Biosynthesis and the metabolic fate of carbon-14 labeled spiramycin I.
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Biomedical subjects
Publications and source records attributed to A Inoue.
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Twenty-eight patients with head and neck cancer were treated with a combination of bleomycin, cyclophosphamide, adriamycin, and methotrexate (BEAM regimen), consisting cyclophosphamide 600 mg/body and adriamycin 40 mg/body on day 1, bleomycin 15 mg/body and methotrexate 20 mg/body on days 1 and 5. Dose modifications were performed according to patient's conditions. Of 18 evaluable patients, 3 patients showed a complete response and 3 patients showed partial response with an overall response rate of 33.3%. In this study, the patients who had already been treated with surgery, radiotherapy, or chemotherapy produced good results. The median duration of response was 4.0 months in the complete responders, and 1.0 month in the partial responders. The median survival was 12.7 months in the complete responders 1.4 months in the partial responders, and 5.6 months in non-responders. The most frequent major toxic effects were leukopenia (66.7%), nausea (60%), and alopecia (57.3%) in the patients receiving the maximum dose of the drugs. Careful monitoring of patients is imperative during this treatment.
We treated a patient with avascular necrosis of the carpal scaphoid associated with progressive systemic sclerosis. Aetiology and histology of this unusual condition are discussed in relation to the underlying disease and the anatomical characteristics of the carpal scaphoid. Resection of the carpal scaphoid and replacement were successful.
Absorption, tissue distribution and excretion of micronomicin (MCR) were studied in rats after intramuscular or 30 minutes drip intravenous administration (10 mg/kg). Serum levels of MCR were measured by bioassay, enzyme immunoassay and high pressure liquid chromatography. The pharmacokinetic studies of MCR after intramuscular or drip intravenous administration were carried out using one-compartment open model or two-compartment open model, respectively. Among 3 assay methods, similar pharmacokinetic parameters of MCR were obtained. In the simulation of serum levels of MCR, the differences between the measured and calculated serum levels after intramuscular or drip intravenous administration were less than 19% of the former levels. After intramuscular or drip intravenous administration of MCR, similar changes of the organ (kidneys, lungs, spleen and liver) levels were observed. Urinary recovery rates of MCR amounted to 82.3% or 91.6% by 24 hours after intramuscular or drip intravenous administration, respectively. After intramuscular or drip intravenous administration of MCR, no metabolites were found in urine of rats.
The pharmacokinetics of micronomicin (MCR) were studied in dogs after intramuscular (i.m.) and drip intravenous (d.i.v., 0.5, 1 and 2 hours) administration (10 mg/kg). After i.m. administration, the plasma levels of MCR followed a one-compartment open model, and after d.i.v. administration it followed a two-compartment open model. The peak plasma levels of MCR after i.m., 0.5, 1 and 2 hours d.i.v. administration were 28.7 +/- 6.5, 36.7 +/- 3.6, 30.2 +/- 5.1 and 20.3 +/- 2.3 mcg/ml, respectively. The pharmacokinetic parameters (T1/2, AUC, Kel, Vd and Cl) of MCR except Cmax and Tmax were not differentiated by the route of administration. Urinary recovery of MCR after d.i.v. administration was equal to that of MCR after i.m. administration.
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Recent advances in immunology have revealed that the "histiocytic" lymphoma of Rappaport is a proliferation of transformed lymphocytes rather than true histiocytes, and that the malignant cells in malignant histiocytosis (MH) are truly transformed histiocytes. We previously reported cases of MH presenting as lethal midline granuloma (MH-LMG) utilising fresh tissue specimens for the detection of cytological markers in a small number of cases. The results showed the true histiocytic nature of the proliferating cells. In this study, paraffin-embedded specimens from 16 cases with MH-LMG were processed for immunoperoxidase procedures to confirm the true histiocytic nature of the proliferating cells. Five cases with nasal and paranasal lymphomas (ML) were also stained to test the usefulness of immunoperoxidase procedures for distinguishing the MH-LMG from ML. Results were as follows; proliferating cells in MH-LMG were histiocytic in nature, staining positive for lysozyme in MH-LMG in contrast to the negative staining in ML.
