[Evaluation of mucociliary clearance mechanisms by radioaerosol inhalation lung scintigraphy--effect of oral bromhexine].
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Biomedical subjects
Publications and source records attributed to K Konno.
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Using radioaerosol inhalation lung cinescintigraphy, pulmonary clearance mechanisms were studied in 21 patients with obstructive airways disease. In none of them did we find homogeneous deposition of inhaled radioaerosol in the lungs, or a steady, constant, axial, and cephalad transport of radioactivity in the major airways. Of the 21 patients, 14 showed temporary but frequent stopping and starting of radioactivity in the airways in the course of lung clearance; in ten there was reversal of flow; in five migration of radioactivity from one bronchus into the opposite, bypassing the trachea and often followed by shuttling between right and left bronchi; and in four there was spiral or zigzag transport of radioactivity. The overall lung retention ratio in the first 2 hr was not abnormal, but the airway deposition ratio was significantly above normal, and airway clearance efficiency was below. The alveolar deposition ratio was also significantly smaller in these patients.
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We extracted glycolipids from adult bovine nasal cartilage and purified some glycolipids by DEAE-Sephadex A-25 and Iatrobeads column chromatography. Cartilage contained 20 nmol of lipid bound sialic acid per gram wet tissue. The relative content of mono, di, tri, and tetrasialo gangliosides were 14%, 40%, 28% and 18%, respectively, as sialic acid content. We characterized some by examining carbohydrate composition, methylation analysis, sialidase treatment and mild acid hydrolysis. The ganglio-N-tetraose series, including GD1a, GD1b, GT1a, GT1b and GQ1b, was identified as one of the major ganglioside groups of this cartilage.
Bronchoalveolar lavage fluid from two cases of pulmonary alveolar proteinosis were analyzed for glycosaminoglycans and glycoproteins. The clinical courses of the two cases were entirely different. In one patient, signs and symptoms recurred despite repeated therapeutic bronchoalveolar lavages. In the other patient, three successive bronchoalveolar lavages brought about complete recovery. It was found that the bronchoalveolar lavage fluid from the former case contained various subtypes of glycosaminoglycans [hyaluronic acid, chondroitin sulfate A(C), dermatan sulfate, and heparan sulfate] and glycoprotein. On the other hand, the bronchoalveolar lavage fluid from the latter case contained glycoprotein, but no detectable amounts of glycosaminoglycans. There was only a slight qualitative difference in glycoprotein of bronchoalveolar lavage fluid between the two cases. The presence or absence of glycosaminoglycans in bronchoalveolar lavage fluid may be related to the prognosis of pulmonary alveolar proteinosis.
Mouse myeloid leukemia (M1) cells were induced to differentiate in vitro by treatment with dexamethasone. After 8 h of treatment, induction of phagocytic and lysozymic activities and depression of DNA synthesis started at the same time and proceeded irreversibly. DNA synthesis in the nuclear system reflected primarily DNA replication rather than repair and this activity declined during M1 cell differentiation.
Syngeneic SL mice inoculated with murine myeloid leukemia cells (M1) all died of leukemia within 30 days. Treatment three times a week with 12.5-50 pmol per mouse of either 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form of vitamin D3, or its synthetic analog, 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3], considerably prolonged the survival time of mice inoculated with M1 cells. 1 alpha(OH)D3 was more effective than 1 alpha,25(OH)2D3 in increasing the survival time of the mice. 1 alpha(OH)D3 also increased the survival time of nude mice inoculated with M1 cells. The 1 alpha(OH)[3H]D3 administered intraperitoneally to tumor-bearing mice was converted very rapidly to 1 alpha,25(OH)2-[3H]D3. The chronic administration of 25 pmol of 1 alpha(OH)D3 to tumor-bearing mice for 30 days caused no appreciable hypercalcemia. These results indicate clearly that 1 alpha,25(OH)2D3 is effective not only in inducing differentiation of M1 cells in vitro, as previously reported [Abe, E., Miyaura, C., Sakagami, H., Takeda, M., Konno, K., Yamazaki, T., Yoshiki, S. & Suda, T. (1981) Proc. Natl. Acad. Sci. USA 78, 4990-4994], but also in prolonging the survival time of mice inoculated with M1 cells.
Twenty antiherpes compounds were compared for their inhibitory activities against five laboratory strains and five clinical isolates of varicella-zoster virus (VZV) in human embryo fibroblast cultures. E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), E-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), and E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) were the most effective. The average values of the 50% inhibitory dose (ID50) for VZV replication were 0.0013, 0.0015, and 0.0024 micrograms/ml, respectively. 1-beta-D-Arabinofuranosyladenine and 9-(2-hydroxyethoxymethyl)guanine were 1.2 and 3.4 times less effective than 5-iodo-2'-deoxyuridine (IDU). The selectivity indexes (ratio of ID50 for host-cell DNA synthesis to ID50 for VZV replication) of BVaraU, IVDU, and BVDU were between 41,000 and 67,000, whereas those of cytosine arabinoside, IDU, and 5-bromo-2'-deoxyuridine were less than 1.1. BVaraU, IVDU, and BVDU were the most potent and the most selective inhibitors of VZV activity. A deoxythymidine kinase deficient mutant of VZV was resistant to most of the compounds tested at concentrations up to 36,000 times greater than the average ID50 for strains that were not deficient.
