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Biomedical subjects

E Kano

Publications and source records attributed to E Kano.

At least 37 records · Page 2Linked to original sources
PubMed1994

Thermosensitization and modification of cytosolic calcium concentration by verapamil and diltiazem in mouse mammary carcinoma cells.

PURPOSE: The cardinal role of Ca2+ signaling in the development of heat damage at 42 degrees C and 44 degrees C and the effect of verapamil and diltiazem on the change of cytosolic Ca2+ concentration, [Ca2+]c, were investigated. METHODS AND MATERIALS: Hyperthermic treatment was performed by immersing the tubes containing the mouse mammary carcinoma FM3A cells in a water-bath set at 42.0 degrees C or 44.0 degrees C. The [Ca2+]c of a single cell after hyperthermia was monitored by a digital image analyzing technique using Fura-2. Influx of Ca2+ was examined by the measurement of the radioactivity of 45Ca2+ incorporated into the cells for 60 min during or after hyperthermia. RESULTS: While the [Ca2+]c of the cells treated at 37 degrees C for 60 min was less than 230 nM, the percentage of the cells showing more than 230 nM increased after 42 degrees C hyperthermia and that of the cells showing more than 300 nM increased after 44 degrees C hyperthermia. When cellular uptake of 45Ca2+ during and after hyperthermia was examined, the increase in 45Ca2+ uptake was observed only for 44 degrees C hyperthermia. Verapamil or diltiazem (100 microM) enhanced a delay of cell growth, an increase in [Ca2+]c and an increase in 45Ca2+ influx for 42 degrees C and 44 degrees C hyperthermia. CONCLUSION: These results are compatible with the view that the increase in [Ca2+]c after 42 degrees C hyperthermia results from intracellular release from calcium store sites whereas the rise in [Ca2+]c after 44 degrees C hyperthermia is mainly due to entry of extracellular Ca2+. Verapamil or diltiazem combined with hyperthermia increased [Ca2+]c, which may play a cardinal role in thermosensitization by these agents.

Animals↗
PubMed1994

Effect of peplomycin or camptothecin-11 on X-ray skin injuries of ICR hairless mice.

In interdisciplinary oncotherapy by radiation and chemical substances, the injurious effects of radiation on the normal skin are occasionally modified by combined chemical substances. In the present experiment, the possible modifying effects of Peplomycin (PEP, 30 mg/kg body weight) and Camptothecin-11, an inhibitor of DNA topoisomerase I (CPT-11, 15 and 50 mg/kg body weight), on radiation skin injury were studied. Macroscopic changes on the thigh skin of male ICR hairless mice (at 8 weeks of age) induced by 10 Gy X-ray irradiation alone and the combined treatment with the anticancer substances were estimated by a modified scoring first reported by Lowy and Baker. Intraperitoneal administration of PEP significantly enhanced radiation skin injury; while CPT-11 (15 mg/kg), within the clinical dose range and in the similar molarities to that of PEP, did not show any appreciable modification effect. Treatment with CPT-11 (50 mg/kg) showed a radiation enhancement without significant difference. The chemotherapeutic radioenhancement ratios of the combined treatments of X-ray and PEP or CPT-11 (15 or 50 mg/kg) were 1.49, 1.17 or 1.34, respectively. Treatment with PEP at the accepted dose showed a radiation enhancement, while CPT-11 did not show any radiation enhancement within the clinical dose.

Animals↗
PubMed1993

Enhancement of cell killing and increase in cytosolic calcium concentration by combined treatments with hyperthermia and TMB-8 in mouse mammary carcinoma FM3A cells.

Mouse mammary carcinoma FM3A cells were exposed 42 degrees C or 44 degrees C hyperthermia for 60 min in a culture medium with or without 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) at a concentration of 100 microM. Cell survival, cytosolic calcium ion concentration, [Ca2+]C, and influx of 45Ca2+ were investigated to examine the cardinal role of intracellular Ca2+ in hyperthermic cell killing. The [Ca2+]C in a single cell was measured by a digital image analyzing technique using Fura-2. TMB-8 enhanced cell killing, increase in [Ca2+]C, and influx of 45Ca2+ induced by both hyperthermic treatments. In contrast, TMB-8 abolished the increase in [Ca2+]C induced by hyperthermia at 42 degrees C and 44 degrees C in the absence of extracellular Ca2+. These results suggest that TMB-8, an agent usually called an inhibitor of intracellular calcium mobilization at 37 degrees C or lower, enhances Ca2+ entry from the extracellular space at 42 degrees C or 44 degrees C and, in turn, promotes cell killing under hyperthermic conditions.

