Paraneoplastic limbic encephalitis presenting as a neurological emergency: a case report

Introduction

Dentin dysplasia is a rare hereditary disturbance of dentin formation characterized by defective dentin development with clinically normal appearing crowns, severe hypermobility of teeth and spontaneous dental abscesses or cysts. Radiographic analysis shows obliteration of all pulp chambers, short, blunted and malformed or absent roots and peri-apical radiolucencies of non carious teeth.

Case presentation

We present a case of dentin dysplasia type I in a 12-year-old Iranian boy, and the clinical, radiographic and histopathologic findings of this condition and treatment are described.

Conclusions

There are still many inconclusive issues in the diagnosis and management of patients with dentin dysplasia. The diagnostic features of this rare disturbance will remain incompletely defined until additional cases have been described. Early diagnosis of the condition and initiation of effective regular dental treatments may help these patients to prevent or delay loss of dentition.     

Clinical features of atypical odontalgia; three cases and literature reviews

Background

Atypical odontalgia (AO) is a disease characterized by continuous pain affecting the teeth or tooth sockets after extraction in the absence of any identifiable cause on clinical or radiographic examination. Antidepressants, such as amitriptyline, are reported to be effective in the treatment of AO; however, their efficacy varies depending on the case. In this article, we report three types of AO and discuss its heterogeneity and management.

Case presentation

In the first case, a 58-year-old woman presented with a heavy, splitting pain in the four maxillary front post-crown teeth, as if they were being pressed from the side. Her symptoms abated with 20 mg of amitriptyline. In the second case, a 39-year-old woman presented with a feeling of heaviness pain on the right side of maxillary and mandibular molar teeth, face, whole palate, and throat. She was unable to function because of her pain. Her symptoms drastically subsided with 3 mg of aripiprazole. In the third case, a 54-year-old woman presented with a tingling sensation on the left mandibular second premolar and first molar, and an uncomfortable feeling on her provisional prosthesis that made it unbearable to keep the caps on. Her symptoms diminished with 2 mg of aripiprazole added to 30 mg of mirtazapine.

Conclusions

AO shows various features and responses to drugs. It is considered not only a purely sensory problem, but also a considerably complex psychological problem, such as rumination about the pain. Investigating the difference in pharmacotherapeutic responses might help to advance the treatment of AO.

     

Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report

Background

Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation.

Case presentation

A 14-year-old Chinese boy suffering from β–thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, and depapillation of tongue indicating an underlying condition of anemia. The poor oral condition due to topical and systemic immunosuppressants was seriously aggravated, and rampant caries developed rapidly, affecting all newly erupted, permanent teeth. The teeth were hypersensitive and halitosis was apparent. Strategies for oral health education and diet modification were given to the patient. Xylitol chewing gum was used to stimulate saliva flow to promote remineralization of teeth. Silver diamine fluoride was topically applied to arrest rampant caries and to relieve pain from hypersensitivity. Carious teeth with pulpal involvement were endodontically treated. Stainless steel crowns were provided on molars to restore chewing function, and polycarbonate crowns were placed on premolars, upper canines and incisors.

Conclusion

This case report demonstrates success in treating a young teenager with severe rampant dental decay by contemporary caries control and preventive strategy.     

Effectiveness of two physical therapy interventions, relative to dental treatment in individuals with bruxism: study protocol of a randomized clinical trial

Background

Bruxism is a parafunctional habit characterized by grinding and/or clenching of the teeth. It may happen while awake (awake bruxism) or while sleeping (sleep bruxism). In adults, the prevalence is 20% for the awake bruxism and 8% for the sleep bruxism. Peripheral, central, and psychosocial factors influence the disorder, which may predispose to pain in the masticatory muscles and neck, headache, decreased pain thresholds in the masticatory and cervical muscles, limitation mandibular range of motion, sleep disorders, stress, anxiety, depression, and overall impairment of oral health. The aim of this study is to compare two distinct physical therapy interventions with dental treatment in pain, mandibular range of motion, sleep quality, anxiety, stress, depression, and oral health in individuals with bruxism.

Methods/Design

Participants will be randomized into one of three groups: Group 1 (n?=?24) intervention will consist of massage and stretching exercises; Group 2 (n?=?24) will consist of relaxation and imagination therapies; and Group 3 (n?=?24) will receive dental treatment. The evaluations will be performed at baseline, immediately after treatment, and at 2-month follow-up. Pain intensity will be assessed using the visual analogical scale, while pain thresholds will be determined using dolorimetry. Mandibular range of motion will be assessed using digital pachymeter. Sleep quality will be assessed by the Pittsburgh Sleep Quality Index, anxiety by the State-Trait Anxiety Inventory, stress by the Perceived Stress Scale-10, depression by the Beck Depression Inventory, and oral health will be assessed using the Oral Health Impact Profile - 14. Significance level will be determined at the 5% level.

