Abnormal Pathologies Research Articles

Alpha-Synuclein

α-Synuclein (αS) is the major component of Lewy bodies in Parkinson’s disease and dementia with Lewy bodies, and glial cytoplasmic inclusions in multiple system atrophy. Immunocytochemical studies revealed widespread abnormal αS pathologies in these diseases, and the prion-like spreading of the αS pathologies has been proposed. To elucidate the prion-like properties of abnormal αS in vitro, in cells, and in animal experimental models, we prepared several kinds of αS aggregates or intermediates under various conditions and examined their seeding ability. The conversion of soluble αS into amyloid-like fibrils was accelerated by addition of small amounts of preformed αS fibrils, and the acceleration was increased in proportion to the sonication time of the fibrils, suggesting that fragmentation of the fibrils is important for the prion-like conversion. In cultured cells, introduction of fragmented αS fibrils also promoted seed-dependent aggregation, and αS fibrils with less than 50 nm in size were the most efficient for prion-like propagation in mice. Furthermore, injection of the αS fibrils into wild-type marmoset brains resulted in spreading of abundant αS pathologies. Robust Lewy body-like inclusions were formed in TH-positive neurons, strongly suggesting the retrograde spreading of abnormal αS. Moreover, a significant decrease in the numbers of TH-neurons was observed. Furthermore, most of the αS inclusions were positive for beta-sheet ligands such as thioflavin-S. These results demonstrate that fragmented αS fibrils are the key pathogenic seeds that trigger prion-like conversion.

Clinical indications for hysteroscopic removal of uterine masses: Time, age at diagnosis, and mass size.

The aim of this study was to investigate clinical factors associated with abnormal pathologies of uterine masses resected via hysteroscopy. Women who underwent hysteroscopic surgery for presumptive diagnoses of abnormal endometrial or endocervical masses, such as polyps or leiomyomas on ultrasonography, between January 2012 and April 2015, were enrolled. Clinical and pathologic data were retrospectively reviewed. Among 189 patients, pathologic diagnoses of the uterine mass were abnormal in 172 (91.0%) cases, including polyps in 119 (63.0%), leiomyomas in 49 (26.0%), endometrial hyperplasia in two (1.0%), and endometrial cancer in two (1.0%). Seventeen (9.0%) women who underwent hysteroscopic removal showed unremarkable results on pathology, and the most common finding among them was the proliferative phase of the normal endometrium. Women aged over 40 years with uterine masses and a time since last menstrual period of over 15 days are four times more likely to be diagnosed with neoplastic masses than others (odds ratio [OR], 4.39, 95% confidence interval [CI], 1.33-14.48 and OR, 4.22, 95%CI, 1.35-13.21, respectively); those with masses over 1.5 cm in size are three times more likely to be neoplastic than others (OR, 3.08, 95%CI, 1.04-9.12). Large mass size, longer time after last menstrual period, and older age are risk factors for abnormal histologies of uterine masses resected via hysteroscopy. Clinicians should take particular care when contemplating hysteroscopic removal for women younger than 40 years, and those with masses of <1.5 cm in size in the proliferative phase of the endometrium to avoid an unnecessary surgery.

Spirodela polyrhiza extract modulates the activation of atopic dermatitis-related ion channels, Orai1 and TRPV3, and inhibits mast cell degranulation

Context: Spirodela polyrhiza (L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash. Objective: The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated. Materials and methods: The dried leaves of SH were extracted by 70% methanol. Effects of SH extract (100 μg/mL) in an HEK293T cell line overexpressing human Orai1 or TRPV3 were assessed. Ion channel modulation in transfected HEK293T cells was measured using a conventional whole-cell patch-clamp technique. IgE-antigen complex-stimulated mast cell degranulation was measured by β-hexosaminidase assay with morphological observation after treatment with 20, 50 and 100 μg/mL SH extract. Results: SH extract (100 μg/mL) significantly inhibited Orai1 activity (63.8 ± 0.97%) in Orai1-STIM1 co-overexpressed HEK293T cells. SH extract significantly increased TRPV3 activity (81.29 ± 0.05% at −100 mV) compared with the positive control 2-APB (100 μM), which induced full activation. SH extract inhibited degranulation in IgE-antigen complex-stimulated RBL-2H3 mast cells by decreasing β-hexosaminidase activity (3.14 ± 0.03, 2.56 ± 0.12 and 2.29 ± 0.08 mU/mg, respectively). Conclusion: Our results suggested that SH extract could treat abnormal skin barrier pathologies in AD through modulation of the activities of the calcium ion channels Orai1 and TRPV3 and inhibition of mast cell degranulation. This is the first report of an herbal effect on the modulation of ion channels associated with skin barrier disruption in AD pathogenesis.

