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  1. Expression of c-erbB3 protein in primary breast carcinomas
    Naidu R, Yadav M, Nair S, Kutty MK
    Br. J. Cancer, 1998 Nov;78(10):1385-90.
    PMID: 9823984
    Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.
    Matched MeSH terms: Breast Neoplasms/pathology; Carcinoma, Intraductal, Noninfiltrating/pathology; Carcinoma, Ductal, Breast/pathology; Carcinoma, Lobular/pathology
  2. Experimental cross-infection of sheep and goats with different isolates of contagious ecthyma virus
    Zamri-Saad M, Roshidah I, al-Ajeeli K
    Aust. Vet. J., 1994 Jul;71(7):218-20.
    PMID: 7945102
    Matched MeSH terms: Ecthyma, Contagious/pathology*; Sheep Diseases/pathology*; Skin/pathology; Goat Diseases/pathology*
  3. Florid cemento-osseous dysplasia in a young Chinese man. Case report
    Ong ST, Siar CH
    Aust Dent J, 1997 Dec;42(6):404-8.
    PMID: 9470284
    Florid cemento-osseous dysplasia refers to a group of fibro-osseous lesions which are exuberant, multiquadrant and arise from the tooth-bearing area of the jaws. It is classically described as a condition occurring almost exclusively in middle-aged black women. A case of florid cemento-osseous dysplasia occurring in a young Chinese male is reported which was rare in regard to race and sex. This 20 year old Chinese man presented with huge symmetrical bony lesions in all four quadrants of the jaws. Clinical presentation, radiological findings and histological features of the excised specimens are described. Treatment of the lesions was unusual. Curettage was first done with minimal benefit and it was followed by mandibular recontouring to improve facial appearance. The outcome of these procedures will be discussed.
    Matched MeSH terms: Cementoma/pathology*; Fibrous Dysplasia of Bone/pathology*; Jaw Diseases/pathology*; Jaw Neoplasms/pathology*
  4. A clinicopathologic study of odontomas: Malaysian findings
    Ng KH, Siar CH
    J Nihon Univ Sch Dent, 1997 Dec;39(4):171-5.
    PMID: 9476429
    This report reviews the clinicopathologic characteristics of 104 cases of odontomas diagnosed in the Division of Stomatology, Institute for Medical Research, Kuala Lumpur, over a 29-year period (1967-1995). The results showed no real predilection in terms of sex (M:F ratio, 1:1), race (45.2% Malays, 40.4% Chinese, 10.6% Indians and 3.8% other races) or site (maxilla:mandible ratio, 1: 1.04) distribution. The mean age at presentation was 24.8 years and the age range was 3-74 years. There were 102 intraosseous and 2 extraosseous odontomas. Swelling was the most common presenting complaint. The majority of cases (81.9%) were clinically diagnosed as odontomas. The treatment of choice was surgical enucleation. Compound (43.3%) and complex (35.5%) odontomas were the two most common histological types encountered. The present findings correlate favorably with reported studies from other geographic areas.
    Matched MeSH terms: Jaw Neoplasms/pathology*; Mandibular Neoplasms/pathology; Maxillary Neoplasms/pathology; Odontoma/pathology*
  5. Intestinal brush border peptidases in cow's milk protein-sensitive enteropathy
    Iyngkaran N, Yadav M, Boey CG
    Acta Paediatr Scand, 1991 May;80(5):549-50.
    PMID: 1678569
    Matched MeSH terms: Intestinal Mucosa/pathology; Jejunum/pathology; Protein-Losing Enteropathies/pathology; Milk Hypersensitivity/pathology
  6. Serological markers in the diagnosis of histopathological types of nasopharyngeal carcinoma
    Sam CK, Prasad U, Pathmanathan R
    Eur J Surg Oncol, 1989 Aug;15(4):357-60.
    PMID: 2547665
    The titres of IgA against Epstein-Barr virus, viral capsid antigens and the titres of IgG against early antigen were found to be useful markers for the diagnosis of different histopathological types of nasopharyngeal carcinoma.
    Matched MeSH terms: Carcinoma/pathology; Carcinoma, Squamous Cell/pathology; Nasopharyngeal Neoplasms/pathology; Nasopharynx/pathology
  7. Fulltext Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation
    Campa D, Pastore M, Capurso G, Hackert T, Di Leo M, Izbicki JR, et al.
    Int J Cancer, 2018 01 15;142(2):290-296.
    PMID: 28913878 DOI: 10.1002/ijc.31047
    Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous  = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous  = 2.07 (1.55-2.77, ptrend  = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.
    Matched MeSH terms: Adenocarcinoma/pathology; Pancreatic Neoplasms/pathology; Carcinoma, Pancreatic Ductal/pathology; Pancreatitis, Chronic/pathology
  8. Lung injury related to consuming Sauropus androgynus vegetable
    Wu CL, Hsu WH, Chiang CD, Kao CH, Hung DZ, King SL, et al.
    J. Toxicol. Clin. Toxicol., 1997;35(3):241-8.
    PMID: 9140317 DOI: 10.3109/15563659709001207
    BACKGROUND: Taking Sauropus androgynus, a Malaysian food, to reduce weight began as a fad in Taiwan in 1994. Some advocates of this fad developed pulmonary dysfunction. The aim of this study is to report the lung injury in patients taking Sauropus androgynus.

    METHODS: From July 1995 to November 1995, we investigated 104 nonsmoking patients (one male and 103 females) with chest roentgenography, pulmonary function, test, and Technetium 99m-labeled diethylene triamine penta-acetate (Tc-99m DTPA) radioaerosol inhalation lung scintigraphy.

    RESULTS: Among the 90 patients receiving Tc-99m DTPA inhalation lung scan, 46 (51.1%) patients had increased clearance of Tc-99m DTPA from lung and 20 (22.2%) patients had inhomogeneous deposition of the submicronic radioaerosol. Eighteen (18/100) patients had obstructive ventilatory impairment in pulmonary function test. Analyzing the results, we found that the patients with respiratory symptoms (n = 42) took more vegetables (p = 0.016), had increased clearance of Tc-99m DTPA (p = 0.010) and had lower FEV1 (p = 0.001), FEV1/FVC (p < 0.001), FEF25-75 (p = 0.001), VC (p = 0.002) and DLCO (p = 0.009) than the patients without respiratory symptoms (n = 62). FEV1 and FEV1/FVC were significantly reduced in patients with severe impairment of alveolar permeability. The cumulative dosage and duration of exposure were significantly associated with the reduction of FEV1 and FEV1/FVC.

    CONCLUSION: The lung injury after taking Sauropus androgynus involves alveoli and/or small airways and is manifest as obstructive ventilatory impairment with inhomogeneous aerosol distribution and increased lung epithelial permeability.
    Matched MeSH terms: Epithelium/pathology; Lung/pathology*; Lung/physiopathology; Plant Poisoning/pathology*; Pulmonary Alveoli/pathology
  9. Fulltext Malignancy in systemic lupus erythematosus (SLE) patients
    Cader RA, Mei Yee AK, Yassin A, Ahmad I, Haron SN
    Asian Pac J Cancer Prev, 2018 Dec 25;19(12):3551-3555.
    PMID: 30583682
    Background: Malignancies are among the leading causes of death in Systemic Lupus Erythematosus (SLE)
    patients with studies reporting a higher prevalence of malignancy in SLE patients compared to the general population.
    We wanted to determine the frequency of cancer in a cohort of SLE patients and identify its associated risk factors.
    Methods: Cross-sectional study involving SLE patients attending the nephrology outpatient clinic, Universiti
    Kebangsaan Malaysia Medical Centre between January and June 2014. Results: We recruited 228 patients (207 female,
    21 male), aged 40.48 ± 12.86 years with mean SLE duration of 11.65 ± 6.46 years. Majority (87%) had lupus nephritis
    and were in remission with a median SLEDAI score 2 (0, 14). Majority (89%) were on corticosteroid with either a
    steroid sparing agent like mycophenolate mofetil (15.4%), azathioprine (36.8%) or ciclosporin (15.4%). One hundred
    and sixty (70.2%) patients were either receiving or had received intravenous cyclophosphamide with median dose
    of 5,173.6 ± 3,242.4 mg. Seven female patients were diagnosed with cancer during the course of their SLE with 56
    (34-78) years being median age at malignancy and SLE duration of 4 (0-12) years. Majority (5/7) had lupus nephritis
    and all patients a median dose of prednisolone 10 (2.5, 10) mg with 10 (4-24) years of steroids. Two patients had a
    family history of cancer with majority developing cancer after the diagnosis of SLE. Two patients received intravenous
    cyclophosphamide prior to the development of cancer for their SLE compared to overall cohort of 160. Three patients
    had colorectal cancer, 2 had cervical cancer, 1 had breast cancer, and one patient had germ cell tumour and one thyroid
    cancer. All patients had their cancer successful treated with no signs of recurrence. Conclusion: We found a lower
    occurrence of cancer in our SLE patients as compared with the reported literature.
    Matched MeSH terms: Lupus Erythematosus, Systemic/pathology*; Lupus Nephritis/pathology; Neoplasm Recurrence, Local/pathology; Neoplasms/pathology*
  10. Fulltext Epithelial-to-mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy
    Poh ME, Liam CK, Mun KS, Chai CS, Wong CK, Tan JL, et al.
    Thorac Cancer, 2019 09;10(9):1841-1845.
    PMID: 31350945 DOI: 10.1111/1759-7714.13156
    Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial-to-mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy. We review the literature and explore the possible mechanisms by which EMT occurs in disseminated tumor cells (DTC) or circulating tumor cells (CTC) in response to adjuvant chemotherapy (cisplatin) as a stressor. We also explore the possible therapeutic strategies to reverse EMT in patients with recurrence. In summary, although adjuvant cisplatin-based chemotherapy in resected NSCLC does extend survival, it may lead to the adverse phenomenon of EMT in disseminated tumor cells (DTC) or circulating tumor cells (CTC) causing recurrence and metastasis.
    Matched MeSH terms: Lung Neoplasms/pathology; Neoplasm Recurrence, Local/pathology; Sarcoma/pathology*; Carcinoma, Adenosquamous/pathology
  11. Retinal vascular fractal and blood pressure in a multiethnic population
    Sng CC, Wong WL, Cheung CY, Lee J, Tai ES, Wong TY
    J Hypertens, 2013 Oct;31(10):2036-42.
    PMID: 23787404 DOI: 10.1097/HJH.0b013e328362c201
    OBJECTIVE(S): To examine the effect of blood pressure (BP) on retinal vascular fractal dimension (Df), a measure of microvascular network complexity and density in a multiethnic cohort.
    METHODS: A population-based study of 3876 Chinese, Malay and Indian participants in Singapore. Retinal Df was measured using a computer-based program from digital retinal photographs. Associations between retinal Df and mean arterial BP (MABP) in the whole cohort and in each racial group were analysed using linear regression analysis. Logistic regression was used to examine the association between retinal Df and hypertension status.
    RESULTS: The mean retinal Df of the study population was 1.45 (standard deviation 0.03). After adjustment for age, sex, race, diabetes, BMI, cholesterol and creatinine levels, persons with smaller Df had higher MABP (mean difference MABP was 6.18 mmHg comparing lowest to highest Df quartiles, P<0.001). This was similar in Chinese, Malay and Indian persons [mean difference 6.40 (P<0.001), 4.72 (P=0.011) and 6.62 (P<0.001)mmHg, respectively]. Persons with smaller retinal Df were more likely to have uncontrolled treated or untreated hypertension [odds ratio 1.79 (P=0.003) and 2.60 (P=0.003), respectively, comparing lowest to highest Df quartiles] than those with no hypertension; this relationship was not seen comparing persons with controlled treated hypertension with no hypertension (odds ratio 1.01, P=0.972).
    CONCLUSION: Hypertension was associated with a sparser retinal vascular network, which was similar across different racial/ethnic groups and most apparent in those with uncontrolled or untreated hypertension. These data suggest that microvascular remodelling can be quantified by measuring retinal vasculature.
    Matched MeSH terms: Hypertension/pathology*; Retina/pathology; Retina/physiopathology; Retinal Diseases/pathology*; Retinal Vessels/pathology*
  12. Fulltext Loss-of-Function Myeloperoxidase Mutations Are Associated with Increased Neutrophil Counts and Pustular Skin Disease
    Vergnano M, Mockenhaupt M, Benzian-Olsson N, Paulmann M, Grys K, Mahil SK, et al.
    Am J Hum Genet, 2020 09 03;107(3):539-543.
    PMID: 32758448 DOI: 10.1016/j.ajhg.2020.06.020
    The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.2031-2A>C) in MPO. This encodes myeloperoxidase, an essential component of neutrophil azurophil granules. MPO screening in conditions phenotypically related to GPP uncovered further disease alleles in one subject with acral pustular psoriasis (c.2031-2A>C;c.2031-2A>C) and in two individuals with acute generalized exanthematous pustulosis (c.1705C>T;c.2031-2A>C and c.1552_1565del;c.1552_1565del). A subsequent analysis of UK Biobank data demonstrated that the c.2031-2A>C and c.1705C>T (p.Arg569Trp) disease alleles were also associated with increased neutrophil abundance in the general population (p = 5.1 × 10-6 and p = 3.6 × 10-5, respectively). The same applied to three further deleterious variants that had been genotyped in the cohort, with two alleles (c.995C>T [p.Ala332Val] and c.752T>C [p.Met251Thr]) yielding p values < 10-10. Finally, treatment of healthy neutrophils with an MPO inhibitor (4-Aminobenzoic acid hydrazide) increased cell viability and delayed apoptosis, highlighting a mechanism whereby MPO mutations affect granulocyte numbers. These findings identify MPO as a genetic determinant of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored.
    Matched MeSH terms: Psoriasis/pathology; Skin/pathology; Skin Diseases/pathology; Neurodegenerative Diseases/pathology
  13. Implication of HMGB1 signaling pathways in Amyotrophic lateral sclerosis (ALS): From molecular mechanisms to pre-clinical results
    Paudel YN, Angelopoulou E, Piperi C, Othman I, Shaikh MF
    Pharmacol Res, 2020 06;156:104792.
    PMID: 32278047 DOI: 10.1016/j.phrs.2020.104792
    Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly progressing neurodegenerative disorder with no effective disease-modifying treatment up to date. The underlying molecular mechanisms of ALS are not yet completely understood. However, the critical role of the innate immune system and neuroinflammation in ALS pathogenesis has gained increased attention. High mobility group box 1 (HMGB1) is a typical damage-associated molecular pattern (DAMP) molecule, acting as a pro-inflammatory cytokine mainly through activation of its principal receptors, the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4) which are crucial components of the innate immune system. HMGB1 is an endogenous ligand for both RAGE and TLR4 that mediate its biological effects. Herein, on the ground of pre-clinical findings we unravel the underlying mechanisms behind the plausible contribution of HMGB1 and its receptors (RAGE and TLR4) in the ALS pathogenesis. Furthermore, we provide an account of the therapeutic outcomes associated with inhibition/blocking of HMGB1 receptor signalling in preventing motor neuron's death and delaying disease progression in ALS experimental models. There is strong evidence that HMGB1, RAGE and TLR4 signaling axes might present potential targets against ALS, opening a novel headway in ALS research that could plausibly bridge the current treatment gap.
    Matched MeSH terms: Amyotrophic Lateral Sclerosis/pathology; Brain/pathology; Motor Neurons/pathology; Spinal Cord/pathology
  14. Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer's disease
    Mihardja M, Roy J, Wong KY, Aquili L, Heng BC, Chan YS, et al.
    Ann N Y Acad Sci, 2020 10;1478(1):43-62.
    PMID: 32700392 DOI: 10.1111/nyas.14436
    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the hallmark pathologies of amyloid-beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin-the pineal hormone primarily responsible for the regulation of the circadian rhythm-targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.
    Matched MeSH terms: Alzheimer Disease/pathology; Brain/pathology; Neurons/pathology; Mild Cognitive Impairment/pathology
  15. Fulltext Cytotoxic Effects of Betel Quid and Areca Nut Aqueous Extracts on Mouse Fibroblast, Human Mouth-Ordinary-Epithelium 1 and Human Oral Squamous Cell Carcinoma Cell Lines
    Al-Tayar BA, Ahmad A, Yusoff ME, Abdullah SF, Mohamad NK, Md Hashim SN, et al.
    Asian Pac J Cancer Prev, 2020 Apr 01;21(4):1005-1009.
    PMID: 32334462 DOI: 10.31557/APJCP.2020.21.4.1005
    BACKGROUND: Betel quid chewing is more common among the older generation in rural areas of Malaysia. Oral cancer in Asia has been associated with the habit of chewing betel quid and areca nut.

