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Biomedical subjects

N Hata

Publications and source records attributed to N Hata.

At least 109 records · Page 6Linked to original sources

Enzyme immunoassay of free triiodothyronine in serum.

In this new solid-phase antibody enzyme immunoassay for free triiodothyronine (FT3) in serum, beta-D-galactosidase conjugated to triiodothyronine is used. Results are uninfluenced by physiological concentrations of thyroxin-binding globulin or albumin. Results correlate well with those determined by equilibrium dialysis (r = 0.95). The mean CVs within and between assays were 6.1 and 9.5%, respectively. The measurable range of FT3 in serum is 0.7 to 26 ng/L; the normal reference interval is 1.9 to 8.9 ng/L. Concentrations of FT3 in serum of patients with hyperthyroidism were high; those of patients with hypothyroidism were within normal limits or low, and those of patients with congenitally decreased or increased TBG were within the normal range. In normal pregnant women, concentrations of FT3 as determined by radioimmunoassay correlated with those of albumin, declining as pregnancy progressed, but FT3 values determined by the proposed method or equilibrium dialysis were within the normal range and did not change during pregnancy.

Adult↗

Effect of pH on antigen binding by clonotypic antibodies with different isoelectric points.

Polyclonal rabbit antibodies to thyroxine, human myoglobin, human growth hormone, human thyrotropin, human alpha-fetoprotein, and human thyroglobulin were fractionated into clonotypic antibodies with different isoelectric points by agarose isoelectric focusing or chromatofocusing. The effect of pH on the binding of these antigens by their respective clonotypic antibodies was assessed by radioimmunoassay. The profiles of the pH effect differed both for different antigens and for different pI's of the antibodies used. The pH optima in the radioimmunoassays for protein antigens were found to be expressed as a function of pI and molecular weight of both antigen and antibody molecules.

Antibodies↗

Measurement of iodide in urine using the iodide-selective ion electrode.

A simple and rapid way to measure the concentration of iodide in urine with an iodide-selective ion electrode was described. Potentiometric equilibrium was attained in less than 5 min, and a linear calibration curve was obtained over the potassium iodide (KI) concentration range of 10(-2) to 10(-6) M. The coefficients of variation ranged from 6.2 to 10.0% within assay, and 5.4 to 14.4% between assays. The serial dilution of 3 urine samples with different concentration of iodide showed good linear correlations passing through zero. In practice, the chloride ions in urine did not cause serious errors in the measurement of iodide at molar ratios of chloride ion to iodide up to 2 X 10(4). A good linear correlation was obtained between iodide concentrations in urine determined by the electrode method and by the conventional chemical method (r = 0.92). A linear correlation was also observed between the iodide concentrations of 24 h collected urine and those of single morning urine (r = 0.91). The normal iodide content in single morning urine specimens from 127 Japanese people was 5.3 to 62.0 X 10(-6) moles/g creatinine.

Adult↗

Fractionation of polyclonal antibody by isoelectric focusing and chromatofocusing: separation of high-affinity rabbit clonotype anti-thyroxine antibody.

Immunoglobulin G fractions prepared from conventional rabbit anti-thyroxine (T4) antisera were fractionated by agarose gel isoelectric focusing (IEF) in the range of pH 3 to 10, and by chromatofocusing using a Fast Protein Liquid Chromatography (FPLC) system. The clonotype antibodies were recovered from the fractions and subjected to Scatchard plot analysis. The highest affinity constants of the initial antibody (shown in parentheses) and those of the antibodies recovered were IEF, 1.8 X 10(9) to 8.3 X 10(9) M-1 (2.2 X 10(9) M-1); FPLC, 2.4 X 10(9) to 6.0 X 10(9) M-1 (2.5 X 10(9) M-1). A sensitive radioimmunoassay of T4 was achieved with the isolated high-affinity anti-T4 antibody. The minimum detectable concentration of T4 was 6.3 X 10(-15) to 1.5 X 10(-14) mol/tube, which was three to five times lower than detectable with the initial antibodies.

Animals↗

The design of a pentavalent 99mTc-dimercaptosuccinate complex as a tumor imaging agent.

