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Harshwardhan M Thaker

Publications and source records attributed to Harshwardhan M Thaker.

14 recordsLinked to original sources
PubMed2006

Prenatal diagnosis of glycogen storage disease type IV.

BACKGROUND: Glycogen storage disease type IV (GSD-IV) is a rare autosomal recessive disorder due to mutations in the GBE1 gene causing deficiency of the glycogen branching enzyme (GBE). Prenatal diagnosis has occasionally been performed by the measurement of the GBE activity in cultured chorionic villi (CV) cells. METHODS: Two unrelated probands with severe hypotonia at birth and death during the neonatal period were diagnosed with GSD-IV on the basis of postmortem histological findings. DNA analysis revealed truncating GBE1 mutations in both families. RESULTS: Prenatal diagnosis was performed in subsequent pregnancies by determination of branching enzyme activity and DNA analysis of CV or cultured amniocytes. Detailed autopsies of the affected fetuses at 14 and 24 weeks of gestation demonstrated intracellular inclusions of abnormal glycogen characteristic of GSD-IV. CONCLUSION: Prenatal diagnosis of GSD-IV by DNA analysis is highly accurate in genetically confirmed cases.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2006

Antenatal sonographic prediction of twin chorionicity.

OBJECTIVE: We sought to determine the accuracy of antenatal diagnosis of twin chorionicity at a single tertiary care center and assess the consequences of incorrect diagnoses. STUDY DESIGN: Twins with chorionicity diagnosed by ultrasound < or = 24 weeks' gestation were retrospectively reviewed. Chorionicity was assigned by sonographic findings including placental location(s), the lambda and T-signs, and/or fetal gender(s). Postnatal diagnosis was determined by placental histopathologic examination. Medical records of antenatal-postnatal discordant chorionicities were reviewed for adverse sequelae. RESULTS: Chorionicity was correctly assigned antenatally in 392/410 (95.6%) twins. The sensitivity, specificity, and positive and negative predictive values of monochorionicity assessed < or = 14 weeks were 89.8%, 99.5%, 97.8%, and 97.5%. Corresponding statistical values for the second trimester were 88.0%, 94.7%, 88.0%, and 94.7%. Two cases of inaccurate antenatal diagnoses affected patient counseling or were associated with adverse clinical outcomes. CONCLUSION: Antenatal assessment of chorionicity is accurate; however, incorrect diagnoses do occur and can affect reliable patient counseling and management.

Chorion↗
PubMed2005

Alpha-thalassemia major presenting in a term neonate without hydrops.

We describe the clinical and pathologic features of an unusual case of alpha-thalassemia major in a patient who survived to term and lived for 9 days. The neonate was nonhydropic and the clinical picture was dominated by severe hypoxia with pulmonary hypertension. The diagnosis was not suspected until postnatal examination of the blood smear, which prompted the performance of hemoglobin electrophoresis and subsequent molecular confirmation. This case illustrates that alpha-thalassemia major should be in the differential diagnosis of hypoxic neonates even in the absence of hydrops.

Diagnosis, Differential↗
PubMed2004

Divided left atrium with obstruction of pulmonary venous return in the setting of hypoplasia of the left heart.

We describe an infant with hypoplasia of the left heart diagnosed prenatally who, at birth, had signs of severe pulmonary venous obstruction. Echocardiography indicated normally connecting pulmonary veins, and showed a paradoxical right-to-left shunt across a patent oval foramen. Postmortem examination revealed that the obstruction was due to a divided left atrium, or cor triatriatum sinister, with an imperforate muscular diaphragm separating completely the two components of the divided atrium.

Cor Triatriatum↗
PubMed2004

Complete hydatidiform mole retaining a chromosome 11 of maternal origin: molecular genetic analysis of a case.

