Search PubMed⌕ Search

Biomedical subjects

K Konno

Publications and source records attributed to K Konno.

At least 361 records · Page 20Linked to original sources

Effect of oral salbutamol on mucociliary clearance mechanisms in the lungs.

The purpose of the study was to investigate whether or not orally administered salbutamol would affect mucociliary clearance function in the lungs. Salbutamol, 4 mg, was given orally 3 times a day for 7 days to 10 and 9 patients with various chest diseases in stable stage, respectively; the former were also currently taking other medications and the latter, none. Lung function tests, chest x-rays and radioaerosol inhalation lung cine-scintigraphy were performed before and after the administration of salbutamol. There was little qualitative or quantitative difference in mucociliary clearance function in either group before and after the administration of oral salbutamol, although it induced some increases in VC and FEV1.0 and a decrease in RV/TLC ratio in the former and some increases in FEV1.0, FEV1.0% and MMF in the latter. Oral salbutamol seems little to affect the mucociliary clearance function in the lungs.

Adult↗

Electron microscopic study of the cell surface of dibekacin-treated Pseudomonas aeruginosa.

Electron microscopy of thin sections of Pseudomonas aeruginosa IAM 1007 treated with dibekacin revealed blebs, disintegration of the outer membrane of the cell wall and degenerative features of the cytoplasm. In the next experiment, the cell wall fraction was isolated from the mechanically disrupted cells, incubated with dibekacin and was subjected to electron microscopy, in order to find a clue to the action mechanism of dibekacin on the cell wall of Pseudomonas aeruginosa IAM 1007. As a result, it was found that unidentified substances were released from the surface of the cell wall and that the outer membrane of the cell wall disappeared. The degree of changes of the cell wall ultrastructure was almost proportional to the length of incubation with dibekacin. These findings strongly suggest that dibekacin directly disintegrates the outer membrane of the cell wall of Pseudomonas aeruginosa IAM 1007.

Cell Membrane↗

[A phase II study of intravenous VP-16-213 in small cell and non-small cell carcinoma of the lung].

A phase II clinical trial of VP-16-213 was carried out in 71 patients with small cell and non-small cell carcinoma of the lung. Forty-eight evaluable cases consisted of 36 small cell carcinomas, 7 epidermoid carcinomas, 4 adenocarcinomas and one unclassified carcinoma. VP-16-213 was administered by drip infusion at dosages of 60-100mg/m2/day for 5-consecutive days at 3-4 week intervals. Twelve of 36 (33.3%) small cell carcinomas had partial responses, while no responses were obtained in non-small cell carcinomas. Median duration of responses was 46 days (range 31-133 days). The dose limiting toxicity was leukopenia. Median number of days to nadir was 14 days and median numbers of days for recovery was 11 days. Nausea (38%), vomiting (12%), anorexia (45%) and alopecia (74%) were major clinical toxicities although these were mild or reversible. We concluded that VP-16-213 was useful in the treatment of small cell lung cancer and the dose schedule used in this study was recommendable with small dose reduction for further trial of combination chemotherapy.

Adult↗

Partial purification of novel differentiation-inducing substances(s) from hot water extract of Japanese pine cone.

The effects of hot-water extract of pine cone (PCE) of Pinus parviflora Sieb. et Zucc. on the growth and differentiation of ML-1 cells, derived from a patient with human myeloblastic leukemia, were investigated. Growth of ML-1 cells was slightly inhibited at 3% (v/v) PCE, and a cytotoxic effect appeared at greater than 10%. Growth inhibition was accompanied by conversion to morphologically macrophage-like cells with alpha-naphthyl acetate esterase activity. In contrast, PCE dose-dependently increased the Fc receptor and nitroblue tetrazolium (NBT)-reducing activity up to 3%; above 3% its effect declined. Most of the cytotoxic activity was extracted from PCE with ethanol, and separated from the insoluble pellet, which contained the differentiation-inducing activity. The differentiation-inducing activity was eluted near the void volume on Sephadex G-200 gel filtration, with a 260-fold increase in the specific activity.

Antineoplastic Agents, Phytogenic↗

[Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group].