Animals↗
PubMed1993

Free radical formation induced by ultrasound and its effects on strand breaks in DNA of cultured FM3A cells.

Recent sonochemical studies have revealed that active oxygen species are formed by pyrolysis of water molecules due to high temperature cavitation bubbles. When aqueous solutions of DNA were sonicated, single-strand breaks and double-strand breaks of DNA were observed. Formation of double-strand breaks due to mechanical effects of cavitation and formation of single-strand breaks mostly due to free radicals were indicated. The sonochemically generated radicals from DNA constituents due to H atom and OH radical reactions, and pyrolysis processes, were identified by spin trapping with 3,5-dibromo-2,6-dideuterio-4-nitrosobenzene sulfonate. When suspensions of mouse mammary carcinoma FM3A cells and aqueous solutions of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were exposed to 1 MHz ultrasound in the presence of Ar, a good correlation between DMPO-OH formation and the cell killing induced by ultrasound were observed. Although single-strand breaks of DNA in the cells were observed at the maximum intensity of DMPO-OH formation and cell killing, double-strand breaks were not. Free radical formation by ultrasound in aqueous solutions and its relation to DNA strand breaks in vitro and in vivo are discussed.

Animals↗
PubMed1993

[Biological basis of thermochemotherapy].

Interactive effects of combined treatment with hyperthermia and chemotherapeutic agents or chemical substances were interpreted in the experimental aspects of medical sciences. It was also interpreted how a physiological circumferential conditions in vivo influenced on thermosensitivities of cells, tissues or individuals. Among the physiological conditions, hypoxia and insufficient nutrition apparently enhance thermosensitivity while reduce radiosensitivity. Interactive effects in combined treatments with hyperthermia and alkylating agents varies among the alkylating agent adopted. DNA strand scission by alkylating agent is increased and repair of the DNA damage is suppressed in combination with hyperthermia. Almost all the antimetabolites and botanic alkaloids are reported to show no appreciable interactive effect in combination with hyperthermia. However, a sort of derivatives of mitotic toxins interacts with hyperthermia (unpublished data). Effects of anticancer antibiotics vary due to the variety of the mechanism of action of the antibiotics. Therefore, interactive effects of these antibiotics with hyperthermia also vary among the antibiotics. Most marked interaction with hyperthermia was shown in Mitomycin C, while the cell killing effect of Actinomycin D itself was reduced reportedly by the combined hyperthermia. Further development in thermophysiology may perform an extent of elevation in human whole body temperature. It has been considered internal heating may be more efficient than external heating for the hyperthermia alone. In the other hand, local heating can chemosensitize within the localized heated area where the blood concentration of anticancer drug is even, although variety of intervention could be devised to localize anticancer drug distribution. Variety of heating modalities and the apparatus would be developed which contribute for further interdisciplinary oncotherapy in near future.

Antineoplastic Agents↗
PubMed1990

[Radiosensitization of mouse intestinal epithelial cells with BudR].

For the radiosensitization of the repair rich epithelial cells of small intestine, BudR (B.U.) was continuously infused into mice. Its uptake into the DNA, as shown by the substitution rate (S.R.) of thymine to B.U., was dose-dependent in low dose, but above the 4 mg/d/head it did not increased. The radiosensitization effect was assayed by the clonogenecity of the cells, and (1) the repair capacity (recovery factor, RF.) of the cells and (2) the isoeffect dose (I.D) were obtained. From these data, their enhancement ratios (E.R) were estimated. E.R. by R.F. increased remarkably both in low dose and in low S.R., but showed the plateau at about 10 level after 4 mg/d/h of dose or 10% of S.R. Whereas E.R. by I.D. increased linearly in dose or it did quadratically in S.R. From these results, it was discussed that radiosensitization by debromozation of B.U. was seen in low dose, and the direct cytocidal effect of B.U. became dominant with the dose-increase. Also the clinical application of B.U. was discussed in cell kinetical aspect of B.U. labelling as well as the progress of infusion techniques.

Animals↗
PubMed1989

Whole-body hyperthermia-induced renal atrophy of mice as evinced by obstruction and degeneration of renal tubules caused by acute ischemia.

