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Biomedical subjects

K Horiuchi

Publications and source records attributed to K Horiuchi.

At least 199 records · Page 11Linked to original sources
PubMed1987

Technetium-99m-labeled monoclonal antibody with preserved immunoreactivity and high in vivo stability.

Recent availability of monoclonal antibodies (MoAb) and their radiolabeling through the use of the bifunctional chelating agents (BCA) have become an alternative procedure for in vivo radioimmunodetection. Using a newly synthesized BCA, a p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), the coupling and technetium-99m (99mTc) labeling of monoclonal IgG against hCG were carried out. In the system presented, factors affecting stability and immunoreactivity were examined. Immunoreactivity of the original IgG (56C) was preserved by conjugating one CE-DTS molecule per molecule of IgG (56C) using the phosphorylazide method, however, 99mTc labeling pH affected the immunoreactivity and limited the 99mTc labeling reaction between pH 4.5 and 6.2. A screening of labeling conditions, such as pH, reaction time, and reducing agent system were then carried out. Technetium-99m-labeled IgG (56C), [99mTc]CE-DTS-IgG (56C), showed good stability upon incubation with mice sera and comparable mice biodistribution to that of indium-111 (111In) DTPA-IgG (56C). Thus, these results indicate the excellent potential of CE-DTS as a BCA for labeling MoAb with 99mTc.

Animals↗
PubMed1987

[A clinical study of urological examinations in uterus malignant tumors before treatment].

Sixty six cases of uterus malignant tumors examined urologically before gynecologic treatment between 1980 and 1984 are reviewed retrospectively. The uterus lesion excluding 1 malignant mixed mesodermal tumor was cervical carcinoma in 55 cases and corpus carcinoma in 10 cases. Pathologically, 46 cases were squamous cell carcinoma, 10 were adenocarcinoma, 3 were squamous adenocarcinoma and 6 were unknown. Clinical staging according to classification of FIGO, was stage 0 in 3 cases, stage I in 23 cases, stage II in 28 cases, stage III in 3 cases, stage IV in 7 cases, and unknown in 2 cases. Only 4 cases (6.1%) had urological symptoms with no special relationship to the uterus lesion. Abnormal findings of urine tests were seen in 15 cases (22.7%). The incidence of hematuria and pyuria, which were seen in 12 and 10 cases, respectively, was high. Cystoscopic abnormality was revealed in 32 (51.6%) out of 62 cases. Protrusion of vesical wall was found in 11 cases (34.3%) and it was an important finding which showed a significant incidence. Edema was seen in 11 cases (34.3%). This was a sign of progression, and the observation on spread of lesion was important. Redness was seen in 3 cases (4.8%). It was considered to be the result of circulatory disturbance. At the same time observations on vascular change, edematous change etc. should be done in detail. Bleeding was seen in 1 case (1.6%), microscopic bleeding was seen more frequently than macroscopic bleeding. Abnormalities of ureteral orifice were significant only after other examinations were reviewed in addition to these signs. IVU was performed in 58 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1987

[A case of retroperitoneal fibrosis].

We report a case of retroperitoneal fibrosis. A 75-year-old man complained of edema of bilateral lower limbs and lumbago. Blood urea nitrogen and serum creatinine were increased. Renal function was improved after he had bilateral percutaneous nephrostomies. Antegrade pyelography showed bilateral hydronephrosis, left ureteral obstruction and medial deviation with narrowing of the right ureter. CT revealed a soft tissue density surrounding the aorta, inferior vena cava and bilateral ureters in the retroperitoneal space. Inferior venocavagraphy displayed stenosis. Bilateral ureterolysis combined with omental sleeve plasty was performed. Post-operatively, the clinical course has continued to be good.

Aged↗
PubMed1987

Formation of light irreversibly sickled cells during deoxygenation-oxygenation cycles.

Changes in density, morphology, and monovalent cation content of sickle (SS) cells caused by repetitive sickling were investigated in vitro with a device by which red cells can be exposed to cycles of deoxygenation and oxygenation (d-o cycles). Experiments were done using the discocyte-rich, less dense fractions of SS cells. When such cells were subjected to d-o cycles in the presence of 2 mmol/L Ca2+, most became dense within 4 hours. The density of these cells was slightly lower than usual for irreversibly sickled cells (ISCs), and because they reverted to the discoidal shape after oxygenation, they were not considered ISCs. However, on further d-o incubation, they did assume the morphology and density typical of ISCs. After an additional incubation (20 hours), most cells decreased in density, became very fragile, and hemolyzed easily. Such light ISCs could also be formed from freshly prepared dense cells on d-o incubation. Once light ISCs were formed, they did not reconvert to dense cells on further incubation. It should be noted that light ISCs created in vitro tended to aggregate much more easily than ordinary (heavy) ISCs did, suggesting that the membrane of these cells may be very adhesive.

