Biomedical subjects

P Shrestha

Publications and source records attributed to P Shrestha.

6 recordsLinked to original sources

PubMed2026

Genomic basis of developmental defects of enamel and sex-specific effects.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3-5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5×10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25×10 9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2x10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

developmental defects of enamel↗

PubMed1992

Proliferating cell nuclear antigen in malignant and pre-malignant lesions of epithelial origin in the oral cavity and the skin: an immunohistochemical study.

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S phase of the cell cycle and immunohistochemical detection of the protein represents a useful marker for the proliferating fraction of cells in tissue specimens. A series of malignant and pre-malignant lesions of the oral cavity and skin were evaluated by the streptavidin biotin immunoperoxidase method for detection of this protein. Monoclonal anti-PCNA antibody (PC 10) labelled proliferating cells in all cases with varying intensity of nuclear staining. In squamous cell carcinoma (n = 48), PCNA positivity correlated with the differentiation and atypia of the tumour cells; however, in poorly differentiated tumours, the relationship between PCNA expression and proliferation was lost. Basal cell carcinoma showed an increased growth fraction in tiny epithelial nests (mean 43.8, SD 6.0, n = 20) than in neoplastic basal cells (mean 30.1, SD 6.9, n = 8). The growth fractions were significantly higher in the pre-malignant lesions (leukoplakia, mean 22.3, SD 7.7, n = 14; Bowen's disease, mean 45.2, SD 11.7, n = 12; senile keratosis, mean 41.2, SD 7.0, n = 12) than in the normal mucosa (mean 9.8, SD 4.9, n = 10), suggesting that cellular growth fractions correlate with the degree of dysplasia in pre-malignant lesions.

Antibodies, Monoclonal↗

PubMed1992

Proliferating cell nuclear antigen in breast lesions: correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer.

Monoclonal anti-proliferating cell nuclear antigen (PCNA PC10), which is directed against a 36 kDa auxiliary protein for DNA polymerase delta specific for the S-phase of cell cycle, was used to measure tumour cell proliferation in 4 lactating breasts and 98 benign and malignant breast tumours. The percentage of PCNA-positive cells determined by point counting was significantly lower in the lactating breast [mean 3.6%, standard deviation (SD) 0.67, n = 5] than in fibroadenoma and mastopathy (mean 23.7, SD 5.0, n = 2). Primary breast carcinoma showed a PCNA index ranging from 2% to 36% (mean 12.3, SD 9.3, n = 50), whereas in recurrent carcinoma the index was mean 28.5, SD 4.0. A high index was correlated with c-erbB-2 and epidermal growth factor (EGF) receptor membrane reactivity, worsening histological grade, poor survival and disease-free survival. The expression of c-erbB-2 and EGF receptor was associated with poor survival and disease-free survival in primary breast cancer patients.

Breast Neoplasms↗

PubMed1992

Rare expression of the c-erbB-2 oncoprotein in salivary gland tumors: an immunohistochemical study.

An immunohistochemical study of c-erbB-2 oncoprotein expression was carried out on 201 cases of primary salivary gland tumors, using a polyclonal antibody, raised to the intracytoplasmic domain of the c-erbB-2 oncogene product. An intense membrane reactivity was observed in one case of sialocarcinoma transformed from pleomorphic adenoma (n = 8) and one case of mucoepidermoid carcinoma (n = 22). A comparative histopathologic evaluation of c-erbB-2 positive tumors showed marked variation in cell size, nuclear pleomorphism, multinucleation, a high mitotic rate and increased lymphoid cell infiltration and an aggressive clinical course with poor survival. The results indicate that c-erbB-2 oncoprotein is rarely expressed in malignant salivary gland tumors. However, the overexpression appears to have a distinct histopathologic feature, but a larger study incorporating histopathology and clinical data would be necessary to correlate the significance of c-erbB-2 oncogene product in salivary malignant tumors.

Adenolymphoma↗

PubMed1992

Epidermal growth factor receptor in odontogenic cysts and tumors.

The expression of epidermal growth factor receptor (EGFR) was investigated in 67 cases of odontogenic cysts and 35 cases of odontogenic tumors using monoclonal antibody to EGFR (Biomarker, Israel) to determine the presence and significance of this transmembrane growth factor receptor. The cystic epithelial cells of odontogenic cystic lesions (keratocyst 60%; primordial cyst 75%; radicular cyst 35%; and follicular cyst 47.4%) were positive to EGFR staining. Cytochemical characterization of EGFR in those cystic epithelium was cell membrane positive type as in the normal epithelium. No expression of EGFR was found in the odontogenic tumors. This diversity of EGFR represents no binding activity of EGF, or loss of EGFR in the tumor cell upon EGFR mediated growth in odontogenic tumors was suggested a different tumor cell growth factor status or microenvironment in cell proliferation mechanism at the cellular level in cysts and tumors of odontogenic origin.

Ameloblastoma↗

PubMed1991

Ameloblastoma--a clinical study of 13 cases.

Ameloblastoma is commonly encountered odontogenic tumour in Bangladesh. A clinical assessment of this tumour is presented in this paper with the particular attention to its age, and sex incidence, clinical presentation, and its management. Complete removal of the neoplasm is the treatment of choice regardless the method of accomplishment to obtain complete cure. Small lesion, particularly in young patients may by given chance to be managed by enucleation and curettage exposing the healthy surrounding tissue. However radical resection of the tumour is the most efficient treatment particularly in large tumours to avoid recurrence.

Adolescent↗