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A Khanna

Publications and source records attributed to A Khanna.

At least 19 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&#xd7;10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25&#xd7;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↗
PubMed2006

Functional hepatocyte-like cells derived from mouse embryonic stem cells: a novel in vitro hepatotoxicity model for drug screening.

The aim of the present study was to differentiate mouse embryonic stem (mES) cells into a high percentage of hepatocyte-like cells, and to demonstrate their utility as an in vitro hepatotoxicity model. We were able to differentiate 80-90% of mES cells using optimized hepatocyte differentiation medium. These differentiated cells showed typical hepatocyte morphology, expressed hepatic specific genes as shown by RT-PCR and displayed antibody detectable expression of markers specific for hepatic maturation. These hepatocyte-like cells also demonstrated evidence of glycogen storage. These cells when exposed to CCl4, a commonly used hepatotoxicant, showed an elevation of liver function enzymes, SGOT, SGPT and LDH, indicating hepatic damage. Further, this increase was prevented by pre-treatment with N-acetylcysteine, a known anti-oxidant. Thus we propose that the hepatocyte-like cells derived by the present method may prove to be useful as an in vitro model of hepatotoxicity, thereby providing a novel and promising alternative for obtaining large numbers of functional hepatocyte-like cells for in vitro drug metabolism and hepatotoxicity screening of potential drug candidates.

Alanine Transaminase↗
PubMed2006

Can we rely on a general practitioner's referral letter to a skin lesion clinic to prioritize appointments and does it make a difference to the patient's prognosis?

INTRODUCTION: This study was designed to: (i) determine if the priority of referral letters by general practitioners to a plastic surgery skin lesion clinic adhered to the national guidelines, what happened to these patients, and what was the histological diagnosis; and (ii) analyse whether the prognosis at diagnosis of malignant melanoma had improved since the introduction of the 2-week wait for patients with suspected cancer. MATERIALS AND METHODS: The study involved a prospective audit questionnaire, retrospective note review and histology report review in the Plastic Surgery Department in a district general hospital and their 'bespoke' out-patient clinics. RESULTS: Of 202 referral letters, 58 (29%) were referred as 2-week cancer referrals of which 13 (22%) suggested diagnoses that did not fall within the guidelines, and 11 gave no diagnosis. In addition, 84 (42%) had no indication of priority, though the text may suggest the need for it, either explicitly or implied. The prognostic indices for malignant melanoma have not altered since the 2-week wait rule has been implemented. CONCLUSIONS: The guidelines are not being adhered to, thus patients with benign lesions are being given undue priority. The history and examination of skin lesions given in the referral letters is insufficient to allow the consultant to prioritize. Since the 2-week rule has be implemented, malignant melanomas have not been diagnosed at an earlier stage.

Appointments and Schedules↗
PubMed2005

Skeletal muscle metastasis from malignant melanoma.

Malignant melanomas commonly metastasise to skin, subcutaneous tissue and lymph nodes. Skeletal muscle metastases from malignant neoplasms are uncommon. There have been very few reports of malignant melanoma metastasising to skeletal muscle. We report a case of malignant melanoma metastasis in the thigh musculature in a young female patient.

Adult↗
PubMed2003

Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion.

Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined, 9 (azoospermia - 8 and oligoasthenospermia - 1) showed partial deletion of AZF. The size of deletion varied among patients but AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the genotype. The frequency of Y-chromosome microdeletion in our samples (approximately 5%) is much lower than the frequency (approximately 10%) reported globally and the two previous reports from India. We contend that the frequency may be affected by population structures in different geographical regions.

Biopsy↗
PubMed2003

Pericardial synovial sarcoma.

A 29-year-old young man presented with acute breathlessness. After investigative work-up he was found to have a massive pericardial tumour. Thoracotomy and near total surgical excision of the pericardial tumour was carried out. Histopathology and immunohistochemical markers study revealed it to be a synovial sarcoma arising from the left lateral pericardial surface. Postoperatively, he received external radiation and chemotherapy. Thirteen months after surgery he developed local recurrence which was unresectable.

Adult↗
PubMed2002

Effect of religious fasting on intra-ocular pressure.

