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  1. Tang WH, Alip A, Saad M, Phua VC, Chandran H, Tan YH, et al.
    Asian Pac J Cancer Prev, 2015;16(5):1901-6.
    PMID: 25773842
    BACKGROUND: Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma (NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used but increasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomes in NSCLC patients receiving local therapy for brain metastases.

    MATERIALS AND METHODS: The case records of 125 patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres from January 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patients receiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariate testing.

    RESULTS: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients with multiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3 metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure (yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgery or SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use of post-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All four factors remained statistically significant on multivariate analysis.

    CONCLUSIONS: ECOG ≤2, presence of seizures, oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapy systemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.

    Matched MeSH terms: Brain/pathology; Carcinoma, Non-Small-Cell Lung/pathology*; Lung Neoplasms/pathology*
  2. Peh SC, Kim LH, Poppema S
    Am. J. Surg. Pathol., 2001 Jul;25(7):925-9.
    PMID: 11420464
    Thymus and activation-regulated chemokine (TARC) has been identified as a lymphocyte-directed CC chemokine that attracts activated T-helper type 2 (Th2) cells in humans. Recent studies showed that the T cells surrounding Reed-Sternberg cells in Hodgkin's lymphomas (HL) are Th2 type. Anaplastic large cell lymphomas (ALCL), T-cell-rich B-cell lymphoma (TCRBCL) can mimic HL in some instances. This study aimed to establish the pattern of TARC expression in these diseases. Immunohistochemical stain using a polyclonal goat anti-human antibody to TARC was performed on 119 cases of confirmed HL; 99 were classical type (43 mixed cellularity, 43 nodular sclerosis, 5 lymphocyte depleted, 4 lymphocyte rich, 4 unclassifiable) and 20 lymphocyte predominant HL. Additional 27 ALCL (9 T-, 18 null-cell phenotype), 16 T-cell and 8 B-cell non-Hodgkin's lymphoma (NHL) were studied. A total of 85.8% of the classical HL, one case of ALCL, and one case of large cell B-cell lymphoma with anaplastic morphology showed positive TARC expression in the tumor cells. The expression was paranuclear and/or diffuse in the cell cytoplasm. The tumor cells in all cases of lymphocyte predominant HL, TCRBCL, null ALCL, and T-NHL did not express TARC. The high frequency of TARC expression in the Reed-Sternberg cells of classical HL may explain the characteristic T-cell infiltrate in this disease. The absence in other types that may be morphologically similar indicates that staining for TARC may aid in differential diagnosis.
    Matched MeSH terms: T-Lymphocytes/pathology*; Lymphoma, B-Cell/pathology; Lymphoma, Large B-Cell, Diffuse/pathology
  3. Rohaizak M, Jasmi AY, Ismail MA, Munchar MJ, Meah FA
    Asian J Surg, 2003 Jul;26(3):183-5.
    PMID: 12925296 DOI: 10.1016/S1015-9584(09)60381-X
    There has been a growing awareness of the association between papillary thyroid carcinoma and familial adenomatous polyposis (FAP). The cases of four young patients with papillary thyroid carcinoma occurring with FAP are presented. Three patients underwent surgery to provide specimens for detailed histological examination. The surgical specimens showed well-encapsulated multicentric tumours exhibiting a predominantly papillary architectural growth pattern. In some areas, follicular architecture and cribriform patterns were noted. Atypical areas of spindle cells in a trabecular or solid configuration, which are not normally seen in classical papillary thyroid carcinoma, were evident. Malignant cells exhibited a graduation of cuboidal to tall cells with abundant amphophilic cytoplasm. The nuclei did not exhibit the typical nuclear clearing as seen in papillary thyroid carcinoma, but nuclear grooving and inclusions were noted. Psammoma bodies were not seen in any of the specimens. In a limited review of these patients, features such as young age at presentation, multicentricity and unusual histology suggest that thyroid carcinoma associated with FAP may represent a distinct form of thyroid cancer.
    Matched MeSH terms: Carcinoma, Papillary/pathology; Adenomatous Polyposis Coli/pathology; Thyroid Neoplasms/pathology
  4. Thambidorai CR, Muin I, Razman J, Zulfiqar A
    Dis Colon Rectum, 2003 Jul;46(7):974-7.
    PMID: 12847376
    PURPOSE: Currarino triad, which comprises anorectal stenosis, anterior sacral defect, and a presacral mass, is an uncommon cause of constipation in children and adults. The presacral mass in this triad is most often caused by an anterior sacral meningocele, a teratoma, or an enterogenous cyst, but rarely may be caused by dual pathology. A neonate with Currarino triad and dual pathology in the presacral mass is described in this report.