Discussion

This project describes the randomization method that will be used to compare two physical therapy interventions with dental treatment in the management of pain, mandibular range of motion, sleep quality, anxiety, stress, depression, and oral health in individuals with bruxism. The study will support the practice of evidence-based physical therapy for individuals with bruxism. Data will be published after study is completed.

Trial registration

ClinicalTrials.gov, NCT01778881     

Early Cretaceous mammals of Western Siberia: 2. Tegotheriidae

New specimens of the tegotheriid docodont Sibirotherium rossicum Maschenko et al., 2003, including a maxillary fragment with two posterior teeth, an isolated upper molar, and mandibular fragments with teeth from the Early Cretaceous Shestakovo locality are described. The dental formula of Sibirotherium is I_{1 + ?}C1P₆M_6?. The upper molars of Sibirotherium, with two main labial and three lingual cusps, are convergently similar to the molars of tribosphenic mammals. In the dentary, the symphysis is short and Meckel’s groove is reduced. Sibirotherium is similar in the structure of lower teeth to Tegotherium from the Upper Jurassic of Mongolia; it is the latest known representative of Docodonta.     

Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis - An open clinical trial-

Background

Pentosan polysulfate sodium (pentosan) is a semi-synthetic drug manufactured from beech-wood hemicellulose by sulfate esterification of the xylopyranose hydroxyl groups. From in vitro and animal model studies, pentosan has been proposed as a disease modifying osteoarthritis drug (DMOAD). The objective of this study was to assess the efficacy, safety, and patient satisfaction in patients with mild radiographic knee osteoarthritis (OA) findings and OA-associated symptoms and signs.

Methods

Twenty patients were assessed clinically at Nagasaki University Hospital. The radiographic indications of OA were grade 1 to 3 using the Kellgren-Lawrence Grading System (K/L grade). Pentosan used in this study was manufactured and supplied in sterile injectable vials (100 mg/ml) by bene GmbH, Munich, Germany. The study was a single-center, open-label trial. Treatment consisted of 6 weekly subcutaneous injections (sc) of pentosan (2 mg/kg). Patients were clinically assessed at entry and 1 to 8, 11, 15, 24 & 52 weeks post treatment. The results were analyzed using one way ANOVA and Dunnett's method.

Results

Hydrarthroses were reduced quickly in all cases. The clinical assessments, i.e., knee flexion, pain while walking, pain after climbing up and down stairs, etc, were improved significantly and these clinical improvements continued for almost one year. The dose used in this study affected the blood coagulation test, but was within safe levels. Slightly abnormal findings were noted in serum triglycerides.

Conclusions

Pentosan treatment in twenty patients with mild knee OA seemed to provide improvements in clinical assessments and C2C level of cartilage metabolism.

Trial Registration

UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002790     

The relationship between PMI (manA) gene expression and optimal selection pressure in Indica rice transformation

Key message

An efficient mannose selection system was established for transformation of Indica cultivar IR58025B . Different selection pressures were required to achieve optimum transformation frequency for different PMI selectable marker cassettes.

Abstract

This study was conducted to establish an efficient transformation system for Indica rice, cultivar IR58025B. Four combinations of two promoters, rice Actin 1 and maize Ubiquitin 1, and two manA genes, native gene from E. coli (PMI-01) and synthetic maize codon-optimized gene (PMI-09) were compared under various concentrations of mannose. Different selection pressures were required for different gene cassettes to achieve corresponding optimum transformation frequency (TF). Higher TFs as 54 and 53 % were obtained when 5 g/L mannose was used for selection of prActin-PMI-01 cassette and 7.5 g/L mannose used for selection of prActin-PMI-09, respectively. TFs as 67 and 56 % were obtained when 7.5 and 15 g/L mannose were used for selection of prUbi-PMI-01 and prUbi-PMI-09, respectively. We conclude that higher TFs can be achieved for different gene cassettes when an optimum selection pressure is applied. By investigating the PMI expression level in transgenic calli and leaves, we found there was a significant positive correlation between the protein expression level and the optimal selection pressure. Higher optimal selection pressure is required for those constructs which confer higher expression of PMI protein. The single copy rate of those transgenic events for prActin-PMI-01 cassette is lower than that for other three cassettes. We speculate some of low copy events with low protein expression levels might not have been able to survive in the mannose selection.     

