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1.
J Neurosurg Case Lessons ; 4(5)2022 Aug 01.
Article in English | MEDLINE | ID: mdl-36088556

ABSTRACT

BACKGROUND: This study aimed to report an aortic pseudoaneurysm, a rare but lethal complication, after a spinal fracture in ankylosing spine. OBSERVATIONS: An 83-year-old obese woman presented with dementia and was nonambulatory after a fall. She was transported to the hospital, and imaging showed a hyperextension-type L1 fracture with diffuse idiopathic skeletal hyperostosis (DISH). After posterior fusion surgery using percutaneous pedicle screws, screw loosening was detected 10 days postoperatively. Fracture dislocation was reduced by changing to transdiscal screws and rodding while in the lateral position. However, the anterior opening persisted. Enhanced computed tomography performed at 6 weeks postoperatively showed a large aortic pseudoaneurysm extending into the vertebral fracture site without screw loosening. Neither endovascular aortic repair nor open surgery was applicable. The patient was transferred to a sanatorium and died of pneumonia 5 months postoperatively without aortic aneurysm rupture. LESSONS: An aortic pseudoaneurysm can occur in hyperextension-type spinal fractures in DISH, even after fusion surgery, when the edge of the fracture is in contact with the aortic wall. The anterior opening dislocation should be reduced as much as possible.

2.
Int J Surg Case Rep ; 88: 106550, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34749171

ABSTRACT

INTRODUCTION: Curative resection generally has a good prognosis if the tumor is a locally advanced colorectal tumor. However, resection of a primary tumor that has invaded the aortoiliac artery is controversial. Herein, we report a case of successful resection of advanced cecal cancer invading the external iliac artery. CASE REPORT: A 29-year-old male patient had advanced cecal cancer invading the right external iliac artery and vein, right ureter, iliopsoas muscle, and sigmoid colon. We collected the patient's pre-/intra-/postoperative, clinical, and histological data. We reviewed the factors that may have contributed to curative resection without complications. We performed a palliative terminal ileum-sigmoid anastomosis for the prevention of intestinal obstruction. The patient received neoadjuvant chemotherapy, and the tumor patently regressed. After arterial reconstruction was performed with a femoral-femoral bypass, we performed radical resection: right hemicolectomy; partial sigmoidectomy; and partial resection of the right ureter, iliopsoas muscle, right testicular, and external iliac vessels. Pathologically, 99% of the tumor cells disappeared after chemotherapy. The patient was discharged on postoperative day 9. No recurrence has been noted 24 months after surgical resection, and the patient is receiving adjuvant chemotherapy. CONCLUSIONS: Thus, we successfully resected advanced cecal cancer without complications. Reconstruction with femoral-femoral arterial bypass and neoadjuvant chemotherapy are useful methods for curative resection without complications.

3.
Kyobu Geka ; 74(12): 1024-1027, 2021 Nov.
Article in Japanese | MEDLINE | ID: mdl-34795147

ABSTRACT

Although the efficacy of thoracic endovascular aortic repair( TEVAR) for blunt thoracic aortic injury (BTAI) has been reported, the determination of the proper endograft size for TEVAR in BTAI cases is yet to be established. The management of BTAI by TEVAR may not be effective if a wrong endograft size is selected, possibly leading to fatal outcomes. In this case report, a hemodynamically unstable patient with BTAI was saved by TEVAR, and the preoperative and postoperative changes in the aortic diameter were compared. In TEVAR for BTAI, the effects of hemodynamic instability should be considered and the appropriate device size should be determined based on blood pressure, pulse, and inferior vena cava diameter.


Subject(s)
Blood Vessel Prosthesis Implantation , Endovascular Procedures , Thoracic Injuries , Vascular System Injuries , Wounds, Nonpenetrating , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/injuries , Aorta, Thoracic/surgery , Blood Vessel Prosthesis , Humans , Retrospective Studies , Thoracic Injuries/diagnostic imaging , Thoracic Injuries/surgery , Treatment Outcome , Vascular System Injuries/surgery , Wounds, Nonpenetrating/diagnostic imaging , Wounds, Nonpenetrating/surgery
4.
Kyobu Geka ; 69(10): 876-9, 2016 Sep.
Article in Japanese | MEDLINE | ID: mdl-27586322

ABSTRACT

A 57-year-old woman with Marfan syndrome had undergone the surgical treatment for pectus excavatum at 15 years of age. She had since been screened regularly by computed tomography(CT) to detect any vascular diseases. CT demonstrated a left subclavian arterial aneurysm at 55 years of age. It enlarged to a diameter of 32 mm, and surgical treatment was performed. The subclavian artery and the aneurysm were identified by echography in order to locate the exact sites of supraclavicular and subclavicular skin incisions. The subclavian artery aneurysm was resected without dividing the clavicle, and replaced by a vascular graft. Echography is useful for precisely locating a subclavian artery aneurysm, which enables feasible resection without dividing the clavicle.


