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K Aikawa

Publications and source records attributed to K Aikawa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Structure-specific inhibition of lysosomal cholesterol transport in macrophages by various steroids.

Cultured mouse peritoneal macrophages effectively take up and metabolize liposomes containing phosphatidylserine and cholesterol, resulting in massive accumulation of cholesteryl esters and triacylglycerols in their cytoplasm (Nishikawa, K., Arai, H. and Inoue, K. (1990) J. Biol. Chem. 265, 5226-5231). With this system, various steroid derivatives were assessed as to their ability to inhibit the cholesteryl ester formation from endocytosed cholesterol in macrophages. Among the steroids tested, one group of steroids having an oxo group at the C17 or C20 position, such as androstenedione, dehydroisoandrosterone, progesterone and pregnenolone, completely inhibited cholesteryl ester formation at 10 microM. Another group of steroids having a hydroxy group at the C17 position, such as testosterone and androstenediol, had a lesser effect; complete inhibition of cholesteryl ester formation was achieved with 100 microM or more. The mechanism underlying the inhibition by the former class of steroids was further studied. These steroids did not block the uptake or lysosomal hydrolysis of liposomes, nor esterification of fatty acyl chains into triacylglycerols. Moreover, dehydroisoandrosterone and pregnenolone, both of which possess a hydroxy group at the C3 position, had essentially no effect on 25-hydroxycholesterol-stimulated esterification of endogenous cellular cholesterol. On the other hand, androstenedione and progesterone, which possess an oxo group at the C3 position, had a mild inhibitory effect on the esterification of endogenous cholesterol. Upon incubation with a steroid having an oxo group at the C17 or C20 position, free cholesterol taken up by macrophages was accumulated in phagolysosomes, as judged from cytochemical study with filipin-cholesterol staining. These results indicate that a series of structurally-related steroids characterized by the presence of an oxo group at the C17 or C20 position inhibit cholesteryl ester formation in macrophages through blocking the intracellular transport of endocytosed cholesterol from lysosomes to endoplasmic reticulum.

Animals↗
PubMed1994

[Significance of surgical treatment for bone metastasis from lung cancer].

To assess significance of surgical therapy for patients who had metastatic bone tumor from primary lung cancer, sites of recurrence in patients who underwent surgical resection for lung cancer lesions were analyzed. Clinical courses of patients who underwent surgical therapy for metastatic bone tumor were analyzed, too. 1) From 1985 to 1989, 88 patients died from lung cancer in our hospital who has underwent pulmonary resection for lung cancer lesions. Of these, 22 patients had metastatic bone tumor. Sixty patients died who had underwent complete resection for lung cancer lesions. In eight patients of these 60 cases, bone were first site of recurrence. Of these eight patients, length from pulmonary resection to detection of bone metastasis were 4-23 months. In the other hand, length from detection of bone metastasis of death were 3-24 months. There was no correlation between two length. All of these eight patients had another metastatic lesions at the time of death. 2) From 1985 to July 1993, twelve patients underwent surgical therapy for their bone metastasis of primary lung cancer. Of these, four had metastatic cancer in thoracic vertebral body, two had in clavicle, two had in rib, three had in femoral bone, another had in tibial bone. Objective of operation were improvement of paralysis or pain, prevention of fracture, and so on. Most cases succeeded to get improvement in a short time, but some cases got worse soon. Surgical treatment was effective to improve paralysis or pain, and to increase quality of life. But it can not be effective except appropriate management in a short time because another symptom raise soon.

Aged↗
PubMed1994

[A case of acute nonlymphocytic leukemia with leukemic cell infiltration to the uterus followed by bone marrow relapse].

A 65-year old female was diagnosed to have acute nonlymphocytic leukemia (M2) in July, 1990. Complete remission was achieved by BHAC-DMP (enocitabine, daunorubicin, 6-mercaptopurine, prednisolone) therapy. Complete remission had continued without symptoms for about two years. Uterial infiltration of leukemic cells occurred in May, 1992, followed by bone marrow relapse after two months. The second hematological complete remission was obtained after one course of the chemotherapy, but uterial infiltration of leukemic cells had still remained.

Aged↗
PubMed1994

[Incidence of nodal involvement of #12u nodes (lymph nodes around the upper lobe bronchus) in cases with right middle lobe, right lower lobe, and left lower lobe carcinoma].

#12u nodes are peribronchial lymph nodes around the upper lobe bronchus which should not be routinely dissected in cases with middle lobe carcinoma or lower lobe carcinoma. In this paper, #12u were examined histologically in 152 lung cancer cases. As a results, 14 of 152 (9.2%) had nodal diseases in #12 nodes. #12u nodes were involved in 3 of 30 N1 diseases (10%), and in 11 of 35 N2 diseases (31.4%). There was a case which had no nodal involvement except for #12u node. And in three cases, we found only one nodal metastasis except for #12u nodes. If we did not dissect #12u nodes, these cases will be relapse in near future. Thus, for curative operation, #12u nodes should be dissected as a standard operation.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, blocks lysosomal cholesterol trafficking in macrophages.

