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Biomedical subjects

T Saga

Publications and source records attributed to T Saga.

At least 145 records · Page 8Linked to original sources
PubMed1991

[The correlation between pulse wave velocity and diabetic angiopathy].

Pulse wave velocity (PWV) of the aorta was measured in 40 patients with diabetes mellitus, in order to study the relation between PWV and diabetic angiopathy. The PWV was significantly faster in diabetic patients on oral hypoglycemic agents than in those on diet alone or on insulin. The PWV correlated significantly and positively with age, systolic blood pressure and urinary albumin index. The PWV significantly faster in diabetics with microalbuminuria than in those without this findings. It was concluded that PWV in addition to known risk factors such as elevated blood pressure, atherogenic abnormalities of plasma lipids and lipoproteins, and elevated blood glucose, may be a reliable index of diabetic micro- and macroangiopathy.

Aged↗
PubMed1991

An approach for immunoradiometric assay with metallic radionuclides: gallium-67-deferoxamine-dialdehyde starch-IgG.

Radiogallium (Ga) labeling of an immunoglobulin-G-deferoxamine conjugate (DF-IgG) to a high-specific radioactivity was performed to allow the development of a radiometallic immunoradiometric assay (IRMA) system. To increase the specific radioactivity of Ga-DF-IgG, we used dialdehyde starch (DAS) as a multi-site spacer for the binding of DF to IgG. Six DF molecules bound to each IgG molecule after DAS conjugation. DF-DAS-IgG was then labeled with the previously reported 67Ga labeling solution, producing labeled IgG with a specific radioactivity of 11,766 MBq/mg IgG. Using this method, we labeled an anti-CA125 tumor-associated antigen monoclonal antibody (130-22), allowing the first application of 67Ga-DF-DAS-IgG to an IRMA system. With this system, a higher sensitivity could be obtained than with 125I IRMA. In addition, a very high correlation (r = 0.995) was obtained between serum CA125 levels as determined by 67Ga IRMA and 125I IRMA. Gallium-67-labeled antibodies with a high-specific radioactivity appear to hold promise for use in highly sensitive radioassay systems.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

[Therapy of malignant pheochromocytoma using I-131 metaiodobenzylguanidine--report of a case].

A 67 year-old-female had multiple metastases to her lung, liver and paraaortic lymph nodes from a post-operative malignant pheochromocytoma. She was treated with 3.7 GBq (100 mCi) of I-131 metaiodobenzylguanidine (MIBG). Metastatic nodules in lung and liver almost disappeared and the secretion of catecholamines decreased than baseline rates. However, major but temporary untoward response, such as hypertension and hyperglycemia, was seen after the I-131 MIBG administration.

3-Iodobenzylguanidine↗
PubMed1990

Estrogen- and androgen-responsive growth of human ovarian adenocarcinoma heterotransplanted into nude mice.

A new line of human serous cystadenocarcinoma of the ovary, designated OVA-5, has been established in athymic nude mice. A strong correlation was noted between tumor volume and plasma CA125 levels in mice bearing OVA-5 tumor. Growth of the OVA-5 tumor in castrated male nude mice was accelerated by s.c. administration of estradiol-17 beta and 5 alpha-dihydrotestosterone but not by progesterone. Estradiol-17 beta and 5 alpha-dihydrotestosterone also accelerated the growth of the OVA-5 tumor heterotransplanted into sialoadenectomized castrated male nude mice. No remarkable change was observed in the histological appearances of the tumors between control groups and hormone-treated groups. Receptor assays revealed that the OVA-5 tumor had both estrogen and androgen receptors. Growth of the OVA-5-tumor is thus responsive to estrogen and androgen.

Adenocarcinoma↗
PubMed1990

Normal bronchial mucus contains high levels of cancer-associated antigens, CA125, CA19-9, and carcinoembryonic antigen.

