Biomedical subjects

Yasuhiro Ogawa

Publications and source records attributed to Yasuhiro Ogawa.

At least 55 records · Page 3Linked to original sources

PubMed2003

A novel type hypertriglyceridemia observed in FLS mice.

The unique inborn hypertriglyceridemia seen in FLS (fatty liver Shionogi) mice was relieved by the administration of purified apolipoprotein (apo) C-II. Lipoprotein lipase (LPL) and its cofactor, apoC-II, play a pivotal role in VLDL metabolism. Therefore, we investigated the genetic background involved in this hypertriglyceridemia. Plasma levels of TG and total cholesterol as well as LPL activity were measured in male FLS mice and C57/BL6J mice. Agarose gel electrophoresis and fast protein liquid chromatography were used to analyze the lipoprotein profile. A cross experiment was done to determine the genetic background of hypertriglyceridemia observed in FLS mice. cDNA sequences of apoC-II and apoC-III of FLS mice were determined. Prealpha-lipoprotein was the predominant lipoprotein class in FLS mouse plasma. LPL activity remained in the range observed in C57/BL6J mice, and purified apoC-II transiently relieved FLS mice from hypertriglyceridemia. Prealpha-lipoproteinemia was inherited in an autosomal recessive manner. ApoC-III appeared to be a causal factor for this unique hypertriglyceridemia. Microsatellite analysis, however, revealed that the responsible chromosome was not 7; rather, apoC-III mapped onto chromosome 9. Therefore, we suggest apoC-III as a candidate causative factor for the hypertriglyceridemia observed in FLS mice because an excessive amount of apoC-III attenuates LPL activity in vivo and in vitro.

Animals↗

PubMed2003

The polymorphism of the beta3-adrenergic receptor gene is associated with reduced low-density lipoprotein particle size.

People with a predominance of small, dense low-density lipoprotein (LDL) particles appear to be at increased risk for coronary disease, independent of LDL cholesterol levels. The Trp64Arg variant of the beta3-adrenergic receptor gene is reported to be associated with abdominal obesity and resistance to insulin, and as a consequence, this variant may be a genetic factor in the development of atherosclerosis. Therefore, we investigated whether the beta3-adrenergic receptor polymorphism contributes to the distribution of LDL particle size in 136 Japanese subjects, aged 33 to 59 years, who visited for a routine annual checkup. None of these subjects were taking any medication. The diameter of LDL particles was determined at their peak size using nondenaturing 2% to 16% polyacrylamide gradient gels using fresh plasma samples. The genotype frequencies were: Trp/Trp, 71.3%; Try/Arg, 22.1%; and Arg/Arg, 6.6%, with allele frequencies of 0.82 for Trp64 and 0.18 for Arg64. The subjects with the Arg/Arg genotype had significantly higher levels of fasting plasma insulin and triglycerides and an insulin resistance index of homeostasis model assessment (HOMA-R), and significantly smaller LDL particle size than did the subjects with the Trp/Trp genotype. After adjusting for fasting insulin, body mass index (BMI), and HOMA-R index, there was no longer an observed difference in LDL particle size. The number of the Arg64 allele in individuals was significantly related with fasting insulin, BMI, triglycerides, glycosylated hemoglobin (HbA1c), and fasting glucose, and it was inversely related with LDL particle size. After adjusting for triglyceride, fasting insulin levels, and HOMA-R index, LDL particle size was no longer inversely correlated with the Arg allele. These findings suggest that the Trp64Arg variant in the beta3-adrenergic receptor gene may be associated with reducing LDL particle size, probably due to insulin resistance.

Adult↗

PubMed2003

Radiation-induced oxidative DNA damage, 8-oxoguanine, in human peripheral T cells.

The mechanism leading to the high level of radiosensitivity of T lymphocytes has not yet been fully described. In our previous study, we demonstrated that human peripheral T lymphocytes revealed early apoptotic changes (annexin V-positive) and late apoptotic changes (propidium iodide-positive), at 13 and 24 h after irradiation of 5 Gy, respectively. Changes in mitochondrial membrane potential were observed at 10 h after irradiation of 5 Gy. Subsequently, mitochondrial cytochrome c release was confirmed. In order to elucidate the mechanism which occurs prior to the mitochondrial membrane potential changes, we examined in the present study the radiation dose and the timing of oxidative DNA damage induced in human peripheral T lymphocytes following 10 MV X-ray irradiation. As a result, the production of 8-oxoguanine, i.e., the product of oxidative DNA damage, was clearly identified starting at 10, 6, and 3 h, after 2, 5, and 20 Gy of irradiation, respectively. Therefore, we concluded that it remains necessary to evaluate the extent of radiation-induced oxidative DNA damage. Furthermore, it is important to analyze superoxide radical production and scavenging in terms of the variety of radiosensitivities found among various types of normal tissue cells and neoplastic cells.

