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Biomedical subjects

Y M D Lo

Publications and source records attributed to Y M D Lo.

9 recordsLinked to original sources

Recent developments in fetal nucleic acids in maternal plasma: implications to noninvasive prenatal fetal blood group genotyping.

The discovery of circulating cell-free fetal DNA in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. Fetal DNA in maternal plasma has been used for the noninvasive prenatal determination of the RhD status of fetuses carried by RhD-negative pregnant women. In such analysis, the possible need of an internal control for the presence of detectable amounts of fetal DNA in a particular maternal plasma sample has been actively discussed. Recently, the development of a robust method for discriminating single nucleotide differences in plasma DNA using single allele base extension reaction (SABER) followed by matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) has opened up the possibilities of using a panel of single nucleotide polymorphisms as such a positive control. A second approach is the recent successful development of fetal epigenetic markers which can be developed into universal fetal DNA markers. These developments hold promise to allow the eventual widespread utilization of maternal plasma DNA analysis for the noninvasive prenatal diagnosis of blood group mismatches between the mother and fetus.

Blood Group Antigens↗

Nuclear beta-catenin and Ki-67 expression in choriocarcinoma and its pre-malignant form.

OBJECTIVE: To study the expression of nuclear beta-catenin and Ki-67 in patients with normal gestation products (NGP), complete hydatidiform moles (CHM), and choriocarcinoma to elucidate their roles in carcinogenesis and their interrelations. METHODS: Expression of nuclear beta-catenin and Ki-67 was studied by immunohistochemistry using paraffin embedded blocks. Sixty NGP, 60 CHM, and 10 choriocarcinomas were analysed. In addition, approximately 400 trophoblasts each in 40 NGP, 40 CHM, and 10 choriocarcinomas from the same batch of samples were microdissected for quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) to compare beta-catenin mRNA concentration among them. RESULTS: In the chorionic villi of NGP, beta-catenin was consistently expressed in the nuclei of cytotrophoblasts but not syncytiotrophoblasts. Nuclear beta-catenin expression was comparatively reduced in CHM trophoblasts and was absent in choriocarcinoma. By contrast, Ki-67 expression was increased from cytotrophoblasts but not in syncytiotrophoblasts in the chorionic villi of NGP to CHM trophoblasts and choriocarcinoma. Using Q-RT-PCR, beta-catenin mRNA was detected in 10 NGP, 13 CHM, and three choriocarcinoma specimens, with median copy numbers of 43,230, 18,229, and 17,334 per 400 trophoblasts, respectively. A housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was detected as a control in the NGP, CHM, and choriocarcinoma specimens, with median copy numbers of 51,300, 54,270, and 97,150 per 400 trophoblasts, respectively. Thus median beta-catenin mRNA values after normalisation were 0.85 in NGP (n = 10), 0.31 in CHM (n = 13), and 0.16 in choriocarcinoma (n = 3). CONCLUSIONS: Decreased nuclear beta-catenin expression and increased Ki-67 expression may be involved in choriocarcinoma carcinogenesis. The findings also suggest that nuclear beta-catenin may play a role in trophoblast differentiation during normal placental development.

Biomarkers, Tumor↗

Evidence of circulating donor genetic material in bone allotransplantation.

Musculoskeletal allotransplantion is the most common form of human tissue transplantation. Unlike solid organ transplants, bone allotransplants undergo rigorous processing and are considered non-viable tissue. In this study, we propose that donor genetic material may exist in circulation after bone allotransplantation. Fifty-one female patients who received bone allotransplants from male donors were assessed. Blood plasma samples were analyzed using real-time quantitative polymerase chain reaction (PCR) with dual labeled fluorogenic probes for the presence of the SRY gene on the Y chromosome. Of the total 51 patients, the SRY sequence was detected in 6 patients. Five were positive at day 1 postoperatively and negative thereafter, with the remaining patient positive at 3 months post-transplantation. Our results document, for the first time, the presence of donor DNA in the circulation of recipients after bone allotransplantation. Our findings suggest a potential new investigative tool to assess the postoperative status of bone allotransplants.

Bone Remodeling↗

Circulating nucleic acid analysis: diagnostic applications for acute pathologies.