Hydatidiform moles are pregnancies characterized by abnormal development of both embryonic and extraembryonic tissues and are associated with the misexpression of imprinted genes. The vast majority of complete hydatidiform moles are diploid and androgenetic, whereas partial hydatidiform moles are triploid, with an extra set of chromosomes of paternal origin. Here, we present an unusual complete mole that showed strong expression of two imprinted, maternally transcribed genes, CDKN1C (encoding p57(KIP2)) and PHLDA2 (TSSC3/IPL), both part of a large imprinted gene domain on chromosome 11. Using microsatellite genotyping and fluorescent in situ hybridization, we show that this paradoxical gene expression was due to retention of a maternal copy of chromosome 11 in addition to the two paternal copies normally present in complete moles. These findings demonstrate that, despite being predominantly androgenetic, some complete moles contain small amounts of DNA of maternal origin. Furthermore, these results provide an explanation for rare false negatives that can arise when p57(KIP2) is used as a diagnostic marker for complete moles.

Adult↗
PubMed2004

Simvastatin preserves cardiac function in genetically determined cardiomyopathy.

Endothelial dysfunction characterizes heart failure (HF). Simvastatin (Sim) increases endothelial nitric oxide (NO) independent of lipid-lowering. We evaluated the effect of Sim on cardiac function, apoptosis, and NO availability in HF. Five-month-old cardiomyopathic (CM) hamsters were divided into 2 groups: Sim (20 mg/kg, 6 weeks, n = 6) and Untreated (n = 6). Age-matched normal hamsters served as controls (n = 6). Serial echocardiograms were performed to measure LV function. Myocardial apoptosis, eNOS, and capillary density were measured at 6 weeks. Cardiomyopathic hamsters had lower LV shortening fraction (SF) compared with controls (17 +/- 3% vs 59 +/- 2%), higher LV end-diastolic volume (30 +/- 3 vs 6 +/- 2 mL/m2), and lower LV mass/volume ratio (0.5 +/- 0.04 vs 0.72 +/- 0.02 mg/ml, P < 0.001). During follow-up, SF decreased (9 +/- 2%) and LV volume increased (38 +/- 1 mL/m2) in untreated hamsters (P < 0.05 from baseline) but did not change significantly in the Sim group (P < 0.05 vs untreated). Myocardial caspase-3 activity was higher and apoptotic nuclear density was lower in Sim compared with untreated CM hamsters (0.072 +/- 0.02% vs 0.107 +/- 0.03%, P < 0.01). Myocardial capillary density was highest in the Sim group (P < 0.05). eNOS expression was not different between groups. Sim retards the progression of HF in CM hamsters. This may be related to an increase in coronary microvasculature, increase in NO availability, and decreased apoptosis.

Angiogenesis Inducing Agents↗
PubMed2004

Immunohistochemistry for the imprinted gene product IPL/PHLDA2 for facilitating the differential diagnosis of complete hydatidiform mole.

OBJECTIVE: To determine if immunohistochemistry for PHLDA2 (also known as IPL and TSSC3), the product of a paternally imprinted, maternally expressed gene, can be used as a tool in the differential diagnosis of molar gestations. STUDY DESIGN: Twenty-five cases (15 complete moles, 5 partial moles and five hydropic abortions) were stained by immunohistochemistry for PHLDA2 and scored (without knowledge of the diagnosis) for positivity in the villous cytotrophoblast and then compared to adjacent sections stained by p57KIP2 immunohistochemistry. RESULTS: All partial moles and hydropic abortions were positive for PHLDA2 and p57KIP2. There was strong PHLDA2 staining of the cytoplasm in virtually all cells of the villous cytotrophoblast, while p57KIP2 was localized to the nucleus in a subset of those cells. All complete moles were negative for both markers in the villous cytotrophoblast. CONCLUSION: Immunohistochemistry for PHLDA2 serves as a practical and reliable diagnostic marker for the discrimination of complete mole from partial mole and hydropic abortion. Since the immunohistochemical diagnosis of complete mole is based on a negative result, absence of staining, the use of both markers (PHLDA2 and p57KIP2) together could increase the level of confidence when making this prognostically important distinction.

Biomarkers, Tumor↗
PubMed2003

Transgenic mouse model for echovirus myocarditis and paralysis.