Anemia, Sickle Cell↗
PubMed1986

The mechanism of in vitro formation of irreversibly sickled cells and modes of action of its inhibitors.

When red blood cells from sickle-cell patients were exposed to repeated cycles of deoxygenation and reoxygenation (one cycle was 5 min), dehydration of the cells was observed after several cycles of the sickling-desickling process. These dehydrated cells still maintained a biconcave form after 1 h of such cycling, but they started to take the form of irreversibly sickled cells after several hours. If red cells were simply kept deoxygenated for 16 h, neither dehydrated cells nor irreversibly sickled cells were formed. The formation of dehydrated cells was inhibited either by elimination of Ca2+ from the medium, or by the increase of K+ concentration in the medium. Under conditions in which dehydrated cells were not formed, i.e., deoxygenation incubation (either in the absence or presence of Ca2+) or the deoxygenation-reoxygenation cycling in the absence of Ca2+, 15-25% of cellular K+ leaked out during 4 h of incubation. When dehydrated cells were formed in deoxygenation-reoxygenation cycling in the presence of Ca2+, 40-50% of K+ was lost in 4 h. Two different types of inhibitor were found. The first type includes inhibitors of the Ca2+-activated K+ efflux, such as quinine, quinidine or tetraethylammonium chloride. These compounds suppressed both the K+ efflux and the formation of dehydrated cells. The second type includes calmodulin-interacting drugs. For example, chlorpromazine (20 microM) inhibited the formation of dehydrated cells almost completely, even though it did not inhibit the K+ efflux remarkably. Several other calmodulin-binding drugs were found to inhibit the formation of dehydrated cells similarly, and the potency of these drugs to inhibit the formation seems to be related to the binding affinity of these drugs to calmodulin.

Adenosine Triphosphate↗
PubMed1986

Interaction between gene II protein and the DNA replication origin of bacteriophage f1.

The origin of DNA replication of the filamentous bacteriophage f1 binds its initiator protein (gene II protein) in vitro to form a complex that can be trapped on nitrocellulose filters. The binding occurs with both superhelical form DNA and linear DNA fragments. A number of defective mutants of the origin were tested for the ability to bind gene II protein. The region of DNA required for the binding is around a second palindrome downstream from the palindrome that contains the DNA replication initiation site. It overlaps, but is not identical to, the region required for the nicking reaction by the protein. The nicking site itself was dispensable for the binding. In vivo, a number of defective deletion mutants of the origin, when in a plasmid, inhibited growth of superinfecting phage if the intracellular level of gene II protein was low. In addition, these defective origins inhibited the activity of the functional phage origin located on the same replicon. The domain of the DNA sequence required for inhibition in vivo was consistent with that for the binding in vitro.

Bacteriophages↗
PubMed1986

The relationship between trypsin activity in amniotic fluid and premature rupture of membranes.

Trypsin activity and concentration of alpha 1-antitrypsin in amniotic fluid were measured in patients with and without premature rupture of membranes. Trypsin activity in amniotic fluid with premature rupture of membranes (127 +/- 57 U/L) was found to be significantly higher than in cases without premature rupture of membranes (14 +/- 20 U/L) (p less than 0.01). The concentration of alpha 1-antitrypsin in amniotic fluid with premature rupture of membranes (6.8 +/- 5.5 mg/dl) was significantly lower than in cases without premature rupture (25.2 +/- 20.2 mg/dl) (p less than 0.01). Trypsin activity and concentration of alpha 1-antitrypsin in amniotic fluid were not influenced by rupture of membranes and labor. These studies suggest that high trypsin activity and low concentration of alpha 1-antitrypsin in amniotic fluid is one cause of premature rupture of membranes.

Amnion↗
PubMed1986

Abnormal membrane properties of the sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia: modes of action of halothane, caffeine, dantrolene, and two other drugs.

The role of sarcoplasmic reticulum (SR) in malignant hyperthermia (MH) was studied using the heavy microsomal fraction prepared from semitendinosus muscles of both normal and genetically MH-susceptible pigs. In the presence of ATP, SR was loaded with 70 nmol Ca2+/mg SR protein. Under these conditions, MH-SR demonstrated Ca2+-induced Ca2+ release (Ca-ICaR) and halothane-induced Ca2+ release (halothane-ICaR; halothane concentrations as low as 10 microM). Normal SR did not demonstrate these release phenomena. Dantrolene inhibited the halothane-ICaR, but did not inhibit the Ca-ICaR. Ruthenium red and tetracaine inhibited both types of Ca2+ release. From the measurement of passive Ca2+ efflux, it was shown that dantrolene did not affect the Ca2+ permeability of the SR itself, but suppressed only the halothane-induced increment of the permeability. The membrane order parameter of the SR, as measured by the spin-probe EPR technique, indicated that halothane disordered the lipid bilayer of MH-SR to a greater extent than it did of normal SR. This halothane disordering effect on MH-SR was antagonized by dantrolene. Ruthenium red and tetracaine did not antagonize the halothane disordering effect. These results raise the possibility that halothane could disturb the structure of the lipoprotein complex in MH-SR in such a way that it could open the Ca2+-release channels. The Ca2+ thus released further opens the channel through the Ca-ICaR mechanism in a positive feedback fashion, thus triggering the MH syndrome. The efficacy of dantrolene in ameliorating the MH syndrome might be related to the inhibition of this halothane effect.

