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Biomedical subjects

K Horiuchi

Publications and source records attributed to K Horiuchi.

At least 217 records · Page 12Linked to original sources
PubMed1986

62Zn-EDDA: a radiopharmaceutical for pancreatic functional diagnosis.

As Zn is closely associated with the exocrine and endocrine functions of the pancreas, exploitation of Zn metabolism for anatomical and functional diagnosis was conceived, namely with the recent availability of positron emitting 62Zn (t1/2 = 9 h). In the present paper, response changes in Zn biodistribution (mice) and Zn excretion through the pancreatic duct (rats) due to the stimulation of gastro-intestinal hormones like secretin, CCK-PZ (exocrine stimulation) and glucose (endocrine stimulation) were studied. Under these stimuli, the pancreatic secretion of radioactive Zn through cannulated pancreatic duct showed increased Zn secretion only under the CCK-PZ effect, 3 h post 65Zn (t1/2 = 270 d) injection. Tissue biodistribution in mice pre-injected with 65Zn showed pancreas specific decrease of radioactive Zn whenever a gastro-intestinal hormone was post-administered, whereas the glucose effect was negligible. Thus, the effective mobilization of the injected radioactive Zn, upon exocrine stimulation, represented by CCK-PZ, favored the exploration of a functional study of the pancreas with the positron computed tomograph (PCT) using short lived nuclide labeled 62Zn-EDDA in dog. Evidence of the applicability of this system in regional function studies of the pancreas was obtained. Demonstration of Zn participation in the exocrine function of the pancreas in-vivo holds considerable promise for diagnosis of pancreatic diseases.

Animals↗
PubMed1986

A cell-binding, immunoglobulin-like protein from human plasma. I. Isolation and subunit structure.

A protein having Mr of more than 900K (900,000) was isolated by chromatography on a column of Sepharose 4B coupled with solubilized elastin, followed by sucrose density gradient centrifugation. The protein is composed of several disulfide-linked subunits. SDS-polyacrylamide gel electrophoresis and immunoblotting indicated that two of the subunits are identical with the heavy chains of IgM and IgG, and one is immunologically related to the heavy chain of IgA. The results suggested that this protein is a new protein that belongs to the category of, or is closely related to, the immunoglobulins. As described in the succeeding paper, it has cell-binding activity (Fukamizu et al. (1986) J. Biochem. 100, 843-848). We tentatively refer to this protein as "cell-binding immunoglobulin-like protein (CIP)."

Amino Acids↗
PubMed1986

A cell-binding, immunoglobulin-like protein from human plasma. II. Cell-binding activity.

Cell adhesion to plastic surfaces coated with a new high-molecular-mass immunoglobulin-like protein from normal human plasma was studied. Mouse subdermal fibroblasts, hamster kidney cells, human umbilical vein endothelial cells, and human skin fibroblasts were found to become attached to the surface, but cancer cells derived from human stomach cancer and human breast cancer did not. The appearance of the attached cells differed from that of cells attached to surfaces coated with fibronectin or concanavalin A. The cell adhesion to the surfaces coated with the protein was inhibited by goat anti-human IgM. Furthermore, the binding of the protein to the cell surfaces was demonstrated by the indirect immunofluorescence method. It is concluded that this protein is a new cell-binding protein.

Animals↗
PubMed1986

Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA.

The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas.

Adult↗
PubMed1986

Nitrendipine, nifedipine and verapamil inhibit the in vitro formation of irreversibly sickled cells.

Nitrendipine, nifedipine and verapamil inhibit the in vitro formation of irreversibly sickled cells. Using a method of forming both dehydrated cells and irreversibly sickled cells in vitro by repeated cycles of sickling and unsickling, the effects of several drugs in inhibiting the formation of these cells were studied. Drugs known as Ca2+ channel antagonists, such as nitrendipine, nifedipine and verapamil were found to inhibit these reactions. Other types of calcium channel blockers, such as lanthanum and zinc, did not inhibit the formation of these cells. The potency of drugs to inhibit irreversibly sickled cell formation was related to the potency of inhibition of calmodulin-activated phosphodiesterase.

Adult↗
PubMed1986

[Development of neutral and bifunctional radiopharmaceuticals using 62Cu-dithiosemicarbazone (DTS) chelate--basic studies on 64Cu chelates].

Recent plausibility of generator produced 62Cu, a positron emitter is attracting the interest of those working in the development of bifunctional radiopharmaceuticals (BR). In our development of bifunctional radiopharmaceuticals containing a neutral dithiosemicarbazone (DTS) metal chelate, tertiary (p-DPA-DTS) and quaternary (p-TPA-DTS) amino DTS derivatives were synthesized. As for the basic understanding of their divalent metal (Cu2+, Ni2+, Zn2+) complex formation and stability, spectrophotometrical studies were carried out, comparatively with KTS. Upon assessment of preferential behavior of Cu chelate, the radiolabeled 64Cu-DTS derivative chelates were tested in mice, and potential use with 62Cu in positron nuclear medicine is discussed.