Modulatory effects of the fruits of Tribulus terrestris L. on the function of atopic dermatitis-related calcium channels, Orai1 and TRPV3

ObjectiveTo examine the effects of Tribulus terrestris L. (T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis. MethodsThe 70% methanol extract of T. terrestris was prepared. Human HEK293T cells with over-expressed calcium release-activated calcium channel protein 1 (Orai1), transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3 (TRPV3) were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique. ResultsT. terrestris extract (100 μg/mL) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate (100 μmol/L), which induces the full activation of TRPV3. ConclusionsOur results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.

A Comparison of Initial and Subsequent Follow-Up Strobovideolaryngoscopic Examinations in Singers

Previous studies have identified abnormal findings in up to 86.1% of singers on initial screening strobovideolaryngoscopy (SVL) examinations. No studies have compared the prevalence of abnormalities in singers on their subsequent follow-up SVL. Our study evaluates the frequency of these findings in both the initial and subsequent examinations. Retrospective charts and SVL reports were reviewed on students from an opera conservatory from 1993 to 2014. All students had initial screening SVL, but only students who later returned with acute voice complaints were included in the study (n=51, 137 follow-up visits). Normal SVL was defined as an examination without structural or functional abnormalities and reflux finding score ≤7. Data were analyzed using the chi-square test. For initial examinations, 90.2% (including reflux) and 88.2% (excluding reflux) were abnormal. In follow-up examinations, 94.9% (including reflux) and 94.2% (excluding reflux) had abnormal findings, which included muscle tension dysphonia (40.1%), vocal fold (VF) masses (unilateral 48.9%, bilateral 30.7%), vascular abnormalities (unilateral 27.0%, bilateral 5.8%), sulcus (unilateral 17.5%, bilateral 5.1%), VF hypomobility (unilateral 36.3%, bilateral 5.9%), phase (30.6%) and amplitude (44.8%) asymmetries, and glottic insufficiency (49.3%). Follow-up examinations revealed a significant increase in laryngopharyngeal reflux (χ(2)=7.043; P<0.05). We found a higher prevalence of abnormal findings compared with previous studies, which we attributed to a more inclusive definition of abnormal pathologies, improvements in SVL technology, and possibly increased experience with SVL interpretation. This high prevalence of abnormal findings in asymptomatic singers further supports the importance of baseline examinations.

Histopathological correlations of appendectomies: a clinical audit of a single center.

Acute appendicitis is a common presentation in surgical assessment units and appendectomy accounts for a large number of emergency operations in the UK. Histopathological examination of the appendectomy specimens are routinely carried out. The aim of this study is to correlate the histological findings of appendectomy specimens with the clinical diagnosis of acute appendicitis. This is a retrospective analysis of 238 appendectomies carried out in a single UK center between January and December 2013. The Histopathology reports of appendectomy specimens were retrieved. A total of 238 appendectomies were performed during the study period. The mean age of the patients was 32 years (range, 7-81 years). Adult patients (>16 years) represented 79.4% of the study population. The female sex accounted for 46.6% of all the patients. Of the 238 resected appendix, 211 (88.7%) had histopathology findings consistent with appendicitis. Approximately 1.7% of the 238 specimens were abnormal pathologies other than inflammation of the appendix. The negative appendectomy (normal appendix on histology) rate was 11.3%. The female sex accounted for 59.1% of the negative appendectomies. Adults (>16 years) represented 77.8% of the negative appendectomies. The observed high rates of negative appendectomy in the female sex can be reduced by utilizing combined clinical assessment and diagnostic imaging modalities. The findings of abnormal pathologies on histopathological examination of the appendix which could potentially impact on the management of the patients justify the current practice of routine histopathological examination of resected appendix.