In our search for a technetium-tumor seeking agent, the chemical characteristic of polynuclear Ga-citrate attracted our attention. On this basis, we selected the ligand dimercaptosuccinic acid (DMS) and appropriate labeling conditions in the design of 99mTc(V)-DMS. Chemical characterization was performed by thin layer chromatography, electrophoresis, Sephadex column chromatography and spectrophotometric studies at the chemical concentration (99Tc). Biodistribution in mice bearing Ehrlich ascites tumor and scintigraphic images in VX-2 tumor-bearing rabbit, indicated the great applicability of 99mTc(V)-DMS as a new tumor imaging agent. Its distinctive characteristic, different from the kidney imaging agent (99mTc-DMSA) is demonstrated and the biological implication of hydrolytic polynucleation of pentavalent technetium, through an anionic specie Tc(V)O3-(4), in the tumor cell is discussed.

Animals↗

Iron(III)-nitrilotriacetate: an agent for reducing the time interval of tumor imaging with gallium citrate.

Increasing interest in the short-lived radionuclide 68Ga (t1/2: 68.2 min) has revived basic studies of gallium radiopharmaceuticals. Ga-citrate (Ga-cit), described as a polynuclear complex, possesses great affinity for tumor cells but is also bound by blood transferrin (Tf). Exploitation of reaction-rate differences in metal ion transference from Ga-cit to Tf (slow) and Fe-nitrilotriacetate (Fe-NTA) to Tf (fast) is put to use to attain a proper tumor/tissue ratio within practical time limits. Studies on administration mode, time and dose offered promising results for future 68Ga-cit tomographic studies.

Animals↗

A comparison of the tumor-seeking agent Tc-99m(V) dimercaptosuccinic acid and the renal imaging agent Tc-99m dimercaptosuccinic acid in humans.

Being aware of the ideal nuclear properties of Tc-99m, our interest has been focused on the design of the (+5) oxidation state Tc-99m(V) dimercaptosuccinic acid (Tc(V)-DMSA) as a tumor-seeking agent. Tc-99m(V) DMSA holds a TcO4(3-) core and, like PO4(3-), has excellent characteristics for tumor uptake, but has a different distribution than the well-known renal scanning agent, Tc-99m DMSA. The differences in chemical behavior of Tc-99m(V) DMSA and Tc-99m DMSA are discussed. Three cases in which neoplasms were studies with Tc-99m(V) DMSA and Tc-99m DMSA are presented. Tc-99m DMSA and Tc-99m(V) DMSA, having a common ligand and tracer but, with the metal ion core in a different oxidation state, the uptake characteristics are altered markedly.

Adrenal Gland Neoplasms↗

Imaging of head and neck tumors with technetium(V)-99m DMSA. A new tumor-seeking agent.

Tumor scintigraphy, using Tc(V)-99m DMSA was performed on 76 patients with head and neck tumors. In 32 cases, SPECT also was performed. Tc(V)-99m DMSA was found to have a sensitivity of 75% (56 cases), a specificity of 85% (20 cases) and an accuracy of 78% on planar imaging. ECT studies showed accumulation of Tc(V)-99m DMSA in all 25 malignant cases studied. However, in benign tumors, four of seven cases (57%) showed radionuclide uptake. Tc(V)-99m DMSA has superior physical properties to Ga-67 and could be of use in the diagnosis of head and neck tumors.

Adult↗

Prominent negative U wave in variant angina pectoris.

The extremely prominent negative U wave occasionally appears during a cardiac attack in variant angina pectoris. The clinical profile of the negative U wave was therefore studied in 80 patients with variant angina pectoris (VA) and 33 controls with resting angina pectoris (RA). The prominent negative U wave appeared in 55 of the patients with VA (68.8% of patients) and in 10 of the patients with RA (30.3%); thus, there was a significant difference in the appearance of the wave between the 2 groups of patients (p less than 0.001). The leads in which the negative U wave appeared were mostly consistent with those in which the ST segment was elevated. The negative U wave began to appear at about the time when ST-segment elevation began to improve; the wave then gradually became very prominent and then eventually disappeared. The patients with VA and also those with RA on whose ECGs the negative U wave appeared during exercise testing also had negative U waves during spontaneous episodes of angina. An investigation of the frequency of appearance of ST deviation and negative U waves during exercise testing, regardless of the type of angina pectoris, disclosed that the negative U wave appeared in 14 of 20 patients with ST-segment elevation (70% of patients), while the negative U wave appeared in only 52 of 519 patients with either no ST change or ST-segment depression (10.4%); thus, there was a significant difference in the appearance of the negative U wave between these 2 groups (p less than 0.001). Coronary cinearteriography failed to disclose any apparent difference between the appearance of the negative U wave and the presence of stenosis. The prognosis of VA and RA in patients with negative U waves was less favorable compared to those without negative U waves. In particular, we noted that of the 10 patients with RA associated with negative U waves, 4 died. Although the mechanism of the negative U wave is not yet known, we believe that the above findings contribute to its elucidation.