Using ESTs for phylogenomics: Can one accurately infer a phylogenetic tree from a gappy alignment?

Background

Specialised leaf-eating is almost universally regarded as the ancestral state of all ruminants, yet little evidence can be cited in support of this assumption, apart from the fact that all early ruminants had low crowned cheek teeth. Instead, recent years have seen the emergence evidence contradicting the conventional view that low tooth crowns always indicate leaf-eating and high tooth crowns grass-eating.

Results

Here we report the results of two independent palaeodietary reconstructions for one of the earliest deer, Procervulus ginsburgi from the Early Miocene of Spain, suggesting that despite having lower tooth crowns than any living ruminant, this species included a significant proportion of grass in its diet.

Conclusion

The phylogenetic distribution of feeding styles strongly supports that leaf-grass mixed feeding was the original feeding style of deer, and that later dietary specialization on leaves or grass occurred independently in several lineages. Evidence for other ruminant clades suggests that facultative mixed feeding may in fact have been the primitive dietary state of the Ruminantia, which would have been morphologically expressed only under specific environmental factors.     

Spindle assembly checkpoint genes reveal distinct as well as overlapping expression that implicates MDF-2/Mad2 in postembryonic seam cell proliferation in Caenorhabditis elegans

Background

The spindle assembly checkpoint (SAC) delays anaphase onset by inhibiting the activity of the anaphase promoting complex/cyclosome (APC/C) until all of the kinetochores have properly attached to the spindle. The importance of SAC genes for genome stability is well established; however, the roles these genes play, during postembryonic development of a multicellular organism, remain largely unexplored.

Results

We have used GFP fusions of 5' upstream intergenic regulatory sequences to assay spatiotemporal expression patterns of eight conserved genes implicated in the spindle assembly checkpoint function in Caenorhabditis elegans. We have shown that regulatory sequences for all of the SAC genes drive ubiquitous GFP expression during early embryonic development. However, postembryonic spatial analysis revealed distinct, tissue-specific expression of SAC genes with striking co-expression in seam cells, as well as in the gut. Additionally, we show that the absence of MDF-2/Mad2 (one of the checkpoint genes) leads to aberrant number and alignment of seam cell nuclei, defects mainly attributed to abnormal postembryonic cell proliferation. Furthermore, we show that these defects are completely rescued by fzy-1(h1983)/CDC20, suggesting that regulation of the APC/C^CDC20 by the SAC component MDF-2 is important for proper postembryonic cell proliferation.

Conclusion

Our results indicate that SAC genes display different tissue-specific expression patterns during postembryonic development in C. elegans with significant co-expression in hypodermal seam cells and gut cells, suggesting that these genes have distinct as well as overlapping roles in postembryonic development that may or may not be related to their established roles in mitosis. Furthermore, we provide evidence, by monitoring seam cell lineage, that one of the checkpoint genes is required for proper postembryonic cell proliferation. Importantly, our research provides the first evidence that postembryonic cell division is more sensitive to SAC loss, in particular MDF-2 loss, than embryonic cell division.     

Factors affecting the dental erosion severity of patients with eating disorders

Background

Intraoral disease is a common occurrence in patients with eating disorders, particularly dental erosion, which frequently becomes severe and may hinder daily life. The severity varies from patient to patient. Understanding the underlying mechanisms may help prevent dental erosion in these patients. Accordingly, we investigated the relationship between the severity of erosion and the behavior of patients with eating disorders, with a focus on daily diet and vomiting behavior.

Methods

A total 71 female eating disorder outpatients from the Clinical Center of Psychosomatic Dentistry of Nippon Dental University Hospital and the Psychosomatic Internal Medicine Department of Kudanzaka Hospital or who were hospitalized at Hasegawa Hospital were enrolled. Dental erosion severity and location were determined by oral examination. Patients who induced vomiting were queried on their behavior during vomiting and on routine diet habits. Patients with dental erosion were further divided into mild and severe groups based on the lesion severity and the groups compared.

Results

Dental erosion was observed in 43 of 50 subjects who induced vomiting. Dental erosion was most frequent on the palatal side of the anterior maxillary teeth, occurring in 81.3% of the subjects. There were significant differences observed between the mild and severe groups according to post-vomiting oral hygiene. Significantly more subjects in the mild group consumed large amounts of water before vomiting, and significantly more subjects in the severe group routinely consumed carbonated beverages or sweetened food.

Conclusions

While self-induced vomiting is the main cause of dental erosion in eating disorder patients, the erosion severity may be affected by behavior when inducing vomiting or by routine consumption of certain foods and beverages. Addressing these factors may help prevent severe dental erosion in patients who chronically induce vomiting.