    METHOD: A male Chinese neonate, who presented with abdominal distention and constipation on the second day of life, was found to have features of Currarino triad. Colostomy was done in the neonatal period, and the presacral mass was excised by posterior sagittal perineal approach at the age of six months.

    RESULTS: The excised presacral mass consisted of an anterior meningocele and a teratoma. The patient continued to have constipation during follow-up and required anorectoplasty to correct residual anorectal stenosis. At the time of this report the patient was three years old and growing normally with normal anorectal function.

    DISCUSSION: Of a total of about 200 cases of complete Currarino triad found in the literature, in only 22 patients did the presacral mass contain both meningocele and teratoma. The features of these 22 patients and the current views on the surgical management of Currarino triad are discussed.

    Matched MeSH terms: Meningocele/pathology*; Pelvic Neoplasms/pathology*; Teratoma/pathology*
  5. Ali TB, Zain RB, Adam BA
    Singapore Dent J, 1994 Jan;19(1):18-21.
    PMID: 9582679
    A case of bullous pemphigoid with extra-oral and intraoral lesions in a 60-year-old female is reported. Diagnosis is based on histopathology and direct immunofluorescence, and the treatment regime described included oral prescription of prednisolone and topical application of a mixture of fluocinonide ointment and triamcinolone acetonide in Orabase on the oral lesions.
    Matched MeSH terms: Mouth/pathology; Mouth Diseases/pathology; Pemphigoid, Bullous/pathology
  6. Whittaker DK, Bakri MM
    Arch Oral Biol, 1996 Jan;41(1):15-9.
    PMID: 8833585
    One hundred and ninety-eight single-rooted teeth from individuals aged 21-90 yr of Caucasian, Malay, Chinese Malay and Indian Malay origin were studied. Single or serial longitudinal sections of extracted teeth were cut following dye imbibition of patent dentinal tubules. The extent of sclerosis of apical dentinal tubules was assessed and correlated with the age of the individual. Correlation with age was higher in the Caucasian than the Malay races and within the Malaysian racial groups correlation with age was highest in the Malays and lowest in the Chinese. It is concluded that factors other than age may be important in the formation of sclerotic apical dentine in teeth of different racial origin. The effect of racial origin should be considered when using sclerosis as a means of age determination in forensic cases.
    Matched MeSH terms: Aging/pathology*; Calcinosis/pathology; Dentin, Secondary/pathology
  7. Looi LM
    Hum Pathol, 1993 Jun;24(6):602-7.
    PMID: 8505038
    Congo red screening of 211 consecutive cardiac biopsy specimens obtained during cardiac surgery from 167 patients revealed 26 (16%) instances of isolated atrial amyloidosis (IAA). The ages of IAA-positive patients ranged from 25 to 52 years (mean age, 39 years). Twenty-three (88%) IAA-positive biopsy specimens were from patients with chronic rheumatic heart disease (CRHD) while three (12%) were from patients with an atrial septal defect (ASD). The prevalence of IAA in the CRHD patients was 23%, appreciably higher than that in the ASD patients (15%) and in other patients with atrial biopsies. The prevalence of IAA in both CRHD and ASD patients was significantly higher (P < .001) than in controls. Controls consisted of 247 healthy adults who were autopsied after traumatic deaths, with an age range of 18 to 89 years (mean age, 38 years). Only seven (3%) control subjects were IAA positive; all were over 40 years of age. Isolated atrial amyloidosis deposits were permanganate resistant and immunohistochemically positive for human amyloid P (AP) protein and negative for human amyloid-associated (AA) protein and immunoglobulin light chains. They were observed as fine congophilic and birefringent deposits in intramyocardial vessel walls, along the myocardial sarcolemma, and in the subendocardium. There was associated myocyte hypertrophy but no atrophy. Electron microscopy demonstrated typical nonbranching amyloid fibrils. It is postulated that stretching of the atria in chronic heart disease results in a raised prevalence of IAA. Recent reports that IAA contains atrial natriuretic peptide, a polypeptide hormone product of atrial myocytes, supports this view.
    Matched MeSH terms: Amyloidosis/pathology; Heart Diseases/pathology; Cardiomyopathies/pathology
  8. Thiruventhiran T, Goh BL, Leong CL, Cheah PL, Looi LM, Tan SY
    Nephrol Dial Transplant, 1999 Jan;14(1):214-7.
    PMID: 10052513
    Matched MeSH terms: Kidney Tubular Necrosis, Acute/pathology; Kidney Tubules/pathology; Acute Kidney Injury/pathology
  9. Franz DR, Lim TS, Baze WB, Arimbalam S, Lee M, Lewis GE
    Am J Trop Med Hyg, 1988 Mar;38(2):249-54.
    PMID: 3281490
    Dexamethasone has recently been shown to block the production of cachectin (implicated in the pathogenesis of cerebral malaria) if administered prior to endotoxin induction of mouse macrophages. Using the hamster cheek pouch-cerebral malaria model, we tested the hypothesis that dexamethasone is effective as a therapeutic agent in severe malaria if given before some yet undefined trigger point in the disease. Infected hamsters were treated with dexamethasone (0.7 mg/kg) daily on days 7-12, 4-12, or 1-12 post-challenge. When treatment was started on day 1, whole body oxygen consumption (used as a measure of erythrocyte transport to sites of diffusion) on day 12 was greater than (P less than 0.05) that of infected control animals, though the degree of anemia was no different in treated and untreated groups. Furthermore, treatment produced a reduction in monocyte accumulation, capillary malfunction, and monocyte/red blood cell aggregate formation observable in the cheek pouch in vivo and a similar reduction in monocyte presence, capillary pathologic change, and multifocal hemorrhage in the brain on postmortem. These data suggest that mediator(s), whose production can be blocked by pretreatment with dexamethasone, are involved in the pathogenesis of disease leading to death of the Plasmodium berghei infected hamster.
    Matched MeSH terms: Brain/pathology; Capillaries/pathology; Malaria/pathology
  10. Sivanesaratnam V, Jayalakshmi P
    Cancer, 1989 Aug 15;64(4):798-800.
    PMID: 2501019
    Patients undergoing radical surgical treatment for Stage IB and IIA cervical carcinoma are at high risk of developing local recurrence and/or distant metastases when one or more of the following factors are present: presence of metastatic pelvic lymph nodes, a large primary growth, full-thickness tumor invasion of the cervix, clinically undetected parametrial extension, and lymphatic/vascular channel permeation in the cervix by tumor cells. Carcinoma of the cervix appears to be behaving like a systemic disease. Therefore, systemic measures should be considered in its therapy. The authors report the initial experience with the use of mitomycin C as a single agent adjuvant in 16 patients with Stage IB carcinoma of the cervix who had undergone Wertheim radical hysterectomy and were thought to be in this high-risk group. Fourteen of the patients are alive and free of disease after durations of follow-up ranging from 16 to 38 months, the disease-free survival at a median follow-up of 29 months being 87.5%. One patient required discontinuation of adjuvant chemotherapy because of severe marrow toxicity; however, in view of the presence of a multiple risk factors, pelvic irradiation was given instead. She died 13 months later from disseminated disease. A second patient died 6 months later from congestive cardiac failure.
    Matched MeSH terms: Adenocarcinoma/pathology; Carcinoma, Squamous Cell/pathology; Uterine Cervical Neoplasms/pathology
  11. Reed WM, Schrader DL
    Poult Sci, 1989 May;68(5):631-8.
    PMID: 2547209
    An avian pox virus was isolated from cutaneous proliferative lesions removed from greater hill mynahs (Gracula religiosa) imported from Malaysia. Cutaneous inoculation of specific pathogen-free chickens and bobwhite quail with the mynah pox virus resulted in severe proliferative cutaneous lesions similar to those seen in the naturally infected mynah birds. Microscopically, the reaction in the chickens and quail at sites of virus inoculation was characterized by marked epithelial hyperplasia with ballooning degeneration and formation of cytoplasmic inclusion bodies. Inoculation of conjunctival and oral mucosae of chickens by applying pox virus with a cotton swab did not result in gross or microscopic lesions. In cross-protection studies, chickens and bobwhite quail immunized with either quail, fowl, pigeon, turkey, or psittacine pox vaccines were not protected from challenge with mynah pox virus. Following vaccination of quail and chickens with mynah pox virus vaccine, there was no resistance to challenge by quail, fowl, pigeon, turkey, or psittacine pox viruses. Significant protection against development of lesions following inoculation with mynah pox virus was attained only when the homologous virus was used as a vaccine.
    Matched MeSH terms: Bird Diseases/pathology; Skin/pathology; Tibia/pathology
  12. Said H, Phang KS, Razi A, Khuzaiyah R, Patawari PH, Esa R
    J Laryngol Otol, 1988 Jul;102(7):614-9.
    PMID: 3411216
    Three cases of embryonal rhabdomyosarcoma in the middle ear and mastoid in children are presented. Diagnosis was confirmed by histopathology. A multidisciplinary approach employing surgery, chemotherapy and radiation therapy is the method of choice in the management of this rare and highly lethal condition.
    Matched MeSH terms: Ear Neoplasms/pathology*; Rhabdomyosarcoma/pathology*; Skull Neoplasms/pathology*
  13. Wang YH, Bychkov A, Chakrabarti I, Jain D, Liu Z, He S, et al.
    Cancer Cytopathol, 2020 Dec;128(12):895-904.
    PMID: 32931161 DOI: 10.1002/cncy.22354
    BACKGROUND: The purpose of the current study was to examine the impact of coronavirus disease 2019 (COVID-19) on various aspects of cytology practice in the Asia-Pacific region.

    METHODS: An online questionnaire was distributed to cytopathology laboratories in 24 Asia-Pacific countries to explore the impact of restrictive measures on access to health care, use of general and personal protective equipment (PPE), and changes in cytology workflow and workload from February to April 2020.

    RESULTS: A total of 167 cytopathology laboratories from 24 countries responded to the survey; the majority reported that restrictive measures that limited the accessibility of health care services had been implemented in their cities and/or countries (80.8%) and their hospitals (83.8%). The respondents noted that COVID-19 had an impact on the cytologic workflow as well as the workload. Approximately one-half of the participants reported the implementation of new biosafety protocols (54.5%) as well as improvements in laboratory facilities (47.3%). Rearrangement or redeployment of the workforce was reported in 53.3% and 34.1% of laboratories, respectively. The majority of the respondents reported a significant reduction (>10%) in caseload associated with both gynecological (82.0%) and nongynecological specimens (78.4%). Most laboratories reported no significant change in the malignancy rates of both gynecological (67.7%) and nongynecological specimens (58.7%) compared with the same period in 2019.

    CONCLUSIONS: The results of the survey demonstrated that the COVID-19 pandemic resulted in a significant reduction in the number of cytology specimens examined along with the need to implement new biosafety protocols. These findings underscore the need for the worldwide standardization of biosafety protocols and cytology practice.

    Matched MeSH terms: Pathology, Clinical/organization & administration*; Pathology, Clinical/standards; Pathology, Clinical/statistics & numerical data
  14. Bhaskaran M, Devegowda VG, Gupta VK, Shivachar A, Bhosale RR, Arunachalam M, et al.
    ACS Chem Neurosci, 2020 10 07;11(19):2962-2977.
    PMID: 32945654 DOI: 10.1021/acschemneuro.0c00555
    Glioblastoma multiforme (GBM), a standout among the most dangerous class of central nervous system (CNS) cancer, is most common and is an aggressive malignant brain tumor in adults. In spite of developments in modality therapy, it remains mostly incurable. Consequently, the need for novel systems, strategies, or therapeutic approaches for enhancing the assortment of active agents meant for GBM becomes an important criterion. Currently, cancer research focuses mainly on improving the treatment of GBM via diverse novel drug delivery systems. The treatment options at diagnosis are multimodal and include radiation therapy. Moreover, significant advances in understanding the molecular pathology of GBM and associated cell signaling pathways have opened opportunities for new therapies. Innovative treatment such as immunotherapy also gives hope for enhanced survival. The objective of this work was to collect and report the recent research findings to manage GBM. The present review includes existing novel drug delivery systems and therapies intended for managing GBM. Reported novel drug delivery systems and diverse therapies seem to be precise, secure, and relatively effective, which could lead to a new track for the obliteration of GBM.
    Matched MeSH terms: Pathology, Molecular
  15. Yip CH, Taib NA, Tan GH, Ng KL, Yoong BK, Choo WY
    World J Surg, 2009 Jan;33(1):54-7.
    PMID: 18958521 DOI: 10.1007/s00268-008-9782-7
    Axillary nodal status is one of the most important prognostic factors in breast cancer. In the present study we used it to determine the predictors of axillary lymph node metastases in breast cancer and to determine if there is a group of patients in whom minimal axillary surgery is indicated.
    Matched MeSH terms: Breast Neoplasms/pathology*; Lymph Nodes/pathology*; Lymphatic Metastasis/pathology
  16. Noor Khairiah AK, Mohamad Nazrulhisham MN, Hazman MN
    Med J Malaysia, 2018 12;73(6):407-409.
    PMID: 30647215
    Malignant intrathoracic disease is the commonest cause of superior vena cava (SVC) obstruction. Life threatening SVC obstruction with intense dyspnoea requires urgent treatment. SVC stenting has been developed in recent years which results in rapid relief of the obstruction. The Yconfiguration technique has been reported to provide support for all three limbs of the bifurcation to prevent restenosis. At present, there are limited reports on the use of Y-configuration stent in stent techniques for endovascular stenting in malignant SVC obstruction. We share our clinical experience of two patients who received balloon-mounted stents using this technique.
    Matched MeSH terms: Adenocarcinoma/pathology; Uterine Cervical Neoplasms/pathology; Lung Neoplasms/pathology
  17. Aziz NF, Ramalingam A, Latip J, Zainalabidin S
    Life Sci, 2021 Mar 15;269:119080.
    PMID: 33465387 DOI: 10.1016/j.lfs.2021.119080