Animals↗
PubMed1986

A radiopharmaceutical for pancreatic exocrine functional diagnosis: 62Zn-EDDA metabolism in pancreas.

The metabolic pathway of radioactive 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid), in the exocrine pancreas was studied with respect to that of endogenous Zn. In pancreatic duct cannulated dog, the secretion of intravenously injected exogenous 62Zn into pancreatic juice increased under the stimulation of CCK-PZ (pancreatic protein secretion stimulating hormone), which closely correlated to endogenous Zn. Moreover, in pancreatic juice, 62Zn as well as endogenous Zn was selectively bound to Zn-metalloenzymes, carboxypeptidase A and B. These results demonstrated the close correlation between the endogenous and the exogenously-administered Zn (62Zn-EDDA), as well as the high availability of 62Zn-EDDA as a marker of pancreatic function for the follow up of carboxypeptidase metabolism.

Animals↗
PubMed1986

[Regional coronary outflow and coronary reserve assessed by the thermodilution technique: an experimental study].

Coronary blood flow distribution and coronary flow reserve were experimentally evaluated by the thermodilution technique. Using a special catheter with two external thermistors 5 cm apart, the great cardiac vein (GCV) outflow and coronary sinus (CS) outflow were measured. Coronary inflows in the left anterior descending (LAD) and circumflex (LCX) arteries were measured by electromagnetic flow probes during arterial occlusion or bolus arterial injection of nitroglycerin and dipyridamole injection in a peripheral vein. On the LAD side, the venous flow due to the interventions increased both GCV and CS outflows, while the interventions in the LCX increased CS outflow without significant changes in the GCV flow. LAD inflow and GCV outflow, and LCX inflow and (CS-GCV) flow correlated well, and there were significant close correlations between each inflow and outflow. Coronary reserve in the LAD and LCX was studied in successive 70% and 90% stenoses produced by a calibrated constrictor. Maximal coronary flow was obtained during reactive hyperemic response after coronary artery occlusion. Although there was no significant coronary reserve in the coronary inflow or outflow in the basal state, coronary reserve in the GCV and CS decreased significantly in stenoses of the LAD and LCX. These results suggest that this method allows practical assessment of drainage from the LAD and LCX areas and that stenosis greater than 70% can be estimated from the changes in regional venous outflows. This method may be helpful in evaluating regional coronary hemodynamics clinically.

Animals↗
PubMed1985

Collagen types in normal and prematurely ruptured amniotic membranes.

Collagen content in preterm amnions with premature rupture of the membranes was significantly lower than that of preterm amnions without premature rupture of the membranes. Collagen types were studied through sodium dodecyl sulfate-polyacrylamide gel electrophoresis in human amnions from pregnant women with or without premature rupture of the membranes. Collagen types I, III, and V were recognized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in all samples. In samples taken from preterm patients with premature rupture of the membranes, the ratios of III/I, III/V, and III/total collagen were significantly lower than those from ones without premature rupture of the membranes. The ratios of I/V, I/total collagen, and V/total collagen showed no change in gestations with and without premature rupture of the membranes, respectively. In term samples there was no significant difference in the ratios of all collagen types between those with and those without premature rupture of the membranes. Elastins were not demonstrable in amnion with and without premature rupture of the membranes. These studies suggest that the reduction of type III collagen content in amnion is related to the cause of premature rupture of the membranes, particularly in preterm samples.

Adult↗
PubMed1985

[125I] radioiodinated metaraminol: a new platelet-specific labeling agent.

In our search for a platelet-specific labeling agent, metaraminol (MA), a low-toxic pharmaceutical for the treatment of hypotension and cardiogenic shock, attracted our attention. Its active incorporation and accumulation by platelets have been recognized. At first, the preparation of 125I radioiodinated metaraminol (125I-MA) was carried out using the chloramine-T method. Then, upon the harvest of platelets as platelet-rich plasma (PRP), their labeling with this new radiopharmaceutical was easily performed by incubation for 10 min at 37 degrees C. The cell-labeling efficiency was dependent on cell density, reaching 63.0% +/- 3.1% at 2.4 X 10(9) cells/ml. The specific incorporation of 125I-MA by an active transport system similar to that of 5-hydroxytryptamine (5-HT) as well as by passive diffusion was demonstrated. In in vitro studies, the unaltered state of 125I-MA-labeled platelets with their cellular functions fully retained was estimated. In vivo studies carried out in rabbits with induced thrombi in the femoral artery showed a rather rapid disappearance of the radioactivity from circulating blood, reaching a high thrombus-to-blood activity ratio of 19.8 +/- 4.3 within 30 min of the administration of 125I-MA-labeled autologous platelets. Thus, with the potential availability of 123I, 123I-MA-labeled platelets appear to be a promising agent for thrombus imaging using single-emission computed tomography (CT) studies.