Animals↗
PubMed1986

In the procurement of stable 99mTc labeled protein using bifunctional chelating agent.

Recently, technetium-99m (99mTc) labeling of proteins through the use of a bifunctional chelating agent (BCA) has been reported. In previous work, a BCA containing a di(N-methylthiosemicarbazone) (DTS) moiety for 99mTc has offered good potential; however, conjugation with bulky proteins has induced some steric interference in the 99mTc labeling step using the stannous chloride method. In order to minimize this effect, changes in the hydrocarbon chain length (spacer) between the DTS and the protein binding site (carboxyl group), as well as the chemical state of the reducing agent, stannous chloride, were considered of interest. DTS molecules with variable spacer length (n = 0, 2, 4) were synthesized, coupled with human serum albumin and labeled with 99mTc. Also, stannous chloride prepared in different media was evaluated. Validity of the present approach is tested and discussed.

Animals↗
PubMed1986

Search for 99mTc labeled DTS bifunctional radiopharmaceutical: role of functional groups in myocardial accumulation.

Development of 99mTc-bifunctional radiopharmaceutical (BR) is attracting the interest of various research groups. In the present paper, various molecules containing a neutral 99mTc-dithiosemicarbazone (DTS) structure as the technetium chelating site, along with various functional groups (amino, carboxyl or isobutyl group with diverse charge) are tested for their chemical or biological functions. The study on the effect of those functional groups is carried out in vitro and in vivo. The validity of introducing an amino group along with the technetium chelating site DTS for myocardial accumulation is discussed.

Animals↗
PubMed1986

Design of bifunctional radiopharmaceutical for the development of 99mTc complexes for myocardial imaging agents.

Several bifunctional radiopharmaceuticals (BR), molecules containing a neutral 99mTc-dithiosemicarbazone (DTS) structure as a chelating site, along with a functional amino group (primary tertiary and quaternary amino group) are tested for their chemical or biological functionalities as myocardial agents. Investigation of these amino compounds is carried out in vitro and in vivo. Mice (ddY) distribution studies show a high radioactivity distribution in heart with every tested derivative, but the highest heart to blood ratio of 2.92 (1 h) is achieved with the quaternary amino DTS. Also, this derivative displays low lung uptake inducing a proper target/non-target ratio for myocardial agent. The role conveyed by the various amino containing side chain in the biodistribution and validity of DTS derivative as BR are discussed.

Animals↗
PubMed1986

Synthesis and evaluation of a new bifunctional chelating agent for 99mTc labeling proteins: p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone).

A new bifunctional chelating agent, p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), containing a di(N-methylthiosemicarbazone) as the technetium coordinating site and an aralkyl carboxylate site for the protein conjugation was synthesized. Coupling to human serum albumin (HSA), selected as a model protein was carried out by the phosphorylazide method using diphenylphosphoryl azide (DPPA). The conjugation level of CE-DTS to HSA played a critical role in its biological evaluation. A 99mTc-CE-DTS-HSA with high in vivo stability was obtained when CE-DTS was coupled to HSA at 1:1 molar ratio. This compound showed similar in vivo stability to 131I labeled HSA in mice and rabbits.

Animals↗
PubMed1986

In the procurement of a neutral and compact monomeric complex of dithiosemicarbazone (DTS) derivative: 99mTc-KTS.

As a basic structure of a bifunctional radiopharmaceutical (BR), dithiosemicarbazone (DTS) enables the formation of a small conjugated chelating ring with divalent metals (Cu2+, Zn2+, Ni2+), yielding stable and compact complexes. In the development of a neutral and compact monomeric DTS complex of technetium (99mTc), a DTS containing ligand, kethoxal-bis(thiosemicarbazone) (KTS) was selected. A well known monomeric Cu-KTS complex (or 64Cu-KTS) is taken as a model compound, and in vitro (TLC, EP, HPLC) and in vivo (mice biodistribution) studies were compared. Using the stannous chloride method, under conditions to avoid the hydrolytic polynucleation of technetium, a good yield of 99mTc-KTS with characteristics resembling the non-charged, compact and stable Cu-KTS is obtained, in in vitro as well as in vivo studies. The importance of DTS as the constituent of a BR is discussed.

Animals↗