A randomized study of mitomycin C (MMC)+5-FU [control group] vs MMC+5-FU+lentinan (LNT) [LNT group] was conducted in order to evaluate the effect of LNT against advanced gastric and colorectal cancers by the envelope method in 166 patients, comprising of 115 cases of gastric cancer and 51 cases of colorectal cancer. Significant increases were observed in the survival rates for the LNT group (p less than 0.05) for both patients with gastric and colorectal cancer. No significant difference was observed in response rates between the aforesaid two groups, though the response rate in the LNT group was slightly higher than the control group. These results suggest that LNT in combination with anticancer drugs prolong the survival time of patients with advanced gastric and colorectal cancer.

Adult↗

[A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration].

A phase I study of VP was undertaken using the methods of a single (40 cases; range of dose levels 30-540 mg/m2) and 5-day (41 cases; range of dose levels 40-140 mg/m2/day) intravenous administration. The dose-limiting toxicity of VP was moderate to severe leukopenia. MTD was estimated to be 540 mg/m2 for a single and 140 mg/m2/day for 5-day administration. The median days to WBC nadir from the start of therapy and to recovery from reaching the nadir were 10 and 10.5 for single, and 15 and 7 for 5-day administration, respectively. Thrombocytopenia was less frequent and less pronounced than leukopenia. Mild gastrointestinal disturbances and alopecia were frequently observed. Transient hepatic dysfunction, fever, headache, fatigue, dyspnea, hypotension, and pain along the vein were also encountered in a small number of patients. There were no cases with renal, neurologic or cardiac toxicity. Objective tumor regression was seen in one case each of IBL(CR), bladder cancer, non-Hodgkin's lymphoma and ATL (PR). The post-infusion plasma decay of VP in 4 cases given 80-120 mg/m2 by a single administration was biphasic with t1/2 alpha ranging from 0.13 to 0.39 h and t1/2 beta ranging from 3.33 to 4.85 h. No accumulation of VP was found in plasma after five repeated daily doses. Doses of 360-480 mg/m2 by single and 80-100 mg/m2/day by 5-day administration repeated every 3 to 4 weeks can therefore be recommended for phase II studies in good-risk patients.

Adult↗

ATP-dependent [3H]Met-enkephalin uptake by bovine adrenal chromaffin granule membrane.

Uptake of [3H]Met-enkephalin by purified chromaffin granule membrane isolated from bovine adrenal medulla was investigated. Addition of a single divalent cation, such as Mg2+ or Ca2+, did not affect the uptake. The presence of 3 mM ATP in the incubation medium stimulated the uptake to two times that of the control. The same stimulation effect was also found in the presence of ATP plus a single divalent cation. The ATP-dependent uptake reached its half-maximal level within 5 min after initiation of the reaction at 25 degrees C, and reached a plateau within 10 min. The apparent Km for [3H]Met-enkephalin uptake by the chromaffin granule membrane was about 2.3 X 10(-6) M. GTP, CTP, UTP and ADP did not stimulate enkephalin uptake. Several calcium inhibitors such as trifluoperazine, verapamil and 3,4,5-trimethoxybenzoic acid 8-(N,N-diethylamino)octylester (TMB-8) markedly inhibited enkephalin uptake. The inhibition exceeded 80%, although these chemicals inhibited Ca2+-ATPase activity in chromaffin granule membrane only 30% under the same conditions. Ethyleneglycol-bis-(beta-aminoethylether)N,N'-tetraacetic acid (EGTA), at 3 mM also inhibited uptake about 30%. The results indicate that uptake of Met-enkephalin by chromaffin granule membrane ghosts was driven not only by ATPase activity, but also by some other Ca2+-ATP-mediated mechanism(s).

Adenosine Triphosphate↗

Abnormal cilia in the small airways of mice induced by bleomycin.

The frequency and types of abnormal cilia in the small airways before and after parenteral administration of bleomycin were examined by transmission electron microscopy. Bleomycin was injected subcutaneously at a dose of 40 mg/kg twice weekly for 6 weeks. Bronchioles less than 0.1 mm in diameter from animals sacrificed 1 day after a single dose, 1 day after three doses, 3 days after 8 doses, and 13 days after 12 doses were selected for evaluation. Although ciliated cells proper did not show pronounced alterations, abnormal cilia such as swollen cilia, compound cilia, and cilia with abnormal axonemes frequently occurred. Repeated injections did not necessarily induce much more abnormal cilia than one dose. The results suggested that ciliated cells remain undamaged and that normal cilia can be restored. The specific type of abnormal cilia induced by bleomycin was not identified.