Animals↗
PubMed1985

In vivo kinetics and thrombus accumulation of 67Ga-labeled urokinase.

Highly purified high and low molecular weight urokinase (H-UK and L-UK) were labeled with 67Ga using deferoxamine (DF) as a bifunctional chelating agent. The labeling efficiency was 91.7% for the H-UK, and 90.4% for the L-UK, respectively. The 67Ga labeled UK (67Ga-DF-UK) fully retained the enzymatic activity of the parent UK. Studies on the in vivo behavior of the 67Ga labeled UK in rabbits showed a very rapid blood clearance with half-life of 4 min (67Ga-DF-L-UK) to 8 min (67Ga-DF-H-UK). Studies carried out in rabbits with induced thrombi in the femoral vein showed thrombus-to-blood 67Ga-DF-UK activity ratios, 2h after injection, of 2.00-3.08 for the H-UK, and 0.84-1.65 for the L-UK, respectively, with thrombi aged 4 to 3 days. A dose effect of the 67Ga-DF-H-UK on its thrombus accumulation was observed. Gel chromatographic analysis of plasma samples withdrawn from those animals injected with this radiopharmaceutical revealed a reduction of the 67Ga-DF-UK effectiveness due to complexation with protein inhibitors. This led to formation of high molecular weight complexes which was reflected in the very fast blood clearance. Its implication in thrombus accumulation is discussed. In conclusion, usefulness of DF for labeling UK with 67Ga or 68Ga with no alteration of UK enzymatic properties was demonstrated. The use of 67Ga-DF-UK as a diagnostic or therapeutic radiopharmaceutical is promising.

Animals↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Sarcoplasmic reticulum membrane of rat skeletal muscle is disordered with chronic alcohol ingestion.

Heavy sarcoplasmic reticulum (SR) was prepared from skeletal muscle of chronic alcoholic rats and control rats. Compared with control rat SR, the SR prepared from alcoholic rats is leakier to Ca2+ and has a lower level of maximum storable Ca2+. With in vitro exposure to ethanol, the Ca2+ release of alcoholic rat SR was not enhanced as much as that of SR prepared from control rats. By using the spin-probes 5-, 7-, 12-, and 16-doxylstearic acid, the disordering effect of ethanol on the SR membrane was studied. The results suggest that SR membrane of chronic alcoholic rats is less ordered than that of control rats even in the absence of in vitro ethanol. However, chronic SR membrane shows a greater resistance to the disordering effect of in vitro addition of ethanol than control rat SR.

Alcoholism↗
PubMed1985

Solubilization and reconstitution of the calcium release channel of skeletal sarcoplasmic reticulum.

Fragmented heavy sarcoplasmic reticulum was solubilized by cholate, and proteins were subsequently fractionated by using diethylaminoethyl-cellulose (DEAE-cellulose) column chromatography. A fraction was collected in which proteins with molecular weights between 31,000 and 45,000 u were major components. This fraction, when incorporated into Ca2+ -loaded liposomes, facilitated the Ca2+ efflux. The rate of efflux was regulated by the external Ca2+ concentration, reaching a maximum at 3 microM Ca2+. The Ca2+ efflux was suppressed by Mg2+.

Animals↗
PubMed1985

Clinical experience with Oka live varicella vaccine in Japan.

A live varicella vaccine (Oka strain) has been developed and used since 1974 in normal and diseased children, particularly those at high risk. Children with acute leukaemia were usually vaccinated while in remission when showing a normal cell-mediated immunity as assessed with phytohaemagglutinin (PHA) or other reagents, and during suspension of all anticancer therapy, except 6-mercaptopurine from 1 week before to 1 week after vaccination. While clinical reactions were observed in only 40 out of 263 (15.2%) of these patients, they were noted in 30 out of 72 (41.7%) children immunized without suspension of chemotherapy. Symptoms were mostly mild; only a few cases of the latter group with T-cell leukaemia or malignant lymphoma developed severe symptoms. An immune response was observed in most vaccinees, but some (11%) developed clinical symptoms after exposure to natural varicella due to immunodepression caused by continuing anticancer chemotherapy. In these cases, revaccination seems advisable. The incidence and severity of zoster in vaccinated acute leukaemic children were less than in those with natural infection. Satisfactory immune responses with few concomitant clinical reactions were observed in approximately 1,500 vaccinees having nonmalignant diseases and in about 4,000 normal children. A 7-10-year follow-up study revealed that the vaccine had conferred solid immunity on the children. These results indicate that live varicella vaccine of the Oka strain is useful in preventing varicella in high-risk as well as in normal children.

Acute Disease↗