Effects of microwave-induced whole-body hyperthermia (WBH) on the mouse kidney were examined histologically for acute and late effects up to 150 days after WBH treatment at 43.5 degrees C (rectal temperature) for 20 min or 42 degrees C for 40 min. As a whole the damage could be divided into two types. One was the damage to distorted epithelial cells in the subcapsular region. This lesion was common in most animals, possibly caused by direct hyperthermic effect of microwave. The other was general renal atrophy accompanied with aqueous or protein-rich cysts due to a chain of physiological reactions of the whole body to WBH. The first reaction was characterized by general stasis of the blood stream in all parts of the kidney, which resulted in acute ischemia of some tissues. This was seen immediately by dilatation of the renal and interlobular veins as well as the bundles of capillaries in the medulla region. The subsequent event was rather specific cell necrosis of distal and collecting tubular epithelium as compared to proximal tubules. The cell destruction induced cell proliferation of the proximal tubular epithelia after two days. Later on, in accord with the recovery of the blood circulation, the proliferated cells were carried away into the lumen, these processes then resulting in obstruction of tubules through formation of protein casts in the lumen. The block incidentally led to the destruction of nephrons. The degenerated area sometimes consisted of aqueous or protein-rich cysts of various sizes after 7 to 30 days. Thereafter these cysts degenerated, decreasing in both number and size. Thus irreversible atrophy of the kidney developed after WBH.

Acute Disease↗
PubMed1989

[Cellular thermosensitivity].

(1) modes of expression of thermosensitivity and theoretical interpretation of thermal dose, (2) differential thermosensitivities between strains of cells and the possible correlation to heat shock proteins and their syntheses, (3) cell phase responses to hyperthermia, (4) low hyperthermia and the induction of thermotolerance, (5) comparative thermosensitivities at the temperatures between below and above 42.5 degrees C -43 degrees C, (6) Arrhenius plot and mean cellular lethal heating periods, (7) step-up heating and the thermotolerance induction, (8) step-down heating and the thermoenhancement, (9) fractionated high hyperthermia and the thermotolerance induction and (10) modification of thermosensitivity by chemical substance including anticancer drugs; are compactly reviewed mainly on cell level.

Cell Cycle↗
PubMed1988

Effect of free radicals induced by ultrasonic cavitation on cell killing.

The present study was undertaken to elucidate the mechanism of in vitro cell killing induced by 1.0 MHz continuous wave ultrasound at an intensity of 5.8 W/cm2. The chemical effects and mechanical effects arising from acoustic cavitation were determined by the amount of liberated iodine and the number of DNA double-strand breaks, respectively. The survival of mouse L cells immediately after irradiation was estimated by counting the number of cells which are not stained by trypan blue and the clonogenicity of surviving cells remaining immediately after irradiation was monitored by colony-forming ability. The effectiveness of the dissolved gases in liberating iodine was in the order O2 greater than Ar greater than N2 greater than N2O approximately 0. However, the effect of dissolved gases on the yield of double-strand breaks of DNA and on the two kinds of end points of cell killing was in the order O2 = Ar = N2 greater than N2O approximately 0. These results suggest that the different amounts of free radicals induced by ultrasound are not directly related to the ultrasonically induced cell killing. The presence of cysteamine (2 mmol dm-3) during sonication completely inhibited a decrease in clonogenicity of surviving cells, but did not inhibit that of cell survival immediately after sonication. These results suggest that the decrease of survival immediately after sonication is due to mechanical shear stress arising from cavitation, while the decrease of clonogenicity of the remaining surviving cells is due to free radicals induced by cavitation. The contribution of free radicals to total cell killing was estimated as about 1 per cent at the level of 95 per cent cell killing immediately after sonication.

Animals↗
PubMed1987

Demonstration of expanding cell populations in mouse pancreatic acini and islets.

The acinar and islet cells of the adult mouse pancreas were examined by radioautography after continuous infusion of 3H-thymidine, for periods varying from 1 to 60 days, to determine whether they behaved like renewing or expanding cell populations. The labeling of both cell types increased with the duration of the continuous infusion and reached 2.22% and 12.0%, respectively, after 60 days. The rate of acinar and islet cell labeling was estimated from the regression line of the labeling index versus time and given as 0.039% and 0.20% cells per day, respectively. The rate of cell labeling was relatively low in these acinar and islet cells in comparison to the relatively high rate in duct cells. Occasionally, acinar cell labeling was not uniform, showing high labeling in the outer peripheral region of a lobe and at the periphery of the islets. Both acinar and islet cells increased in number in the adult, and at a rate indicating they are expanding cell populations. Their doubling times were estimated as 2,564 days (7.0 years) and 500 days (1.3 years), respectively. Duct epithelial cell populations were dividing at a rate indicating that they are renewing cell populations.

