Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 37 records · Page 2Linked to original sources

PubMed2003

Determination of indices of the corpus callosum associated with normal aging in Japanese individuals.

Indices of the corpus callosum with normal aging and their sex differences were elucidated using quantitative MRI. We studied 94 Japanese men (mean+/-SD 57.3+/-20.8 years, range 6-90 years) and 111 Japanese women (mean+/-SD 61.2+/-17.6 years, range 9-86 years) who had no intracranial lesions on MRI and no history of neurological illness. The widths of the rostrum, body and splenium, the anterior to posterior length, and the maximum height in the midsagittal image were selected for measurement. The Evans index, which is the relative ratio of lateral ventricle expansion, and the maximum width of the third ventricle in the axial image were also estimated for comparison. The widths of rostrum, body and splenium of the corpus callosum became thinner with age. Conversely, the anterior to posterior length and the maximum height of the corpus callosum increased with age. The ratio of the width of the body to the length of the corpus callosum and the ratio of the width of the body to the height of the corpus callosum are best correlated with age. No sex differences in regional size of corpus callosum, including these two ratios, were observed in any raw measures, although ventricular indices were larger in men than women. Evaluation of the ratio of the width of the body to its length and the ratio of the width of the body to its height may enable accurate estimation of normal or pathological changes of the corpus callosum. Aging and pathological atrophy of corpus callosum can be evaluated without any adjustment for gender.

Adolescent↗

PubMed2003

Mechanical analyses of morphological and topological transformation of liposomes.

Liposomes are micro-compartments made of lipid bilayer membranes possessing the characteristics quite similar to those of biological membranes. To form artificial cell-like structures, we made liposomes that contained subunit proteins of cytoskeletons: tubulin or actin. Spherical liposomes were transformed into bipolar or cell-like shapes by mechanical forces generated by the polymerization of encapsulated subunits of microtubules. On the other hand, disk- or dumbbell-shaped liposomes were developed by the polymerization of encapsulated actin. Dynamic processes of morphological transformations of liposomes were visualized by high intensity dark-field light microscopy. Topological changes, such as fusion and division of membrane vesicles, play an essential role in cellular activities. To investigate the mechanism of these processes, we visualized the liposomes undergoing topological transformation in real time. A variety of novel topological transformations were found, including the opening-up of liposomes and the direct expulsion of inner vesicles.

Biomechanical Phenomena↗

PubMed2003

Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice.

Deficiency of laminin alpha2 is the cause of one of the most severe muscular dystrophies in humans and other species. It is not yet clear how particular mutations in the laminin alpha2 chain gene affect protein expression, and how abnormal levels or structure of the protein affect disease. Animal models may be valuable for such genotype-phenotype analysis and for determining mechanism of disease as well as function of laminin. Here, we have analyzed protein expression in three lines of mice with mutations in the laminin alpha2 chain gene and in two lines of transgenic mice overexpressing the human laminin alpha2 chain gene in skeletal muscle. The dy(3K)/dy(3K) experimental mutant mice are completely deficient in laminin alpha2; the dy/dy spontaneous mutant mice have small amounts of apparently normal laminin; and the dy(W)/dy(W) mice express even smaller amounts of a truncated laminin alpha2, lacking domain VI. Interestingly, all mutants lack laminin alpha2 in peripheral nerve. We have demonstrated previously, that overexpression of the human laminin alpha2 in skeletal muscle in dy(2J)/dy(2J) and dy(W)/dy(W) mice under the control of a striated muscle-specific creatine kinase promoter substantially prevented the muscular dystrophy in these mice. However, dy(W)/dy(W) mice, expressing the human laminin alpha2 under the control of the striated muscle-specific portion of the desmin promoter, still developed muscular dystrophy. This failure to rescue is apparently because of insufficient production of laminin alpha2. This study provides additional evidence that the amount of laminin alpha2 is most critical for the prevention of muscular dystrophy. These data may thus be of significance for attempts to treat congenital muscular dystrophy in human patients.

Animals↗

PubMed2003

Milrinone improves lung compliance in patients receiving mechanical ventilation for cardiogenic pulmonary edema.