     

Polyphenols, tannins and antioxidant activities of eight true mangrove plant species in South China

Background and aims

(i) compare the concentrations of total polyphenols (TP) and condensed tannins (CT), and CT profiles in different organs of mature trees and seedlings of eight true mangrove species in Hong Kong; (ii) examine the antioxidant activities of CT and (iii) relate the non-enzymatic antioxidative defence system with the vertical zonation pattern of mangrove species.

Methods

Mature trees and seedlings of eight species were collected from a Hong Kong mangrove swamp to determine TP and CT concentrations and the antioxidant activities of CT.

Results

According to TP concentrations, the true mangrove species could be broadly classified into three groups, (i) Lumnitzera racemosa and Aegiceras corniculatum > (ii) Heritiera littoralis, Excoecaria agallocha, Bruguiera gymnorrhiza and Kandelia obovata > (iii) Acanthus ilicifolius and Avicennia marina. The last two are pioneer species in the most foreshore location. They also had significantly lower antioxidant activities, CT concentrations and different CT profiles than the other six species in mid- and low-tides.

Conclusions

Classification of the eight true mangrove species into three groups based on polyphenols was similar to their vertical zonation from land to sea. The relationships between these antioxidants and zonation should be further verified by transplantation studies.     

The influence of different anticoagulants and sample preparation methods on measurement of mCD14 on bovine monocytes and polymorphonuclear neutrophil leukocytes

Background

Brief tobacco intervention has been used in promoting smoking cessation and preventing the initiation of smoking. We used a cohort born in 1979 (n = 2 586) from four cities in Finland. Those born on odd days received up to four brief tobacco interventions during their annual school dental check-ups in 1992-1994 (at the age of 13-15). Those who were born on even days were used as a control group. In 2008 a follow-up questionnaire was sent to the cohort. The aim of this study was to ascertain the long-term effectiveness of brief tobacco intervention given in dental health care during school age.

Findings

Responses were received from 529 people in the intervention group and 491 in the control group. In the intervention group and control group by the age of 29 there were 15.3% and 18.5% smokers respectively. This difference was not statistically significant. The difference between groups was similar to that observed when they were 14 years old.

Conclusions

Brief tobacco intervention performed in dental health care in adolescence did not show effectiveness in the long-term follow-up. This type of intervention alone is insufficient to prevent smoking but supports other anti-smoking activities.

Trial Registration

This study was registered at http://clinicaltrials.gov (NCT01348646).     

Quantifying the effect of soil moisture content on segmenting root system architecture in X-ray computed tomography images

Aims

A commonly accepted challenge when visualising plant roots in X-ray micro Computed Tomography (μCT) images is the similar X-ray attenuation of plant roots and soil phases. Soil moisture content remains a recognised, yet currently uncharacterised source of segmentation error. This work sought to quantify the effect of soil moisture content on the ability to segment roots from soil in μCT images.

Methods

Rice (Oryza sativa) plants grown in contrasting soils (loamy sand and clay loam) were μCT scanned daily for nine days whilst drying from saturation. Root volumes were segmented from μCT images and compared with volumes derived by root washing.

Results

At saturation the overlapping attenuation values of root material, water-filled soil pores and soil organic matter significantly hindered segmentation. However, in dry soil (ca. six days of drying post-saturation) the air-filled pores increased image noise adjacent to roots and impeded accurate visualisation of root material. The root volume was most accurately segmented at field capacity.

Conclusions

Root volumes can be accurately segmented from μCT images of undisturbed soil without compromising the growth requirements of the plant providing soil moisture content is kept at field capacity. We propose all future studies in this area should consider the error associated with scanning at different soil moisture contents.     

Allometric scaling in the dentition of primates and prediction of body weight from tooth size in fossils

Tooth size varies exponentially with body weight in primates. Logarithmic transformation of tooth crown area and body weight yields a linear model of slope 0.67 as an isometric (geometric) baseline for study of dental allometry. This model is compared with that predicted by metabolic scaling (slope = 0.75). Tarsius and other insectivores have larger teeth for their body size than generalized primates do, and they are not included in this analysis. Among generalized primates, tooth size is highly correlated with body size. Correlations of upper and lower cheek teeth with body size range from 0.90–0.97, depending on tooth position. Central cheek teeth (P and M) have allometric coefficients ranging from 0.57–0.65, falling well below geometric scaling. Anterior and posterior cheek teeth scale at or above metabolic scaling. Considered individually or as a group, upper cheek teeth scale allometrically with lower coefficients than corresponding lower cheek teeth; the reverse is true for incisors. The sum of crown areas for all upper cheek teeth scales significantly below geometric scaling, while the sum of crown areas for all lower cheek teeth approximates geometric scaling. Tooth size can be used to predict the body weight of generalized fossil primates. This is illustrated for Aegyptopithecus and other Eocene, Oligocene, and Miocene primates. Regressions based on tooth size in generalized primates yield reasonable estimates of body weight, but much remains to be learned about tooth size and body size scaling in more restricted systematic groups and dietary guilds.     

