Folic acid deficiency in hemochromatosis: probably due to a defective storage of folic acid in the liver.
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Anemia, Aplastic↗
Biomedical subjects
T Konno
Publications and source records attributed to T Konno.
Conjugation of enzymes on polymer nanoparticles covered with phosphorylcholine groups.
We investigated the bioconjugation of enzymes on polymer nanoparticles covered with bioinert phosphorylcholine groups. A water-soluble amphiphilic phospholipid polymer (PMBN) was specially designed for preparation of nanoparticles and conjugation with enzymes on them. The PMBN was prepared by random copolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC), n-butyl methacrylate, and p-nitrophenylester bearing methacrylate. The PMBN was used as an emulsifier and a surface modifier to prepare the poly(l-lactic acid) nanoparticles by a solvent evaporation technique in aqueous medium. The nanoparticles covered with phosphorylcholine groups were stably dispersed in an aqueous solution and a phosphate buffered saline. The diameter and surface zeta-potential of the nanoparticles were ca. 200 nm and -6 mV, respectively. The p-nitrophenyl ester groups, which are active ester units for the amino groups of the protein, were located at the surface of the nanoparticles. Both acetylcholine esterase and choline oxidase were co-immobilized (dual-mode conjugation) by the reaction between the p-nitrophenyl ester group and the amino group of these enzymes. The enzymatic reactions on the nanoparticles were followed using a microdialysis biosensor system with a microtype hydrogen peroxide electrode in the probe. The nanoparticles conjugated with these enzymes could detect the acetylcholine chloride as hydrogen peroxide, which is a product of the enzymatic reactions on the surface of the nanoparticles in the probe. Namely, continuous enzyme reactions could be occurring on the surface of the nanoparticles. It is concluded that the nanoparticles are a promising tool for a highly sensitive and microdiagnostic system.
Animals↗
Location of a delta-subunit region determining ion transport through the acetylcholine receptor channel.
The combination of complementary DNA expression and single-channel current analysis provides a powerful tool for studying the structure-function relationship of the nicotinic acetylcholine receptor (AChR) (refs 1-5). We have previously shown that AChR channels consisting of subunits from different species, expressed in the surface membrane of Xenopus oocytes, can be used to relate functional properties to individual subunits. Here we report that, in extracellular solution of low divalent cation concentration, the bovine AChR channel has a smaller conductance than the Torpedo AChR channel. Replacement of the delta-subunit of the Torpedo AChR by the bovine delta-subunit makes the channel conductance similar to that of the bovine AChR channel. To locate the region in the delta-subunit responsible for this difference, we have constructed chimaeric delta-subunit cDNAs with different combinations of the Torpedo and bovine counterparts. The conductances of AChR channels containing chimaeric delta-subunits suggest that a region comprising the putative transmembrane segment M2 and the adjacent bend portion between segments M2 and M3 is involved in determining the rate of ion transport through the open channel.
Animals↗
Application of dye-enhanced laser ablation for liver resection. Production of protein sealant on the cut surface of the liver by enhanced thermal energy of low power diode laser.
BACKGROUND: Dye-enhanced laser ablation (DLA) using a low-power diode laser for indocyanine green (ICG)-stained tissue has proven its effectiveness in dye-enhanced laser photocoagulation of retinal vessels or endoscopic surgical mucosectomy. We have applied DLA in hepatectomy and described its histological distinction in comparison with the cavitron ultrasonic surgical aspirator (CUSA). METHODS: A diode laser (UDL-60 Laser unit, Olympus, Tokyo, Japan) with 810 +/- 20 nm wavelength was employed for this study. The ICG dye (Diagnogreen, Daiichi Pharmaceutical, Tokyo, Japan) with a peak absorption wavelength at 800-810 nm was injected topically into the resection plane of the liver. The liver tissue was divided by touching the tip of the diode laser. Three different concentrations of ICG solution such as 2.0, 1.0 and 0.5 mg/ml were tested in the preliminary animal experiment. The use of a low-power diode laser at 10 W with an ICG concentration of 0.5 mg/ml was the appropriate combination for liver resection. In the clinical series, 27 hepatectomies were performed by DLA, and 10 with CUSA. RESULTS: DLA demonstrated smooth cutting and good hemostasis in liver resection. Among the hepatectomy cases given DLA, no postoperative hemorrhage or bile leakage was noted. The postoperative hospital stay was significantly shorter in the DLA than the CUSA group. The cut surface of the liver was sealed microscopically with a layer of protein coagulum. CONCLUSIONS: A layer of protein sealant on the cut surface of the liver contributes to the short postoperative hospital stay when using DLA.
Adult↗
Epstein-Barr virus-associated lymphoproliferative disorder after unrelated bone marrow transplantation in a young child with Wiskott-Aldrich syndrome.