Much research interest has been shown in recent years for the development of molecular diagnostic strategies based on the analysis of DNA/RNA molecules that are present in the plasma/serum of human subjects. Reported applications include the diagnosis, prognostication or monitoring of malignancies and pregnancy-associated complications. While researchers have speculated that cell death is a potential mechanism that leads to the release of DNA/RNA into the circulation, studies have demonstrated that indeed increased amounts of plasma DNA and RNA could be detected in patients sustaining acute traumatic injuries. The degree of plasma DNA elevation correlated with the severity of injury. Similarly, plasma DNA concentrations have been shown to correlate with indices of prognostic significance in patients with acute stroke. It is expected that new diagnostic markers based on plasma RNA detection could be developed for the evaluation of acute pathologies.

Animals↗

Nuclear beta-catenin expression is rare and its potential association with short survival in colorectal signet-ring cell carcinoma.

Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer and the prognosis is usually very poor. The biologic pathways involved in its oncogenesis are unknown. beta-catenin, a key target in the Wnt-signaling pathway, is recognized to play an important role in the carcinogenesis in conventional colorectal carcinoma. This study explores the involvement of Wnt-signaling molecules beta-catenin and cyclin D1, cell cycle regulators cyclin D3, proliferative index Ki-67, apoptotic index, and angiogenic indicator CD31 in 20 colorectal SRCC paraffin-embedded specimens. Results showed that there were 2 specimens with nuclear beta-catenin and higher expression of cyclin D1 than the remaining 18 specimens. Surprisingly, those 2 patients had a much shorter survival of 6 months than the remaining 15 patients, who had around 24 months. Moreover, all colorectal SRCC specimens had an overexpression of cyclin D1, cyclin D3, and Ki-67, as well as much more angiogenesis and apoptosis than adjacent normal epithelial tissues. The authors make the preliminary comment that nuclear beta-catenin is a rare phenomenon in colorectal SRCC, but the involvement of it may indicate a worse prognosis with shorter survival than colorectal SRCC without nuclear beta-catenin expression. Besides, overexpression of cyclin D1, cyclin D3, Ki-67, and increased angiogenesis and apoptosis may play a vital role in promoting colorectal SRCC development.

Apoptosis↗

Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR.

The purpose of this study was to quantify the level of serum DNA in different groups of primary breast cancer patients and in healthy controls using real-time quantitative PCR in order to determine whether such measurements have diagnostic or prognostic value. A total of 96 serum samples of patients with primary breast cancer before surgery (with positive or negative lymph nodes and with high or low relapse-free survival) as well as 24 healthy controls were analysed. DNA concentrations in the serum of the patients differed significantly from the concentration of serum DNA in the controls (medians were 221 and 63 ng x ml(-1), respectively, P<0.001 M-W test). However, no statistically significant difference was observed between the patient groups (P=0.87, M-W test). The serum DNA levels were elevated independently of the size of primary tumour or lymph node metastases. The overall survival of patients with serum DNA concentrations >221 ng x ml(-1) was better than patients with serum DNA concentration <or=221 ng ml(-1) (Kaplan-Meier, P=0.028).

Adult↗

Genomic characterisation of the severe acute respiratory syndrome coronavirus of Amoy Gardens outbreak in Hong Kong.

Severe acute respiratory syndrome (SARS) is a global health concern. In Hong Kong, two major outbreaks, one hospital based and the other in the Amoy Gardens apartments, were identified. The frequency of diarrhoea, admission to intensive care, and mortality differed significantly between the two outbreaks. We did genomic sequencing for viral isolates from five Amoy Gardens patients. The virus sequence was identical in four of these five patients. The sequence data from one hospital case and the four identical community cases had only three nucleotide differences. Alterations in the SARS coronavirus genome are unlikely to have caused the distinctive clinical features of the Amoy Gardens patients, and these results highlight the importance of non-viral genomic factors in this outbreak.

Base Sequence↗

Circulating nucleic acids as a tumor marker.

Patients suffering from malignant diseases have been shown to have increased amounts of cell free nucleic acids in their circulation. As genetic and epigenetic alterations are increasingly characterized in different types of tumors, such changes can be used to detect tumor-derived nucleic acids in the circulation. To date, nearly all tumor-associated nucleic acids have been detected in the plasma or serum of cancer patients. Moreover, increased levels of circulating viral nucleic acids have also been demonstrated in patients with certain cancers associated with viral infections. The concentration of these tumor-associated nucleic acid species is generally related to the tumor load and the extent of the disease. Serial monitoring of plasma nucleic acids thus provides a good way to follow disease progress and to predict the outcome of such patients. In this review, different approaches of detecting tumor-related nucleic acids in the circulation and their potential as tumor markers in the screening, monitoring and prognostication of malignant diseases are discussed.

Biomarkers, Tumor↗