The ligand Sas and its receptor PTP10D drive tumour-suppressive cell competition.

Normal epithelial cells often exert anti-tumour effects against nearby oncogenic cells. In the Drosophila imaginal epithelium, clones of oncogenic cells with loss-of-function mutations in the apico-basal polarity genes scribble or discs large are actively eliminated by cell competition when surrounded by wild-type cells. Although c-Jun N-terminal kinase (JNK) signalling plays a crucial role in this cell elimination, the initial event, which occurs at the interface between normal cells and polarity-deficient cells, has not previously been identified. Here, through a genetic screen in Drosophila, we identify the ligand Sas and the receptor-type tyrosine phosphatase PTP10D as the cell-surface ligand-receptor system that drives tumour-suppressive cell competition. At the interface between the wild-type 'winner' and the polarity-deficient 'loser' clones, winner cells relocalize Sas to the lateral cell surface, whereas loser cells relocalize PTP10D there. This leads to the trans-activation of Sas-PTP10D signalling in loser cells, which restrains EGFR signalling and thereby enables elevated JNK signalling in loser cells, triggering cell elimination. In the absence of Sas-PTP10D, elevated EGFR signalling in loser cells switches the role of JNK from pro-apoptotic to pro-proliferative by inactivating the Hippo pathway, thereby driving the overgrowth of polarity-deficient cells. These findings uncover the mechanism by which normal epithelial cells recognize oncogenic polarity-deficient neighbours to drive cell competition.

A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model.

Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates.

Gauze blotting technique: a novel method to identify parathyroid glands during thyroid surgery without tissue damage.

Hypoparathyroidism is a major complication of thyroid surgery. To avoid this complication, visual identification of the parathyroid glands is essential. However, its effectiveness depends heavily on the surgeon's expertise. Here, we describe a novel method, the gauze blotting technique, to immunochemically identify the parathyroid glands during thyroid surgery. Twenty-three patients who underwent thyroid lobectomy were enrolled in this study; 16 and 7 had benign and malignant thyroid diseases, respectively. After visually identifying candidate nodules for the parathyroid gland, a piece of dry gauze (5 mm × 10 mm) was applied to each tissue until it was moistened by exudates from the tissue. Pieces of gauze were also applied to the thyroid gland and adipose tissue located away from the candidate nodules. The gauze was immersed in saline, and the intact PTH (i-PTH) level of the supernatant was measured. The median PTH level for the parathyroid glands was 1,060 pg/mL, which was significantly higher than that for the thyroid gland (34 pg/mL) and adipose tissue (28 pg/mL) (p < 0.001). The cut-off value to distinguish the parathyroid gland from other tissues was 68 pg/mL with a positive predictive value, negative predictive value, sensitivity, and specificity of 84.6%, 88.8%, 86.8%, and 86.7%, respectively. A value ≥250 pg/mL yielded a 100% positive predictive value. Our novel gauze blotting technique can identify the parathyroid glands without damaging tissues during thyroid surgery.

Observational management of papillary microcarcinoma appearing in the remnant thyroid after hemithyroidectomy.

Active surveillance for papillary thyroid microcarcinomas (PTMCs) initiated in Japan is becoming adopted worldwide as a management option. However, it remains unclear how to manage newly appearing PTMCs in the remnant thyroid after hemithyroidectomy. We investigated the outcomes of similar observational management (OM) for PTMCs appearing in the remnant thyroid after hemithyroidectomy for papillary thyroid carcinoma (PTC) and benign thyroid nodules. Eighty-three patients were newly diagnosed with PTMC in the remnant thyroid between January 1998 and March 2017. Of these, 42 patients underwent OM with >3 times ultrasound examinations. Their initial diagnoses were PTC (initially malignant group) in 37 patients and benign nodule (initially benign group) in 5 patients. We calculated the tumor volume doubling rate (TV-DR) during OM for each PTMC. The TV-DR (/year) was <-0.1, -0.1-0.1, 0.1-0.5, and >0.5 in 12, 19, 5, and 6 patients, respectively. The TV-DRs in both groups did not statistically differ, but six patients (16%) in the initially malignant group showed moderate growth (TV-DR >0.5/year). They underwent conversion surgery and none of them had further recurrence. The remaining 36 patients retained OM without disease progression. The TV-DR in the initially malignant group was not significantly associated with patients' backgrounds or their initial clinicopathological features. None of the patients in this study showed distant metastases/recurrences or died of thyroid carcinoma. Although a portion of PTMCs appearing after hemithyroidectomy for thyroid malignancy are moderately progressive, OM may be acceptable as a management option for PTMCs appearing in the remnant thyroid after hemithyroidectomy.