Animals↗
PubMed1987

Enhancement of hyperthermic cell killing by non-thermal effect of ultrasound.

The present study was performed to elucidate the mechanism of enhanced hyperthermic cell killing by a non-thermal effect (cavitation and direct effect) of ultrasound under various gas conditions. Cavitation, as indicated by formation of DNA double-strand breaks and liberation of potassium iodide, was completely inhibited under N2O-saturated conditions, while it was promoted under O2-, Ar-, and N2-saturated conditions. Mouse L cells were treated with ultrasound (1 MHz continuous wave, spatial peak temporal average intensity; 3.7 W/cm2) and/or 44 degrees C hyperthermia in medium saturated with O2, Ar, N2 (with cavitation) or N2O (with direct effect). The synergism on cell killing by ultrasound and 44 degrees C hyperthermia was observed under N2O-saturated conditions (enhancement ratio = 1.39). On the other hand, additive enhancement was observed under O2-, Ar-, or N2-saturated conditions. In addition, when cells were treated with 44 degrees C hyperthermia before or after sonication under N2O-saturated conditions, synergistic cell killing was not observed. These results suggested that the direct effect of ultrasound alone did not influence cell killing, but enhanced the hyperthermic cell killing synergistically, when both agents simultaneously acted on the cells.

Animals↗
PubMed1987

Absence of synergistic enhancement of non-thermal effects of ultrasound on cell killing induced by ionizing radiation.

The present study was performed to elucidate the role of non-thermal effects (cavitation and direct effects) of ultrasound, in simultaneous combination with X-irradiation on the cytotoxicity of mouse L cells. Firstly, mouse L cells were exposed to X-rays and ultrasound (1 MHz continuous wave, spatial peak temporal average intensity; 3.7 W/cm2) simultaneously at 37 degrees C under O2 or Ar saturated conditions to examine the cavitational effect of ultrasound. Secondly, cells were exposed to X-rays and ultrasound at 37 degrees C under N2O saturated conditions, which suppresses the cavitation, to examine the direct effects of ultrasound. The cavitational effect under O2 and Ar saturated conditions induced an exponential decrease in cell survival, and resulted in an additive effect on cell killing with the combination of X-rays and ultrasound. The direct effect in the N2O conditions induced no cell killing and did not modify the cell killing induced by X-rays. These results suggested that the non-thermal effects of ultrasound did not interact synergistically with X-rays for cell killing.

Animals↗
PubMed1987

[A new evaporation procedure for monitoring of iodine-125 in liquid waste].

A simplified monitoring method of 125I in liquid waste was devised. The waste water of 200 cm3 was taken on a Saran (polyvinylidene chloride) film covering a stainless steel vat. A stable iodine (20 mg) and sodium hydroxide (1 mmol) was added. The water was evaporated using an infra-red lamp. After heating to dryness, the Saran film was folded and transferred into a polyethylene tube. The radioactivity of 125I was counted with a well type NaI(Tl) scintillation counter. When a multi-channel analyzer was available for counting, an absolute decay rate of 125I was calculated with single and sum photo-peak counts. The radioactivity of 125I counted by a single-channel counter must be corrected with the counting efficiency of about 55%, with a special emphasis of a self absorption of photons. The recovery of 125I for concentrations below the permissible level was more than 98%.

Iodine Radioisotopes↗
PubMed1987

[Fundamentals of thermochemotherapy of cancer].

Different activation energy for heat cell killing is observed between ranges of temperatures at above and below 43 degrees C, i.e. ca. 150 and 360 kcal/mol, respectively, resulting in the different concept and mode of application in clinical heating for oncotherapy. Cell phase response to heat is characterized in more thermosensitivity of S-phase cells rather than G2, M and G1 phases, while less radiosensitive of S-phase. Reduced partial Oxygen tension (pO2), nutrition and pH as the cell-extrinsic circumstances result in enhanced thermosensitivity, respectively. Not synthesis but cellular content of heat shock proteins (HSPs) as part of physiological stress proteins, which are produced by the cells principally after and occasionally even during the sublethal heating with the contrary reduction of the other proteogeneses or otherwise which are produced constitutively, concern development of thermotolerance. Among the combined thermotherapy with anticancer drug(s), that with MMC or BLM showed interactive, or more than additive, cell killing effect, while that with ADR occasionally showed less than additive effect up to the modality of the combination. Benzaldehyde showed no appreciable cytotoxicity at 37 degrees C while enhanced thermosensitivity and inhibited development of thermotolerance. Study on therapeutic ratio in in vitro cells enables that effect of each of the above-mentioned extrinsic factors on the cellular thermosensitivity is investigated independently, while study on that in vivo may not distinguish the effect of the each factor since those are given by a single cause of inadequate vascularization of tumor tissue rather than the normal counter part.

