzamide derivative by palladium catalyzed stannylation using bis(tributyltin). The radiolabeled product, [125I]DAB, was obtained by an iododestannylation reaction in high radiochemical yields (85-94%, radiochemical purity, > 98%) using chloramine-T as an oxidizing agent. The specific activity was greater than 1600 Ci/mmol. The biodistribution studies in nude mice implanted with human malignant melanoma xenograft showed a good tumor uptake (6.14% ID/g at 1 h, 2.81% ID/g at 6 h and 0.42% ID/g at 24 h) of [125I]DAB. Unfortunately, a high uptake in the non-target organs, such as liver and lung, was found. At 1 h post-injection the activity level in liver and lung was 11.76 and 7.58% ID/g, respectively. A slow clearance of activity from liver and lung was observed at 6 h (3.43 and 0.49% ID/g). These results demonstrate that iodinated IDAB is a potential radiopharmaceutical for the management of patients with malignant melanoma.

Animals↗

PubMed1993

Similarity and co-expression of tumour-associated antigens recognised by different monoclonal antibodies.

The concentration of carcinoembryonic antigen (CEA), CA130, CA125, SLX, CA19-9, SPan1, and tumour-associated glycoprotein 72 (TAG-72) in the culture supernatant of 15 cancer cell lines and in the sera of 58 cancer patients was measured, and the co-expression of these antigens was examined by double determinant immunoradiometric assays. The high correlation coefficient of the concentrations and significant binding in the double determinant assays indicated a close relationship between CA125 and CA130 and between CA19-9 and SPan1. There was variable binding of the 125I-labelled anti-SLX, anti-CA19-9, and anti-SPan1 antibodies to anti-CA130 beads that had been pre-incubated with the culture supernatants, suggesting the presence of the epitopes of SLX, CA19-9, and SPan1 on the molecule expressing CA130. Similarly, the epitopes of SLX, CA19-9, and SPan1 could be present on the molecule expressing CEA. 125I-labelled anti-CA19-9, anti-SLX, and anti-TAG-72 antibodies were bound in variable proportions to anti-CA130 beads or to anti-CEA beads that had been pre-incubated with patients' sera. However, CEA and CA130 were not expressed on the same molecule, either in the culture supernatant, or in patients' sera. In conclusion, the carbohydrate epitopes of CA19-9, SPan1, SLX, and TAG-72 could be present on the molecule recognised by the anti-CA130 or anti-CEA antibody; however, the epitopes of CA130 and CEA did not co-exist on the same molecule.

Antibodies, Monoclonal↗

PubMed1993

Construction of immunoradiometric assay for circulating c-erbB-2 protooncogene product in advanced breast cancer patients.

The human c-erbB-2 protooncogene product (erbB-2 protein) is a 185 kilodalton glycoprotein closely related to epidermal growth factor receptor protein. In this study, we measured the concentration of circulating erbB-2 protein in cancer patients by means of a new immunoradiometric assay (IRMA). Two monoclonal antibodies (MoAbs), SV2-61 gamma and 6G10, recognize erbB-2 protein but bind to separate epitopes. SV2-61 gamma was used as an immunoadsorbent and 6G10 as an 125I-labeled probe. A serum was considered positive for erbB-2 protein if the percent binding exceeded the mean of the normal group by more than 3 standard deviations. Eleven of 21 patients with advanced breast cancer and 1 of 15 with advanced gastric cancer were positive. Serum erbB-2 protein levels correlated well with the therapy and the status of the patients with breast cancer. On the contrary, all patients with advanced colon, ovarian, or pancreatic cancers, showed levels below the cut-off value. These results suggest that circulating erbB-2 protein can be measured using the newly constructed IRMA. Since c-erbB-2 protooncogene amplification and overexpression are accepted as a good marker of aggressiveness, relapsing potency, and poor prognosis, this IRMA should be a promising tool with which to help manage breast cancer patients.

Adenocarcinoma↗

PubMed1993

Semilunar valve replacement with a cylindrical valve.

A cylindrical valve was designed to prevent regurgitation of the semilunar valve. The valve is made of a sheet of polytetrafluoroethylene (PTFE) or porcine pericardium, and has three cusps and three commissures. The diameter of the valve is equal to the height of the cusps. We have used these valves in pulmonary stenosis after Jatene's operation and total correction of tetralogy of Fallot, and for truncal valve regurgitation. Regurgitation was trivial on color Doppler echocardiography in all cases. Advantages in comparison with the implantation of commercially available artificial valves include the ability to insert a larger size and no compression of the valve ring when closing the sternum. Outflow tract obstruction does not occur even when the valve is implanted in a small infant. In the present report, we describe this simple technique.