Animals↗

Exposure of actin thiols by the removal of tightly held calcium ions.

The removal of bound metal ions from G-actin uncovered two thiols, Cys-10 and Cys-257. The uncovering of these thiols requires a free calcium concentration lower than 10 nM. Therefore, participation of one or both thiols in Ca2+ binding is suggested. Actin labeled with N-(5-fluoresceinyl)maleimide in the absence of calcium moves as a doublet in NaDodSO4/PAGE. It is suggested that two conformers are induced by metal removal and labeling.

Actins↗

Characterization of the lacto series of gangliosides, especially of disialo-lacto-N-norhexaosyl ceramide isolated from adult bovine nasal cartilage.

A disialosylganglioside was isolated from adult bovine nasal cartilage, and its structure was determined by analysis of sugar composition, permethylation analysis, exoglycosidase treatment, and mild acid hydrolysis. The structure of this ganglioside was identified as disialo-lacto-N-norhexaosyl ceramide, NeuNAc(alpha 2-8)NeuNAc-(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(1-4)Glc(1-1)Cer. Furthermore, we also isolated from this cartilage gangliosides whose structures were presumed to be monosialo-lacto-N-norhexaosyl ceramide, and mono- and disialo-lacto-N-neotetraosyl ceramide. The major fatty acids of the four gangliosides isolated were palmitic, stearic, behenic and lignoceric acids. The predominant long chain bases were sphingenine, heptadecasphingenine and hexadecasphingenine.

Animals↗

Trinitrophenylation of rabbit skeletal myosin by 2,4,6-trinitrobenzene sulfonate and treatment of trinitrophenyl myosin with dithiothreitol.

Rabbit skeletal myosin was trinitrophenylated with 2,4,6-trinitrobenzene sulfonate (TNBS) in the presence or absence of inorganic pyrophosphate (PP1). When myosin trinitrophenylated either in the presence or absence of PP1 was treated with dithiothreitol (DTT), the absorbance at 345 nm of both trinitrophenylated myosins was decreased, as though the trinitrophenyl groups bound to myosin were removed. The DTT treatment also essentially reversed the inhibition of the EDTA-ATPase and Ca-ATPase activities that was caused by trinitrophenylation of myosin. These effects of trinitrophenylation and of DTT treatment were independent of the presence or absence of PP1 during the trinitrophenylation. In contrast, the PP1-induced formation of a difference spectrum of trinitrophenylated myosin was not affected by the DTT treatment. On the basis of these observations, it is suggested that the "reactive lysine residues," trinitrophenylation of which resulted in inhibition of the ATPase activities, are different from those whose trinitrophenyl groups show an altered spectrum on addition of PP1.

Adenosine Triphosphatases↗

Effect of regulatory light chain on chymotryptic digestion of scallop adductor myosin.

Chymotryptic digestability of scallop myosin was studied by measuring (a) changes in the gel electrophoretic pattern and (b) production of the soluble fraction obtained by centrifugation. Chymotryptic digestion of essential light chain (SH-LC) was strongly inhibited by association of regulatory light chain (R-LC) with myosin. This is in agreement with the observation of Stafford et al. (Biochemistry 18, 5273 (1979]. SH-LC and R-LC were both more resistant to the chymotryptic digestion when R-LCs were associated with myosin in the presence of calcium than when they dissociated from myosin in the presence of EDTA. In contrast, heavy chains of scallop myosin were digested more quickly in the presence of calcium than EDTA. This suggests that association of R-LC induces reversible changes in the heavy chain conformation, which lead to an increase in the chymotryptic digestability of heavy chains. The chymotryptic digestability of scallop myosin increased in two distinct phases as the calcium concentration in the digestion medium was increased, but monophasically as the magnesium concentration was increased. The magnesium increased the digestability by approximately half as much as did calcium. These findings suggest two types of attachment between regulatory light chains and desensitized myosin: one mediated specifically by low concentrations of calcium ions, the second by higher concentrations of either calcium or magnesium.

Animals↗