Echoviruses have been implicated in multiple human disease syndromes, including aseptic meningitis, paralysis, and heart disease, but no animal model is available for studying the pathogenesis of infection. Production of human integrin very late antigen 2, a receptor for echovirus type 1, in transgenic mice conferred susceptibility to viral infection. Intracerebral inoculation of newborn transgenic mice with echovirus leads to paralysis and wasting. No disease was observed in infected nontransgenic mice. In paralyzed mice significant damage was observed in the outer layers of the cerebrum, and numerous condensed neuronal nuclei were present. In contrast, intracerebral inoculation of adolescent (3- to 4-week-old) transgenic mice with echovirus type 1 did not lead to paralysis but an acute wasting phenotype and myocarditis. These findings establish human very late antigen 2 transgenic mice as a model for echovirus pathogenesis.

Aging↗
PubMed2003

Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue.

Human and mouse paralogues of the evolutionarily conserved mammalian HRAD9 and Mrad9 cell cycle checkpoint control genes have been isolated and called HRAD9B and Mrad9B, respectively. HRAD9B encodes a protein that is 414 amino acids long and is 55% similar and 35% identical to the HRAD9 gene product. The Mrad9B protein is 398 amino acids long and is 50% similar and 35% identical to its paralogue. We demonstrate that the encoded human protein is nuclear and can physically interact with checkpoint proteins HRAD1, HRAD9, HHUS1, and HHUS1B, much like HRAD9. Northern blot analysis to detect tissue specificity indicates that the human and mouse genes are expressed predominantly in the testis. The abundance of HRAD9B RNA, as judged by quantitative reverse transcription-PCR, is very low in most testicular tumors, particularly those of germ cell origin, i.e., seminomas, relative to normal testis control, nonseminomas, or Leydig tumor cells. RNA levels corresponding to HRAD17, another checkpoint control gene, demonstrated a similar pattern, but in general, higher quantities of this message were detected in samples. Furthermore, normal/tumor tissue differences were not as dramatic or consistent from sample to sample, especially for the seminomas. Our results demonstrate for the first time that HRAD9 and Mrad9 are part of a gene family and reveal a new genetic element encoding a product that interacts with multiple, known cell cycle checkpoint control proteins. The findings also indicate that HRAD9B can serve as a biomarker in particular for testicular seminomas and might be causally related to the disease.

Amino Acid Sequence↗
PubMed2003

Foamy podocytes.

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed2002

Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition.

Wilms' tumor (WT) has been considered a prototype for arrested cellular differentiation in cancer, but previous studies have relied on selected markers. We have now performed an unbiased survey of gene expression in WTs using oligonucleotide microarrays. Statistical criteria identified 357 genes as differentially expressed between WTs and fetal kidneys. This set contained 124 matches to genes on a microarray used by Stuart and colleagues (Stuart RO, Bush KT, Nigam SK: Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci USA 2001, 98:5649-5654) to establish genes with stage-specific expression in the developing rat kidney. Mapping between the two data sets showed that WTs systematically overexpressed genes corresponding to the earliest stage of metanephric development, and underexpressed genes corresponding to later stages. Automated clustering identified a smaller group of 27 genes that were highly expressed in WTs compared to fetal kidney and heterologous tumor and normal tissues. This signature set was enriched in genes encoding transcription factors. Four of these, PAX2, EYA1, HBF2, and HOXA11, are essential for cell survival and proliferation in early metanephric development, whereas others, including SIX1, MOX1, and SALL2, are predicted to act at this stage. SIX1 and SALL2 proteins were expressed in the condensing mesenchyme in normal human fetal kidneys, but were absent (SIX1) or reduced (SALL2) in cells at other developmental stages. These data imply that the blastema in WTs has progressed to the committed stage in the mesenchymal-epithelial transition, where it is partially arrested in differentiation. The WT-signature set also contained the Wnt receptor FZD7, the tumor antigen PRAME, the imprinted gene NNAT and the metastasis-associated transcription factor E1AF.

Adenovirus E1A Proteins↗
PubMedDate not supplied

Ascending aortic aneurysm in a fetus due to a benign nodular myofibroblastic lesion.

A fetal echocardiogram at 20 weeks of gestation revealed a large ascending aortic aneurysm in the presence of a normal aortic root and normal intracardiac anatomy. No other abnormalities were noted in the fetus. Upon termination of pregnancy, histopathological examination revealed an isolated benign nodular myofibroblastic lesion of likely hamartomatous origin, a first description of such pathology contributing to the formation of an aneurysm in the ascending aorta.

Adult↗