AIM: The objective of this study was to find out the effect of religious fasting on intra-ocular pressure. METHODS: Intra-ocular pressure by applanation tonometer was measured four times a day in 38 healthy young adult male patients. The mean age of patients was 29 years. Body weight was measured to assess the extent of dehydration caused by fasting. RESULTS: There was a statistically significant difference between the intra-ocular pressure during fasting and the non-fasting period (P < 0.001). There was weight loss ranging from 0.4 to 1.5 kg. CONCLUSION: Fasting alters the diurnal intra-ocular pressure in the study population, ie young males 22-38 years.

Adult↗
PubMed2002

Intravaginal foreign body--a rare cause of large bowel obstruction.

Intravaginal foreign body rarely causes bowel obstruction. A 60-year-old female presented with pain in lower abdomen. On examination, her abdomen was found distended with muscle guard. Per rectal examination revealed a hard mass 3-4 cm away from the anal verge. There was leucocytosis and straight x-ray showed features of large bowel obstruction. Exploratory laparatomy was performed. The large bowel was distended with a hard mass felt in the pelvis. On manipulation the mass of about 15 cm x 12 cm x 12 cm size came out of the vagina and it happended to be a brick. The recovery was uneventful.

Female↗
PubMed2001

The role of transforming growth factor-beta in the modulation of mouse cranial suture fusion.

Transforming growth factor-beta (TGF-beta) is actively expressed during mouse calvarial suture fusion. However, the role TGF-beta plays in this process remains unclear. The present study was performed to investigate whether modulation of suture fusion can be achieved by blocking the bioavailability of TGF-beta. Both in vitro and in vivo models were studied. For the in vitro model, the posterior frontal sutures from 24-day-old mice were harvested and cultured for 2, 3, or 4 weeks in the presence of 20 microg/ml of pan-specific TGF-beta polyclonal antibody or rabbit IgG as a control. Culture media were changed every 48 hours and fresh antibody or rabbit IgG was added during each media change. Suture fusion was evaluated by histometric analysis. For the in vivo model, TGF-beta antisense plasmid DNA complexed with lipofectamine was injected into the subgaleal layer along the frontal suture of 22-day-old mice under anesthesia. For control groups, empty vector plasmid DNA+ complexed with lipofectamine was used. The posterior frontal sutures were harvested at various time points and examined by histometric analysis and reverse transcription and polymerase chain reaction for the detection of messenger RNA. The in vitro studies demonstrated that the presence of TGF-beta antibody in culture media delayed posterior frontal suture fusion. By 3 weeks in culture, new bone area was only 20 percent of that in control groups as determined by histometric analysis. By the end of the fourth week, suture fusion was only 25 percent completed compared with controls. The in vivo studies demonstrated that, compared with the control, posterior frontal suture fusion was significantly delayed in the animals injected with antisense plasmid DNA. Suture fusion was complete in control animals by postnatal day 45. There was a 70 percent inhibition of suture fusion (new bone area) in antisense groups measured with histometric analysis. Four days after antisense plasmid DNA injection (age of 26 days), messenger RNA expression for TGF-beta 1 was 77 percent lower than in the control group. We have demonstrated that modulation of TGF-beta affects calvarial suture formation in vitro and in vivo with TGF-beta antibody and TGF-beta1 antisense plasmid DNA treatment, respectively. These data indicate that TGF-beta may play a causative role in mouse posterior frontal suture fusion. Modulation TGF-beta 1 gene expression in vivo can alter the natural history of cranial suture fusion.

Animals↗
PubMed2001

DNA image analysis combined with routine cytology improves diagnostic sensitivity of common bile duct brushing.