BACKGROUND: Cardiogenic pulmonary edema is a frequent cause of respiratory failure. We investigated whether milrinone improved lung compliance. METHODS: We selected 10 patients with respiratory failure due to severe cardiogenic pulmonary edema to receive mechanical ventilation. Patients were administered a bolus injection of milrinone (50 microg kg-1) over 10 min, followed by continuous intravenous infusion (0.5 microg kg-1 min-1). Lung compliance, blood gas values, hemodynamic parameters, and sample plasma milrinone levels were assessed over 120 min after the onset of the continuous infusion of milrinone. RESULTS: Ten min following milrinone infusion, dynamic compliance (Cdyn) and static compliance (Cst) increased from 37 +/- 12 to 42 +/- 12 ml cmH2O-1 and from 40 +/- 13 to 45 +/- 12 ml cmH2O-1, respectively (P < 0.01). Plasma milrinone levels reached a therapeutic level for vasodilator and positive inotropic effect at 10 min after milrinone infusion. A significant decrease in mean pulmonary artery pressure and pulmonary artery wedge pressure occurred simultaneously with an increase in respiratory system compliance. However, an increase in cardiac index was observed later than these changes. There were significant correlations between the mean pulmonary artery pressure and Cdyn (r = -0.39, P < 0.01) and Cst (r = -0.38, P < 0.01). CONCLUSIONS: Milrinone-induced improvement in lung compliance along with an improvement of hemodynamics was found together with an inverse relationship between compliance and mean pulmonary artery pressure.

Aged↗

PubMed2003

Sister chromatid cohesion and genome stability in vertebrate cells.

For successful eukaryotic mitosis, sister chromatid pairs remain linked after replication until their kinetochores have been attached to opposite spindle poles by microtubules. This linkage is broken at the metaphase-anaphase transition and the sisters separate. In budding yeast, this sister chromatid cohesion requires a multi-protein complex called cohesin. A key component of cohesin is Scc1/Mcd1 (Rad21 in fission yeast). Disruption of the chicken orthologue of Scc1 by gene targeting in DT40 cells causes premature sister chromatid separation. Cohesion between sister chromatids is likely to provide a substrate for post-replicative DNA repair by homologous recombination. In keeping with this role of cohesion, Scc1 mutants also show defects in the repair of spontaneous and induced DNA damage. Scc1-deficient cells frequently fail to complete metaphase chromosome alignment and show chromosome segregation defects, suggesting aberrant kinetochore function. Consistent with this, the chromosomal passenger protein, INCENP (inner centromere protein) fails to localize to centromeres. Survivin, another passenger protein and one which interacts with INCENP, also fails to localize to centromeres in Scc1-deficient cells. These results show that cohesin maintains genomic stability by ensuring appropriate DNA repair and equal chromosome segregation at mitosis.

Animals↗

PubMed2003

Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint.

OBJECTIVE: To determine whether the joint space is a suitable environment for embryonic stem (ES) cells to grow and form cartilage. METHOD: We transplanted ES cells into the knee joint and a subcutaneous space of mice with severe combined immunodeficiency. RESULTS: Teratomas formed in both areas. Those in the joints grew and destroyed the joints. The incidence of cartilage formation was the same in the knee joint and subcutaneous space, but the ratio of cartilage to teratoma was higher in the knee joint than in the subcutaneous space. The teratomas were proved to have been derived from the transplanted ES cells by detection of the neomycin-resistance gene that had been transfected into the ES cells. CONCLUSIONS: It is currently not possible to use ES cells to repair joint tissues. Further optimization of donor ES cells to differentiate as well as inhibit tumour growth may help to meet these challenges.

Animals↗

PubMed2003

Effects of the Japanese herbal medicine Keishi-bukuryo-gan and 17beta-estradiol on calcitonin gene-related peptide-induced elevation of skin temperature in ovariectomized rats.