Animals↗

PubMed1993

[The effect of various factors on changes in the levels of unsaturated fatty acid in plasma and serum lipids after administration of icosapentaenoic acid ethyl ester].

We administered a highly purified icosapentaenoic acid ethyl ester (IPA-E) preparation orally for 12 weeks to 32 male and 22 female patients aged 43 to 85 (average 67 years) with arteriosclerosis to investigate the effects of various factors on changes in the levels of unsaturated fatty acid in plasma and serum lipids. On administration of 1800 mg/day of IPA-E, the plasma level of IPA increased significantly, while the plasma level of DHLA decreased significantly, but no significant changes were observed in plasma DHA and AA concentrations. There were significant inverse correlations between the pretreatment levels of plasma IPA and IPA/AA, and the volumes and ratios of changes in their plasma levels following administration of IPA-E. There was no significant correlation between patient age or concomitant administration of calcium antagonists and baseline plasma IPA level and IPA/AA value or changes in these parameters after administration of IPA-E. In male patients, the plasma IPA level before treatment was higher than that in female patients, while the increase in plasma IPA level after administration of IPA-E tended to be smaller than in female patients. In diabetic patients and those receiving diuretics concomitantly, plasma IPA/AA values before treatment with IPA-E were higher, while the increase in IPA/AA values after treatment tended to be smaller than other groups of patients. On analysis of covariance on modified baseline volume before treatment, the effect of age, sex, presence of diabetes mellitus and concurrent use of calcium antagonist or diuretics was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[The effect on changes in serum lipids and factors that may affect those changes after administration of icosapentaenoic acid ethyl ester].

The effects of high-purity IPA-E administration on changes in serum lipids and factors that may affect those changes were investigated in 55 patients with arteriosclerotic disease (34 males and 21 females, aged 43-85) under a regular daily diet. Daily administration of 1800 mg or 900 mg IPA-E resulted in a significant decrease or tendency to decrease in serum TG, TC and LDL-C 4 weeks after the initial administration, which continued throughout the administration period. Apo-protein analysis revealed a significant increase in A-I and a significant decrease in B and E after the administration of IPA-E. Lipoprotein analysis disclosed decreasing tendency of VLDL, IDL, LDL and TG, where the changes in VLDL-C, VLDL-TG and TG were significant. The amount and rate of change in TG, TC and LDL-C after IPA-E administration had a significant negative correlation with their respective pre-administration values. The decrease from pre-administration values was significant for patients with abnormal values in both dosage groups. The average rate of decrease in TC and LDL-C were greater in the group receiving administration of 1800 mg/day than that receiving 900 mg/day, but the difference in the change was not significant between the 2 groups. Correlations between the amount or rate of decrease in TC or LDL-C and the baseline value, achieved value, or amount or rate of increase in plasma IPA concentration and IPA/AA ratio were not significant. However, the negative correlation between the rate of change in TG and achieved IPA concentration was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

A malignant melanoma imaging agent: synthesis, characterization, in vitro binding and biodistribution of iodine-125-(2-piperidinylaminoethyl)4-iodobenzamide.

In order to develop improved radiopharmaceuticals for imaging malignant melanoma, we have synthesized and characterized 125I-and 131I-labeled (2-piperidinylaminoethyl)4-iodobenzamide (PAB). In vitro binding profiles of IPAB and N-(2-diethylaminoethyl)4-iodobenzamide (IDAB, a structurally related analog of IPAB) for a variety of neurotransmitter receptors suggested that both IPAB and IDAB possessed a high sigma-1 affinity and a low affinity for sigma-2 sites. In vitro homologous competition binding studies of [125I]PAB with human malignant melanoma cell A2058 showed that the tracer was bound to the cells with a high affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribution studies in nude mice implanted with human malignant melanoma xenografts showed good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 hr and 1.02% ID/g at 24 hr) of [125I]PAB. High tumor-to-nontarget organ ratios were obtained at 24 hr postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01, respectively. Tumor imaging with [131I]PAB in a nude mice model xenografted with human malignant melanoma at 24 hr clearly delineated the tumor with very little activity in any other organ. These results demonstrate that sigma-1 receptors could be used as external markers for malignant melanoma.

Animals↗

PubMed1993

[Successful surgical management of postinfarction left ventricular free wall rupture in a case of systemic lupus erythematosus].

A 58-year-old woman of postinfarction left ventricular free wall rupture (LVFWR) was surgically treated with good results. She had been treated with Prednisolon for 15 years with the diagnosis of systemic lupus erythematosus. The rupture was noted six hours after the onset of myocardial infarction and she was taken to the emergent surgical intervention. During the operation, active bleeding was found in the higher anterior wall of the left ventricle and a Dacron graft was sutured to cover the infarcted area. The postoperative course was uneventful. This report seemed to be the first one of the successful surgical management of LVFWR in the course of the treatment for SLE in the literature.

Emergencies↗

PubMed1993

[A ciclosporin A responsive case of Behçet's disease associated with IgA nephropathy].

A case of Behçet's disease with IgA nephropathy was reported in a 17 year old man. He presented with microscopic hematuria which was pointed out by urinary mass screening for school children at age of 14. As he was subsequently evolved proteinuria, a renal biopsy was performed at age of 16. The specimen showed diffuse proliferation of mesangial cells. Immunofluorescent studies showed granular deposition of IgA. At age of 17, he showed typical symptoms of Behçet's disease, namely aphthous stomatitis, perianal ulcers, erythema nodosum-like lesions, uveitis and genital aphtha. Furthermore he showed an increasing of proteinuria and an impairment of his renal function. Serum IgA level and immune complexes during the exacerbation stage were elevated. The uveitis markedly improved with ciclosporin A therapy. Reduction of proteinuria and improvement of renal function were simultaneously observed. These findings may suggest that IgA nephropathy and Behçet's a disease have common immunological pathogenesis, including circulating immune complexes.

Adolescent↗

PubMed1992

Different antigenic nature in apparently healthy women with high serum CA 125 levels compared with typical patients with ovarian cancer.

BACKGROUND: CA 125 is a representative ovarian cancer-associated antigen defined by monoclonal antibody OC125. Recently, monoclonal antibodies were produced (designated 130-22 and 145-9) that were reactive with CA 125 but bound to a separate epitope named CA 130. There was a close correlation between serum CA 125 and CA 130 values in most instances. However, among more than 8000 serum samples, 5 apparently normal women had high serum CA 125 values, despite having normal CA 130 values. In this study, the antigenic nature of these five women was investigated. METHODS: Using gel chromatography, the molecular masses of CA 125 and CA 130 were estimated that were found in the five women with false-positive CA 125 values. The sera were examined using double-determinant assays combining iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OCI25-coated or 145-9-coated beads. RESULTS: The molecular masses of both CA 125 and CA 130 were estimated as greater than 1000 kilodaltons (KD); the CA 130 mass from one of the five women with an abnormal CA 125 level was approximately 200 KD using gel chromatography. Using the double-determinant assays that combined iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads, high radioactivity was found only in the homologous assay using iodine-125-labeled OC125 with OC125-coated beads. These results suggest that the antigenic nature of CA 125 found in apparently healthy women differs from that found in patients with ovarian cancer and that CA 130 epitopes are not present. CONCLUSIONS: Measurement of serum CA 130 concentrations may be useful for excluding women with falsely elevated CA 125 values.

Acrylic Resins↗

PubMed1992

Human/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA).

Human anti-murine antibody (HAMA) response is a serious problem in the repeated infusion of murine monoclonal antibodies (MoAbs). HAMA positive sera were obtained from seven patients with colorectal cancer, pancreas cancer, malignant melanoma or myocardial infarction who had previously received radiolabelled MoAbs. The nature of HAMA was analysed using size exclusion high performance liquid chromatography (HPLC) after incubating with radiolabelled MoAbs including IgG, Fab or human/mouse chimeric Abs. Immune complexes composed of HAMA and MoAbs were formed. The percentage of radioactivity with a high molecular weight was related to HAMA levels determined by enzyme linked immunosorbent assay. Most radioactivity present in immune complex shifted to the antibody fraction after the addition of normal murine serum. All of seven sera were reactive with all four murine IgGs and this suggests that HAMA in these patients recognised the constant region of MoAbs. In one patient, HAMA was considered to recognise the variable region and to be anti-idiotypic. There was no significant binding with human/mouse chimeric Abs in any HAMA positive serum, although five out of seven patients were reactive with murine MoAb Fab, indicating that HAMA was composed of Abs responsive to the CH1 or CL region of murine IgG. These results suggest that (1) HAMA was composed of Ab responsive to Fc portion and/or CH1 or CL region of murine IgG, and (2) human/mouse chimeric Abs look promising in the repeated infusion of MoAb in HAMA positive patients.

Aged↗

PubMed1992

Hepatocyte response to continuous low dose-rate radiation in radioimmunotherapy assessed by micronucleus assay.

The response of hepatocytes to low dose-rate irradiation was examined in mice following the injection of radiolabelled monoclonal antibody. Mice were injected intravenously with an 131I-labelled monoclonal antibody 196-14 which recognizes CA125 antigen, and the effect of continuous low dose-rate irradiation on hepatocytes was assessed using the micronucleus assay. The frequency of micronuclei increased in a dose-dependent fashion, but it was lower than the frequency induced by conventional external X-rays which was determined immediately after the irradiation. A linear quadratic model (micronucleus frequency = aD+bD2+c) showed that the value of b decreased with low dose-rate irradiation from the radiolabelled antibody. It is concluded that the micronucleus assay is useful for the evaluation of the response of hepatocytes to irradiation in radioimmunotherapy.

Animals↗

PubMed1992

[Time-course changes of regional cerebral blood flow by SPECT with N-isopropyl-p-[123I]-iodoamphetamine in childhood partial seizures].

Single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]-iodoamphetamine was performed twice at different times in 18 children suffering from partial seizures to evaluate the time-course changes of the hemodynamics in the focal region. Comparison of the 2 SPECT images revealed that a decreased regional cerebral blood flow (CBF) in the first was normalized in 4 cases (22.2%) and contracted in 7 cases (38.9%). The region of decreased blood flow in the second was contralateral to that in the first in 1 case (5.6%) and unchanged in 6 cases (33.3%). Most of the normalized and contracted cases were those in which clinical seizures disappeared and the EEG findings were normalized. In these cases which responded to treatment, the decreased regional CBF was also found to be improved. Repeated SPECT appears to be useful for evaluating the therapeutic efficacy. On the other hand, most of the unchanged cases were those in which clinical seizures were frequent or uncontrolled, or which persistently showed the abnormalities in their EEG. SPECT was considered to reflect well the conditions of the epileptic foci. These results indicate that repeated SPECT for observing the time-course changes of the regional CBF represents a useful technique with can be applied in evaluating the therapeutic efficacy or deciding the time to discontinue treatment and for pathogenetic elucidation of the epileptic foci.

Adolescent↗

PubMed1991

Drug effects on CA125 antigen expression and antibody binding to cancer cells.

CA125 is a high-molecular weight glycoprotein expressed on most serous-type ovarian cancer and some lung adenocarcinoma tissues. The effects of various drugs on the release of CA125 antigen into culture medium and on monoclonal antibody (MAb) binding to cancer cells were studied using 8 human cancer cell lines, all of which expressed CA125 on their cell surfaces. The effect of dexamethasone was seen at as low a concentration as 10(-9) M dexamethasone, and the release of CA125 and the binding of radiolabelled anti-CA125 antibody were completely inhibited after exposure to 10(-7) M dexamethasone. The number of antibody binding sites markedly decreased. In contrast, sodium butyrate increased CA125 expression. These findings were clearly detected in only 3 cancer cell lines and a significant effect was not seen in the 5 other cancer cell lines. Interferon-gamma, examined in 3 cell lines, suppressed in a dose-dependent manner in 2 CA125 expression cell lines, but enhanced it in one line. No apparent effects were seen after exposure to tissue necrosis factor or interleukin-2. These results suggest that drugs may regulate the CA125 antigen expression in some, but not all, cancer cells and may affect the biodistribution of radiolabelled MAbs.

Antibodies, Monoclonal↗

PubMed1991

Scintigraphic detection of overexpressed c-erbB-2 protooncogene products by a class-switched murine anti-c-erbB-2 protein monoclonal antibody.

Class-switched monoclonal antibody SV2-61r recognized the extracellular domain of c-erbB-2 protooncogene products separate from the epidermal growth factor receptor. We studied the potential of SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells, which has been reported to have prognostic value in adenocarcinoma patients. Radiolabeled SV2-61r specifically bound to various adenocarcinoma cells in addition to c-erbB-2-transfected NIH-3T3 cells (A4) with the affinity constant of 4.4 x 10(8) M-1. SV2-61r injected i.v. localized well to A4 cells xenografted in nude mice. Tumor uptake and localization index of radioiodinated SV2-61r were lower than those of 111In-labeled SV2-61r, probably due to the internalization and dehalogenation of formed antibody-antigen complexes. Biodistribution and specificity of targeting were assessed by comparison among three cells, A4, lung cancer SBC-3 (c-erbB-2 weakly positive) and B-lymphoblastoid Manca cells (c-erbB-2 negative). Tumor:blood ratios, obtained 48 h after injection, were 5.63, 1.45, and 0.68, respectively, indicating the potential of 111In-labeled SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells. Because of its close relationship with carcinogenesis and the uniform expression, c-erbB-2 protooncogene products seem to be the optimal target of imaging and therapy of adenocarcinoma patients.

Animals↗