    OBJECTIVE:   This study aims to investigate the cytotoxic effects of betel quid and areca nut extracts on the fibroblast (L929), mouth-ordinary-epithelium 1 (MOE1) and oral squamous cell carcinoma (HSC-2) cell lines.

    METHODS: L929, MOE1 and HSC-2 cells were treated with 0.1, 0.2 and 0.4 g/ml of betel quid and areca nut extracts for 24, 48 and 72 h. MTT assay was performed to assess the cell viability.

    RESULTS: Both extracts, regardless of concentration, significantly reduced the cell viability of L929 compared with the control (P<0.05). Cell viability of MOE1 was significantly enhanced by all betel quid concentrations compared with the control (P<0.05). By contrast, 0.4 g/ml of areca nut extract significantly reduced the cell viability of MOE1 at 48 and 72 h of incubation. Cell viability of HSC-2 was significantly lowered by all areca nut extracts, but 0.4 g/ml of betel quid significantly increased the cell viability of HSC-2 (P<0.05).

    CONCLUSION: Areca nut extract is cytotoxic to L929 and HSC-2, whereas the lower concentrations of areca nut extract significantly increased the cell viability of MOE1 compared to the higher concentration and control group. Although betel quid extract is cytotoxic to L929, the same effect is not observed in MOE1 and HSC-2 cell lines. Further investigations are needed to clarify the mechanism of action.
    .

    Matched MeSH terms: Carcinoma, Squamous Cell/pathology*; Fibroblasts/pathology; Mouth Neoplasms/pathology*; Neoplasms, Glandular and Epithelial/pathology*
  16. The myopathology of floppy and hypotonic infants in Singapore
    Premasiri MK, Lee YS
    Pathology, 2003 Oct;35(5):409-13.
    PMID: 14555385
    AIMS: This study attempts to determine the type and relative frequency of muscle diseases contributing to floppy and hypotonic infants in Singapore.

    METHODS: Eighty consecutive muscle biopsies in the Department of Pathology, National University of Singapore, in the period 1978-2000, in which a clinical diagnosis of floppy or hypotonic infant was made, were reviewed.

    RESULTS: The commonest cause of severe hypotonia in infancy was spinal muscular atrophy, which accounted for 33% of cases followed by congenital muscular dystrophy (13%). Eight cases (10%) of infantile type II glycogenosis (Pompe's disease) were encountered. There were seven cases of congenital myopathy, of which four were centronuclear myopathy, and one each of central core myopathy, nemaline myopathy and congenital fibre type disproportion. One case of centronuclear myopathy was associated with type I fibre smallness. Type II atrophy, which is generally considered a non-specific change, was encountered in five cases. Of interest is the relatively large number of muscle biopsies (29%) in which no significant pathological features were encountered at the light microscopic, histochemical as well as ultra-structural level.

    CONCLUSIONS: The study has revealed a great variety of pathology affecting the muscle of children presenting as floppy infants or with hypotonia. The muscle diseases included spinal muscular atrophy, congenital muscular dystrophies, congenital myopathies and metabolic myopathies. However, 23 (29%) cases showed no significant pathology. For this group of floppy and hypotonic infants further studies are needed.