Adult↗

Enzyme immunoassay of free thyroxin in dried blood samples on filter paper.

We describe a double-antibody enzyme immunoassay for determination of free thyroxin (FT4) in dried blood samples on filter paper, with use of a T4-beta-D-galactosidase complex. The measurable range of FT4 concentration in two 3-mm blood discs, each of which contained about 2.7 microL of blood, was 1.9 to 93 ng/L, as determined by comparison with concentrations of FT4 in known serum standards. FT4 in blood samples dried on filter paper was stable for at least four weeks when kept dry at -20 degrees C, room temperature, or 37 degrees C. The mean coefficients of variation were 7.6% (within assay) and 6.4% (between assays). Results for FT4 by this method correlated well with those for serum determined by radioimmunoassay (r = 0.98). The proposed method can be used to differentiate persons with hyper- and hypothyroidism from normal subjects and those with abnormal concentrations of thyroxin-binding globulin. The procedure seems suited for screening studies.

Adult↗

Fractionation of polyclonal antibody by isoelectric focusing--differences in cross-reactivity and affinity of rabbit clonotype anti-human thyrotropin antibody.

Immunoglobulin G (IgG) fractions prepared from three different batches of rabbit antihuman thyrotropin (hTSH) antisera were fractionated by agarose isoelectric focusing (IEF) in the pH ranges 3 to 10 and 5 to 8. Staining of protein in agarose gel after IEF showed that polyclonal IgG separated into more than 20 protein bands with isoelectric points (pIs) ranging from 6 to 9. The clonotype antibodies to hTSH were recovered from the fractions and subjected to radioimmunoassay for determination of the binding-affinity for hTSH and the cross-reactivity with human chorionic gonadotropin (hCG). The affinity constants of the antibodies recovered ranged from 6.4 X 10(9) M-1 to 3.1 X 10(10) M-1, and the cross-reactivities of the clonotype antibodies differed greatly. A good correlation was observed between the pIs of antibody molecules and their cross-reactivities: antibodies with higher pIs bound hCG more strongly than those with lower pIs. The correlation coefficients between the pIs and cross-reactivities were 0.83, 0.84, and 0.87 in three batches of antibody.

Animals↗

Imaging of soft tissue tumors with Tc(V)-99m dimercaptosuccinic acid. A new tumor-seeking agent.

Tumor scintigraphy, using Tc(V)-99m dimercaptosuccinic acid (Tc(V)-DMS) was performed in 58 patients with soft tissue tumors, and the results were compared with that of Ga-67 citrate. Tc(V)-DMS was found to have a sensitivity of 90% for malignant tumors including aggressive fibromatosis compared to that of Ga-67 citrate, which was 56%. However, the specificity of Tc(V)-DMS for these tumors was 71% but with Ga-67 citrate the specificity was 80%. The imaging accuracy in soft tissue tumors with Tc(V)-DMS and Ga-67 citrate was 78% and 71%, respectively. Although the accumulation of Tc(V)-DMS has been detected in some benign soft tissue tumors, the reduced accumulation in inflammatory lesions compared to Ga-67 citrate was recognized, and Tc(V)-DMS could be of great use in the detection of extension or location of malignant soft tissue tumors.

Abscess↗

Enzyme immunoassay of thyroxin-binding globulin in dried blood samples on filter paper.

A double-antibody enzyme immunoassay was developed for determination of thyroxin-binding globulin in dried blood samples on filter paper. The measurable concentration range of thyroxin-binding globulin in two 3-mm blood discs was 3.3 to 52 mg/L equivalent of serum (i.e., equivalent to the concentrations in known serum standards). Thyroxin-binding globulin in dried blood samples on filter paper was stable for at least four weeks when kept dry at -20 degrees C, 4 degrees C, or room temperature. The mean coefficients of variation were 6.6% (within assay) and 5.9% (between assays). The concentrations of thyroxin-binding globulin in dried blood samples determined by this method correlated well with those in serum determined by radioimmunoassay (r = 0.95) and by enzyme immunoassay (r = 0.96). This method is applicable for detecting cases of thyroxin-binding globulin deficiency and avoids the false-positive results for neonatal hypothyroidism obtained by measuring thyroxin.

Adolescent↗