Evaluation of the diagnostic utility of the aminotransferase/lactate dehydrogenase ratio for the suspension of tissue specimens during thyroid surgery for the identification of parathyroid tissue.

Identification of the parathyroid glands during surgery is crucial for preventing postoperative hypoparathyroidism. Kikumori et al. reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio for the saline suspension of a suspicious tissue can differentiate parathyroid tissue from other tissues. The aim of this study was to evaluate the utility of this method and investigate the appropriate time for measurement. We obtained 465 tissue specimens during thyroidectomy of 102 patients with papillary thyroid carcinoma (PTC), and 422 specimens (129 parathyroid, 92 PTC, and 201 other tissues) with measurable AST and LDH were analyzed. Small pieces of the tissues were immersed in saline and sent for measurement of AST and LDH. The assay was performed immediately after thyroidectomy for 245 specimens (the same-day group) and during the next morning for the remaining 177 specimens (the next-day group). The accuracy of diagnosing parathyroid tissue was significantly better in the same-day group than in the next-day group. A cut-off value of 0.18 gave the best diagnostic precision, with an area under the receiver operating characteristic curve of 0.95 and 88.7% sensitivity and specificity in the same-day group. When the cut-off value was set to 0.20, the specificity for excluding carcinomatous tissues was 100%. When measured on the day of the surgery, the AST/LDH ratio for the saline suspension of the surgical specimens is useful for discriminating parathyroid tissues from other tissues. This method can be utilized at most hospitals where intraoperative frozen sections or rapid parathyroid hormone assays are not available.

Subset analysis of the Japanese risk classification guidelines for papillary thyroid carcinoma.

Guidelines published by the Japan Association of Endocrine Surgeons (JAES)/Japanese Society of Thyroid Surgery (JSTS) for patients with papillary thyroid carcinoma describe four risk classes (very low-, low-, intermediate- and high-risk) for deciding on therapeutic strategies. Here, we investigate cause-specific survival (CSS) of high- and intermediate-risk patients, taking their age into consideration. CSS of intermediate-risk patients ≥55 years was poorer than that of those <55 years (p < 0.0001) (20-year CSS rates, 96.9% vs. 98.7%). CSS of intermediate-risk patients <55 years was excellent but still poorer (p = 0.0152) than that of low- or very low-risk patients (20-year CSS rates, 100%). CSS of high-risk patients <55 years (20-year CSS rates, 96.0%) was similar (p = 0.7412) to that of intermediate-risk patients ≥55 years, while high-risk patients ≥55 years (20-year CSS rates, 80.6%) showed much poorer prognosis (p < 0.0001) than the others. In high-risk patients <55 years, distant metastasis (M1), extrathyroid extension (Ex), node metastasis ≥3 cm, and extranodal tumor extension, and in those ≥55 years, M1, Ex, and tumor size >4 cm were regarded as prognostic factors on multivariate analysis. We therefore conclude that 1) prognosis of high-risk patients ≥55 years should be carefully treated because of significantly poor prognosis, 2) prognostic factors of high-risk patients vary according to patient age, and 3) overtreatment of intermediate-risk patients and young high-risk patients should be avoided; however, appropriate treatment strategies need to be established, considering that their prognoses are excellent, but still poorer than low- or very low-risk patients.

