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Biomedical subjects

K Kusama

Publications and source records attributed to K Kusama.

82 records · Page 5Linked to original sources

Induction of apoptosis by flavones, flavonols (3-hydroxyflavones) and isoprenoid-substituted flavonoids in human oral tumor cell lines.

Various flavones, flavonols (3-hydroxyflavones) and isoprenoid-substituted flavones (flavonols) were investigated for their cytotoxic activity. Most of these compounds were more cytotoxic against human oral squamous cell carcinoma and salivary gland tumor cell lines than human gingival fibroblasts. The cytotoxic activity of flavonoids was generally higher than that of tannin-related compounds. Flavonoids induced apoptotic cell death characterized by DNA fragmentation (as identified by TUNEL method) and activation of caspase(s) (as identified by degradation products of cytokeratin 18 with M30 monoclonal antibody). ESR spectroscopy revealed that higher concentrations of flavonoids produced radicals under alkaline conditions. However, not all of them enhanced the radical intensity of sodium ascorbate, suggesting that the redox potential of flavonoids differs considerably from samples to samples. Catalase failed to eliminate the cytotoxic activity of flavonoids, reducing the possibility of the involvement of hydrogen peroxide for the cytotoxicity induction by them.

Apoptosis↗

Role of carbohydrate moiety in granulocyte colony stimulating factor.

Biological activities of two granulocyte-colony stimulating factor (G-CSF) preparations with (Lenograstim) or without (Filgrastim) sugar moiety were compared. Both G-CSF preparations similarly enhanced the N-Formyl-Met-Leu-Phe-induced-migration of human peripheral blood polymorphonuclear cells, but did not significantly affect the proliferation of human oral tumor cell lines (HSC-2, HSG). However, Lenograstim induced cytotoxicity (accompanied by the production of cytoplasmic vacuoles and large DNA fragments) in human promyelocytic leukemic cells HL-60, more potently than Filgrastim. Lenograstim, but not Filgrastim, enhanced the cytotoxic activity of sodium ascorbate. In contrast to Lenograstim, Filgrastim was degraded gradually, but too slowly to explain its lower biological activity. These data suggest that the carbohydrate moiety in G-CSF might confer unique biological activities.

Ascorbic Acid↗

Interaction between chlorogenic acid and antioxidants.

The interaction between chlorogenic acid (CGA) and antioxidants was investigated by two different parameters: radical intensity and cytotoxicity induction. ESR spectroscopy shows that CGA produced radicals under alkaline condition. The CGA radical was scavenged by 100-300-fold lower concentrations of sodium ascorbate or N-acetyl-l-cysteine (NAC), whereas the ascorbate radical was not completely scavenged by CGA. The cytotoxic activity of CGA against human oral tumor cells (HSC-2, HSG) was completely eliminated by lower concentrations of sodium ascorbate or NAC, whereas that of sodium ascorbate or NAC was only slightly reduced by CGA. The present study demonstrated that CGA induces cytotoxicity by its radical-mediated oxidation mechanism and suggests the applicability of ESR spectroscopy for the screening of drug to drug interaction.

Acetylcysteine↗

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in human salivary glands and pleomorphic adenomas.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by the cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the extent of apoptosis in human salivary glands and pleomorphic adenomas. The distribution of CK18 in the salivary glands and adenomas was also determined and compared with that of the product detected by MAb M30. CK18 was detected in the cytoplasm of serous acinar and ductal cells in normal human salivary glands. In pleomorphic adenomas, CK18 was observed mainly in the tumor cells of duct-like structures, but not in those of myxomatous or chondroid tissues. Positive MAb M30 reaction products were found in the cytoplasm of acinar cells in the restricted lobules of normal salivary glands and in the luminal contents of duct-like structures in pleomorphic adenomas. These results suggest that a mechanism which suppresses apoptosis may be linked to the growth of human pleomorphic adenomas.

Adenoma, Pleomorphic↗

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in Warthin's tumor (adenolymphoma) of the parotid glands.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the presence and extent of apoptosis in 36 cases of Warthin's tumor (WT) of the parotid glands. The distribution of CK18 in WT was also determined and compared with that of the product detected by MAb M30. In WT, CK18 was observed mainly in the tumor cells of duct-like structures, but not in the cells of lymphatic tissues. Positive MAb M30 reaction products were found in luminal contents, duct-like structures and the cytoplasm of some macrophages in lymphatic areas near the duct-like structures in WT. These findings indicated that apoptotic cells are phagocytosed and eliminated as waste by macrophages. It is suggested that a mechanism which regulates the balance of proliferative activity and apoptosis may be closely linked to the growth of WT.