Subject(s)
Aneurysm/surgery , Marfan Syndrome , Subclavian Artery/surgery , Aneurysm/diagnostic imaging , Clavicle , Female , Humans , Imaging, Three-Dimensional , Middle Aged , Subclavian Artery/diagnostic imaging , Tomography, X-Ray Computed
5.
Bioresour Technol ; 196: 225-34, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26241842

ABSTRACT

Molasses wastewater contains high levels of organic compounds, cations, and anions, causing operational problems for anaerobic biological treatment. To establish a high organic loading treatment system for industrial molasses wastewater, this study designed a combined system comprising an acidification tank, a thermophilic multi-stage (MS)-upflow anaerobic sludge blanket (UASB) reactor, mesophilic UASB reactor, and down-flow hanging sponge reactor. The average total chemical oxygen demand (COD) and biochemical oxygen demand removal rates were 85%±3% and 95%±2%, respectively, at an organic loading rate of 42kgCODcrm(-3)d(-1) in the MS-UASB reactor. By installation of the acidification tank, the MS-UASB reactor achieved low H2-partial pressure. The abundance of syntrophs such as fatty acid-degrading bacteria increased in the MS-UASB and 2nd-UASB reactors. Thus, the acidification tank contributed to maintaining a favorable environment for syntrophic associations. This study provides new information regarding microbial community composition in a molasses wastewater treatment system.


Subject(s)
Bioreactors/microbiology , Microbial Consortia , RNA, Ribosomal, 16S/genetics , Wastewater/chemistry , Water Purification/methods , Biological Oxygen Demand Analysis , Molasses
6.
Hum Genome Var ; 1: 15016, 2015.
Article in English | MEDLINE | ID: mdl-27081516

ABSTRACT

Glutaric aciduria type II (GAII) is a rare inborn error of metabolism clinically classified into a neonatal-onset form with congenital anomalies, a neonatal-onset form without congenital anomalies and a mild and/or late-onset form (MIM #231680). Here, we report on a GAII patient carrying a homozygous novel c.143_145delAGG (p.Glu48del) mutation in the ETFB gene, who presented with a neonatal-onset form with congenital anomalies and rapidly developed cardiomegaly after birth.

7.
PLoS One ; 8(8): e71135, 2013.
Article in English | MEDLINE | ID: mdl-24015183

ABSTRACT

Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity. Moreover, we demonstrated an association between the effects of geldanamycin on the major heat shock proteins (HSPs) and the overall survival of highly metastatic human osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70 whose activity is at least partly responsible for cancer development and drug resistance. On the other hand, geldanamycin induced upregulation of Hsp60 gene expression, and a simultaneous loss of hyperacetylated Hsp60 mitochondrial protein pool resulting in decreased viability and augmented cancer cell death. Hyperacetylation of Hsp60 seems to be associated with anticancer activity of geldanamycin. In light of the fact that mitochondrial dysfunction plays a critical role in the apoptotic signaling pathway, the presented data may support a hypothesis that Hsp60 can be another functional part of mitochondria-related acetylome being a potential target for developing novel anticancer strategies.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Benzoquinones/pharmacology , Bone Neoplasms/drug therapy , Chaperonin 60/metabolism , Lactams, Macrocyclic/pharmacology , Mitochondrial Proteins/metabolism , Osteosarcoma/drug therapy , Acetylation , Bone Neoplasms/metabolism , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Mitochondria/metabolism , Osteosarcoma/metabolism , Protein Processing, Post-Translational , Protein Transport , Signal Transduction
8.
Kyobu Geka ; 66(10): 861-9, 2013 Sep.
Article in Japanese | MEDLINE | ID: mdl-24008633