PTH-328 High resolution spectral imaging: novel diagnostics in colorectal cancer

Introduction Colorectal cancer is the second most common cause of cancer death in the UK and accounts for 13% of all new cancer cases each year. 1 Most of these arise from pre-existing adenomatous polyps. 2 Recent research has supported an early diagnosis and prevention approach with the aim of improving survival and reducing overall mortality from colorectal cancer death. 3 The Bowel Cancer Screening Programme (BCSP) was commenced to drive early diagnosis of colorectal cancer but generates a huge volume of tissue for analysis from biopsy and polypectomy. The aim of this study was to investigate and demonstrate the use of novel high resolution infrared spectroscopy in colonic tissue to differentiate and classify a representative range of abnormal pathologies. Method 65 cases from 5 different pathology groups were identified from 2010 to 2014. These formalin-fixed and paraffin-embedded samples were routinely processed and thin sections placed on calcium fluoride slides. High resolution infrared imaging with a pixel resolution of 1.1 microns was performed on the tissue and the absorption spectra measured for each case. Accepted methods of multivariate spectral analysis were undertaken to elucidate the spectral differences across the dataset and classify the tissue spectra representative of the tissue biochemistry. Results High resolution infrared spectral imaging was successfully performed on thin sections of unstained colonic tissue. Specimen analysis generated over 1.5 million spectra which were used to discriminate the 5 pathological groups. The epithelial spectra from each case were identified and then principal component and linear discriminant analysis applied, and a classification model built to demonstrate the spectral differences. Leave one sample out cross validation (LOSOCV) resulted in a sensitivity of 65% and specificity of 82.3% for the technique to successfully discriminate normal from cancerous tissue. Dysplasia and cancer were also successfully discriminated with a sensitivity of 75.3% and specificity of 61.3%. Conclusion High resolution infrared spectral imaging is a novel technique which has been proven to be successful, reliable and rapid in the analysis of paraffin-embedded colonic pathology. It demonstrates suitability for automated analysis of specimens and therefore the potential for use as an adjunct in the diagnostic pathway for both early polyp and invasive cancer, particularly in high volume BCSP cases or where the traditional pathological diagnosis is time-consuming or difficult. Disclosure of interest None Declared. References www.cancerresearchuk.org Scholefield JH. BMJ . 2000; 321 :1004–6 Winawer SJ, Fletcher RH, Miller L, et al . Gastroenterology. 1997;112:594–642

Equivalent survival in patients with and without steatosis undergoing resection for colorectal liver metastases following pre-operative chemotherapy

BackgroundWe previously reported that the presence of steatosis did not adversely influence survival in patients undergoing resection for colorectal liver metastases (CLM) without pre-operative chemotherapy. Here, this hypothesis is tested in patients undergoing resection for CLM following pre-operative chemotherapy. MethodsWe assessed the effects of background liver pathology, categorized as ‘normal’, ‘steatosis’ and ‘other’, on perioperative mortality, overall survival (OS) and cancer-specific survival (CSS) in LiverMetSurvey patients. Survival analyses included log-rank tests and multivariate Cox models, incorporating well-established prognosticators. In secondary analyses, re-populating the model with non-chemotherapy patients, the effect modification of chemotherapy on the impact of steatosis on survival was tested. ResultsOf 4329 patients undergoing first-time liver resection following pre-operative chemotherapy, histologies were normal in 1913 (44%), steatosis in 1675 (39%), and other abnormal pathologies in 741 (17%). For normal, steatosis and other, 90-day mortalities were 2.1%, 2.3%, and 3.5% (P = 0.103). For the three histo-pathological groups, 5-year OS rates were 39%, 42%, and 36% (Plogrank = 0.363); 5-year CSS rates were 43%, 45% and 41% (Plogrank = 0.496), respectively. The associations of steatosis with OS and CSS were materially unchanged in the multivariate models. Chemotherapy did not interact with the effect of steatosis on survival. ConclusionThe findings of equivalent survivals challenge the common perception that steatosis in CLM patients after pre-operative chemotherapy is associated with increased peri-operative mortality and poorer long-term survival.

Su2020 Autoimmunity to Vinculin in Humans May Be Important in the Pathophysiology of IBS

G A A b st ra ct s tissue myeloperoxidase (MPO) activity and qPCR quantification of TLR4 gene expression, as markers for immune cell infiltration and host-gut flora interactions, respectively (6 samples/ mouse). Results: Our studies showed a strong, yet conditional, correlation between stereomicroscopy and histology, and treatment effect. For ileitis, there was a strong exponential correlation (y=6.7216*e0.1889x; R2=0.8919), which was explained by a plateau effect of histological scores between (10-12/18) as the severity of 3D-steromicroscopic abnormalities in SAMP increased. Such correlation differed from that of other studies with ileitis-free mice (R2<0.3), indicating that histological scores need to be validated or adjusted for a diverse categories of intestinal pathologies. For colitis, the correlation between stereomicroscopy and histology was strong as it correlated with the high histological scores observed in DSScolitis, and intermediate or low after dexamethasone or placebo treatments (y=8.03x+13.369; R2=0.908). The variability observed between the two methods, was explained by nonrandom segmental distribution of 3-D abnormal pathologies, not captured by the integer histological scoring system. Of immunological and statistical relevance, the ability for MPO and TLR4 to differentiate the groups was significantly enhanced when the analysis was stratified by the degree of 3-Dmucosal abnormalities (p<0.01). Conclusion: Stereomicroscopy is a very cost effective visualization tool that can be used as a complementary research and diagnostic tool in studies of therapeutic and intestinal pathology.

Evidence for oral agmatine sulfate safety – A 95-day high dosage pilot study with rats

Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3g/l agmatine sulfate in their drinking water for 95days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals’ body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine.

Histopathological findings of endometrial specimens in abnormal uterine bleeding

The aim of this study was to assess the frequency of different histopathological findings obtained from dilatation and curettage (D&C) specimens in patients with abnormal uterine bleeding (AUB). In a retrospective review of 591 specimens, the included subjects were all women with AUB who underwent D&C between 2002 and 2006 in Be'sat Hospital, Tehran, Iran. The pathological diagnoses were analyzed in four groups from normal to malignant endometrium. The pathological groups were evaluated for patients' characteristics including demographic data and medical history. The majority of patients (61.6%) were in the 41-50 year age group. Totally, 81.4% of patients had normal pathology. The disordered proliferative endometrium/polyps, hyperplasia, and malignant pathology were found in 15.4, 2.5, and 0.7% of specimens, respectively. The abnormal pathologies were seen more among patients with postmenopausal status, nulli-/primigravid women, and those with hypertension, diabetes, hypothyroidism, and polycystic ovary syndrome. The proliferative endometrium and secretory endometrium were the most common histopathological observations in AUB patients in our region, and except normal endometrium, disordered proliferative endometrium was the most common cause of AUB.

Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer’s disease brain

BackgroundIntracytoplasmic inclusions composed of filamentous tau proteins are defining characteristics of neurodegenerative tauopathies, but it remains unclear why different tau isoforms accumulate in different diseases and how they induce abnormal filamentous structures and pathologies. Two tau isoform-specific antibodies, RD3 and RD4, are widely used for immunohistochemical and biochemical studies of tau species in diseased brains.ResultsHere, we show that extensive irreversible post-translational deamidation takes place at asparagine residue 279 (N279) in the RD4 epitope of tau in Alzheimer’s disease (AD), but not corticobasal degeneration (CBD) or progressive supranuclear palsy (PSP), and this modification abrogates the immunoreactivity to RD4. An antiserum raised against deamidated RD4 peptide specifically recognized 4R tau isoforms, regardless of deamidation, and strongly stained tau in AD brain. We also found that mutant tau with N279D substitution showed reduced ability to bind to microtubules and to promote microtubule assembly.ConclusionThe biochemical and structural differences of tau in AD from that in 4R tauopathies found in this study may therefore have implications for prion-like propagation of tau.

Concomitant findings and clinical significance of a fluid crescent between the iliacus muscle and iliac bone on MRI

Some routine magnetic resonance imaging (MRI) examinations show a thin line of fluid signal intensity along the iliac crest ("fluid crescent") between the iliacus muscle and the iliac bone. This fluid crescent has not been described before. To evaluate the clinical context and significance of the fluid crescent. MRI examinations of the abdomen and pelvis performed over 1 year were retrospectively reviewed twice for the presence of a fluid crescent. The relationship between the presence of a fluid crescent and associated abnormal findings, including ascites, iliopsoas compartment, and bone and soft tissue pathologies, was evaluated. Forty-one out of 254 MRI studies (male:female ratio, 136:118; mean age, 42 years) demonstrated a fluid crescent (16%). Thirty-eight of them had associated MRI pathologies: edema of the hip muscles = 24, ascites = 11, iliac bone = 21, and iliopsoas compartment = 7. Correlations between the presence of a fluid crescent and pathological findings were highly significant (P < 0.0001), except for the presence of fluid in the hip joint. A fluid crescent is an abnormal MRI finding strongly associated with iliopsoas compartment pathology, ascites, hip muscle edema, and pelvic bone abnormalities. The nature of this fluid crescent is yet to be determined.