Screening for periodontal disease in research dogs - a methodology study

Background

It has been shown that the prevalence of both clinical attachment loss (CAL) ≥1 mm and pocket probing depth (PPD) ≥4 mm is relatively high even in younger dogs, but also that only a minority of the dogs have such clinical signs of periodontal disease (PD) in more than a few teeth. Hence, a minority of dogs carry the major PD burden. These epidemiological features suggest that screening for PD in larger groups of dogs, allowing for rapid assessment of treatment planning, or for the selection of dogs with or without PD prior to be included in experimental trials, should be possible. CAL is the central variable in assessing PD extent and severity while PPD is the central variable used in treatment planning which make these two variables obvious in a screening protocol with the dual aim of disease identification and treatment planning. The main purpose of the present study in 98 laboratory Beagle dogs was to construct a fast, simple and accurate screening tool, which is highly sensitive for the identification of dogs with PD.

Results

Examination of the maxillary P4, P3, P2, I1 and C would, in this population, result in the identification of 85.5% of all dogs and 96% of all teeth positive for CAL ≥1 mm, and 58.9% of all dogs and 82.1% of all teeth positive for PD ≥4 mm.Examination of tooth pairs, all C’s, maxillary I2, M2 and the mandibular P4 would, in this population result in identification of 92.9% of all dogs and 97.3% of all teeth positive for PD ≥4 mm, and 65.5% of all dogs and 83.2% of all teeth positive for CAL ≥1 mm. The results presented here only pertain to the present study population.

Conclusions

This screening protocol is suitable for examination of larger groups of laboratory Beagle dogs for PD and our findings indicate that diseased dogs are identified with a high degree of sensitivity. Before this screening can be used in clinical practice, it has to be validated in breeds other than Beagle dogs and in populations with larger age variation.

     

Dumpy-30 family members as determinants of male fertility and interaction partners of metal-responsive transcription factor 1 (MTF-1) in Drosophila

Background

Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV) disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s) underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth) induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM). Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives.

Results

E11 mouse mandibular processes (MANs) were infected with mouse CMV (mCMV) for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins.

Conclusion

Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal cells and surrounding matrix. Moreover, since it is critically important that signaling molecules are expressed in appropriate cell populations during development, the aberrant localization of components of relevant signaling pathways may reveal the pathogenic mechanism underlying mandibular malformations.     

Variation in responses to boron in rice

Background and aims

Boron (B) deficiency depresses grain set and grain yield of wheat and maize while having little effect on their vegetative growth. This paper describes effects of B deficiency in rice and how these vary with planting season and variety.

Methods

Three rice varieties (KDML105, CNT1, SPR1) were grown in sand culture without (B0) and with 10 μM (B10) B added to the nutrient solution, in the cool season of 2007/08 and 2008/09 and the hot season of 2011 in Chiang Mai, Thailand (18°47′N, 98°59′E). Boron responses were measured in growth and yield parameters, pollen viability and B concentration of the flag leaf and anthers at anthesis.

Results

Grain weight was strongly depressed by B deficiency ranging from 28 % in SPR1 to 79 % in CNT1, and the yield was much lower in the cool season than in the hot season plantings. The variation in grain weight was closely associated with grain set and number of spikelets but not with shoot dry weight or tillering. Grain set was closely related to pollen viability, and both were increased with increasing anther B concentration at >20 mg B kg^?1. In addition to its adverse effect on grain set, B deficiency also depressed grain filling and weight of individual grains in rice.

Conclusions

Boron deficiency depressed rice grain yield through adverse effects on reproductive growth, panicle and spikelet formation and grain filling, in addition to grain set as in wheat and maize.     

lemmingA encodes the Apc11 subunit of the APC/C in Drosophila melanogaster that forms a ternary complex with the E2-C type ubiquitin conjugating enzyme, Vihar and Morula/Apc2

Background

The spindle assembly checkpoint (SAC) inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually override mitotic arrest by a process known as mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons.

Results

Here we describe mitotic slippage in yeast bub2?? mutant cells that are defective in the repression of precocious telophase onset (mitotic exit). Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments.

Conclusions

The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase) causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans.