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1.  Presentation of solitary caecal diverticulitum imitating acute appendicitis 
BMJ Case Reports  2013;2013:bcr2013010228.
PMCID: PMC3736080  PMID: 23904424
2.  A rare occurrence and management of familial schwannomatosis 
BMJ Case Reports  2013;2013:bcr2013008843.
We are presenting a familial schwannomatosis without the features of neurofibromatosis (NF). We retrospectively reviewed the hospital charts, radiology films, operative notes and pathology slides of the patient. There was a family history of schwannomatosis. The patient had contrast-enhanced MRI, which was negative for vestibular schwannomas. The patient underwent surgical excision of symptomatic lesions. Histopathology confirmed these lesions as schwannomas consisting of areas of Antoni A and B, and immunohistochemical study was positive for S-100 protein. We recommend surgery for symptomatic lesions. Asymptomatic tumours can be monitored. Regular follow-up is essential as they may develop fresh lesions at any time. The relevant literature is discussed.
PMCID: PMC3645446  PMID: 23595180
3.  Evaluation of the efficacy of titanium plates as denture markers under various heat sources and pressure - An in vitro study 
Denture Markers are used as one of the main identifying aid in mass disasters. Dental description of missing person in mass disasters plays a vital role in forensic research. Difficulties arise when the teeth are missing. In such situation the prosthodontic identification (ID) of replaced teeth becomes the priority. Till recently, there was no development of denture marker that could withstand massive fire accidents.
To determine the use of titanium chips with identity code engraved on it as denture markers that could withstand high temperature and pressure.
Materials and Methods:
Wax patterns were fabricated with identity code moulded on a rubber stamp. It was invested and casted with titanium. Titanium chips were inserted into the polymethylmethacrylate (PMMA) block and subjected to various heat treatments.
There was no loss of identity when subjected to 1,500°C overnight but only residues left under pressure of 200 kg/cm3.
The literature recommends the metallic denture markers in order to withstand the post morten assaults. Titanium denture markers could be a preferred option as it can withstand high temperatures under pressure also.
PMCID: PMC4330621  PMID: 25709322
Denture markers; forensic odontology; personal identification; titanium
4.  Management of a xeroderma pigmentosum case with oral findings in a dental setup 
BMJ Case Reports  2012;2012:bcr2012007521.
Xeroderma pigmentosum (XP) is heterogeneous group of disorder transmitted as autosomal recessive trait. It is characterised by photosensitivity, freckled pigmentation and premature skin ageing and malignant tumour development. The manifestations are due to a cellular hypersensitivity to ultraviolet light resulting from a defect in DNA repair. Multiple cutaneous neoplasms develop at a young age in persons with XP. Two important causes of mortality are metastatic malignant melanoma and squamous cell carcinoma (SCC). We report a case of XP in a 22 year-old male patient who developed SCC of lower lip with in a short period of 1 month.
PMCID: PMC4543547  PMID: 23257645
5.  Molecular Genetics of the Usher Syndrome in Lebanon: Identification of 11 Novel Protein Truncating Mutations by Whole Exome Sequencing 
PLoS ONE  2014;9(9):e107326.
Usher syndrome (USH) is a genetically heterogeneous condition with ten disease-causing genes. The spectrum of genes and mutations causing USH in the Lebanese and Middle Eastern populations has not been described. Consequently, diagnostic approaches designed to screen for previously reported mutations were unlikely to identify the mutations in 11 unrelated families, eight of Lebanese and three of Middle Eastern origins. In addition, six of the ten USH genes consist of more than 20 exons, each, which made mutational analysis by Sanger sequencing of PCR-amplified exons from genomic DNA tedious and costly. The study was aimed at the identification of USH causing genes and mutations in 11 unrelated families with USH type I or II.
Whole exome sequencing followed by expanded familial validation by Sanger sequencing.
We identified disease-causing mutations in all the analyzed patients in four USH genes, MYO7A, USH2A, GPR98 and CDH23. Eleven of the mutations were novel and protein truncating, including a complex rearrangement in GPR98.
Our data highlight the genetic diversity of Usher syndrome in the Lebanese population and the time and cost-effectiveness of whole exome sequencing approach for mutation analysis of genetically heterogeneous conditions caused by large genes.
PMCID: PMC4161397  PMID: 25211151
6.  Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7 
To date, two maternal-effect genes have been shown to have causative roles in recurrent hydatidiform moles (RHMs); NLRP7 that is mutated in 48–60% of patients with RHMs and C6orf221 (HUGO-approved nomenclature is now KHDC3L), a recently identified gene, that is mutated in 14% of patients with RHMs who are negative for NLRP7 mutations. We sequenced KHDC3L in 97 patients with RHMs and reproductive loss who are mostly negative for NLRP7 mutations. We identified three unrelated patients, each homozygous for one of the two protein-truncating mutations, a novel 4-bp deletion resulting in a frameshift, c.299_302delTCAA, p.Ile100Argfs*2, and a previously described 4-bp deletion, c.322_325delGACT, p.Asp108Ilefs*30, transmitted on a shared haplotype to three patients from different populations. We show that five HM tissues from one of these patients are diploid and biparental similar to HMs from patients with two defective NLRP7 mutations. Using immunofluorescence, we show that KHDC3L protein displays a juxta perinuclear signal and colocalizes with NLRP7 in lymphoblastoid cell lines from normal subjects. Using cell lines from patients, we demonstrate that the KHDC3L mutations do not change the subcellular localization of the protein in hematopoietic cells. Our data highlight the similarities between the two causative genes for RHMs, KHDC3L and NLRP7, in their subcellular localization, the parental contribution to the HM tissues caused by them, and the presence of several founder mutations and variants in both of them indicating positive selection and adaptation.