Antineoplastic Agents↗
PubMed1986

Dynamic features of duct epithelial cells in the mouse pancreas as shown by radioautography following continuous 3H-thymidine infusion.

The possibility of turnover of the epithelial duct cells was examined in the adult mouse pancreas by radioautography following continuous administration of 3H-thymidine for periods varying from 1 h to 60 days. One hour after an injection of 3H-thymidine, the label observed in small and large ducts was low but increased with the duration of the continuous infusion of 3H-thymidine and reached a level of about 67% cells labeled after 60 days. The rate of duct cell labeling was estimated from the regression line of the labeling index vs. time in four types of ducts classified according to their inner diameter and the presence of the adventitia and was given as 0.60% cells per day in small (adventitia-free) ducts (phi 4-12 micron), 0.89%, 1.02%, and 1.23% cells per day in large (adventitia-including) ducts (phi 15-29, 30-49, and 50-160 micron respectively). In contrast, the labeling index of aciner cells after a 60-day infusion indicated an addition of only 0.02-0.07% per day, and that of islet cells 0.14-0.22% per day. It is known that most parenchymal cells belong to either expanding or renewing cell populations. The acinar cells of the pancreas have been shown to constitute an expanding population, a conclusion confirmed by the low addition of cells observed in the present work. However, the relatively high rate of cell addition in the duct epithelia indicates that they may turn over in a period of 2.7 months in the case of large ducts and 5.6 months in the case of small ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of methyl mercuric chloride and sulfhydryl inhibitors on phospholipid synthetic activity of lymphocytes.

The effect of methyl mercuric chloride on the activity of phospholipid synthesis of rat lymph node lymphocytes was compared with that of sulfhydryl inhibitors. Measurement of the radioactivity of [14C]oleic acid and [14C]acetate incorporated into lecithin of cells during short-term incubation showed that all the inhibitors tested similarly reduced the incorporation. However, methyl mercuric chloride (MMC) was the strongest inhibitor, being effective at 4 microM and causing more than 80% decrease at 20 microM. Inhibition by the sulfhydryl inhibitors, at less than 40 microM, ranked as follows: N-ethylmaleimide greater than alpha-chloroacetophenone greater than hydroquinone greater than iodoacetamide. MMC also obstructed the enhancement by phytohemagglutinin of [14C]oleic acid incorporation into lecithin. MMC was effective at 2 microM, while the other agents had little or no effect at this concentration. Further investigation suggested that inhibition of phospholipid synthesis did not depend on reduced incorporation of oleic acid into the cellular membrane but on decreased turnover of the fatty acid into phospholipids after the incorporation. The viability of lymphocytes incubated with the agents was measured by trypan blue dye-exclusion test. More than 90% of the cells treated with MMC at a concentration as low as 20-40 microM died, but the SH inhibitors, including NEM which greatly inhibited the phospholipid synthesis, produced few cell deaths at these concentrations. These observations show that the SH inhibitors affect enzymes in phospholipid synthesis, whereas MMC not only inhibits the enzymes but kills cells.

Animals↗
PubMed1986

Influence of dissolved gases on chemical and biological effects of ultrasound.

The influence of dissolved gases (O2, Ar, N2O, and CO2) on the chemical and biological effects of 1.2 MHz continuous wave ultrasound was investigated. Spin-trapping of OH and H radicals with 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) and observation of iodine liberation from a potassium iodide-starch solution were employed for monitoring the chemical effects, while lysing of mouse L5178Y cells was employed for monitoring the biological effects. The effectiveness of the dissolved gases in producing OH-DMPO adducts and H-DMPO adducts was O2 greater than Ar greater than N2O = CO2 approximately equal to O and Ar greater than O2 = N2O = CO2 approximately equal to O, respectively. A result similar to the yield of OH-DMPO was obtained from the liberation of iodine induced by ultrasound. In addition, the effectiveness of the dissolved gases in lysing mouse L5178Y cells by ultrasound was O2 = Ar greater than N2O = CO2 approximately equal to O. These results suggest that both dissolved N2O and CO2 gases in solution suppressed not only the chemical effect but also the biological effect.

Animals↗