Dissociation and association of regulatory light chains of scallop myosin were found to be accompanied by changes in the fluorescence intensity and in the UV absorption spectrum. The changes in the two optical properties of scallop myosin and the dissociation and association of regulatory light chains were studied as a function of the magnesium and calcium concentrations. The results thus obtained suggested that there are two different types of attachment between regulatory light chains and "desensitized" myosin; one type is a calcium-specific attachment, and the other type of attachment can be mediated by either calcium or magnesium ions. These changes in the optical properties of scallop myosin were distinguishable from those induced by Mg-ATP; for example, with "desensitized" scallop myosin, the former changes were not observed but the latter were.
1. The reactivities of scallop myosin with 5,5'-dithiobis-(2-nitrobenzoate) (DTNB) and with 2,4,6-trinitrobenzene sulfonate (TNBS) were found to be affected by dissociation and association of regulatory light chains (RLC) of myosin. 2. Approximately 4 mol of sulfhydryl groups of "desensitized" myosin (DM) were masked on association of DM with RLC. When these sulfhydryl groups were reacted with DTNB, the modified DM became incapable of associating with RLC, but when the modified DM was treated with 2-mercaptoethanol, the ability to associate with RLC was fully recovered. 3. The DTNB-reactivity of scallop myosin and its RLC content were measured as a function of calcium and magnesium concentrations. The results thus obtained could be explained in terms of our previous suggestion (J. Biochem. 94, 1061 (1983] that there are two different attachments between DM and RLC. 4. The relation between the TNBS-reactivity and the RLC content was not simple but complex. Not the extent, but the rate of trinitrophenylation of scallop myosin was affected by dissociation and association of DM with RLC; thus, the involved TNBS-reactive lysine residues did not seem to be in the regions on DM and RLC that would be physically covered upon DM-RLC association. 5. The amount of the involved lysine residues was estimated to be only 1 mol per mol of myosin. Modification of the specific lysine residues resulted in a partial decrease in the DM-RLC association.
Hydrosoluble substances from BCG were prepared by cold water extraction and by hot phenol-water extraction. Chemical analyses revealed that both of them were derived from cytoplasm. The cold water extract (CWE) was effective in the treatment of C3H/He mice which had received an intraperitoneal inoculation of a syngeneic ascites hepatoma, MH134. The growth of a graft in footpad of mastocytoma P815 in CDF1 mice was retarded by intraperitoneal injections of CWE. A peptidoglycan from cell wall prepared by digestion with lysozyme exerted no antitumor activity in the same experimental condition as for the evaluation of antitumor effect of CWE. These results indicate that the antitumor activity of CWE was not due to the presence of a cell wall component.
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Twenty-eight cancer patients were treated with intramuscular butorphanol tartrate, a new non-narcotic analgesic, for investigating its clinical benefits in controlling cancer pain. Remarkable analgesic effects were observed approximately 30 minutes after administration by the single dose of either 1 or 2 mg of butorphanol. The effects lasted actively for 3 to 4 hours. Tolerance or drug dependency was rarely recognized even in the cases receiving repeated injections of the drug. Adverse effects, such as dizziness, nausea, thirst, numbness of the hands etc, observed in 5 patients were transient and required no medication. The above results may warrant a long-term administration of the drug for controlling varieties of pain in the cancer patients.
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The frequency and severity of side effects, above all, phlebitis, associated with an intravenous use of cephapirin (CEPR) or cephalothin (CET) was compared in 69 patients with infections. Two grams of each drug were administered intravenously twice a day with a 21-G vein needle in one of the two arms of the patients. CEPR was administered to 32 patients, and CET to 37 patients respectively. After treatment, the status of the veins was checked, and laboratory findings and other side effects were evaluated daily. Each drug appeared to be equally efficacious in the treatment of infections. The administration of CEPR was associated with a slightly lower rate of phlebitis and other side effects, but the difference between the 2 drugs was not significant (0.05 less than P less than 0.10). Phlebitis was observed in 1 patient (3.1%) of CEPR group and in 3 patients (8.1%) of CET group. Side effects, including phlebitis, were observed in 4 patients (12.5%) of CEPR group and in 12 patients (32.4%) of CET group. In CET group, drug exanthema (3 cases), drug fever (3 cases), and abnormalities in liver function (4 cases) were observed. These findings, together with the results of other reports, suggest that CEPR is a safe and useful drug in the treatment of infection as compared with CET.