Certain steroids having an oxo group at the C-17 or C-20 position such as pregnenolone and dehydroisoandrosterone inhibit the cholesterol transport from lysosomes to other cellular sites. Taking advantage of the fact that the inhibition is reversed upon removal of the steroids, we studied the factors that control the cholesterol transport from lysosomes to other cellular sites in macrophages. Macrophages that accumulated unesterified cholesterol in their lysosomes were prepared by incubating cells with liposomes containing cholesterol and phosphatidylserine in the presence of a steroid inhibitor. These cells were chased by means of steroid washout, and then the effects of various pharmacological agents on the subsequent metabolism of cholesterol were examined. When the cells were chased in the absence of the agents, some of the cholesterol was converted to cholesteryl esters in the cells, and others were desorbed into the medium as unesterified forms, suggesting recovery of lysosomal cholesterol trafficking. Among the agents tested, bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, completely blocked both cholesterol esterification and cholesterol desorption at 10 nM. Moreover, agents that neutralize the lysosomal proton gradient, such as ammonium chloride and chloroquine, also reduced both of the processes. Fluorescent microscopic examination of bafilomycin A1-treated cells revealed extensive filipin-cholesterol staining of perinuclear lysosomes. From these data, we conclude that acidic pH is required for the efflux of cholesterol from lysosomes to other cellular sites.

Animals↗
PubMed1993

Relationship between content of hepatic glutathione S-transferases and the kinetics of indocyanine green elimination in various liver diseases.

The glutathione (GSH) S-transferases are believed to have dual functions as hepatic detoxifying enzymes and intrahepatic binding proteins. Little is known about their alterations in human liver diseases. Therefore, we have studied the relationship between the enzyme activity and rose bengal (RB) binding in hepatic cytosol and plasma indocyanine green (ICG) kinetics in patients with various liver diseases. The enzyme activity was measured in samples of hepatic cytosol obtained from 52 patients. In addition, the content of cationic and neutral transferases was estimated in 17 biopsy samples by densitometry of Coomassie blue stained sodium dodecyl sulphate polyacrylamide gel electrophoretograms. RB binding studies also were performed on cytosol samples. ICG kinetic parameters were determined using the two-compartment open model in 17 patients who were given the dye (0.5 mg kg-1) intravenously. Correlations between the enzyme activity and liver function tests, content of the enzyme, RB binding and ICG kinetic parameters were evaluated. The following results were obtained. (1) The enzyme activities were high in alcoholic liver disease, fatty liver and Gilbert's syndrome, and low in cirrhosis. (2) The enzyme activities were positively correlated with serum cholinesterase activity, serum albumin level and hepaplastin test, and negatively correlated with ICG retention rate at 15 min. (3) The enzyme activity, its content and RB binding affinity of the cytosol were positively correlated with each other. (4) The enzyme activity was positively correlated with hepatic ICG distribution volume. These results are consistent with the role of the GSH S-transferases as ligandins in intracellular storage of dyes.

Adenoma, Bile Duct↗
PubMed1993

Temperature-dependent antimutagenic activity of acrolein in Escherichia coli.

The effect of temperature on the antimutagenic activity of acrolein was investigated using UV-irradiated E. coli B. When incubated at lower temperatures (30 degrees C or 37 degrees C), acrolein greatly reduced the mutation frequency in WP2 (wild-type strain), but no such effect was observed with WP2s and ZA159 (excision repair-deficient strains). The antimutagenic activity of acrolein increased when cells were incubated at higher temperatures (40 degrees C or 42 degrees C). Particularly in excision repair-deficient strains, the antimutagenic activity was observed only at higher temperatures. In heat shock response-deficient background, however, the antimutagenic activity was observed at 30 degrees C even in the excision repair-deficient strains.

Acrolein↗
PubMed1993

[A case of middle ear carcinoma with high plasma G-CSF level].

Malignant tumors sometimes yield a variety of paraneoplastic syndrome. We report a case of middle ear cancer demonstrating unusual granulocytosis which was considered to belong to this syndrome. A patient, 67-year-old male, noticed left facial nerve palsy in June 1989, and was operated on under the diagnosis of chronic otitis media. However, middle ear tumor was suspected during the operation, which was confirmed to be squamous cell carcinoma. He was referred to our hospital for radiotherapy. Six months after irradiation, spontaneous liqorrhea due to the dural necrosis occurred. When intracranial repair of dura was performed, tumor invasion into the dura was noticed. Subtotal resection of the temporal bone with iridium implant was done in vain to control the recurrent tumor, which spread quickly to adjacent tissues. A month before the death, progressive granulocytosis without appreciable inflammatory signs started. Numbers of WBC rapidly increased, maximally reaching 88,300/cmm. Plasma G-CSF concentration was assayed at this time, showing about ten times as much as that of normal controls. It was thus postulated that production of this substance by the tumor was responsible for granulocytosis.