DNA Damage↗

PubMed2003

Radiation-induced reactive oxygen species formation prior to oxidative DNA damage in human peripheral T cells.

Previously, we demonstrated that human peripheral T lymphocytes revealed early apoptotic changes (annexin V-positive) and late apoptotic changes (propidium iodide-positive), at 13 and 24 h, respectively, after irradiation of 5 Gy. Changes in mitochondrial membrane potential were observed at 10 h after irradiation of 5 Gy. Subsequently, mitochondrial cytochrome c-release was confirmed. In order to elucidate the mechanism which acts prior to the mitochondrial membrane potential changes, we examined in the previous study the radiation dose and the timing of oxidative DNA damage induced in human peripheral T lymphocytes following 10 MV X-ray irradiation. As a result, the production of 8-oxoguanine, i.e., the product of oxidative DNA damage, was clearly identified starting at 10, 6, and 3 h, after 2, 5, and 20 Gy of irradiation, respectively. Therefore, we examined in the present study reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy of irradiation. Using a CCD camera system, we monitored fluorescence in T lymphocytes loaded with the succinimidyl ester of dichlorodihydrofluorescein diacetate (H2DCFDA), which is non-fluorescent until oxidized by ROS. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation.

DNA Damage↗

PubMed2003

Role of apoptosis inhibition in various chondrocyte culture systems.

Apoptosis may limit the utility of cell-based therapies for articular cartilage disorders. We tested the hypothesis that chondrocyte apoptosis can be reduced by optimizing the conditions employed to expand chondrocyte numbers in culture. Chondrocyte apoptosis was examined in monolayer and suspension culture, in the presence of fetal bovine serum (FBS) or autologous serum, and for culture periods of 2 or 4 days. The effect of these variables was assessed by measuring cell viability, Annexin V labeling and mitochondrial membrane potential. After 2 days of culture, the greatest increase in viable cell number (3.7-fold) occurred in monolayer cultures with autologous serum. After 4 days of culture, the greatest increase in cell number (9.0-fold) occurred in monolayer cultures supplemented with FBS. By Annexin V staining, the proportion of cells undergoing apoptosis after 2 days was not affected by the type of serum used or by culture in monolayer versus suspension. After 4 days of culture, the proportion of apoptotic cells was significantly reduced (35% to 13%, p<0.02) in suspension cultures with autologous serum. Apoptosis assessed by loss of mitochondrial membrane potential was decreased in the presence of autologous serum. These data suggest that suspension culture with autologous serum is useful in simultaneously maintaining cell proliferation and minimizing apoptosis in cultured human articular chondrocytes.

Annexin A5↗

PubMed2003

Comparison of radiation-induced reactive oxygen species formation in adult articular chondrocytes and that in human peripheral T cells: possible implication in radiosensitivity.

Previously, we examined the formation of reactive oxygen species (ROS) in T lymphocytes following 5 Gy of irradiation. Using a CCD camera system, we monitored fluorescence in T lymphocytes loaded with the succinimidyl ester of dichlorodihydrofluorescein diacetate (H2DCFDA), which is non-fluorescent until oxidized by ROS. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In this study, we examined radiation-induced ROS formation in adult articular chondrocytes, which were demonstrated to be highly resistant to apoptosis in our previous study. We found that ROS formation was actually scarcely seen after irradiation of up to 20 Gy in these cells. Therefore, the origin of the great difference of radiosensitivity between T lymphocytes and adult articular chondrocytes is considered to lie in the degree of ROS formation following irradiation, with this difference possibly resulting from the scavenging acuity of these two kinds of normal tissue cells for free radicals including hydroxyl radicals.

Chondrocytes↗

PubMed2003

Metabolic effects of X-ray irradiation on adult human articular chondrocytes.