The effects of a Japanese herbal medicine, Keishi-bukuryo-gan, and 17beta-estradiol on calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature were investigated in ovariectomized (OVX) rats. Ovariectomy not only potentiated CGRP-induced elevation of skin temperature and arterial vasorelaxation but also induced a lower concentration of endogenous CGRP in plasma and up-regulation of arterial CGRP receptors, suggesting that lowered CGRP in plasma due to ovarian hormone deficiency increases the number of CGRP receptors and consequently amplifies the stimulatory effects of CGRP to elevate skin temperature. Oral Keishi-bukuryo-gan (100-1000 mg/kg, once a day for 7 days) restored a series of CGRP-related responses observed in OVX rats by normalizing plasma CGRP levels in a dose-dependent manner as effectively as s.c. injection. 17Beta-estradiol (0.010 mg/kg, once a day for 7 days). However, Keishi-bukuryo-gan did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, although the hormone replacement of 17beta-estradiol restored them. These results suggest that Keishi-bukuryo-gan, which does not confer estrogen activity on plasma, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy is contraindicated, as well as menopausal women.

Administration, Oral↗

PubMed2003

[Adhesion or organization during surgery due to mediastinoscopy before induction therapy for non-small cell lung cancer].

We conducted a retrospective study to investigate amounts of adhesion or organization during surgery due to mediastinoscopy before induction therapy for non-small cell lung cancer (NSCLC). A case series of 13 patients (c-stage IIIA in 11 and IIIB in 2) with right-side NSCLC who underwent induction therapy were assessed. They were between 39 and 71 years old and 8 males and 5 females. Induction therapy was chemotherapy alone in 4 cases and chemo-radiotherapy in 9 cases. The mediastinocopy was used in 4 cases. Mediastinal lymph node resection was incomplete in 3 of the 4 (75%) cases among the mediastinoscopy group but the no-mediastioscopy group had no incomplete resection (p = 0.01), though 2 of the 9 (22%) cases among the chemo-radiation group and 1 of the 4 (25%) among the chemo alone group (p > 0.9). Severe adhesion or organization can occur after the mediastinoscopy and induction therapy, which might be a course of incomplete mediastinal lymph node resection.

Adult↗

PubMed2002

Long-term treatment with nicardipine for severe pre-eclampsia.

OBJECTIVE: To evaluate the safety of long-term nicardipine treatment in severely pre-eclamptic women and their fetuses/newborns. METHODS: We divided 50 pregnant women into three groups according to the length of their treatment: short-term treatment of severely pre-eclamptic women (7 days or less, n=20); medium-term treatment also of severely pre-eclamptic women (8-28 days, n=20); and long-term treatment of women with severe superimposed pre-eclampsia (29 days or more, n=10). RESULTS: Nicardipine significantly lowered both systolic (P<0.01) and diastolic blood pressures (P<0.025) in all three groups. The incidence of delivery before 28 weeks of gestation was very low in all three groups. There were no maternal or fetal/neonatal adverse effects. CONCLUSION: Our results suggest that long-term treatment with nicardipine for severe pre-eclampsia is as effective and safe as a short- and medium-term treatment.

Adult↗

PubMed2002

ED-71, a vitamin D analog, is a more potent inhibitor of bone resorption than alfacalcidol in an estrogen-deficient rat model of osteoporosis.

Although active vitamin D is used in certain countries for the treatment of osteoporosis, the risk of causing hypercalcemia/hypercalciuria means that there is only a narrow therapeutic window, and this has precluded worldwide approval. The results of our previous animal studies have suggested that the therapeutic effect of active vitamin D on bone loss after estrogen deficiency can be dissociated at least partly from its effect of enhancing intestinal calcium absorption and suppressing parathyroid hormone (PTH) secretion. To test this, we compared the effects of ED-71, a hydroxypropoxy derivative of 1alpha,25-dihydroxyvitamin D3, with orally administered alfacalcidol, on bone mineral density (BMD) and the bone remodeling process as a function of their effects on calcium metabolism and PTH, in a rat ovariectomy (ovx) model of osteoporosis. ED-71 increased bone mass at the lumbar vertebra to a greater extent than alfacalcidol, while enhancing calcium absorption (indicated by urinary calcium excretion) and decreasing serum PTH levels to the same degree as alfacalcidol. ED-71 lowered the biochemical and histological parameters of bone resorption more potently than alfacalcidol, while maintaining bone formation markers. These results suggest that active vitamin D exerts an antiosteoporotic effect by inhibiting osteoclastic bone resorption while maintaining osteoblastic function, and that these anticatabolic/anabolic effects of active vitamin D take place independently of its effects on calcium absorption and PTH. The demonstration that ED-71 is more potent in these properties than alfacalcidol makes it an attractive candidate as an antiosteoporotic drug.

Administration, Oral↗

PubMed2002

Changes in osteoprotegerin and markers of bone metabolism during glucocorticoid treatment in patients with chronic glomerulonephritis.

It is well known that long-term glucocorticoid treatment causes osteoporosis, but the precise mechanism remains unclear. Recently, osteoprotegerin (OPG) has been identified as a cytokine that inhibits osteoclast differentiation. We have previously demonstrated that serum OPG is suppressed by glucocorticoids. Therefore, the present study was carried out to clarify the interrelationships between OPG and other markers of bone metabolism during glucocorticoid treatment. Thirteen patients (7 men, 6 women; 44.1 +/- 5.9 years old) with chronic glomerulonephritis who were to be treated with glucocorticoids for the first time were chosen for this study. Markers of bone metabolism, including serum OPG, osteocalcin (OC), bone-specific alkaline phosphatase activity (bAP), parathyroid hormone (PTH), tartrate-resistant acid phosphatase (TRAP), and bone mineral density (BMD), were measured before and during the treatment period. Glucocorticoids significantly reduced BMD of the lumbar spine in the 6 month treatment period (p < 0.01). Serum OPG was decreased significantly by glucocorticoids within 2 weeks (p < 0.001), and serum TRAP, a marker of bone resorption, was markedly increased (p < 0.001). On the other hand, there were no remarkable changes in serum PTH. Serum OC and bAP, markers of bone formation, were transiently reduced during the treatment period (p < 0.01). Furthermore, only serum OPG was positively and independently correlated with percentage BMD of age-matched reference (%AMR). These findings imply that glucocorticoid-induced bone loss develops rapidly via enhanced bone resorption and suppressed bone formation. Moreover, the increased bone resorption caused by glucocorticoids may be, at least in part, mediated by inhibition of OPG, not increment of PTH.

Adult↗

PubMed2002

Haemodynamic and splanchnic organ blood flow responses during sevoflurane-induced hypotension in dogs.

BACKGROUND AND OBJECTIVE: The safety of hypotension induced by sevoflurane and splanchnic organ blood flow remains to be clarified. The aim was to investigate the effects of sevoflurane-induced hypotension on systemic haemodynamics and splanchnic organ blood flows in dogs. METHODS: Mean arterial pressure was maintained at 60 mmHg by increasing sevoflurane concentrations. The renal, hepatic and pancreatic blood flows were measured by using the hydrogen clearance method. RESULTS: Hypotension induced by sevoflurane resulted in a 50% decrease of mean arterial pressure due to a 30% reduction in systemic vascular resistance associated with a 30% decrease in cardiac index. The mechanisms causing the lower cardiac index were produced by the decreases in heart rate and left ventricular dP/dt(max). Renal, hepatic and pancreatic blood flow were reduced, but the whole-body oxygen consumption did not change during the hypotensive period. CONCLUSIONS: The haemodynamic changes induced by sevoflurane were caused by the suppression of arterial baroreflexes and myocardial depression, but splanchnic organ blood flows, though reduced, could provide adequate peripheral perfusion to meet the decrease in oxygen supply.

Anesthetics, Inhalation↗

PubMed2002

Haemodynamic and splanchnic organ blood-flow responses to hypotension induced by the calcitonin gene-related peptide and sodium nitroprusside in dogs.

BACKGROUND AND OBJECTIVE: To elucidate the effects of various degrees of hypotension induced by the calcitonin gene-related peptide (CGRP) on the splanchnic circulation, we investigated the renal and hepatic blood flow during hypotension induced by either the calcitonin gene-related peptide or sodium nitroprusside in the isoflurane-anaesthetized dog. METHODS: Anaesthesia was maintained with 1.3% isoflurane in oxygen. After the baseline period, mean arterial pressure was reduced to 60 mmHg in the CGRP60 and nitroprusside groups, and to 50 mmHg in the CGRP50 group. The splanchnic organ blood flow was measured by hydrogen clearance. RESULTS: The cardiac index in the CGRP60 group increased (P < 0.01), but in the CGRP50 group it decreased (P < 0.01), and in the nitroprusside group it remained unchanged during hypotension. Mean pulmonary artery and pulmonary capillary wedge pressures in the CGRP60 group remained unchanged, but in the CGRP50 and nitroprusside groups they decreased (P < 0.01) during hypotension. Cardiac contractility in the CGRP60 group remained unchanged, whereas in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) during hypotension. Renal blood flow in the CGRP60 group was relatively well maintained but in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) throughout the observation. Hepatic blood flow in all three groups was reduced (P < 0.01) during hypotension. The reductions in hepatic blood flow between the Calcitonin gene-related peptide groups were associated with a dose-dependent decrease in mean arterial pressure. CONCLUSIONS: The results suggest that calcitonin gene-related peptide acts as an arteriolar vasodilator at low doses but as a vasodilator of the arteriolar and venous systems at higher doses, and that profound hypotension induced by the calcitonin gene-related peptide may impair splanchnic circulation.

Analysis of Variance↗

PubMed2002

Adeno-associated virus vector-mediated gene transfer into dystrophin-deficient skeletal muscles evokes enhanced immune response against the transgene product.

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscular disorder caused by a defect in the DMD gene. AAV vector-mediated micro-dystrophin cDNA transfer is an attractive approach to treatment of DMD. To establish effective gene transfer into skeletal muscle, we examined the transduction efficiency of an AAV vector in skeletal muscles of dystrophin-deficient mdx mice. When an AAV vector encoding the LacZ gene driven by a CMV promoter (AAV-CMVLacZ) was introduced, beta-galactosidase expression markedly decreased in mdx muscle 4 weeks after injection due to immune responses against the transgene product. We also injected AAV-CMVLacZ into skeletal muscles of mini-dystrophin-transgenic mdx mice (CVBA3'), which show ameliorated phenotypes without overt signs of muscle degeneration. AAV vector administration, however, evoked substantial immune responses in CVBA3' muscle. Importantly, AAV vector using muscle-specific MCK promoter also elicited responses in mdx muscle, but at a considerably later period. These results suggested that neo-antigens introduced by AAV vectors could evoke immune reactions in mdx muscle, since increased permeability allowed a leakage of neo-antigens from the dystrophin-deficient sarcolemma of muscle fibers. However, resident antigen-presenting cells, such as myoblasts, myotubes and regenerating immature myofibers, might also play a role in the immune response.

Adenoviridae↗

PubMed2002

The effect of head posture on the pharyngeal airway space (PAS).

The purpose of this study was to investigate the relationship between cranio-cervical inclination and pharyngeal airway space (PAS) by measuring these parameters at different head postures in the same subjects and to obtain a regression equation to correct the values measured. Fifty lateral cephalometric radiographs taken at five different head postures per individual were obtained from ten adults (seven males and three females) aged from 25 to 30 years with nose breathers and Class I occlusion. The changes in cranio-cervical inclination produced by head extension were correlated with changes in the variables describing the PAS. The OPT/NSL (cranio-cervical inclination in the second vertebrae) and C3-Me (distance between the third vertebrae and the Menton) correlated strongly with PAS-TP (the most proximal distance measured between the posterior pharyngeal wall and the tongue base) in the pharyngeal airway space (r = 0.807 and 0.854 respectively). The regression equations were Y = - 27.177+0.39X (Y = PAS-TP, X = OPT/NSL), and Y = -21.105+0.402X (Y = PAS-TP, X = C3-Me), respectively. From these equations we could conclude that an increase of 10 degrees in OPT/NSL or 10 mm in C3-Me increased the pharyngeal airway space (PAS-TP) by about 4 mm.

Adult↗

PubMed2001

Design of an artificial light-harvesting unit by protein engineering: cytochrome b(562)-green fluorescent Protein chimera.