Aged↗
PubMed1992

[Clinical results of prophylactic intravesical chemotherapy on superficial bladder cancer using the dye exclusion assay].

A chemosensitivity test was carried out on superficial bladder cancer using the dye exclusion assay for the purpose of screening chemosensitive drugs for prophylactic intravesical chemotherapy. Bladder cancer cells of each patients were incubated, in vitro, in the presence of adriamycin, (2"R)-4'-0-tetrahydropyranyladriamycin, mitomycin C, pepleomycin and 4'-epi-adriamycin (500 micrograms/ml) at 5%, CO2, 37 degrees C for 2 hours. The cytotoxic effect of the drugs was evaluated by the ratio of stained cells by trypan-blue. The most effective drug was instilled postoperatively into the bladder 3 times for the first week, and every 2 weeks during the following 14 weeks. In 18 patients followed more than 4 months the prophylactic effect was evaluated. Fifteen of the 18 patients completed the protocol, but the remaining 3 patients failed to complete to the instillation because of severe irritability of the bladder. Tumor recurrence was demonstrated in two patients. Non-recurrence rates of tumors at 12 and 24 months were 93.8% and 82.0%, respectively. These results suggested that this rapid and handy assay was useful for the purpose of screening chemosensitive drugs for the intravesical chemotherapy.

Administration, Intravesical↗
PubMed1992

[Postoperative intravesical instillation of THP for superficial bladder tumor: clinical results of prophylactic effects on the recurrence. Fukushima THP Research Group].

Intravesical instillation of pirarubicin (THP) was performed on 66 patients with superficial bladder cancer after transurethral resection to evaluate the prophylactic effect against tumor recurrence. Intravesical chemotherapy was carried out at the concentration of 20mg/40ml. THP was initially instilled three times for one week, following instillation of every two weeks for ten times, and then every one month for seven times. Bladder irritability was demonstrated 21 of 66 cases (31.8%). Although there was a case of contracted bladder, generalized side effect was no case. Eligible cases for evaluation of efficacy were 43 out of 66 patients. The non-recurrence rate (by Kaplan-Meier's method) at one and two years were 90.4% and 77.8%, respectively. Intravesical THP instillation seems to be effective for the purpose of prophylaxis against the recurrence of superficial bladder tumor.

Administration, Intravesical↗
PubMed1992

[Effects of age on blood pressure, heart rate, and sensory blockade by spinal anesthesia with plain 0.5% bupivacaine].

To discover the influence of age on spinal blockade with plain bupivacaine, 23 patients were administered a subarachnoid injection of approximately 4.0 ml of 0.5% bupivacaine. The patients were divided into two groups. One group consists of patients with ages under 65 years (younger group, n = 13), and the other group consists of patients older than 65 years (elder group, n = 10). The following results were obtained. The time to onset of anesthetic effects (pinprick discrimination, temperature discrimination, and light touch discrimination) decreased with age. At 180 min after the administration, spinal blockade level did not have a significant difference. The degree of the decrease of systolic arterial pressure was greater in the elder group than in the younger group. However, the degree of the decrease of heart rate was greater in the elder group than in the younger group.

Adolescent↗
PubMed1991

[Effects of halothane on spinal dorsal horn WDR(wide dynamic range) neuronal activity in cats].

The effects of halothane (0.2%, 0.5%, and 1.0%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity was studied in either spinal cord intact or spinal transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind foot pads of intact or decerebrate, spinal cord transected (L 1-2) cats. When 10 micrograms of bradykinin was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cat, all of 7 WDR neurons gave excitatory responses which were not depressed by 0.2% and 0.5% halothane but were depressed significantly by 1.0%. On the other hand, when the injection of 10 micrograms of bradykinin into the femoral artery ipsilateral to the recording site was used in the intact cat, 7 of 14 WDR neurons (50%) gave excitatory responses, which were not depressed by 0.2% halothane but were significantly depressed by 0.5% and 1.0% halothane, and 7 of 14 WDR neurons (50%) gave inhibitory responses, which were significantly depressed by 0.2%, 0.5%, and 1.0% halothane. We have found that halothane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by bradykinin injection.

Animals↗
PubMed1991

[A case of adrenal black adenoma associated with Cushing's syndrome].

The patient was a 24-year-old female, who had clinical and laboratory findings of Cushing's syndrome with slight virilizative changes. CT scan, ultrasound sonography and scintigraphy demonstrated that there was a functioning tumor at the right adrenal region. Thus we performed right adrenalectomy. The tumor was a characteristic black adenoma of adrenal gland, and it microscopically consisted of compact cells with remarkable intracellular pigmented granules. Thirty-two cases of functioning adrenal black adenoma have been reported in our country and all of them were associated with Cushing's syndrome.

Adenoma↗