ABSTRACT

We carried out a retrospective evaluation of the early and mid-term outcomes of aortic valve replacement (AVR) for aortic stenosis in hemodialysis patients. Between 2004 and 2012, a total of 40 dialysis patients underwent AVR with or without an additional procedure. Hemodialysis was performed routinely the day before and during the operation. At surgery, decalcification was performed using a cavitron ultrasonic surgical aspirator(CUSA) and a high performance mechanical valve was then implanted, with the exception of elderly patients or those in whom use of oral anticoagulation is contraindicated. A mechanical valve was used in 33 patients and a bioprosthetic valve in 7 patients. Hemodialysis was resumed on the 2nd postoperative day in the majority of patients. There was no intra-operative death and in-hospital mortality was 5%, due to sepsis and intestinal ischemia in 2 of the 40 patients. The mean follow-up period was 33 months. There was no structural valve deterioration in patients with the bioprosthetic valve. Of the 8 late deaths, the reason for deaths was cardiac in 4 patients. Overall survival in the 40 patients was 92%, 79%, and 54% at 1, 3, and 5 years, respectively. Our study demonstrated good early and mid-term outcomes for aortic valve replacement in hemodialysis patients. CUSA was useful for patients with a calcified valve and annulus. A bioprosthetic valve was acceptable for use in elderly patients.


Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Renal Dialysis , Aged , Aged, 80 and over , Aortic Valve Stenosis/mortality , Bioprosthesis , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
9.
Kyobu Geka ; 66(5): 360-5, 2013 May.
Article in Japanese | MEDLINE | ID: mdl-23674031

ABSTRACT

OBJECTIVES: The purpose of the present study is to assess the clinical results of aortic root replacement using the Carbo-Seal composite graft( CS) compared with the other type of homemade composite grafts. Fifty-nine patients who underwent aortic root replacement between January 1998 to December 2010 were retrospectively analyzed. Twenty-six received homemade composite graft( group 1;1998 ~ 2005) and 33 received CS( group 2;2005 ~ 2010). RESULTS: The duration of operation was longer in group 1:469.2±143.5 min versus 380.3±153.9 min (p=0.03). Although there was no statistically significant difference, group 2 had a higher complex operation rate compared with group1(23.1% versus 45.5%, p=0.07). Overall hospital mortality was 11.5% in group1 versus 3.0% in group2. Prevalence of major complication was significantly lower in group 2 (46.2% versus 18.2%, p=0.02).Requirement of intraoperative blood transfusion (group 1;1,130.8±854.7 ml versus group 2;598.2±836.4 ml) and amount of blood loss in the 1st 12 hours post operation (group 1;628.3±474.6 ml versus group 2;447.8±253.2 ml) were significantly lower in group 2. By univariate analysis, duration of operation, duration of cardio-pulmonary bypass (CPB), blood transfusion, acute dissection were independent risk factors and CS use was negative risk factor for major events. Aortic root replacement with use of CS can be performed with a relatively low early mortality and morbidity. Because a complicated operation is increasing in recent years, use of CS graft may simplify a Bentall operation.


Subject(s)
Aorta/surgery , Blood Vessel Prosthesis Implantation/methods , Blood Loss, Surgical , Blood Transfusion , Blood Vessel Prosthesis Implantation/mortality , Cardiopulmonary Bypass , Female , Humans , Male , Middle Aged , Operative Time , Retrospective Studies
10.
Kyobu Geka ; 65(1): 81-5, 2012 Jan.
Article in Japanese | MEDLINE | ID: mdl-22314160

ABSTRACT

An 86-year-old man was admitted for abdominal pain. Dissected descending thoracic aortic aneurysm and infrarenal abdominal aortic aneurysm were observed under computed tomographic (CT) scan. Hematologic studies revealed low platelet count and an increase in fibrin degradation products (FDP), and disseminated intravascular coagulation( DIC) associated with dissecting aortic aneurysm was highly suspected. Platelet transfusion was performed and gabexate mesilate was administered, however, no improvement of DIC could be obtained. An increase in aortic diameter was observed under CT scan and surgery was performed. The infrarenal aneurysm was replaced with a bifurcated prosthetic graft under open repair. Simultaneously, an endovascular stent-graft was delivered from the left limb of the abdominal graft and implanted into the descending thoracic aorta. The postoperative recovery was uneventful but platelet count did not improve in this case.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Disseminated Intravascular Coagulation/complications , Aged, 80 and over , Blood Vessel Prosthesis , Humans , Male
11.
FEBS Lett ; 584(22): 4606-10, 2010 Nov 19.
Article in English | MEDLINE | ID: mdl-20965172