There have been few reports regarding the metabolic effects of X-ray irradiation on adult human articular chondrocytes. The purpose of this study was to evaluate whether exposure to X-ray irradiation during tumor surgery can cause impaired metabolism in adult articular cartilage. To achieve this we exposed cultured chondrocytes isolated from normal or degenerated cartilage to varying doses of X-ray irradiation, then measured apoptosis, and the production of chondroitin sulfates (CS), prostaglandin E2 (PGE2) and p38 mitogen-activated protein kinase (MAPK) in these cells. The number of apoptotic cells was not affected by irradiation in chondrocytes from normal or degenerated cartilage. Likewise, the production of C6S and C4S was not altered by irradiation in either group. The concentration of PGE2 in non-degenerated chondrocyte cultures did not change with radiation in a dose-dependent manner. However, the concentration of PGE2 in degenerated chondrocytes increased in a radiation dose-dependent manner. Irradiation at 10 Gy, in degenerated chondrocytes, induced remarkable activation of p38. This suggests that it is important to consider whether there is an osteoarthritic joint in the area that is to receive radiation therapy during tumor surgery.

Adult↗

PubMed2003

Mechanism of apoptotic resistance of human osteosarcoma cell line, HS-Os-1, against irradiation.

In our previous study, we examined reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy of irradiation. Using a CCD camera system, we monitored fluorescence in T lymphocytes loaded with the succinimidyl ester of Dichlorodihydrofluorescein diacetate (H2DCFDA), which is non-fluorescent until oxidized by ROS. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In this study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1, which was established from an osteoblastic tumor that arose in the left humerus of an 11-year-old girl and was already morphologically characterized in vitro and in vivo. We found that ROS formation and oxidative DNA damage were actually scarcely seen after irradiation of up to 30 Gy in these cells; that mitochondrial membrane potential was preserved; and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. Therefore, the origin of the close similarity of radiosensitivity between adult articular chondrocytes and the human osteosarcoma cell line HS-Os-1, is considered to involve the low degree of ROS formation following irradiation; the similarity possibly results from the strong scavenging ability of these two kinds of cells for free radicals including hydroxyl radicals.

Annexin A5↗

PubMed2003

Mechanism of hydrogen peroxide-induced apoptosis of the human osteosarcoma cell line HS-Os-1.

In our previous study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1, which was established from an osteoblastic tumor that arose in the left humerus of an 11-year-old girl and was already morphologically characterized in vitro and in vivo. We found that ROS formation and oxidative DNA damage were scarcely seen after irradiation of up to 30 Gy in these cells; that mitochondrial membrane potential was preserved; and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. Based on these results, the radioresistance of the human osteosarcoma cell line HS-Os-1, was considered to arise, at least in part, from the low level of ROS formation following irradiation, which in turn may have resulted from the strong scavenging ability of the cells for free radicals, including hydroxyl radicals. Therefore, in this study, we examined the effect of exogenous hydrogen peroxide, which causes a potent oxidative stress and has been demonstrated to be a potent apoptosis-inducer in many kinds of cells. We found that addition of 1 or 10 mM hydrogen peroxide induced ROS formation, oxidative DNA damage, dysfunction of the mitochondrial membrane potential, and early apoptotic changes in the human osteosarcoma cell line HS-Os-1. We therefore concluded that intracellular ROS formation is involved in the hydrogen peroxide-induced apoptosis of HS-Os-1 cells.

Annexin A5↗

PubMed2003

Apoptotic-resistance of the human osteosarcoma cell line HS-Os-1 to irradiation is converted to apoptotic-susceptibility by hydrogen peroxide: a potent role of hydrogen peroxide as a new radiosensitizer.

In our previous study, we demonstrated that the radioresistance of the human osteosarcoma cell line HS-Os-1, was considered to arise, at least in part, from the low level of ROS formation following irradiation, which in turn may have resulted from the strong scavenging ability of the cells for free radicals, including hydroxyl radicals. Following the study, we found that addition of 1 or 10 mM hydrogen peroxide induced ROS formation, oxidative DNA damage, dysfunction of the mitochondrial membrane potential, and early apoptotic changes in the human osteosarcoma cell line HS-Os-1. We therefore speculated that combined use of irradiation and hydrogen peroxide might exert an additive effect for apoptotic-resistant tumors such as the human osteosarcoma cell line HS-Os-1, in terms of preservation of the radiation-induced hydroxyl radical production supported by the intracellular ROS formation that is induced by exogenous hydrogen peroxide addition. Therefore, in this study, we examined the effect of various doses of irradiation on the existence of 0.1 mM hydrogen peroxide in the culture medium. We found that irradiation with 10 or 20 Gy, under the condition of the presence of 0.1 mM hydrogen peroxide, induced ROS formation, oxidative DNA damage, dysfunction of the mitochondrial membrane potential, and early apoptotic changes in the human osteosarcoma cell line HS-Os-1, though ROS formation and oxidative DNA damage were scarcely seen in response to irradiation of up to 30 Gy, as was shown in our previous study. We therefore concluded that the combined modality of irradiation and such a low concentration of hydrogen peroxide (0.1 mM) is potentially applicable in clinical radiotherapy for many kinds of apoptotic-resistant neoplasms in terms of achieving both local control and improving survival benefit of patients.

Annexin A5↗

PubMed2002

Contractile responses of smooth muscle cells differentiated from rat neural stem cells.

To characterize the functional differentiation of neural stem cells into smooth muscle cells, multipotent stem cells in the central nervous system (CNS) were isolated from rat embryonic day 14 (E14) cortex and cultured by neurosphere formation in serum-free medium in the presence of 10 ng ml(-1) of basic fibroblast growth factor. Differentiation was induced by the addition of 10 % fetal bovine serum to low-density cultures (2.5 x 10(3) cells cm(-2)). Immunological analyses and reverse transcriptase-polymerase chain reaction indicated that the differentiated cells expressed smooth-muscle-specific marker proteins such as SM-1, SM-2, and SMemb myosin heavy chains, SM-22, basic calponin and alpha-smooth-muscle actin, but not the astrocyte marker glial fibrillary acidic protein. To examine whether smooth-muscle-like cells that are differentiated from CNS stem cells possess the characteristics of contractile smooth muscle, we prepared reconstituted collagen gel fibres and measured their contractile tension. The reconstituted fibres were prepared by thermal gelation of collagen and the differentiated cells. The fibres contracted in response to treatment with KCl (80 mM), ACh (100 microM), endothelin-1 (10 nM), endothelin-2 (10 nM), and prostaglandin F2alpha (100 microM). ACh-induced contraction was partially inhibited by the L-type voltage-dependent Ca(2+) channel inhibitor nifedipine and by the intracellular Ca(2+) chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor Y-27632, dibutyryl cAMP and 8-bromo-cGMP. These results suggest that CNS stem cells give rise to smooth muscle cells in vitro that have an identical contractile function to smooth muscle in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2002

Relaxant properties mediated by nitroglycerin in aortic coarctation hypertensive rats.

Nitroglycerin-mediated vasorelaxation is chiefly attributed to the cyclic guanosine monophosphate (cGMP)-dependent pathway, and partly to the cGMP-independent pathway via calcium-activated K(+) channels (K(Ca)). To investigate whether chronic hypertension alters responses of vascular smooth muscle to vasoactive agonists, we determined nitroglycerin-mediated relaxation of aortic rings from coarctation hypertensive rats. Banding the abdominal aorta above the renal arteries for 4 weeks elevated blood pressure and caused cardiac hypertrophy by 49%. In response to nitroglycerin, the relaxation of aortic rings precontracted with 10(-7) M norepinephrine was lower in the banded group than in the sham-operated group. Methylene blue, a guanylate cyclase inhibitor, suppressed a greater part of nitroglycerin-mediated relaxation and reached similar levels of relaxation in the two groups. Charybdotoxin, a specific K(Ca) channel blocker, also suppressed the relaxation by about 40% in the aortic rings from sham-operated animals, but not in those from the banded group. The response to charybdotoxin was markedly diminished or virtually eliminated in the banded group in the presence or absence of methylene blue. The combination of charybdotoxin and methylene blue nearly abolished nitroglycerin-mediated relaxation in the sham-operated group, whereas nitroglycerin-mediated relaxation was seen to remain in the banded group. These results indicate that the involvement of cGMP-independent K(Ca) channels in nitroglycerin-mediated relaxation disappeared after the development of hypertension produced by aortic coarctation.

Animals↗

PubMed2002

Size and oxidative susceptibility of low-density lipoprotein particles in breast cancer patients with tamoxifen-induced fatty liver.

The purpose of the present study was to investigate the effects of tamoxifen on the size and oxidative susceptibility of low-density lipoprotein (LDL) particles in breast cancer patients with tamoxifen-induced fatty liver. We investigated the following breast cancer patients: 13 receiving no tamoxifen (group A), 13 receiving tamoxifen 40 mg daily but without fatty liver (group B), and 13 receiving tamoxifen 40 mg daily with fatty liver (group C). Plasma lipids and diameter of LDL particles were measured. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO(4) while monitoring conjugated diene formation and assaying thiobarbituric acid reactive substances (TBARS). Plasma total and LDL cholesterol concentrations in groups B and C were significantly lower than those in group A. In group C, concentrations of plasma triglyceride (TG) and TBARS were significantly greater, but LDL particle diameter and lag time for LDL oxidation were significantly smaller than those in groups A and B. Plasma TG concentrations correlated negatively with computed tomography ratio of liver to spleen (r = -0.76; P < 0.001). LDL particle diameter correlated negatively with plasma TG (r = -0.62; P < 0.001) and TBARS (r = -0.44; P < 0.01), but positively with LDL lag time (r = 0.47; P < 0.01). Tamoxifen-induced fatty liver in breast cancer patients may be atherogenic, via increased TG and consequent small, easily oxidized LDL particles.

Adult↗

PubMed2002

Tamoxifen-induced nonalcoholic steatohepatitis in breast cancer patients treated with adjuvant tamoxifen.

OBJECTIVE: The benefits of 5-year tamoxifen administration for patients with estrogen receptor-positive breast cancer undoubtedly outweigh the risk of any adverse effects. Massive hepatic steatosis is an example of its side effects. Here we show risk factors for the development of massive hepatic steatosis and describe a representative clinical course of these patients treated with fibrates for the first time. METHODS: Computed tomography (CT) numbers of the liver and spleen were measured and correlated to body mass index (BMI) and pregnanetriol/pregnanediol ratio in urine (P3/P2 ratio). PATIENTS: We enrolled 56 premenopausal women treated with breast conservation treatment. They received oral tamoxifen (40 mg/day for 2 to 3 years) as adjuvant endocrine therapy with systemic chemotherapy. RESULTS: Serum estradiol level in 48 of 56 patients treated with tamoxifen was less than 10 pg/ml. The ratio of hepatic CT number to splenic CT number<0.9 was related to increased BMI (>23.6 kg/sqm) and reduced P/P2 ratio (<1). Fibrates are potent enough to improve hepatic steatosis in tamoxifen-induced hepatic steatosis. CONCLUSION: P3/P2 ratio<1 was related to sufficient blockade of estrogen receptor proven by the development of massive hepatic steatosis. Therefore, we propose that tamoxifen is not a mere antagonist of estrogen, but it may also suppress estrogen synthesis when estrogen receptor is blocked sufficiently. The undetectable level of serum estrogen in tamoxifen-treated premenopausal women may partially explain why tamoxifen was so effective in estrogen receptor-positive early breast cancer.

Adult↗

PubMed2002

Scintigraphic prediction of response to chemotherapy in patients with breast cancer: Technetium 99m-tetrofosmin and thallium-201 dual single photon emission computed tomography.

We have investigated the usefulness of dual-isotope single photon emission computed tomography (SPECT) for predicting the response to chemotherapy in patients with breast cancer. Twenty-five patients with breast cancer were analyzed by SPECT using both 99m-technetium-tetrofosmin (99mTc-TF) and 201-thallium-chloride (201Tl). The relationship between response to chemotherapy and retention of each tracer was analyzed. 99mTc-TF retention was significantly higher in responders (42.0+/-37.9) than in non-responders (-11.3+/-34.6) (p=0.003). Ten of 13 patients (76.9%) with high 99mTc-TF retention (>15%) showed good response to chemotherapy, whereas 11 of 12 patients (91.7%) with low 99mTc-TF retention (<15%) did not respond to the therapy. The overall predictability to the response to chemotherapy was 84.0%. 201Tl retention (responders, 47.5+/-60.2% vs. non-responders, 55.8+/-45.0%; p=0.443) was not useful in therapeutic prediction, but was required to identify the lesion on the SPECT image. This is the first report to find that dual-isotope SPECT using 99mTc-TF and 201Tl is useful in predicting the response to chemotherapy in patients with breast cancer. Low 99mTc-TF retention is a strong predictor of therapeutic resistance, and high 99mTc-TF retention suggests a favorable response to chemotherapy.