Previously, several workers reported that at very low ionic strength and in the presence of ATP, the extent of binding of S-1 with the F-actin-tropomyosin-troponin complex or regulated actin (FA-TM-TN) is unaffected by removal of Ca2+. However, in this study we found that during the ATPase reaction at physiological ionic strength, the extent of binding of HMM with FA-TM-TN decreased markedly upon removal of CA2+. Therefore, the effects of Ca2+ were studied on the intermediate steps in the acto-HMM or acto-S-1 ATPase reaction. 1. The nucleotide-induced dissociation of acto-s-1 was studied using AMPPNP as substrate. The extent of binding of S-1 with regulated actin in the presence of Mg2+-AMPPNP increased in a sigmoidal manner as the S-1 concentration increased. When the molar ratio of actin monomer to S-1 was higher than 5-10, the removal of Ca2+ shifted the equilibrium of the dissociation reaction, FA-S-1-AMPPNP in equilibrium FA + S-1-AMPPNP, to the right. 2. The recombination rate of HMMPADP or S-1PADP with regulated actin in the absence of free Mg2+-ATP was estimated by measuring the time course of recovery in light-scattering intensity after addition of ATP. The rate decreased upon removal of Ca2+, when the molar ratio of actin monomer to S-1 was higher than 5-10. 3. The decomposition rate of HMMPADP was measured in the presence of Mg2+-ATP. In the absence of Ca2+, regulated actin did not affect this rate, whereas in its presence, regulated actin markedly accelerated the rate. These findings clearly indicated that at physiological ionic strength, removal of Ca2+ affects various elementary steps in the ATPase reaction to promote the dissociation of myosin heads from FA-TM-TN.
The influence of ionic strength on the isometric tension, stiffness, shortening velocity and ATPase activity of glycerol-treated rabbit psoas muscle fiber in the presence and the absence of Ca2+ has been studied. When the ionic strength of an activating solution (containing Mg2+-ATP and Ca2+) was decreased by varying the KCl concentration from 120 to 5 mM at 20 degrees C, the isometric tension and stiffness increased by 30% and 50%, respectively. The ATPase activity increased 3-fold, while the shortening velocity decreased to one-fourth. At 6 degrees C, similar results were obtained. These results suggest that at low ionic strengths ATP is hydrolyzed predominantly without dissociation of myosin cross-bridges from F-actin. In the absence of Ca2+, with decreasing KCl concentration the isometric tension and stiffness developed remarkably at 20 degrees C. However, the ATPase activity and shortening velocity were very low. At low ionic strength, even in the absence of Ca2+ myosin heads are bound to thin filaments. The development of the tension and stiffness were greatly reduced at 6 degrees C or at physiological ionic strength.
Conjugated estrogens injected into the lateral brain ventricle in awake rats elicited behavioral excitation and vasopressor responses. Magnitude of pressor responses was greater in spontaneously hypertensive rats (SHR) than in normotensive Kyoto Wistar rats (WKY). Pressor responses in SHR were abolished by central pretreatments of either captopril or angiotensin II analog. Under urethane anesthesia, conjugated estrogens still produced greater pressor responses in SHR, but accompanying increases in sympathetic nerve firings were the same in both WKY and SHR. These results suggest that while centrally-administered estrogens may activate the brain renin-angiotensin system to increase sympathetic nerve firing and thereby elevated blood pressure, SHR have larger pressor responses only because peripheral vascular reactivity has been increased.
Intracisternal injections of hypertonic NaCl elicited the pressor responses in urethane anesthetized spontaneously hypertensive and normotensive Wistar rats. The intracisternal pretreatment of 1-Sar-8-Ile-angiotensin II, angiotensin II analog, could abolish the pressor responses to intracisternal injections of 5% NaCl in urethane anesthetized spontaneously hypertensive rats, while basal blood pressure was not affected by these pretreatment. Both intracisternal and intravenous administration of captopril, an angiotensin I converting enzyme inhibitor, did not alter the pressor effect of hypertonic NaCl in normotensive rats. Basal blood pressure was lowered by intravenous injection of captopril. The involvement of angiotensin II in the pressor mechanism of hypertonic NaCl was confirmed by the enhanced pressor responses to intracisternal injections of 5% NaCl in urethane anesthetized rats pretreated intracisternally with angiotensin II. These findings suggest that angiotensin II itself could play an important role in the pressor responses to intracisternal injections of hypertonic NaCl without involving a converting enzyme system.
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