A Multi-Center, Single-Arm, International, Feasibility Clinical Study of IOGYN Hysteroscopic Morcellation System. Preliminary Clinical Results

The primary objective of this study is to evaluate the performance of the IOGYN System in removing abnormal uterine pathologies including submucosal myomas and endometrial polyps. Secondary objectives involve: Assessing the performance of the Fluid Management System; tissue characterization including histopathology; and other system and procedure performance characteristics. A Multi-Center, International, Single-Arm, Feasibility Clinical Study. Five investigational centers in Mexico and Hungary. A total of up to 50 Women diagnosed with submucous fibroids and/or endometrial polyps. IOGYN Procedure. The primary safety evaluation is the occurrence of adverse events. Primary effectiveness evaluation is performed by assessing the adequacy of removal of abnormal uterine pathologies including submucosal myomas and endometrial polyps. Secondary objectives involve: Assessing the performance of the Fluid Management System; tissue characterization including histopathology; and other system and procedure performance characteristics. Most up to date clinical results from this in-progress study will be reported. This multi-center, international, feasibility clinical study will be the first to generate information regarding the performance of the IOGYN System in removing benign uterine pathology.

OP08.06: AMIPROM: a pilot RCT on serial transabdominal amnioinfusion versus expectant management in very early PROM

matched controls. Additionally, the second purpose was to determine the relationship between the placental pathologies and uterine artery (UtA) Doppler findings. Methods: 172 patients with singleton pregnancies between 24 and 35 weeks who presented with signs of preterm labor and 169 healthy pregnant women with correlative properties who admitted for routine pregnancy visits were recruited for the study. UtA blood flows were evaluated with Doppler ultrasonography during uterine inertia for both patients having preterm labor signs and for the control group. Each patient followed until the birth and delivery in 48 hours/7 days/14 days were recorded. The placental pathologies were interpreted (Redline 2007) and the relationship between the Doppler findings and placental pathologies were investigated. Results: Placental pathologies were found to be higher in the study group compared to their controls (P = 0.002). According to placental pathology patterns; the study group had significantly higher subclinical chorioamnionitis (P = 0.014), maternal vascular maldevelopment (P = 0.000) and maternal vascular loss of integrity (P = 0.021) than the control group. In the study group, the patients’ who delivered in 48 hours/7 days/14 days, presence of abnormal placental pathologies were also found to be higher (P = 0.001/P = 0.000/P = 0.000) than the patients who did not deliver. The study group with abnormal placental pathologies had substantially higher UtA PI (0.98 ± 0.39) than the patients without placental pathologies (0.74 ± 0.21) (P = 0.001). Conclusions: An underlying abnormal placental pathology was found to be higher in patients showing preterm labor symptoms and in the patients particularly who deliver in early time periods. With this study, it’s shown for the first time that the placental lesions prosecuted for preterm delivery were associated with antenatal UtA blood flows.

Effects of Relaxin on Arterial Dilation, Remodeling, and Mechanical Properties

Administering relaxin to conscious rats and humans elicits systemic and renal vasodilation. The molecular mechanisms vary according to the duration of relaxin exposure-so-called "rapid" (within minutes) or "sustained" (hours to days) vasodilatory responses-both being endothelium-dependent. Rapid responses are mediated by G(αi/o) protein coupling to phosphoinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of nitric oxide synthase. Sustained responses are mediated by vascular endothelial and placental growth factors, as well as increases in arterial gelatinase activity. Thus, after hours or days of relaxin treatment, respectively, arterial MMP-9 or MMP-2 hydrolyze "big" endothelin (ET) at a gly-leu bond to form ET(1-32), which in turn activates the endothelial ET(B) receptor/nitric oxide vasodilatory pathway. Administration of relaxin to conscious rats also increases global systemic arterial compliance and passive compliance of select isolated blood vessels such as small renal arteries (SRA). The increase in SRA passive compliance is mediated by both geometric remodeling (outward) and compositional remodeling (decreased collagen). Relaxin-induced geometric remodeling has also been observed in brain parenchymal arteries, and this remodeling appears to be via the activation of peroxisome proliferator-activated receptor-γ. Given the vasodilatory and arterial remodeling properties of relaxin, the hormone may have therapeutic potential in the settings of abnormal pregnancies, heart failure, and pathologies associated with stiffening of arteries.

Correlation of misfolded transthyretin in abnormal vitreous and high myopia related ocular pathologies

BackgroundHigh myopia is usually defined as eyes with −6 dioptres (D) of myopia, or >26.0mm in axial length. Progressive and excessive elongation of the eyeball leads to secondary ocular diseases such as macular detachment (MD) and macular hole (MH). Higher transthyretin (TTR) levels had been detected in abnormal serums, but the situation in vitreous humor and the mechanism are still unclear. MethodTransthyretin concentrations in vitreous of 80 high myopia patients and 20 healthy controls were determined by ELISA. After affinity purification, SDS-PAGE, Western-blot, and circular dichroism (CD) spectroscopy were employed for the secondary structure research. ResultsVitreous transthyretin concentration of MD patients was ~1.1 times higher than that of MH patients, and 4.1 times higher than that of healthy controls. TTR in MD patients' vitreous showed a much more stable tetrameric structure. In neutral condition, compared with the secondary structure of healthy TTR, purified TTR in MD and MH vitreous samples showed lower β-sheets content; ~50% of β-sheets of the TTR in MD vitreous samples were lost. ConclusionsThe results suggested that MD and MH patients had higher vitreous TTR concentrations; TTR in MD vitreous had an abnormally stable tetrameric structure, possibly due to misfolding.

Atraumatic splenic rupture

Atraumatic splenic rupture is an uncommon but poorly defined clinical condition. Its diagnosis may be missed or delayed because of low clinical suspicion, especially in the absence of trauma. The primary aim of this study was to describe the experience with atraumatic splenic rupture in a district general hospital. Over a 6-year period (2004-2010), seven patients were identified, producing an incidence of 1.2/year. Computed tomography confirmed the diagnosis preoperatively in all the cases where it was performed (n=5). All patients required total splenectomy; indications included peritonitis, hypovolaemic shock and failed conservative treatment. Five splenectomies were performed within 24 h of admission. In four cases, no pathological abnormality was identified (atraumatic-idiopathic); abnormal pathologies (atraumatic-pathological) in the remaining three were amyloidosis, lymphoma and focal thrombosis. A high index of suspicion should be maintained by emergency physicians and surgeons during initial evaluation of these patients. Computed tomography scan facilitates the diagnosis and early total splenectomy is often needed.

"Protein cancers" hypothesis for neurodegenerative diseases

Intracellular filamentous inclusions composed of amyloid-like proteins are common neuropathological features of many neurodegenerative disorders. Although the extent of the abnormal protein pathologies is closely correlated with the disease progression, little attention has been given to the molecular mechanisms to explain how these pathological proteins spread. We developed a novel method for introducing amyloid seeds into cells, and presented experimental evidence of seed-dependent polymerization, leading to the formation of filamentous protein deposits and cell death. Overexpression of alpha-synuclein itself does not generate abnormal inclusions, but if fibril seeds are introduced, abundant alpha-synuclein inclusions positive for PSer129 and ubiquitin are developed, and the cells undergo cell death. This was also clearly demonstrated in cells expressing different tau isoforms by introducing the corresponding tau fibril seeds. These results obtained from biochemical analyses of abnormal proteins in patients strongly suggest that amyloid-like proteins, including tau, alpha-synuclein and TDP-43, propagate from cell to cell and this propagation is the cause of disease progression, analogously to metastasis of cancer cells to multiple different tissues in cancer progression. From this point of view, I have proposed as a hypothesis that neurodegenerative diseases with amyloid-like proteins can be regarded as "protein cancers".

Gray-level co-occurrence matrix bone fracture detection

Fractures of bone are a common affliction in orthopedic wards at any given time. Trained radiologists generally identify abnormal pathologies including fractures with a relatively high level of accuracy. However studies examining reader accuracy have shown that in some cases the miss rate can be as high when reading x-rays containing multiple abnormalities. Accurate diagnosis of fractures is vital to the effective management of patient injuries. As a result, detection of long-bone fractures is an important orthopedics and radiologic problem, and it is proposed that a novel computer aided detection system could help lowering the miss rate. This paper examines the development of such a system, for the detection of long-bone fractures. This project fully employed MATLAB 7.8.0 (.r2009a) as the programming tool for loading image, image processing and user interface development. Results obtained demonstrate the performance of the femur's long bone fracture detection system with some limitations.