Adult↗

PubMed2002

The role of apoptotic resistance in irradiated adult articular chondrocytes.

There have so far been no studies on the apoptosis of adult articular chondrocytes after X-ray irradiation. The purpose of this study was to assess the apoptotic resistance of articular chondrocytes in X-ray radiation, in order to examine the possibility of irradiated allogenic chondrocyte implantation. Adult human chondrocytes of the non-degenerated cartilage group without X-ray irradiation did not show positive cells of Annexin V and PI staining in a 48 h culture. The Annexin V positive chondrocytes did not increase in a radiation dose dependent manner, and the PI positive cells were slightly increased at 30 Gy irradiation. In the degenerated cartilage group, the PI positive chondrocytes without irradiation were present, and both the Annexin V and PI positive chondrocytes increased in a radiation dose dependent manner. The Annexin V and PI positive staining of chondrocytes in the non-degenerated cartilage group was less than that of the degenerated cartilage group in the same dose of X-ray irradiation exposure. Loss of the mitochondrial membrane potential, revealed in an early stage of apoptosis, did not show in the irradiated chondrocytes of the non-degenerated cartilage, but were demonstrated in those of the degenerated cartilage. These results demonstrated that the non-degenerated chondrocytes of X-ray irradiation were highly resistant for apoptosis, and this knowledge could be applied to allogenic chondrocytes implantation.

Annexin A5↗

PubMed2002

Mitochondrial cytochrome c release in radiation-induced apoptosis of human peripheral T cells.

We examined sequential changes in post-irradiated peripheral blood T cells taken from normal volunteers, using a microscopy-video system, mitochondrial membrane potential assay, annexin V, propidium iodide, and cytochrome c ELISA kit. After 5 Gy irradiation with 10 MV X-ray from a linear accelerator, the percentages of apoptotic T cells were estimated as approximately 5, 10, 20, 35, and 70%, at 0, 3, 6, 10, and 20 h after irradiation, respectively, as observed with the microscopy-video system. Using a CCD camera-equipped fluorescence microscope and MitoCapture, a mitochondrial membrane potential indicator, approximately half of the T cells showed dysfunction of mitochondrial membrane potential at 10 h after 5 Gy irradiation. With regard to annexin V and propidium iodide, approximately 40 and 5% of the human peripheral T cells showed positivity against annexin V and propidium iodide at that time, respectively. Mitochondrial cytochrome c release from the mitochondria to the cytosol was confirmed to start at 10 h and to reach a maximum at 20 h after 5 Gy of irradiation. These results demonstrated that mitochondrial cytochrome c release occurred following dysfunction of mitochondrial membrane potential in radiation-induced T cell apoptosis.

Annexin A5↗

PubMedDate not supplied

Tissue harmonic imaging sonography of the axillary lymph nodes: evaluation of response to neoadjuvant chemotherapy in breast cancer patients.

In breast cancer patients, the number of surgically resected metastatic axillary lymph nodes has been considered to correlate with prognosis. Therefore, the lymph nodes' response to chemotherapy may provide a favorable prognosis by suggesting an appropriate regimen of post-operative chemotherapy. In the present study, we evaluated the therapeutic efficacy of neoadjuvant chemotherapy of the axillary lymph nodes of breast cancer patients, using tissue harmonic imaging ultrasonography. Thirty-three female patients with breast cancer >2 cm in the longest diameter were examined by tissue harmonic imaging both before and following neoadjuvant chemotherapy. Nodes were defined as metastasis positive or negative on the basis of Yang's criteria, at each ultrasonography examination. The ultrasonography findings were correlated with the histopathologic results of the surgically resected specimens. Patients with constantly positive nodes over two ultrasonography examinations had a higher pathological nodes positive rate (8/9, 88.9%) than those (3/10, 30.0%) whose lymph nodes shrunk from the first to second ultrasonography exam (p=0.02, Fisher's exact method). All patients with negative nodes at both ultrasonography examinations had negative pathological results. Thus, changes in consecutive tissue harmonic imaging findings may be used to accurately evaluate the response of axillary lymph nodes to neoadjuvant chemotherapy.

Adult↗