Prognostic value of the 8th tumor-node-metastasis classification for follicular carcinoma and poorly differentiated carcinoma of the thyroid in Japan.

Follicular thyroid carcinoma (FTC), a form of differentiated thyroid carcinoma, is the second most common malignancy arising from thyroid follicular cells. Recently, the tumor-node-metastasis (TNM) classification for differentiated thyroid carcinoma was revised from the 7th to the 8th edition. The diagnostic criteria for poorly differentiated carcinoma (PDC) were also updated in the latest World Health Organization (WHO) classification. In this study, we investigated whether these changes are appropriate for accurately predicting prognosis. Three hundred and twenty-nine patients diagnosed with postoperative pathologically confirmed FTC, who underwent initial surgery at our hospital between 1984 and 2004, were enrolled. For this study, patients were re-evaluated and diagnosed with FTC (N = 285) or PDC (N = 44) without typical nuclear findings of papillary thyroid carcinoma. For FTC, the 8th TNM classification was a more accurate predictor of prognosis than the 7th TNM classification. In the 8th TNM classification, cause-specific survival became significantly poorer from Stage I to IVB. The cause-specific survival of PDC based on the latest WHO classification was worse than, but did not significantly differ from, that of PDC based only on the former WHO classification. For PDC, neither of the TNM classifications could accurately predict prognosis. Taken together, we conclude that (1) the 8th TNM classification more accurately reflects the prognosis of FTC than the 7th TNM classification; (2) PDC based on the former WHO classification should be retained, at least in Japan; and (3) the TNM classification may not be suitable for predicting the prognosis of PDC.

Prognostic value of the 8th edition of the tumor-node-metastasis classification for patients with papillary thyroid carcinoma: a single-institution study at a high-volume center in Japan.

The tumor-node-metastasis (TNM) staging system is most commonly adopted to evaluate the prognosis of patients with thyroid carcinoma. The 8th edition of the TNM staging system, an extensively revised version of the 7th edition, was recently released. We aimed to investigate whether and how well the 8th edition reflects the cause-specific survival (CSS) of patients with papillary thyroid carcinoma by analyzing the cases in 5,892 patients who underwent initial surgery at Kuma Hospital between 1987 and 2005. The median postoperative follow-up duration was 178 months (range: 6-357 months). One patient with T4b disease was excluded from the analysis. Overall, 116 (2.0%) patients died of thyroid carcinoma. The proportion of variance explained (PVE) for CSS in the 7th and 8th editions was 10.69 and 10.97, respectively. Using the 7th edition, CSS of patients with stage IVA and stage III disease was similar (p = 0.32). In contrast, using the 8th edition, CSS was poorer in stage II than in stage I (p < 0.001), in stage III than in stage II (p < 0.001), and in stage IVB than in stage III (p < 0.001). Similar results were observed for disease-free survival. Although we could not establish any objective evidence that the 8th edition is superior to the 7th edition, the 8th edition is simpler and more convenient, as it includes fewer stages and addresses the issue of the 7th edition where stage IVA and III patients had similar prognoses.

Role for phospholipid flippase complex of ATP8A1 and CDC50A proteins in cell migration.

Type IV P-type ATPases (P4-ATPases) and CDC50 family proteins form a putative phospholipid flippase complex that mediates the translocation of aminophospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the outer to inner leaflets of the plasma membrane. In Chinese hamster ovary (CHO) cells, at least eight members of P4-ATPases were identified, but only a single CDC50 family protein, CDC50A, was expressed. We demonstrated that CDC50A associated with and recruited P4-ATPase ATP8A1 to the plasma membrane. Overexpression of CDC50A induced extensive cell spreading and greatly enhanced cell migration. Depletion of either CDC50A or ATP8A1 caused a severe defect in the formation of membrane ruffles, thereby inhibiting cell migration. Analyses of phospholipid translocation at the plasma membrane revealed that the depletion of CDC50A inhibited the inward translocation of both PS and PE, whereas the depletion of ATP8A1 inhibited the translocation of PE but not that of PS, suggesting that the inward translocation of cell-surface PE is involved in cell migration. This hypothesis was further examined by using a PE-binding peptide and a mutant cell line with defective PE synthesis; either cell-surface immobilization of PE by the PE-binding peptide or reduction in the cell-surface content of PE inhibited the formation of membrane ruffles, causing a severe defect in cell migration. These results indicate that the phospholipid flippase complex of ATP8A1 and CDC50A plays a major role in cell migration and suggest that the flippase-mediated translocation of PE at the plasma membrane is involved in the formation of membrane ruffles to promote cell migration.