ABSTRACT

There is growing evidence of mitochondrial membrane raft-like microdomains that are involved in the apoptotic pathway. The aim of this study was to investigate the effect of methyl-beta-cyclodextrin (MßCD), being a well-known lipid microdomain disrupting agent and cholesterol chelator, on the structure and bioenergetics of rat liver mitochondria (RLM). We observed that MßCD decreases the function of RLM, induces changes in the mitochondrial configuration state and decreases the calcium chloride-induced swelling. These data suggest that disruption of mitochondrial raft-like microdomains by cholesterol efflux on one hand impairs mitochondrial bioenergetics, but on the other hand it protects the mitochondria from swelling.


Subject(s)
Cholesterol/metabolism , Energy Metabolism/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , beta-Cyclodextrins/pharmacology , Animals , Calcium Chloride/pharmacology , Membrane Microdomains/chemistry , Membrane Microdomains/drug effects , Membrane Microdomains/metabolism , Mitochondria/chemistry , Mitochondria/enzymology , NADH Dehydrogenase/metabolism , Rats , Rats, Wistar
12.
Int J Artif Organs ; 33(2): 72-5, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20306433

ABSTRACT

Intraoperative autologous blood predonation is reported to be useful for the prevention of homologous blood transfusion in cardiac operations, especially in on-pump coronary artery bypass grafting (CABG). However, CABG is now performed more often off-pump than on-pump. We analyzed the major factors of homologous blood transfusion in 25 consecutive cases of valvular heart operation with intraoperative autologous blood predonation except those with preoperative autologous blood donation. Homologous blood was not transfused in 18 cases, but was in 7 cases only after cardiopulmonary bypass (CPB). The homologous transfusion was not correlated with body weight, CPB dilution or duration, or preoperative hematocrit level, but was found to correlate with age (r2=0.289, p=0.0413), bleeding output (r2=0.197, p=0.0485), and predonation blood volume (r2=0.436, p=0.0152). In conclusion, suitable intraoperative predonation may reduce the necessity for homologous blood transfusion in valvular heart operations.


Subject(s)
Blood Transfusion, Autologous/methods , Coronary Artery Bypass/methods , Blood Loss, Surgical/prevention & control , Coronary Artery Bypass, Off-Pump/methods , Heart Valve Diseases/surgery , Hematocrit , Humans , Intraoperative Care , Preoperative Care , Retrospective Studies
13.
J Phys Chem B ; 112(45): 14132-9, 2008 Nov 13.
Article in English | MEDLINE | ID: mdl-18939787

ABSTRACT

The particle dispersibility of barium ferrite and iron oxide magnetic particles in carrageenan gels was investigated, and the influence of the dispersibility on the giant reduction in the dynamic modulus of the gels was discussed. The gels containing barium ferrite demonstrated giant reductions in the storage Young's modulus on the order of 10 (5) Pa due to magnetization; however, small reductions in the storage modulus of less than 10 (4) Pa were observed for the gels containing iron oxide. The storage modulus of gels with barium ferrite did not follow the Krieger-Dougherty equation above volume fractions of 0.06, indicating the heterogeneous dispersion of the magnetic particles; however, the modulus of the gels with iron oxide satisfied the equation at all volume fractions, suggesting the random dispersion of the particles. It was noted that the gels with barium ferrite demonstrated enhanced nonlinear viscoelasticity and a large value of the loss tangent, while the gels with iron oxide exhibited weak nonlinear viscoelasticity and a small value of the loss tangent. Magnetic measurements indicated high values of remanent magnetization for barium ferrite and low values for iron oxide. After magnetization at 1 T, the magnetic gels with barium ferrite became elongated parallel to the magnetic field and shrunk perpendicular to the field. In contrast, the magnetic gels with iron oxide did not undergo a marked deformation. These results strongly indicate that the giant reduction in the storage modulus requires both enhanced nonlinear viscoelasticity and magnetostriction which originate from the particle dispersibility. The relationship between the dispersibility of magnetic particles and the giant reduction in the storage modulus is discussed using rheological and morphological data.

14.
Mitochondrion ; 7(1-2): 119-24, 2007.
Article in English | MEDLINE | ID: mdl-17300998

ABSTRACT

Apoptosis is induced not only during morphogenesis and embryogenesis but also under various pathological conditions, especially related to oxidative stress. Apoptotic cells are phagocytized by neighboring cells while necrotic cells cause local and general reactions sometimes lethal to our bodies. Data have been accumulated to demonstrate that the switch of the cell death mode from apoptosis to necrosis does occur. However, detailed mechanisms involved in the switch mechanism remain unsolved although decreases in the intracellular level of ATP and a burst in the cellular level of reactive oxygen species (ROS) have been proposed. Recently, we have shown that the population of apoptotic cells reaches maximum in human osteosarcoma 143B cells treated for 6h with menadione (MEN) while necrotic cells become predominant at 9h of the treatment. In the present study we have attempted to clarify the role of cellular ATP in the switch mechanism using rho(0) cells derived from human osteosarcoma rho+ cells. Results are summarized as follows: (1) Apoptotic and necrotic changes in rho(0) cells are much faster than rho+ cells after the treatment with MEN. (2) Cellular level of ATP in rho(0) cells remains essentially in the same level before and after the MEN-treatment while intracellular levels of superoxide continuously increase after the MEN-treatment. (3) rho+ cells treated with MEN in the presence of antimycin A plus oligomycin show similar changes to those of MEN-treated rho(0) cells. (4) MEN-induced increases in the cellular level of superoxide are distinctly suppressed by inhibitors of NADPH oxidase. These results suggest that the intracellular level of superoxide may be a key factor directly related to the switch mechanism from apoptosis to necrosis, and that decreases in cellular level of ATP accelerate both apoptotic and necrotic changes of the cells.


Subject(s)
Apoptosis/physiology , Necrosis/physiopathology , Oxidative Stress/physiology , Antimycin A/pharmacology , Humans , Microscopy, Electron , Oligomycins/pharmacology , Tumor Cells, Cultured , Vitamin K 3/pharmacology
15.
Ambio ; 35(1): 36-42, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16615698

ABSTRACT

The silica deficiency hypothesis holds that increases of still waters caused by hydraulic alterations and high nitrogen (N) and phosphorus (P) discharges enhance the growth of freshwater diatoms, which take up the dissolved silicate (DSi) supplied by natural weathering. The consequent decrease in the DSi supply to the sea is advantageous to flagellates (nonsiliceous and potentially harmful) but not to diatoms (siliceous and mostly benign) in coastal marine ecosystems. Verification of this hypothesis has been hampered by lack of relevant data, particularly in Asia. We investigated the aquatic continuum composed of Lake Biwa, the Yodo River, and the Seto Inland Sea, Japan, where the natural conditions make the silica deficiency less likely to emerge due to the inherently rich supply of DSi. The results showed that the silica was retained both in the lake and nearby the estuary. The relative dominance of diatom and flagellates could not be explained solely by the stoichiometric arguments but by the supportive discussion on the difference of their behavioral characteristics and the process nearby the estuary, where direct inputs of N and P and effluent Si enhanced diatom bloom, even though the Si/N ratio was lowered in the upstream reservoir. Thus the retention of DSi occurred in two places: in the lake and nearby the estuary, where the other N and P are loaded directly. The rate of DSi retention correlated with socio-economic changes, such as rapid economic growth in the 1960s and mitigations implemented after the 1980s. Sensitivity of this continuum to the Si processes suggests the global significance of this hypothesis.


Subject(s)
Diatoms/physiology , Ecosystem , Geologic Sediments/chemistry , Silicon Dioxide/chemistry , Environmental Monitoring , Eukaryota , Fresh Water/chemistry , Japan , Nitrogen/analysis , Phosphorus/analysis , Rivers
16.
Biol Neonate ; 89(3): 177-82, 2006.
Article in English | MEDLINE | ID: mdl-16219999

ABSTRACT

BACKGROUND: Partial liquid ventilation (PLV) with perfluorochemical (PFC) has been advocated as a new therapy for acute respiratory distress syndrome in both clinical and animal studies, meconium aspiration syndrome, and RDS. PFC is referred to as liquid PEEP because it gets distributed to the most gravity-dependent regions of the lung due to its density. High-frequency oscillation (HFO) has been shown to prevent both acute and chronic lung injury in the management of very low birth weight infants with RDS, with gentle ventilation approach. Specifically, HFO with aggressive and adequate lung volume recruitment has been shown to reduce the incidence of chronic lung disease in very low birth weight infants. We hypothesized that PLV along with HFO might be effective in ARDS in an adult rabbit model. OBJECTIVES: To examine the efficiency of low-dose PLV with with HFO on pulmonary gas exchange and lung compliance in a surfactant-depleted rabbit model. METHODS: After induction of severe lung injury by repeated saline lung lavage, 19 adult white Japanese rabbits were randomized into two groups that received PLV with HFO (n=9) or HFO gas ventilation (n=10). Physiological and blood gas data were compared between the two groups by analysis of variance. RESULTS: The HFO-PLV group showed improved total lung compliance with maintenance of significantly lower mean airway pressure as compared with the HFO-GAS group so as to keep SpO2>90%. CONCLUSIONS: The addition of a low dose of PFC with HFO was effective in achieving adequate oxygenation, with a reduction in further lung injury in neonates.


Subject(s)
Fluorocarbons/therapeutic use , High-Frequency Ventilation , Liquid Ventilation/methods , Lung Compliance , Lung Diseases/therapy , Animals , Disease Models, Animal , Hydrocarbons, Brominated , Lung Diseases/etiology , Pulmonary Surfactants , Rabbits , Sodium Chloride , Therapeutic Irrigation
17.
J Electron Microsc (Tokyo) ; 54(2): 127-38, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15994205

ABSTRACT

Detailed mechanisms of the switch of the cell death mode from apoptosis to necrosis remain to be solved, although the intracellular level of ATP and that of free radicals have been postulated to be the major factors involved in the mechanisms. In the present study menadione (MEN)-induced cell injury processes were studied using rho0 cells derived from human osteosarcoma 143B cells and parental rho+ cells co-treated with inhibitors of electron transfer chain of mitochondria or oligomycin, an inhibitor of ATP synthesis. Treatment of rho+ cells with 100 microM MEN induced apoptosis, which reached the maximum at 6 h, and was followed by an abrupt decrease thereafter, while necrotic cells (NC) increased continuously when they were judged by Annexin V and PI double staining. On the other hand, MEN induced apoptotic and necrotic changes much faster in rho0 cells compared to rho+ cells. The frequency to find apoptotic cells (AP) in the former cells was distinctly smaller than that to find NC judged by Annexin V and PI double staining. Electron microscopically, a major population of rho0 cells treated with MEN for 6 h consisted of intermediate cells, and a small number of AP co-existed. At 9 h of the treatment intermediate cells were exclusively seen, and AP were hardly detected. When parental rho+ cells were treated with MEN in the presence of oligomycin or oligomycin plus antimycin A both apoptotic and necrotic changes of the cells were distinctly accelerated. The intracellular level of superoxide in rho0 cells continuously increased after the MEN treatment, whereas that of ATP remained distinctly low before and after the MEN treatment compared to that in rho+ cells. These data suggest that the intracellular level of superoxide may be a key factor controlling the switch from apoptosis to necrosis.


Subject(s)
Apoptosis/physiology , Mitochondria/physiology , Necrosis/metabolism , Adenosine Triphosphate/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Electron Transport/drug effects , Flow Cytometry , Humans , Membrane Potentials , Microscopy, Electron, Transmission , Mitochondria/drug effects , Mitochondria/ultrastructure , Oligomycins/pharmacology , Oxidative Phosphorylation , Protein Synthesis Inhibitors/pharmacology , Reactive Oxygen Species/metabolism , Vitamin K 3/pharmacology
18.
J Electron Microsc (Tokyo) ; 53(6): 635-47, 2004.
Article in English | MEDLINE | ID: mdl-15582977

ABSTRACT

Effects of jasplakinolide (JSP), a stabilizer of F-actin, and latrunculin A (LTA), a destabilizer of F-actin, on a series of events occurring in the execution phase of staurosporine (STS)-induced apoptotic processes were studied using human osteosarcoma 143B cells. Time-dependent apparent increases of the population of cells with collapsed membrane potential of mitochondria (Delta Psi(m)) caused by STS treatment were not due to actual decreases in the Delta Psi(m) per cell, but due to the fragmentation of cells resulting in decreases in the number of active mitochondria per cell. Decreases in the Delta Psi(m) in fragmented cells occurred late in the execution phase. Both JSP and LAT failed to prevent STS-induced release of cytochrome c from mitochondria followed by the activation of caspases 3 and 9, the cleavage of poly (ADP-ribose) polymerase (PARP) and apoptotic nuclear fragmentation. However, both drugs prevented STS-induced apoptotic cell fragmentation and decreases in the Delta Psi(m). These results indicate that physicochemical states of actin filaments play a certain role in the execution phase of STS-induced apoptotic processes.