    S-Allylcysteine (SAC) is an extensively studied natural product which has been proven to confer cardioprotection. This potentiates SAC into many clinical relevance possibilities, hence, the use of it ought to be optimally elucidated. To further confirm this, an ischemia/reperfusion model has been used to determine SAC at 10 mM and 50 mM on cardiac function, cardiac marker, and mitochondrial permeability. Using Langendorff setup, 24 adult male Wistar rats' hearts were isolated to be perfused with Kreb-Henseleit buffer throughout the ischemia/reperfusion method. After 20 min of stabilization, global ischemia was induced by turning off the perfusion for 35 min followed by 60 min of reperfusion with either Kreb-Henseleit buffer or SAC with the dose of 10 mM or 50 mM. The cardiac function was assessed and coronary effluent was collected at different timepoints throughout the experiment for lactate dehydrogenase (LDH) measurement. The harvested hearts were then used to measure glutathione while isolated mitochondria for mPTP analysis. SAC-reperfused hearts were shown to prevent the aggravation of cardiac function after I/R induction. It also dose-dependently upregulated glutathione reductase and glutathione level and these were also accompanied by significant reduction of LDH leakage and preserved mitochondrial permeability. Altogether, SAC dose-dependently was able to recover the post-ischemic cardiac function deterioration alongside with improvement of glutathione metabolism and mitochondrial preservation. These findings highly suggest that SAC when sufficiently supplied to the heart would be able to prevent the deleterious complications after the ischemic insult.
    Matched MeSH terms: Heart/physiopathology; Ischemia/pathology; Mitochondria/pathology; Myocardial Reperfusion Injury/pathology
  18. Yambot AV, Song YL, Sung HH
    Dis Aquat Organ, 2003 Mar 31;54(2):147-56.
    PMID: 12747640
    The ciliated protozoan parasite Cryptocaryon irritans infecting marine fishes in Taiwan is described. Developmental characteristics and sequences of the ribosomal DNA regions such as part of 18 S, the entire first internal transcribed spacer, and part of 5.8 S of various Taiwan isolates of C. irritans were investigated. A total of 5 isolates was obtained from different fish-host species and localities, the majority from cultured fish species. C. irritans from Taiwan is able to shift its developmental characteristics, i.e. from non-adherent to adherent tomonts, from individualistic to aggregate-forming tomonts, from infection of the gills only to infection of the gills and body. Thus, it is not possible to classify strains of C. irritans on the basis of these parameters. Premature tomonts that developed from dead fishes were able to produce theronts that could infect fish host. Isolates from Pingtung and the USA had identical nucleotide sequences while an isolate from Malaysia was identical to an Israel isolate. Percentage variation among pairs of Taiwan isolates showed a higher degree of variation than isolate sequences listed in GenBank. Sequence analysis revealed highly aberrant isolates in Taiwan, and a phylogenetic tree distinguished a marine and a low-salinity variant. C. irritans from marine fishes in Taiwan, therefore, display some characteristics not previously reported. Since manipulation of salinity in brackishwater ponds and marine cage sites is not feasible, there is a need to develop new strategies for the control and prevention of cryptocaryoniasis.
    Matched MeSH terms: Fish Diseases/pathology; Gills/pathology; Ciliophora Infections/pathology
  19. Md Din N, Tomkins-Netzer O, Talat L, Taylor SR, Isa H, Bar A, et al.
    J Glaucoma, 2016 07;25(7):598-604.
    PMID: 26900824 DOI: 10.1097/IJG.0000000000000379
    PURPOSE: To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness.

    PATIENTS AND METHODS: Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP.

    RESULTS: IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 μm) compared with NU eyes (142.1±32.0 μm, P=0.043).

    CONCLUSIONS: Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

    Study site: Moorfields Eye Hospital, London
    Matched MeSH terms: Arthritis, Juvenile/physiopathology*; Glaucoma/physiopathology*; Nerve Fibers/pathology*; Ocular Hypertension/physiopathology; Optic Disk/pathology; Retinal Ganglion Cells/pathology*; Uveitis/physiopathology*
  20. Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, et al.
    Nat Genet, 2017 Jul;49(7):1113-1119.
    PMID: 28530674 DOI: 10.1038/ng.3874
    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10-8, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
    Matched MeSH terms: Arteries/pathology*; Coronary Artery Disease/pathology; Coronary Artery Disease/physiopathology; Muscle, Smooth, Vascular/pathology
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