Distribution and morphological changes of the Golgi apparatus during Drosophila spermatogenesis.

In spermatogenesis, the Golgi apparatus is important for the formation of the acrosome, which is a sperm-specific organelle essential for fertilization. Comprehensive examinations of the spatiotemporal distribution and morphological characterizations of the Golgi in various cells during spermatogenesis are necessary for functional analyses and mutant screenings in the model eukaryote Drosophila. Here, we examined the distribution and morphology of the Golgi during Drosophila spermatogenesis with immunofluorescence and electron microscopy. In pre-meiotic germ cells, the Golgi apparatuses were distributed evenly in the cytoplasm. In contrast, they were located exclusively in two regions near the poles during the meiotic metaphase, where they were segregated prior to the chromosomes. In cells in anaphase to telophase, the Golgi were predominantly left behind in the equatorial region between the separating daughter nuclei. After completion of meiosis, the dispersed Golgi were assembled at the apical side of the spermatid nucleus to form the acrosome. Further investigation of the Golgi distribution in ß2-tubulin mutants showed aberrant and uneven distributions of the Golgi among sister cells in the meiotic spermatocytes and in the post-meiotic spermatids. At the ultrastructural level, the Golgi apparatus in pre-meiotic spermatocytes comprised a pair of stacks. The two stacks were situated adjacent to each other, as if they had duplicated before entering into meiotic division. These results highlight the dynamic nature of the Golgi during spermatogenesis and provide a framework for analyzing the correlations between the dynamics of the Golgi and its function in sperm development.

The double-stranded break-forming activity of plant SPO11s and a novel rice SPO11 revealed by a Drosophila bioassay.

BACKGROUND: SPO11 is a key protein for promoting meiotic recombination, by generating chromatin locus- and timing-specific DNA double-strand breaks (DSBs). The DSB activity of SPO11 was shown by genetic analyses, but whether SPO11 exerts DSB-forming activity by itself is still an unanswered question. DSB formation by SPO11 has not been detected by biochemical means, probably because of a lack of proper protein-folding, posttranslational modifications, and/or specific SPO11-interacting proteins required for this activity. In addition, plants have multiple SPO11-homologues. RESULTS: To determine whether SPO11 can cleave DNA by itself, and to identify which plant SPO11 homologue cleaves DNA, we developed a Drosophila bioassay system that detects the DSB signals generated by a plant SPO11 homologue expressed ectopically. We cytologically and genetically demonstrated the DSB activities of Arabidopsis AtSPO11-1 and AtSPO11-2, which are required for meiosis, in the absence of other plant proteins. Using this bioassay, we further found that a novel SPO11-homologue, OsSPO11D, which has no counterpart in Arabidopsis, displays prominent DSB-forming activity. Quantitative analyses of the rice SPO11 transcripts revealed the specific increase in OsSPO11D mRNA in the anthers containing meiotic pollen mother cells. CONCLUSIONS: The Drosophila bioassay system successfully demonstrated that some plant SPO11 orthologues have intrinsic DSB activities. Furthermore, we identified a novel SPO11 homologue, OsSPO11D, with robust DSB activity and a possible meiotic function.

Crossing over does occur in males of Drosophila ananassae from natural populations.

Spontaneous crossing over in males of Drosophila ananassae has been well demonstrated using F(1) individuals from crosses between marker stocks and wild type strains. However, the question of its occurrence in males from natural populations remained open. Here we present the cytological evidence that crossing over does occur in males of D. ananassae from two Brazilian populations, sampled nearly 21 years apart, and in two recently sampled populations, one from Indonesia and one from Okinawa, Japan. Cytological analysis of meiosis in males collected from nature and in sons of females from the same population inseminated in nature revealed the presence of chiasmata, inversion chiasmata, and isosite chromosome breakages in the diplotene cells in all sampled populations. These data demonstrate that reciprocal and nonreciprocal exchanges and chromosome breakages, previously reported as related events of male crossing over, do occur at variable frequencies among males from natural populations.

NBRP databases: databases of biological resources in Japan.

The National BioResource Project (NBRP) is a Japanese project that aims to establish a system for collecting, preserving and providing bioresources for use as experimental materials for life science research. It is promoted by 27 core resource facilities, each concerned with a particular group of organisms, and by one information center. The NBRP database is a product of this project. Thirty databases and an integrated database-retrieval system (BioResource World: BRW) have been created and made available through the NBRP home page (http://www.nbrp.jp). The 30 independent databases have individual features which directly reflect the data maintained by each resource facility. The BRW is designed for users who need to search across several resources without moving from one database to another. BRW provides access to a collection of 4.5-million records on bioresources including wild species, inbred lines, mutants, genetically engineered lines, DNA clones and so on. BRW supports summary browsing, keyword searching, and searching by DNA sequences or gene ontology. The results of searches provide links to online requests for distribution of research materials. A circulation system allows users to submit details of papers published on research conducted using NBRP resources.

Efficacy of Nerve Root Block for the Treatment of Lumbar Spinal Canal Stenosis in Adults Older Than 80 Years of Age.

BACKGROUND: Patients with advanced lumbar spinal canal stenosis (LCS) often prefer non-operative treatment owing to decreased physiological function and comorbidities. Although the therapeutic value of selective nerve root block (SNRB) for LCS is confirmed, there are few reports of its effectiveness in the elderly. We investigated the efficacy of SNRB for LCS in patients over 80 years of age. METHODS:  The subjects were 112 patients aged over 80 years (mean age: 84 years; 45 men and 67 women ) with medication-resistant LCS without cauda equina syndrome who underwent SNRB. Cases with acute-onset lumbar disc herniation were excluded. We retrospectively investigated and compared the presence or absence of surgery, effect of SNRB, number of procedures, duration of disease, and magnetic resonance imaging findings. Patients who could avoid the surgery by SNRB were defined as the effective group. Patients whose symptoms were not relieved by SNRB and who underwent surgery and those whose symptoms were not relieved but who continued conservative treatment were defined as the ineffective group. A total of one to seven SNRBs were performed in both groups, and the same spine surgeon performed the entire procedure from SNRB to surgery. RESULTS:  There were 86 nonoperative patients (69 effective cases) and 26 operative patients; the overall rate of effectiveness was 61% (69/112 patients). The area of the spinal canal at the responsible level was 108.63 mm2 in the effective group compared with 77.06 mm2 in the ineffective group. This was significantly narrower in the ineffective group (p=0.0094). There was no significant difference in the duration of illness, number of blocks, or hernia complication rate between the groups. No patient experienced severe neuralgia that may have been caused by neuropathy during SNRB. DISCUSSION: Our outcome showed that more than 60% of older patients with LCS showed symptomatic improvement with SNRB. SNRB can be performed relatively safely in the elderly and appears to be a favorable treatment option for older patients with various risks, such as poor general condition. CONCLUSIONS: Multiple sessions of SNRB may provide older patients with symptomatic improvement and may be an option for treatment.

Factors Affecting Postoperative Spinal Epidural Hematoma and the Optimal Order of Vertebral Body Decompression in Multivertebral Microendoscopic Laminectomy.

Purpose Symptomatic postoperative spinal epidural hematoma (POSEH) is a complication of spine surgery that occurs infrequently but may cause ongoing serious neurological damage. Due to the narrow entry portal, the risk of hematoma is increased after microendoscopic laminectomy (MEL) compared with conventional open surgery, and the risk might be even higher for multivertebral MEL (m-MEL). The purpose of this study was to clarify the factors affecting the development of POSEH after m-MEL and identify the optimal order for the decompression of vertebral bodies. Methods A total of 313 patients who underwent m-MEL from 2016 to 2020 were retrospectively assessed. The cohort comprised 238 patients who underwent two-level MEL, 67 who underwent three-level MEL, and eight who underwent four-level MEL. Symptomatic POSEH was defined as the presence of an epidural hematoma at the surgical site on MRI with symptoms such as lower extremity pain or muscle weakness. We elucidated the incidence of POSEH at each vertebral level and investigated the relationship between POSEH and possible risk factors such as clinical and operative variables. Results There were 41 patients in the POSEH group and 272 patients in the non-POSEH group. Seven patients in the POSEH group underwent reoperation. The occurrence of POSEH was related to the number of decompressed vertebral bodies. Patients who underwent L2/3 and L3/4 decompression at the end of the procedure also showed a higher incidence of POSEH at the surgical level. Conclusion In patients undergoing m-MEL, treatment of the upper lumbar vertebrae at the end of decompression surgery might be a risk factor for symptomatic POSEH. The incidence of POSEH was particularly increased at L2/3, suggesting that L2/3 decompression should not be performed at last and that careful hemostasis should be applied.

Poorly Differentiated Thyroid Carcinoma Coexisting with Graves' Disease Involving T3 Thyrotoxicosis due to Increased D1 and D2 Activities.

Background: Poorly differentiated thyroid carcinoma is rare and patients are typically euthyroid. We report a novel rare case of poorly differentiated thyroid carcinoma with triiodothyronine (T3) thyrotoxicosis. Patient's Findings: A 77-year-old man presented to Kuma Hospital due to a neck tumor. A thyroid ultrasonography revealed a 220-mL mass in the right lobe. Laboratory data showed low serum thyrotropin (TSH), low free thyroxine (fT4), and high free T3 (fT3) levels. Anti-TSH receptor antibodies and thyroid-stimulating antibodies were positive. 131I scintigraphy showed diffuse uptake only in the left thyroid lobe. The patient underwent a total thyroidectomy and histological examination identified as poorly differentiated thyroid carcinoma. He was diagnosed with poorly differentiated thyroid carcinoma coexisting with Graves' disease. The tumor showed elevated type 1 iodothyronine deiodinases (D1) and type 2 iodothyronine deiodinases (D2) activities compared with that of the left thyroid lobe. Summary and Conclusions: Increased D1 and D2 activities in poorly differentiated carcinoma resulted in T3 toxicosis with a high serum fT3/fT4 ratio.

Marked Decrease Over Time in Conversion Surgery After Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma.

Background: Active surveillance for low-risk papillary microcarcinoma (PMC) of the thyroid is an accepted and safe management strategy. However, some patients undergo conversion surgery after the initiation of active surveillance for various reasons. We investigated the reasons for conversion surgery and whether and how they changed over time. Methods: We enrolled 2288 patients with PMC who underwent active surveillance. Of these, 162 (7.1%) underwent conversion surgery >12 months after initiating active surveillance due to disease progression (57 patients), patient preference (43 patients), physician preference (31 patients), other associated thyroid or parathyroid diseases (24 patients), and other reasons (7 patients). We analyzed cumulative conversion rates not only in the whole cohort but also in the first three major subsets based on the reasons for surgery. We also divided our whole cohort into two groups based on the period of active surveillance commencement: the first-half group (February 2005-November 2011; 561 patients) and the second-half group (December 2011-June 2017; 1727 patients). Results: The criteria for PMC progression did not differ between the first- and second-half groups. The proportion of female patients in the physician preference group was significantly higher than that in the disease progression and the patient preference groups. Tumor size at surgery was larger, and tumor volume-doubling rate was higher in the disease progression group than in the other two groups. Patients in the second-half group were significantly less likely to undergo conversion surgery than those in the first-half group. Furthermore, conversion surgery rates in the second-half group were significantly lower than those in the first-half group in the patient preference, physician preference, and disease progression groups. Conclusions: Patients with PMC in the second-half group were significantly less likely to undergo conversion surgery than those in the first-half group regardless of the reason. This is probably because data accumulation of favorable outcomes with active surveillance significantly contributed to physicians' confidence and patients' trust and understanding of this disease.

Angioscopic study of silent plaque disruption in nonischemic related coronary artery in patients with stable ischemic heart disease.

Plaque disruption, which may be associated with some coronary risk factors, plays a key role in the development of acute coronary syndromes and progression of atherosclerosis. However, the clinical profile of asymptomatic plaque disruption in stable ischemic heart disease has not been well evaluated. The aim of the present study was to investigate the frequency and determinants of silent plaque disruption (SPD) in patients with stable ischemic heart disease using coronary angioscopy. Forty-one patients with stable angina or old myocardial infarction (OMI) without any complaints within 3 months were included in the present study. Angioscopy was successfully performed through 49 nonischemic related coronary arteries. The presence of SPD and coronary risk factors were recorded. Silent plaque disruption was found in 12 patients with stable ischemic heart disease (12/41, 29.3%), and the frequency of SPD in nonischemic related coronary arteries was 26.5% (13/49). A significantly higher frequency of SPD was noted in yellow plaques than in white plaques (35.3% versus 6.7%, P = 0.043). Overall, the independent clinical risk factors of SPD in nonischemic related coronary arteries were diabetes mellitus (P = 0.018; OR, 18.8209; 95% CI, 1.6525 to 214.3523) and hypertension (P = 0.0313; OR, 6.6485; 95% CI, 1.1850 to 37.3019). These results suggest silent plaque disruption was commonly observed in nonischemic related coronary arteries in patients with stable ischemic heart disease and its determinants were diabetes mellitus and hypertension.

Proteome mapping of the Drosophila melanogaster male reproductive system.

The fruit fly Drosophila melanogaster is an excellent model organism for studying insect reproductive biology. Although the gene expression profiles of both male and female reproductive organs have been studied in detail, their proteomic profiles and functional characteristics largely remained to be clarified. In this study, we conducted proteome mapping of the male internal reproductive organs using 2-DE. We identified a total of 440 protein components from gels of the male reproductive organs (testis, seminal vesicle, accessory gland, ejaculatory duct, and ejaculatory bulb). A number of proteins associated with odorant/pheromone-binding, lipid metabolism, proteolysis, and antioxidation were expressed tissue specifically in the male reproductive system. Based on our proteomic data set, we constructed reference proteome maps of the reproductive organs, which will provide valuable information toward a comprehensive understanding of Drosophila reproduction.

Mutations in orbit/mast reveal that the central spindle is comprised of two microtubule populations, those that initiate cleavage and those that propagate furrow ingression.

We address the relative roles of astral and central spindle microtubules (MTs) in cytokinesis of Drosophila melanogaster primary spermatocytes. Time-lapse imaging studies reveal that the central spindle is comprised of two MT populations, "interior" central spindle MTs found within the spindle envelope and "peripheral" astral MTs that probe the cytoplasm and initiate cleavage furrows where they contact the cortex and form overlapping bundles. The MT-associated protein Orbit/Mast/CLASP concentrates on interior rather than peripheral central spindle MTs. Interior MTs are preferentially affected in hypomorphic orbit mutants, and consequently the interior central spindle fails to form or is unstable. In contrast, peripheral MTs still probe the cortex and form regions of overlap that recruit the Pav-KLP motor and Aurora B kinase. orbit mutants have disorganized or incomplete anillin and actin rings, and although cleavage furrows initiate, they ultimately regress. Our work identifies a new function for Orbit/Mast/CLASP and identifies a novel MT population involved in cleavage furrow initiation.