The presence of cancer-associated antigens CA125, CA19-9, and carcinoembryonic antigen (CEA) in apparently normal respiratory system was demonstrated histochemically and immunochemically. Epithelial cells lining central airways (trachea, bronchi, and bronchioli) and respiratory glands were specifically stained by antibodies recognizing CA125, CA19-9, and CEA. Most, if not all, bronchial mucus obtained from patients without pulmonary diseases during general anesthesia contained remarkably high levels of CA125, CA19-9, and CEA ranging from 190 to 41,000 U/ml (594-4803 U/mg protein), 210 to 95,000 U/ml (294-197,917 U/mg protein), and 6 to 940 ng/ml (14-209 ng/mg protein), respectively, whereas serum antigen levels were normal in all cases examined. These results suggest that CA125, CA19-9, and CEA are synthesized and secreted by normal epithelial cells of central airways and/or respiratory glands and that these substances are not specific indicators of abnormal cellular activity.

Adolescent↗
PubMed1990

An antibody-tumor model for the targeting of CA125-producing gynecologic malignancies.

By immunizing a mouse with HOUA-1 cells established from an endometrial cancer patient, two murine monoclonal antibodies designated 196-14 and 196-28 were generated, which were reactive with ovarian cancer-associated antigen CA125, originally defined by OC125 antibody. Antigenic determinants of these antibodies, although overlapping each other, were different from that of OC125 and the combined use of 125I-labeled 196-14 and OC125-coated beads markedly increased the sensitivity of measuring CA125 antigen. Both radioiodinated and 111In-labeled 196-14 localized well in CA125-producing human ovarian cancer tissues OVA-5 xenografted in nude mice. The biodistribution of radioiodinated 196-14 was quite different from that of 111In-labeled 196-14. Radioiodine was cleared faster from the OVA-5 tumor, making a clear contrast to the prolonged retention of 111In the tumor. Initial tumor uptake of radioiodinated 196-14 was the same as that of 111In-labeled 196-14 but decreased thereafter, due to the dehalogenation of radioiodinated antibody in the tumor. This antibody-tumor model seems to be suitable for examining the usefulness of monoclonal antibody-conjugates in the diagnosis and therapy of CA125-producing endometrial or ovarian cancers.

Adenocarcinoma↗
PubMed1990

Influence of cocktails of labeled monoclonal antibodies on the localization of antibodies in human tumor xenografts.

In order to evaluate the usefulness of cocktails of labeled monoclonal antibodies (MoAbs) recognizing different antigen molecules to localize human cancer xenografts, we have compared the potential of three MoAbs recognizing representative cancer-associated CA 19-9, 17-1A and CEA antigens when administered alone or in combination. Specific binding of radioiodinated F(ab')2 fragments of these three MoAbs was observed to human colorectal cancer cell lines SW1116, LS180 and Co-3. The percentage of in vitro cell binding of a cocktail of any two MoAbs to cancer cells was equal to the average of those obtained with the two MoAbs alone. The three MoAbs were preferentially localized in tumor tissues xenografted in nude mice. When cocktails of any two MoAbs were used, the obtained tumor-to-normal tissue ratios and percent of injected dose per gram of tumor were between the levels obtained for each MoAb when administered alone, in all three tumors transplanted in nude mice. These data suggest that, although cocktails of labeled MoAbs recognizing different antigens may extend the spectrum of tumor specificities, their use does not improve the tumor localization ability of MoAb-conjugates.

Animals↗
PubMed1990

Immunohistochemical localization of CA130 in fetal tissues, and in normal and neoplastic tissues of the female genital tract.

A murine monoclonal antibody, 130-22, produced against a human lung adenocarcinoma cell line (PC-9) has been suggested as recognizing an antigenic determinant (CA130) which is different from an epitope recognized by OC125 on CA125 glycoprotein molecules. The immunohistochemical reactivity with the 130-22 antibody (anti-CA130) was examined in human fetal tissues, and normal and neoplastic tissues of female genital tracts, and compared to those using OC125. Among the fetal tissues, the amnion and the cells of coelomic epithelium and mullerian-derived epithelia reacted with anti-CA130. In normal adult tissues, cervical and endometrial gland cells, tubal epithelial cells, and ovarian surface cells reacted with anti-CA130. In addition, predecidual cells in the late secretory endometrium and decidual cells during gestation were positive. Among the neoplastic tissues, tubal and endometrial adenocarcinomas and epithelial ovarian tumors were positive for anti-CA130. There were no differences in the respective specimens between the immunohistochemical localization of anti-CA130 and of OC125. Therefore, anti-CA130 is considered to be useful in the immunohistochemical detection of CA125 glycoprotein molecules as well as OC125.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Use of magnetite particles as a contrast agent for MR imaging of the liver.

To evaluate the potential of dextran-coated magnetite (DM) particles in enhancing the detection of hepatocellular carcinoma with magnetic resonance (MR) imaging, the authors induced liver tumors in rats by oral administration of diethylnitrosamine and examined the rats before and after intravenous injections of DM with various iron concentrations. Because of the intense and preferential T2 relaxativity of DM, use of DM with an iron concentration of 10 mumol/kg yielded effective MR signal reduction in each normal liver at 1 hour after the injection. Because no significant signal change in the tumors was observed on DM-enhanced MR images, the contrast between hepatocellular carcinoma and adjacent uninvolved liver increased remarkably on even relatively T1-weighted images. The detection rate for the 89 tumors, including small tumors less than 2 mm in diameter, increased from 10% (nine of 89) before DM administration to 65% (58 of 89) with DM-enhanced T1-weighted imaging. Iron staining of rat liver performed about 1 hour after DM administration showed sparse deposits of DM selectively in reticuloendothelial cells but not in liver tumors.

Animals↗
PubMed1990

Construction of an immunoradiometric assay for ovarian cancer associated antigen CA125 recognizing different antigenic determinant.

We generated five murine monoclonal antibodies reactive with ovarian cancer-associated antigen CA125. These monoclonal antibodies seemed to bind to separate epitopes from OC125 antibody, known to recognize CA125. A series of immunoradiometric assays for measuring serum CA125 values rapidly and sensitively were devised using these monoclonal antibodies. The antigenic determinant of a new immunoradiometric assay was different from that of a currently used CA125 kit employing OC125 both as a catcher and a tracer. However, serum antigen levels were closely correlated to each other and were elevated not only in patients with ovarian cancer, but also in patients with endometriosis and in some normal females during menstruation. These results suggest that CA125 has at least two antigenic determinants close to each other and this new rapid assay is useful, although not specific for ovarian cancer, in patients with gynecological disorders.

Animals↗
PubMed1990

[Levels of CA130 in maternal sera and amniotic fluid at various gestational ages].

We examined the CA130 concentration in the amniotic fluid, maternal sera, amnion, chorion, decidua and placenta. CA130 in the maternal sera showed an initial increase during early pregnancy, remained low from the 15th weeks of pregnancy until delivery, and then increased after term delivery (249u/ml, mean, n = 27) or mid-trimester abortions (844u/ml, n = 22). The CA130, concentration in the amniotic fluid was high in the mid-trimester and remarkably low at term. Among the tissues examined, amnion and decidua contained a relatively high concentration of CA130. Immunohistochemical examination also demonstrated abundant CA130 in the cytosol of amnion and decidua tissues. The pattern of changes in CA130 in amniotic fluid was similar to that in the amnion and decidua tissue. The results suggest that the amnion cells are the source of CA130 in the amniotic fluid and that the high concentration of CA130 in maternal serum after delivery originates in decidua tissue affected by the separation of the placenta.

Amnion↗
PubMed1990

In vitro and in vivo properties of human/mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen.

A human/mouse chimeric monoclonal antibody specific for a common acute lymphocytic leukemia antigen was efficiently obtained by ligating human heavy-chain enhancer element to the chimeric heavy- and light-chain genes. Cell binding and competitive inhibition assays of both radioiodine and indium-111- (111In) labeled chimeric antibodies demonstrated in vitro immunoreactivity identical with that of the parental murine monoclonal antibodies. The biodistribution of the radiolabeled chimeric antibody in tumor-bearing nude mice was similar to that of the parental murine antibody. Tumor accumulation of radioiodinated parental and chimeric antibodies was lower than that of 111In-labeled antibodies, probably because of dehalogenation of the radioiodinated antibodies. Indium-111-labeled chimeric antibody clearly visualized xenografted tumor. These results suggest that a human/mouse chimeric antibody can be labeled with 111In and radioiodine without the loss of its immunoreactivity, and that chimeric antibody localizes in vivo in the same way as the parental murine antibody.

Animals↗
PubMed1990

[Light and electron microscopic study of orbital cavernous hemangioma].

We examined the specimens of tumors from three patients with orbital cavernous hemangioma by light and electron microscopy. The tumors mostly consisted of many vessels of various sizes. A part of the tumor tissues showed irregular vascular inner spaces like sinusoids. Apart from the sinusoid-like vessels, we divided the other vessels into 10 groups at every 100 microns-interval based on the difference of the inner diameter and measured the maximum and minimum width of the media. The average maximum width increased until the inner diameter reached 300-400 microns, while the average minimum width increased until it reached 200-300 microns. In groups with greater inner diameter, the average maximum and average minimum widths were approximately constant. There were three kinds of vessels: vessels of cuboid endothelia, of flat endothelia, and of both cuboid and flat endothelia. The width of media of the vessels having cuboid and flat endothelia was greater than that of the other types of vessels. The lamina densa of endothelia was broken or stratified. Myofibroblast-like cells proliferated among the vessels and could not be distinguished from tumor cells of hemangiopericytoma. These results indicate that smooth muscle cells proliferate by an unknown mechanism and proliferation is associated with changes of endothelia in cavernous hemangioma, and strongly suggest that this tumor is hamartoma.

Endothelium, Vascular↗
PubMed1990

Secretion of tears in patients with hemifacial spasm.

Hemifacial spasm can cause abnormal tear secretion on the affected side. Thirty patients with this disease were examined using the Schirmer's test without topical anesthetic. Twelve of them showed more tear secretion on the affected side than on the unaffected side. The average Schirmer test value was 30.4 +/- 12.3 mm (+/- SD) on the affected side in the patients and 17.4 +/- 10.9 mm (n = 148) in the control subjects (P less than 0.001). Microvascular decompression surgery reduced the hypersecretion of tears. The results suggest that compression of the facial nerve by a blood vessel causes an excitatory stimulus for tear secretion in patients with hemifacial spasm.

Adult↗
PubMed1989

Effect of tumor mass and antigenic nature on the biodistribution of labeled monoclonal antibodies in mice.

The effect of tumor mass and antigenic nature on the biodistribution of 111In- and 125I-labeled monoclonal antibodies (MoAbs) was studied using F(ab')2 fragments of three representative anti-tumor MoAbs and SW1116 human colorectal carcinoma grown in nude mice. The 19-9, F33-104 anti-CEA, and 17-1A MoAbs showed specific binding to SW1116 cells. The former two MoAbs recognize circulating CA 19-9 with molecular weights of more than 5,000,000 and CEA of Mr 170,000-180,000, respectively, whereas 17-1A reacts with a nonshedding antigen. Both percentage injected dose per gram tumor and tumor-to-blood ratios were inversely proportional to the tumor mass in nude mice administered 111In- and 125I-labeled 19-9, but liver uptake increased as tumor size increased. Analysis of serum samples and tumor homogenates demonstrated the presence of a high-molecular-weight species, probably due to the antibody binding to CA 19-9. In the case of 111In-labeled anti-CEA MoAb, tumor uptake also decreased and liver uptake increased with tumor size, but this effect was less obvious than that of 19-9. In contrast, tumor and liver uptake of 125I-labeled anti-CEA MoAb, 111In- and 125I-labeled 17-1A and control antibodies were independent of tumor mass. The absolute tumor uptake and tumor-to-blood ratios of all 125I-labeled antibodies were lower than those of the 111In-labeled ones. And the effect of tumor mass was also weaker with 125I-labeled antibodies, probably due to in vivo dehalogenation. These results indicate that the effect of tumor size on the incorporation of labeled MoAb into tumors is dependent on the antigenic nature to be targeted and/or radionuclides used for labeling and that high concentrations of circulating high molecular weight antigens may limit in vivo use of MoAb conjugates.

Animals↗
PubMed1989

Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice.

In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a "gold standard" of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v.

Animals↗