BACKGROUND: Cytologic evaluation of common bile duct brushings has a low sensitivity for diagnosing malignancy because of scant cellularity, poor cellular preservation, or sampling errors occur. The aim of this study was to evaluate whether cytology combined with image analysis improves the diagnostic accuracy of bile duct brushing in comparison with cytology alone. METHODS: Forty-nine specimens of bile duct brushings obtained from 45 patients during endoscopic retrograde cholangiopancreatography were evaluated using cytology and image analysis. Specimens were classified as negative, atypical, suspicious, or malignant by using cytologic evaluation. DNA histograms were classified as diploid (D), broad diploid (BD), aneuploid (A), or tetraploid (T). Degree of hyperploidy (DH), representing cells with a DNA content > 5C was evaluated using a cutoff value of > or = 1%. Final diagnosis of cancer was based on tissue specimens that were obtained by fine-needle aspiration or surgical biopsy and clinical fol- low-up. RESULTS: Thirty-four patients ultimately proved to have a malignancy. Cytology revealed 19 negative cases, 15 atypical cases, 9 suspicious cases, and 6 malignant cases. Together, suspicious and malignant cytology cases yielded a sensitivity of 44% and a specificity of 100% for a cytologic diagnosis of cancer. The DNA histogram pattern was D in 24 cases, BD in 9 cases, and A in 16 cases. BD and A patterns were significantly associated with malignancy (P < 0.001). A DH > or = 1% was noted in 22 cases. DH alone had a sensitivity of 62% and a specificity of 91% and was significantly associated with malignancy (P < 0.004). Atypical cytology alone had a false-negative rate of 29%, but in combination with a DH > or = 1%, the false-negative rate decreased to 7%. Additionally, when the authors combined atypical, suspicious, and malignant cytology with a DH > or = 1%, the diagnostic sensitivity increased to 88%, but the specificity decreased to 73%. CONCLUSIONS: Combined cytology and image analysis of bile duct brushing increased diagnostic sensitivity compared with cytology alone. The findings suggest that image analysis may help select patients having atypical cytology who should undergo a more rigorous evaluation for malignancy. A larger prospective study of the usefulness of combined cytology and image analysis of bile duct brushing is warranted.

Adult↗
PubMed2001

Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation.

BACKGROUND: The adoption of calcineurin inhibitors (CNI) as the mainstay of immunosuppression has resuited in a significant decrease of acute rejection and improvement of short-term graft survival. However, because of the irreversible nephrotoxicity associated with the chronic use of the CNI, the magnitude of the improvement of long-term graft survival has been more modest. Therefore, an effective immunosuppression regimen that does not rely on CNI may result in improvement of long-term outcome and simplification of the management of transplant recipients. METHODS: Ninety-eight patients of primary cadaver or living donor kidneys at low immunologic risk were enrolled in a CNI avoidance study. The immunosuppression regimen consisted of daclizumab, a humanized monoclonal antibody that binds to the alpha chain of the interleukin-2 receptor (IL-2Ralpha), administered for a total of five doses at biweekly intervals; 3 gm/day mycophenolate mofetil for the first 6 month and 2 gm thereafter; and conventional corticosteroid therapy. Patients who underwent rejection episodes could be started on CNI. The primary efficacy end-point was biopsy-proven rejection during the first 6 months posttransplant. RESULTS: Biopsy-proven rejection was diagnosed in 48% of patients during the first 6 months after transplantation. The majority of rejection episodes were Banff grade I and IIA and were fully reversed with corticosteroid therapy. The median time to the first biopsy-proven rejection among patients who experienced this event during the first 6 months was 39 days. In 22 patients with delayed graft function, the proportion of patients with biopsy-proven rejection was 50% at 6 months. However in the first 2 weeks posttransplant, only 1 of 22 patients with delayed graft function developed biopsy-proven rejection. At 1 year, patient survival was 97% and graft survival was 96%. Only two grafts were lost secondary to rejection. At 1-year posttransplant, 62% of patients had received CNI for more than 7 days. At 1-year posttransplant, the mean serum creatinine in the nonrejectors with no CNI use was 113 micromol/L (95%, confidence interval [CI], 100.7 to 125.3 micromol/L) and in the rejectors or patients with CNI use (more than 7 days) was 154 micromol/L (95% CI, 135.0 to 173.0 micromol/L). In selected patients with rejection, analysis of circulating and intragraft lymphocytes revealed complete IL-2Ralpha saturation. CONCLUSIONS: This CNI avoidance study in immunologic low-risk patients, while only partially successful in preventing acute rejection, provided benefits to a sizable minority of patients who have not required chronic CNI therapy. However, wide acceptance of a CNI-sparing immunosuppression regimen may require a lower rate of acute rejection, possibly through the addition of a non-nephrotoxic dose of CNI. However, because complete IL-2Ralpha blockade was present during rejection, it can be assumed that alternative pathways, such as IL-15, may be responsible for the rejection; thus, the incorporation of non-nephrotoxic immunosuppressive agents, such as sirolimus, may provide a more strategic approach.

Antibodies, Monoclonal↗