We report a case of a 16-month-old Wiskott-Aldrich syndrome (WAS) patient with a WASP gene mutation who received human leukocyte antigen (HLA)-matched, unrelated allogeneic bone marrow transplantation (BMT) followed by an Epstein-Barr virus-associated lymphoproliferative disorder (EB-LPD), diagnosed by clinical findings, polymerase chain reaction detection of the EB virus genome, and spontaneous lymphocyte proliferation of donor cell origin. EB-LPD is one of frequent lethal complications in HLA-mismatched or unrelated BMT in this syndrome. Adoptive immunotherapy with donor leukocyte transfusion, including appropriate numbers of CD3-positive T cells, was effective for the EB-LPD, achieving almost complete recovery 1 year later without any findings of graft-versus-host disease.
Bone Marrow Transplantation↗
K-ras gene mutations in non-small cell lung cancer in Japanese.
To evaluate the association of mutations in the K-ras gene with the incidence of non-small cell lung cancer (NSCLC) in Japanese patients, 410 patients treated surgically were studied. DNA was extracted from frozen specimens, and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) hybridization assay was used to examine K-ras mutations in codons 12, 13 and 61. K-ras mutations were found in 33 patients (8.0%), and all were smokers or ex-smokers. There were no significant differences in clinical or pathological stage between wild-type cases and mutant cases. The most frequently identified mutation was a G-->T transversion (25/33, 75.8%) that resulted in the substitution of a glycine for a cysteine or a valine. Previous studies have shown that the majority of K-ras mutations among smokers are G-->T transversion. In our study, K-ras mutations were found only in smokers, and there was a high frequency of G-->T transversions. A clear correlation exists between smoking and K-ras gene mutations.
Adenocarcinoma↗
Bone and joint manifestations of Rieger's syndrome: a report of a family.
Rieger's syndrome is a disease characterized by ocular anomalies usually associated with glaucoma but very rarely with bone and joint abnormalities. In three cases in a family with Rieger's syndrome, the proband was a 6-year-old girl, with involvement of her 9-year-old sister and 39-year-old father. The skeletal abnormalities found in these three individuals were a prominent posterior clinoid process (sella turcica), hypoplasia of the maxilla and the mandibula, pseudoepiphyseal center of the metatarsus and the metacarpus, and irregular ossification of the femoral head, the distal femoral, and distal tibial epiphyses and the short second and fifth metatarsi.
Adult↗
Tumor targeting by arterial administration of lipids: rabbit model with VX2 carcinoma in the liver.
We previously found that a lipid contrast medium, Lipiodol, remained selectively in liver tumors for a prolonged time after injection via the hepatic artery. We now extend this technique to other lipids including linoleic acid, olive oil, tea seed oil, and medium-chain triglyceride (MCT). MCT is a semisynthetic triglyceride with a lower viscosity than that of the other lipids. Each lipid was mixed with 14C linoleic acid, and the mixture with or without anticancer agent smancs was injected via the proper hepatic artery of rabbits with VX2 carcinoma in the liver. The 14C count in the tumor tissue was always more than 100 times that of the plasma or kidney, and the radioactivity 15 min after injection of MCT was more than 2500 times greater than that of blood plasma. At 24 hr after injection, the radioactivity recovered in the tumor was 4.9-37.0% (average 19.6%) of the dose, which indicated the greatest retention in the tumor tissue; there was rapid clearance from the rest of the body primarily via the bile. Advantages of the administration of lipid-solubilized drugs are: (i) remarkable tumor-selective targeting (a decisive anticancer effect with fewer side effects); (ii) prolonged drug retention (resulting in infrequent administration); (iii) various choices of different fatty acids with various pharmacokinetic characteristics as the carriers of the anticancer agents; and (iv) arterial administration is practicable in most hospitals.
Animals↗
Intracavitary treatment of malignant ascitic carcinomatosis with oily anticancer agents in rats.
The anticancer effects and pharmacokinetics of intraperitoneal (ip) injection were determined for doxorubicin (DOX) dissolved in a lymphographic oily contrast medium, Lipiodol Ultrafluid (Lipiodol) (DOX/Lipiodol), using AH 130 ascitic tumor in rats. A high percentage (50%) of long-term survivors (cure) was observed with only a single ip injection of the DOX/Lipiodol on the seventh day after tumor inoculation, by which time the tumor ascites accumulated to a level similar to that seen clinically. The cure rate of this lipid formulation was much better than that for DOX dissolved in saline (DOX/saline) (17%). An immunopotentiating agent, Picibanil, given in 1 KE (clinical unit) or 5 KE doses was no better than the saline group, indicating that the above effect was not a result of immunopotentiation by Lipiodol. The severity of toxic side effects of DOX was also reduced by lipid solubilization. Pharmacokinetic study showed that DOX/saline was absorbed rapidly into the blood stream from the peritoneal cavity, whereas DOX/Lipiodol was retained in the ascites at a higher concentration for a much longer time. Thus the present results suggest that lipid formulations of anticancer agents have augmented therapeutic efficacy by intracavitary injection. The lipid formulations show increased stability in and prolonged slow release from the lipid milieu. Thus this therapeutic tactic of using oily anticancer agents appears to be promising for the control of pleural and peritoneal carcinomatoses.