PMCID: PMC3746251  PMID: 23232697
KHDC3L; 4-bp deletion; diploid biparental hydatidiform mole; NLRP7; colocalization
7.  Thoracic fetus in fetu 
A rare case of thoracic fetus in fetu is reported. Complete excision was curative.
PMCID: PMC3519000  PMID: 23243374
Fetus in fetu; teratoma; thoracic tumor
8.  Calcineurin signaling and PGC-1α expression are suppressed during muscle atrophy due to diabetes 
Biochimica et biophysica acta  2010;1803(8):960-967.
PGC-1α is a transcriptional coactivator that controls energy homeostasis through regulation of glucose and oxidative metabolism. Both PGC-1α expression and oxidative capacity are decreased in skeletal muscle of patients and animals undergoing atrophy, suggesting that PGC-1α participates in the regulation of muscle mass. PGC-1α gene expression is controlled by calcium- and cAMP-sensitive pathways. However, the mechanism regulating PGC-1α in skeletal muscle during atrophy remains unclear. Therefore, we examined the mechanism responsible for decreased PGC-1α expression using a rodent streptozotocin (STZ) model of chronic diabetes and atrophy. After 21d, the levels of PGC-1α protein and mRNA were decreased. We examined the activation state of CREB, a potent activator of PGC-1α transcription, and found that phospho-CREB was paradoxically high in muscle of STZ-rats, suggesting that the cAMP pathway was not involved in PGC-1α regulation. In contrast, expression of calcineurin (Cn), a calcium-dependent phosphatase, was suppressed in the same muscles. PGC-1α expression is regulated by two Cn substrates, MEF2 and NFATc. Therefore, we examined MEF2 and NFATc activity in muscles from STZ-rats. Target genes MRF4 and MCIP1.4 were both significantly reduced, consistent with reduced Cn signaling. Moreover, levels of MRF4, MCIP1.4, and PGC-1α were also decreased in muscles of CnAα-/- and CnAβ-/- mice without diabetes indicating that decreased Cn signaling, rather than changes in other calcium- or cAMP-sensitive pathways, were responsible for decreased PGC-1α expression. These findings demonstrate that Cn activity is a major determinant of PGC-1α expression in skeletal muscle during diabetes and possibly other conditions associated with loss of muscle mass.
PMCID: PMC2885580  PMID: 20359506
skeletal muscle; atrophy; calcineurin; PGC-1α; diabetes; streptozotocin
9.  Calcineurin A-β is required for hypertrophy but not matrix expansion in the diabetic kidney 
Calcineurin is an important signalling protein that regulates a number of molecular and cellular processes. Previously, we found that inhibition of calcineurin with cyclosporine reduced renal hypertrophy and blocked glomerular matrix expansion in the diabetic kidney. Isoforms of the catalytic subunit of calcineurin are reported to have tissue specific expression and functions. In particular, the β isoform has been implicated in cardiac and skeletal muscle hypertrophy. Therefore, we examined the role of calcineurin β in diabetic renal hypertrophy and glomerular matrix expansion. Type I diabetes was induced in wild-type and β−/− mice and then renal function, extracellular matrix expansion and hypertrophy were evaluated. The absence of β produced a significant decrease in total calcineurin activity in the inner medulla (IM) and reduced nuclear factor of activated T-cells (NFATc) activity. Loss of β did not alter diabetic renal dysfunction assessed by glomerular filtration rate, urine albumin excretion and blood urea nitrogen. Similarly, matrix expansion in the whole kidney and glomerulus was not different between diabetic wild-type and β−/− mice. In contrast, whole kidney and glomerular hypertrophy were significantly reduced in diabetic β−/− mice. Moreover, β−/− renal fibroblasts demonstrated impaired phosphorylation of Erk1/Erk2, c-Jun N-terminal kinases (JNK) and mammalian target of rapamycin (mTOR) following stimulation with transforming growth factor-β and did not undergo hypertrophy with 48 hrs culture in high glucose. In conclusion, loss of the β isoform of calcineurin is sufficient to reproduce beneficial aspects of cyclosporine on diabetic renal hypertrophy but not matrix expansion. Therefore, while multiple signals appear to regulate matrix, calcineurin β appears to be a central mechanism involved in organ hypertrophy.
PMCID: PMC3822805  PMID: 19778355
calcineurin; cyclosporine; diabetes; renal hypertrophy
10.  Phylogeography of mtDNA haplogroup R7 in the Indian peninsula 
Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic) speaking populations originated in India or derive from a relatively recent migration from further East.
Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of ~12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1), is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari) of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between genetic variation and geography, rather than between genes and languages.
Our high-resolution phylogeographic study, involving diverse linguistic groups in India, suggests that the high frequency of mtDNA haplogroup R7 among Munda speaking populations of India can be explained best by gene flow from linguistically different populations of Indian subcontinent. The conclusion is based on the observation that among Indo-Europeans, and particularly in Dravidians, the haplogroup is, despite its lower frequency, phylogenetically more divergent, while among the Munda speakers only one sub-clade of R7, i.e. R7a1, can be observed. It is noteworthy that though R7 is autochthonous to India, and arises from the root of hg R, its distribution and phylogeography in India is not uniform. This suggests the more ancient establishment of an autochthonous matrilineal genetic structure, and that isolation in the Pleistocene, lineage loss through drift, and endogamy of prehistoric and historic groups have greatly inhibited genetic homogenization and geographical uniformity.
PMCID: PMC2529308  PMID: 18680585

Results 1-10 (10)