We have generated a novel model protein for an artificial light-harvesting complex composed of two proteins, cytochrome b(562) (cytb(562)) and enhanced green fluorescent protein (EGFP), in which two chromophores are fixed in each protein matrix. Cytb(562) was appended to the N-terminus of EGFP via a Gly-Ser linker and the resultant fusion protein was successfully expressed in Escherichia coli as a mixture of the apo- and the holo-forms as to the cytb(562) moiety. The fluorescence of EGFP was substantially quenched when the apo-form was reconstituted with hemin. Based on the fluorescence lifetime measurements, it appeared that light energy entrapped by EGFP is transferred to the heme of cytb(562) by resonance energy transfer (energy transfer yield: 65%). Spatial organization of two chromophores using small and stable protein matrices will be promising toward the construction of an artificial light-harvesting complex by protein engineering.

Cytochrome b Group↗

PubMed2001

Ionic channel structures in [(M+)x([18]crown-6)][Ni(dmit)2]2 molecular conductors.

The [(M+)x[18]crown-6)] supramolecular cations (SC+), in which M+ and [18]crown-6 are alkali metal ions (M+ = Li+, Na+, and Cs+) and 1,4,7,10,13,16-hexaoxacyclooctadecane, respectively, form ionic channel structures through the regular stacks of [18]crown-6 in [Ni(dmit)2]-based molecular conductors (dmit2+ = 2-thioxo-1,3-dithiole-4,5-dithiolate). In addition to the [Ni(dmit)2] salts that have the ionic channel structures (these salts are abbreviated as type I salts), Li+ and Na+ form dimerized [(M+)2([18]crown-6)2] units in the crystals (type II salts). The K+ and Rb+ are coordinated tightly into the [18]crown-6 cavity to form typical disk-shape SC+ units in the corresponding [Ni(dmit)2] salts (type III salts). The type I, II, and III salts have typical stoichiometries of [(M+)x([18]crown-6)][Ni(dmit)2]2, [(M+)([18]crown-6)(H2O)x(CH3CN)(1.5 - x)][Ni(dmit)2]3 (x = 1 for Li+ or 0.5 for Na+), and [M+([18]crown-6)][Ni(dmit)2]3, respectively: the salts of the same type are isostructural. In agreement with the trimer structures of [Ni(dmit)2] in the type II and III salts, they exhibit semiconducting behavior with electrical conductivities at 300 K (sigma(300 K)) of 0.01-0.1 S cm(-1). Type I salts contain a regular stack of partially oxidized [Ni(dmit)2] units, which form a quasi one-dimensional metallic band within the tight-binding approximation regime. The electrical conductivities at 300 K are 10-30 S cm(-1), and an almost temperature-independent conductivity was observed at higher temperatures. However, the one-dimensional electronic structures in these salts are strongly influenced by the static and dynamic structures of the coexisting ionic channel. The Na+ salt is a semiconductor, whose magnetic behavior is described by the disordered one-dimensional antiferromagnetic chain. On the other hand, the Cs+ salt is a exhibits metallic properties with 2 kF instability at room temperature. The Li+ salt shows a gradual transition from the high-temperature metallic phase to the low-temperature one-dimensional antiferromagnetic semiconductor phase, which was associated with the freezing of Li+ motion at lower temperatures. The preferential crystallization of type I salts was possible by controlling the equilibrium constant (Kc) of the complex formation between M+ ions and the [18]crown-6 molecule. The ionic channel structures were obtained when the KC was low in the electrocrystallization solution, while type II or III salts were formed in the high Kc region.

Journal Article↗

PubMed2001

Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells.

Anaphase-promoting complex (APC) is activated by two regulatory proteins, Cdc20 and Cdh1. In yeast and Drosophila, Cdh1-dependent APC (Cdh1-APC) activity targets mitotic cyclins from the end of mitosis to the G1 phase. To investigate the function of Cdh1 in vertebrate cells, we generated clones of chicken DT40 cells disrupted in their Cdh1 loci. Cdh1 was dispensable for viability and cell cycle progression. However, similarly to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G1, resulting in abrogation of G1 arrest caused by treatment with rapamycin, an inducer of p27(Kip1). Further more, we found that Cdh1(-/-) cells fail to maintain DNA damage-induced G2 arrest and that Cdh1-APC is activated by X-irradiation-induced DNA damage. Thus, activation of Cdh1-APC plays a crucial role in both cdk inhibitor-dependent G1 arrest and DNA damage-induced G2 arrest.

Anaphase-Promoting Complex-Cyclosome↗