[Anemias, metals and diseases of the extrapyramidal system].
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Biomedical subjects
Publications and source records attributed to K Horiuchi.
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A new type of host-dependent mutant, azure mutant, of bacteriophage f2 has been isolated. Growth of these mutants was restricted specifically by amber suppressor genes in the host bacteria. Restriction of the formation of infective centers by different bacterial suppressor genes was 98 percent, 90 percent, and 70 percent with Su-3, Su-1, and Su-2 genes, respectively. Restriction, like suppression, was the dominant phenotype. The block in growth of the mutants occurred in an early stage of the infection cycle. Once infection was established, however, an infected cell produced approximately the same number of progeny phage as a cell without the suppressor genes did. It is proposed that the azure codon is the same as the amber codon (uracil, adenine, guanine) and that restriction results from improper termination of protein chains of the phage RNA polymerase. Similar mutants may exist in other systems.
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The type, incidence, and severity of complications of balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices should be precisely estimated. Complications were evaluated in 38 patients who had fundic gastric varices and 43 B-RTO procedures during injection of ethanolamine oleate (phase 1), within 4 h after injection (phase 2), 24 h after injection (phase 3), and from 24 h to 10 days after injection (phase 4). Endoscopic evaluation at 8 weeks showed resolution of gastric varices in 35 of 38 patients (92%) and smaller varices in the remaining three (8%). B-RTO caused transient hypertension in 35% of patients, hemoglobinuria in 49%, and fever in 33% during phases 1, 2, and 3, respectively. Pleural effusion, pulmonary infarction, ascites, gastric ulcers with unique appearance, localized mosaic-like change of gastric mucosa, and hemorrhagic portal hypertensive gastropathy were noted in phase 4. There were no fatalities. Lactate dehydrogenase, aspartate aminotransferase, and bilirubin increased on day 1. Each datum was retrieved within 7 days. The severity of lactate dehydrogenase elevation correlated significantly with the volume of infused ethanolamine oleate. Thus, B-RTO is a safe and effective management of fundic varices. However, short-term hemodynamic change after B-RTO may cause gastric mucosal damage. Pulmonary infarction and pleural effusion are potential complications.
Recently, urinary pyridinoline and deoxypyridinoline have been commonly employed as bone resorption markers. We studied these markers in 17 patients with hyperthyroidism, 15 undergoing long-term anticonvulsant drug therapy, and 28 with postmenopausal osteoporosis. Both markers had significantly higher levels than those in age-matched control groups. Values of urinary pyridinoline and deoxypyridinoline correlated well with urinary hydroxyproline levels in patients with hyperthyroidism (r = 0.856, p < 0.001 for pyridinoline and hydroxyproline; r = 0.919, p < 0.001 for deoxypyridinoline and hydroxyproline); however, poor correlations were observed, especially between urinary deoxypyridinoline and urinary hydroxyproline (r = 0.357, NS) in patients with postmenopausal osteoporosis. To compare the discriminatory ability of urinary pyridinoline and deoxypyridinoline, receiver operating characteristic (ROC) curves were generated for each of these patient groups using data from age-matched healthy females as the control group. The areas under the curves for both markers were 100.0% in hyperthyroidism. The areas under the curves for pyridinoline in patients undergoing long-term anticonvulsant drug therapy (mean +/- SE; 98.1 +/- 2.8%) and postmenopausal osteoporosis (77.9 +/- 5.7%) were significantly higher than those for deoxypyridinoline in anticonvulsant drug therapy (92.4 +/- 3.3%) and in osteoporosis (64.9 +/- 4.3%). Using data from premenopausal healthy females as the control group, areas under ROC curves for urinary pyridinoline (100.0%) and deoxypyridinoline (94.8 +/- 5.9%) were significantly higher than those for urinary hydroxyproline (73.8 +/- 9.4%) in patients undergoing long-term anticonvulsant drug therapy. In patients with postmenopausal osteoporosis, those for urinary pyridinoline (97.0 +/- 2.8%) were also significantly higher than those for urinary hydroxyproline (74.0 +/- 6.4%).(ABSTRACT TRUNCATED AT 250 WORDS)
A novel heparin bonding method has been developed for in situ surface modification using ozone oxidation, and evaluated in vitro and in vivo during prolonged extracorporeal membrane oxygenation (ECMO) experiments. The ECMO system consisted of a Capiox hollow fiber membrane oxygenator (MO; Terumo Corp., Tokyo, Japan) with an integral heat exchanger, a Capiox centrifugal pump (CP), and an extracorporeal circuit. The blood contacting surfaces of the system were completely modified using the heparin bonding process, and evaluated in a chronic sheep model for extended period of time, ranging from 96 to 168 hr, under minimal systemic heparinization. The heparin bonded surface was able to maintain high levels of heparin bioactivity, and showed improved blood compatibility in in vitro epifluorescent video microscopy experiments by suppressing platelet adhesion/activation and complement activation. For the ECMO experiments, extracorporeal blood flow was maintained at 3 L/min and the activated clotting time was maintained at 150 sec. There was no significant change in the gas transfer capability or mean pressure drop across the MO over experimental times of up to 168 hr. Platelet count and other coagulation parameters remained stable within the physiologic range throughout the experiment. There were no detectable thrombi in the CP, tubing, or connectors in the test circuit. Local thrombus formation was noted in a stagnant area of the MO, although this did not interfere with its function or lead to any significant embolization. Based on these results, the heparin bonded ECMO system appears to be a safe and effective device for prolonged extracorporeal circulation under minimal systemic heparinization.
The authors previously demonstrated that heparin immobilized surfaces showed excellent nonthrombogenic properties for extracorporeal membrane oxygenation experiments as long as 168 hr. The characteristics of the heparin immobilized surfaces include high heparin bioactivity and prevention of platelet adhesion and complement activation. However, it is not known whether the heparin immobilized surfaces would be effective for in vivo long-term implantation. Heparin bioactivity may be lost because of complete degradation or blocking of binding sites on heparin by adsorbed proteins. This study attempted to elucidate the in vivo long-term fate of heparin immobilized surfaces. The blood contacting surfaces of the ventricular assist device (VAD) made from polyurethane was modified with heparin immobilization and evaluated in a long-term sheep left VAD (LVAD) model for as long as 3 months. After removal of the VAD, heparin bioactivity was measured by Factor Xa assay. The blood contacting surfaces were analyzed with a scanning electron microscope, and the adsorbed proteins on the surfaces of the diaphragm were analyzed by SDS-PAGE and Western blotting. The thickness of adsorbed proteins on the surfaces also was measured by a confocal laser microscope. For the control ventricular assist devices, thrombus formation was observed within 1 month, whereas heparin immobilized VADs were able to operate thrombus free for periods as long as 3 months. The control surfaces demonstrated a thick adsorbed protein layer on thin surfaces, whereas heparin immobilized surfaces maintained thinner adsorbed proteins on thin surfaces. Anti Factor Xa activity of the heparinized surfaces disappeared after 15 days, but the surfaces remained nonthrombogenic even after heparin bioactivity was completely lost. The protein composition analyzed by SDS-PAGE showed an albumin dominant pattern on the heparinized surfaces. The band of 110 kD corresponding to C3b was detected only on the control surfaces, which possibly activated complement, and subsequently activated platelets and coagulation. Immunoblot showed degradation products of fibronectin and vitronectin on the control surfaces, which probably were promoted by surface generated protease, whereas the heparinized surfaces showed minimal degradation throughout the experimental periods. These results suggest that the heparin moiety has an ability to control adsorbed proteins, thereby inhibiting thrombus formation during in vivo long-term implantation.