    Matched MeSH terms: Muscle Hypotonia/pathology*; Muscular Diseases/pathology*; Spinal Muscular Atrophies of Childhood/pathology; Muscle, Skeletal/pathology*
  17. Leptin and its receptor: can they help to differentiate chromophobe renal cell carcinoma from renal oncocytoma?
    Ng KL, Del Vecchio SJ, Samaratunga H, Morais C, Rajandram R, Vesey DA, et al.
    Pathology, 2018 Aug;50(5):504-510.
    PMID: 29970253 DOI: 10.1016/j.pathol.2018.01.007
    One of the challenges in differentiating chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) is overlapping morphology between the two subtypes. The aim of this study was to investigate the usefulness of expression of leptin (Ob) and its receptor (ObR) in discriminating chRCC from RO. Sections from paraffin-embedded, formalin-fixed tumour nephrectomy specimens of 45 patients, made up of 30 chRCC (15 eosinophilic variant and 15 non-eosinophilic variant) and 15 RO, were used in this study. Samples (30) of clear cell RCC (ccRCC), the most common histological subtype, were used to verify staining patterns found by others in our cohort of Australasian patients. Matched morphologically normal non-cancer kidney tissues were included for each specimen. Sections were batch-immunostained using antibodies against Ob and ObR. Stained sections were digitally scanned using Aperio ImageScope, and the expression pattern of Ob and ObR was studied. In this cohort, male to female ratio was 2:1; median age was 64 (45-88 years); and median tumour size was 3.8 cm (range 1.2-18 cm). There were 47 (62.7%) T1, seven T2, 20 T3 and one T4 stage RCC. Two patients with ccRCC presented with metastases. Nuclear expression of Ob was significantly higher in RO compared with chRCC. The increased nuclear expression of Ob in RO compared with chRCC may be a useful aid in the difficult histological differentiation of RO from chRCC, especially eosinophilic variants of chRCC.
    Matched MeSH terms: Carcinoma, Renal Cell/pathology*; Kidney/pathology; Kidney Neoplasms/pathology; Adenoma, Oxyphilic/pathology
  18. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis
    Fong CY, Aye AM, Peyman M, Nor NK, Visvaraja S, Tajunisah I, et al.
    Pediatr Infect Dis J, 2014 Apr;33(4):424-6.
    PMID: 24378951 DOI: 10.1097/INF.0000000000000137
    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease.
    Matched MeSH terms: Central Nervous System Diseases/pathology*; Herpes Simplex/pathology*; Pregnancy Complications, Infectious/pathology*; Retinal Necrosis Syndrome, Acute/pathology*
  19. Establishment of rat brain endothelial cells susceptible to rat cytomegalovirus ALL-03 infection
    Camalxaman SN, Zeenathul NA, Quah YW, Loh HS, Zuridah H, Hani H, et al.
    In Vitro Cell Dev Biol Anim, 2013 Mar;49(3):238-44.
    PMID: 23435855 DOI: 10.1007/s11626-012-9553-5
    Endothelial cells have been implicated as key cells in promoting the pathogenesis and spread of cytomegalovirus (CMV) infection. This study describes the isolation and culture of rat brain endothelial cells (RBEC) and further evaluates the infectious potential of a Malaysian rat CMV (RCMV ALL-03) in these cultured cells. Brain tissues were mechanically fragmented, exposed to enzymatic digestion, purified by gradient density centrifugation, and cultured in vitro. Morphological characteristics and expression of von Willebrand factor (factor VIII-related antigen) verified the cells were of endothelial origin. RBEC were found to be permissive to the virus by cytopathic effects with detectable plaques formed within 7 d of infection. This was confirmed by electron microscopy examination which proved the existence of the viral particles in the infected cells. The susceptibility of the virus to these target cells under the experimental conditions described in this report provides a platform for developing a cell-culture-based experimental model for studies of RCMV pathogenesis and allows stimulation of further studies on host cell responses imposed by congenital viral infections.
    Matched MeSH terms: Brain/pathology; Cytomegalovirus Infections/pathology; Endothelium, Vascular/pathology; Endothelial Cells/pathology
  20. Fulltext Autophagy is deregulated in cancer-associated fibroblasts from oral cancer and is stimulated during the induction of fibroblast senescence by TGF-β1
    Tan ML, Parkinson EK, Yap LF, Paterson IC
    Sci Rep, 2021 01 12;11(1):584.
    PMID: 33436723 DOI: 10.1038/s41598-020-79789-8
    Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.
    Matched MeSH terms: Carcinoma, Squamous Cell/pathology*; Fibroblasts/pathology*; Mouth Neoplasms/pathology*; Myofibroblasts/pathology
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