Animals↗
Targeted vinblastine chemotherapy with two preparations of lipiodol contrast medium.
BACKGROUND: Long-term survival and cure can not be achieved in patients with unresectable metastatic liver cancer. In this study, to improve the antitumor activity of oily anticancer agents, which enable targeted cancer chemotherapy, various concentrations of vinblastine dissolved in Lipiodol ultrafluid (vinblastine/Lipiodol U) or Lipiodol F, which has three times the viscosity of Lipiodol ultrafluid, were used. MATERIALS AND METHODS: Rabbits bearing VX2 tumors measuring 1 to 2 cm in diameter in the liver received arterial injections of 0.2 ml of these drugs, and antitumor activity were examined. RESULTS: Complete necrosis of the tumor was observed in three of nine rabbits received vinblastine/Lipiodol U at 2.5 mg/ml. Complete necrosis of the tumor was observed in all eleven rabbits which received vinblastine/Lipiodol U at 5 mg/ml. At concentrations of 7.5 and 10 mg/ml, the necrotic area spread from the tumor to the liver parenchyma surrounding the tumor. The antitumor activity of vinblastine dissolved in Lipiodol F was increased compared with that of vinblastine dissolved in Lipiodol ultrafluid. CONCLUSIONS: The antitumor activity of a kind of the oily anticancer agents, vinblastine/Lipiodol increased with increasing amounts of vinblastine dissolved in Lipiodol ultrafluid and with the increasing viscosity of the carrier, Lipiodol.
Animals↗
Correlation between arteriographic and electrocardiographic features during spasm in the left anterior descending coronary artery.
BACKGROUND: The clinical role of collateral vessels, which are transiently augmented during coronary artery spasm, remains controversial. OBJECTIVE: To examine the correlation between coronary arteriographic and electrocardiographic features during spasm in the left anterior descending artery (LAD). METHODS: We studied 45 patients in whom LAD spasms were induced by administration of acetylcholine or ergonovine maleate into the left coronary artery, or in whom spontaneous LAD spasms were documented during diagnostic cardiac catheterization. RESULTS: During spasm, only three patients had transient appearance or augmentation of collateral flow opacifying the LAD. In these three patients, electrocardiograms obtained from anterior precordial chest leads during LAD spasm showed ST-segment depression, ST-segment elevation followed by ST-segment depression, and only T-wave change, respectively. Except for these three patients, ST-segment elevations were observed in all other patients (31 of 34) with main-branch spasm of the LAD. However, ST-segment elevation was observed in only two of 11 patients in whom spasm of the diagonal branch alone was induced. CONCLUSIONS: Our observations suggest that the electrocardiographic changes during spasm are not always a sensitive indicator of LAD side branch spasm or LAD main-branch spasm associated with collateral circulation. From consideration of the angiographic features of the collaterals in the three patients with LAD main-branch spasm, we speculate that the balance of tonus of both the recipient and donor arteries, and the degree of organic stenosis of the recipient artery, may have important roles in the mechanism responsible for the change in the appearance of collaterals in patients with coronary spasm.
Acetylcholine↗
Intracavitary administration: pharmacokinetic advantages of macromolecular anticancer agents against peritoneal and pleural carcinomatoses.
BACKGROUND: Pleural and peritoneal carcinomatoses are quite difficult to control in patients with advanced cancer. We have devised a suitable formulation of anticancer agents to be injected by the intracavitary route. MATERIALS AND METHODS: The pharmacokinetics of macromolecular anticancer agent, copoly(styrene/maleic acid)-conjugated neocarzinostatin (smancs) and radiolabeled albumin were studied after intraperitoneal administration to ascitic tumor-bearing rats and mice, and were compared with the pharmacokinetics of other low-molecular-weight anticancer agents, mitomycin C (MMC) and doxorubicin (DOX). RESULTS: Pharmacokinetic analyses indicated that smancs showed a much higher drug concentration for a longer time in the peritoneal cavity, and a much lower drug concentration in the blood circulation than did MMC or DOX. The cavity/blood ratios of the area under the concentration curve (AUC), of smancs, bovine serum albumin (BSA), DOX, and MMC were 9.69, 7.06, 1.38, 1.15, respectively. CONCLUSION: These results suggest that macromolecular agents are cleared more slowly from the cavitary compartment and remain there at a high concentration while the blood concentration remains low.
Animals↗