Subject(s)
Actin Cytoskeleton/drug effects , Apoptosis/physiology , Enzyme Inhibitors/pharmacology , Staurosporine/pharmacology , Actin Cytoskeleton/metabolism , Antineoplastic Agents/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Caspases/drug effects , Caspases/metabolism , Cell Line, Tumor , Depsipeptides/pharmacology , Humans , Immunoblotting , Membrane Potentials/drug effects , Microscopy, Confocal , Mitochondria/drug effects , Mitochondria/pathology , Thiazoles/pharmacology , Thiazolidines
19.
J Electron Microsc (Tokyo) ; 53(6): 659-70, 2004.
Article in English | MEDLINE | ID: mdl-15582979

ABSTRACT

Treatment of 143B cells with microtubule-active drugs (MADs) including taxol, nocodazole and colchicine induced distinct structural changes, such as rounding of the cells with perinuclear clustering of mitochondria, when the cells were treated for up to 10 h. When the incubation time with MADs was longer than 10 h, multinuclear cells appeared, and their population increased with time. In this study perinuclear clustering of mitochondria i.e. mitochondria encircling the aggregated chromatin of the nucleus that had lost the nuclear membrane was detected. This observation was distinct from that reported in the literature. Mitochondria were aligned in a few lines; the occurrence of mitochondria in even a single line is an extreme case, resulting in one plane of section for electron microscopy. Three-dimensional reconstructions of confocal microscopic images of mitochondria revealed that they were assembled as a spherical structure. The majority of the cells with perinuclear clustering of mitochondria remained intact for up to 24 h. Mitochondria were observed to be clustered around the nucleus in the orthodox configuration or in some cases they were moderately condensed, as observed electron microscopically. Annexin V and PI double staining of cells showed that more than 90% of cells were viable. In the case of treatment with taxol, membrane potential of mitochondria per cell was well maintained although it was moderately lowered in the case of treatment with nocodazole. Taking into consideration the previous data reported from our laboratory, the present results may assist in elucidation of the behaviour of mitochondria during the dividing processes of mammalian cells, which is yet to be clarified.


Subject(s)
Chromatin/ultrastructure , Microtubules/drug effects , Mitochondria/ultrastructure , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Nucleus/ultrastructure , Colchicine/pharmacology , Flow Cytometry , Humans , Immunohistochemistry , Microscopy, Confocal , Microscopy, Electron, Transmission , Microtubules/physiology , Nocodazole/pharmacology , Paclitaxel/pharmacology
20.
Acta Biochim Pol ; 51(4): 1015-22, 2004.
Article in English | MEDLINE | ID: mdl-15625573

ABSTRACT

The effects of inhibitors of plasma membrane NADPH oxidase on menadione-induced cell injury processes were studied using human osteosarcoma 143B cells. The intracellular level of superoxide in the cells treated with menadione for 6 h reached a maximum followed by an abrupt decrease. The population of apoptotic cells detected by Annexin V and propidium iodide double staining also reached its maximum at 6 h of menadione-treatment while that of necrotic cells increased continuously reaching 90% of the total population at 9 h of the treatment. Pretreatment of the cells with inhibitors of NADPH oxidase, including diphenyliodonium chloride, apocynin, N-vanillylnonanamide and staurosporine was effective in lowering the menadione-induced elevations of superoxide, and also in the suppression of the switch of the cell death mode from apoptosis to necrosis in menadione-treated cells except for the case of staurosporine. These results strongly suggest that superoxide generated by NADPH oxidase, besides that generated by the mitochondria, may contribute to the remarkable increase in the intracellular level of superoxide in the cells treated with menadione for 6 h resulting in the switch from apoptosis to necrosis, although a direct evidence of the presence of active and inactive forms of NADPH oxidase in control and menadione-treated 143B cells is lacking at present.


Subject(s)
Apoptosis , Cell Membrane/enzymology , NADH, NADPH Oxidoreductases/physiology , Necrosis , Vitamin K 3/toxicity , Cell Line, Tumor , Humans , NADH, NADPH Oxidoreductases/antagonists & inhibitors , NADPH Oxidases , Superoxides/metabolism
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