Adenolymphoma↗

Tumor-specific action of sodium 5,6-benzylidene-L-ascorbate in N-nitrosodiethylamine-administered mouse model.

In order to elucidate the mechanisms of antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA), we established a mouse hepatocellular carcinoma model by oral administration of N-nitrosodiethylamine (NDA) and examined the ascorbate radical intensity and putrescine content in the liver. The oral intake of NDA induced precancerous lesion and a significant increase in putrescine content among three major polyamines. When the oral intake of NDA was stopped, morphological changes were reversed. ESR spectroscopy showed that the homogenate of precancerous tissues produced greater amounts of ascorbate radical than that of normal liver tissue. Intravenous administration of SBA 30 minutes before removal of the liver prolonged the higher level of ascorbate radical generation in the homogenate of precancerous tissue. The antitumor activity of SBA might be due to the long-term production of radicals in tumor tissues by its prooxidant action.

Animals↗

Modification of apoptosis-inducing activity of gallic acid by saliva.

Gallic acid, a structural unit of tannin, induced apoptotic cell death, characterized by nuclear condensation and caspase activation in human oral tumor cell lines (HSC-2, HSG). Agarose gel electrophoresis demonstrated that gallic acid produced large DNA fragments in these cells, as well as in T-cell leukemia (MOLT-4) and erythroleukemia (K-562) cells, whereas it induced internucleosomal DNA fragmentation in human myelogenous leukemic cell lines (HL-60, ML-1, U-937, THP-1). This indicates that induction of internucleosomal DNA fragmentation or production of large DNA fragments depends on both target cells and inducers. Addition of total saliva dose-dependently reduced the cytotoxicity induction by gallic acid. These data suggested that the biological action of gallic acid might be modified by physiological fluids.

Antioxidants↗

Inhibition of chlorogenic acid-induced cytotoxicity by CoCl2.

Chlorogenic acid (CGA) induced apoptotic cell death in human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines. CGA exhibited oxidation potential in the culture medium, as demonstrated by NO monitor. Both cytotoxic activity and oxidation potential were significantly reduced by the addition of CoCl2. ESR spectroscopy showed that CGA produced seven peaks of radicals under alkaline condition, while addition of CoCl2 altered the spectral pattern and diminished the radical intensity of CGA. CoCl2 accelerated the CGA-induced coloration of the culture medium and modified the difference spectrum at around 325 nm, an absorption maximum characteristic of CGA. These data suggest that CoCl2 induced conformational changes in the CGA molecule.

Carcinoma, Squamous Cell↗

Dynamic MRI with slow injection of contrast material for the diagnosis of pituitary adenoma.

Magnetic resonance (MR) imaging of pituitary adenoma is usually carried out in dynamic studies with bolus contrast material injections, with the result that few strong images are obtained. Dynamic studies using a slowly injected contrast material were carried out in 14 cases of pituitary adenomas. The examinations were performed with a 1.5 Tesla superconducting MR imaging system using the spin-echo technique. Gd-DTPA (0.1 mmol/kg) was slowly injected (within 90 sec) by hand, providing seven to nine dynamic images during 350 sec from the start of injection. The average time to reach the maximum signal intensity was 170.6 sec in adenoma and 156.2 sec in normal gland tissue. The maximum contrast signal intensity ratio of adenoma to normal gland was 0.527 in the fifth image. The contrast of adenoma to normal gland tissue was calculated by the following formula: ASII (adenoma signal intensity index) = (adenoma signal intensity-tissue signal intensity)/tissue signal intensity. The most remarkable contrast between adenoma and normal tissue was obtained from the fourth to eighth images. In other words, we could obtain the strongest contrast at 144.8 sec to 299.6 sec from the start of contrast injection. Our results with slow injection suggest that stronger images can be obtained a longer period after contrast injection.

Adenoma↗

A case of the incomplete double aortic arch diagnosed in adulthood by MR imaging.

Double aortic arch is a rare vascular anomaly, particularly in adults. Most of patients were infants or children. In this report we describe a case of the incomplete double aortic arch in a 55 years old woman complaining of esophageal symptoms was found by esophagography and examined by MR imaging. This anomaly had double aortic arch with partial atresia of the left arch. The right common carotid artery (RCCA) and the right subclavian artery (RSA) arose from the large right aortic arch (RAA). The left common carotid artery (LCCA) and subclavian artery (LSA) arose from the left aortic arch (LAA). Aortic diverticulum was detected at the interior site of the descending aorta connected with the left subclavian artery (LSA). The mediastinal organs were surrounded by the vascular ring (RAA, LAA, LSA and aortic diverticulum).

Aorta, Thoracic↗