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Edward L Chan

Publications and source records attributed to Edward L Chan.

9 recordsLinked to original sources
PubMed2007

Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant progression in a murine model of skin carcinogenesis.

Mice with conditional gene deletions have been extremely valuable in allowing investigators to study the genes of interest in a tissue-specific manner. The Cre-loxP recombination system provides a powerful tool to produce targeted rearrangements of particular genes. The keratin 5-Cre recombinase (K5Cre) transgenic mouse line has been used to generate skin specific gene deletions. We found that the K5Cre mice display a unique phenotype when bred to homozygosity. The K5Cre(+/+) mice have a wavy hair coat and curly whiskers. Histologically, the hair follicles appear disoriented. Over time, the K5Cre(+/+) mice develop patches of alopecia. These mice are also runted when compared to wild-type controls. Fostering the K5Cre(+/+) pups to wild-type mothers results in normal weight gain, suggesting a maternal defect in milk production. When the K5Cre(+/+) mammary glands were examined, we not only found a significant decrease in the number of mammary branches in the virgin females, but also a greater number of quiescent alveoli units in the lactating glands. When the K5Cre(+/+) mice were bred to v-Ha-ras (Tg . AC) transgenic mice, the resulting Tg . AC(+/-) K5Cre(+/+) offspring were utilized in a chemically induced skin carcinogenesis model. The mice were treated with 2.5 microg of 12-O-tetradecanoylphorbol-13-acetate (TPA) weekly for 10 wk. No difference was observed in the time to onset of papilloma formation, the number of papillomas and the average papilloma volume between the Tg . AC(+/-) K5Cre(+/+) mice and their corresponding controls. Surprisingly, however, the K5Cre(+/+) papillomas displayed an accelerated tendency to malignant progression; in addition, the frequency of malignant transformation of the papillomas is significantly enhanced. Although the K5Cre(+/+) mice resemble waved-1 and -2 mutants, the molecular basis for the K5Cre(+/+) phenotype is probably different. In conclusion, we discovered a unique phenotype associated with the K5Cre(+/+) transgenic line.

Alopecia↗
PubMed2007

Favorable histology, MYCN-amplified 4S neonatal neuroblastoma.

We report a neonate with 4S neuroblastoma and MYCN amplification, but favorable Shimada histology, successfully treated with chemotherapy and 13-cis-retinoic acid without stem cell transplantation. MYCN amplification in neuroblastoma is usually associated with unfavorable Shimada histology; the presence of these features in infants with 4S disease confers a poor prognosis. A small number of infants with 4S neuroblastoma and MYCN amplification have favorable Shimada histology. In this subgroup of infants, histopathology may be equally important in predicting outcome.

Adrenal Gland Neoplasms↗
PubMed2005

Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis.

Recent studies demonstrate that the receptor tyrosine kinase (TK) Ron is tumorigenic when overexpressed and plays a role in regulating skin homeostasis. We hypothesized that Ron signaling promotes skin carcinogenesis. To test this hypothesis, mice deficient in the TK domain of Ron (TK(-/-) mice) were crossed with v-Ha-ras (Tg.AC) transgenic mice; the resulting TK(-/-) Tg.AC(+/-) mice, and their controls, were utilized in a model of chemically induced Ras-mediated skin carcinogenesis. The mice were treated with 2.5 microg of 12-O-tetradecanoylphorbol-13-acetate applied weekly to the shaved back of 36 control (TK(+/+) Tg.AC(+/-)) and 35 experimental (TK(-/-) Tg.AC(+/-)) mice. In an analysis of the resulting papillomas, a reduction in cellular proliferation and papilloma volume was found in the TK(-/-) Tg.AC(+/-) mice compared to controls. Further, Ron protein expression was upregulated during papilloma formation. Ablation of Ron signaling resulted in partial defects in MAPK and Akt signaling that may account for the decreased papilloma growth in the TK(-/-) Tg.AC(+/-) mice. The papilloma-bearing mice were monitored for the occurrence of malignant skin tumors and other malignant tumor types for a period of 48 weeks. Loss of Ron receptor signaling significantly reduced the percent of papillomas that underwent malignant conversion as well as the number of mice developing other malignant tumor types. In conclusion, these studies demonstrate that Ron signaling augments papilloma growth and malignant conversion in vivo.

Animals↗
PubMed2005

High-throughput qualitative multiplex 5' nuclease assay using post-only PCR analysis.

Homogenous fluorescence PCR assays offer distinct advantages for qualitative testing and are gaining immense popularity in fields like diagnostic microbiology. To meet the demand of high-volume laboratories, we developed a protocol for qualitative multiplex 5' nuclease assays using post-only PCR analysis. This novel approach overcomes throughput problems encountered with the established methods for TaqMan detection on the ABI PRISM 7700 Sequence Detection system and permits off-site TaqMan PCR, which can be analyzed several days after the reactions are completed. We have validated this novel protocol using an assay for the identification of Bordetella pertussis against real-time and plate-read analysis methods and have shown that our proposed protocol produces no difference in qualitative calls.

Bordetella pertussis↗
PubMed2004

The laboratory diagnosis of gonorrhoea and syphilis infection.

Following a decline in prevalence during the 1980s and early 1990s, gonorrhoea and syphilis infections are once again posing a threat to public health. In addition, the antibiotic sensitivity pattern for gonorrhoea appears to have changed with an increased prevalence of resistance. Both syphilis and gonorrhoea appear to disproportionately affect MSM and black ethnic minorities, and are concentrated in urban areas. Their diagnosis requires microbiological tests to be performed appropriately, and a rapid diagnosis can often be provided in GUM clinics using near-patient microscopy. Early diagnosis and effective, rapid treatment is crucial in limiting the morbidity for the affected individual and the public health risks resulting from the spread of infection.

Adult↗
PubMed2002

Receptor tyrosine kinase Ron is expressed in mouse reproductive tissues during embryo implantation and is important in trophoblast cell function.

Ron is a receptor tyrosine kinase that is activated by the binding of hepatocyte growth factor-like (HGFL) protein. Mutations in the catalytic domain of this receptor result in an aggressively invasive phenotype. Conversely, deletion of the entire receptor results in an embryonic lethality by Embryonic Day 7.5. The specific cellular localization and mechanisms of action of Ron and HGFL during embryo implantation are not known. Therefore, this report characterizes the temporal and spatial distribution of this receptor during mouse embryo implantation and placentation. Reverse transcription-polymerase chain reaction analysis demonstrated the presence of Ron transcripts in the uterus, placenta, testis, and epididymis, whereas HGFL transcripts were found in the cervix, placenta, epididymis, and testis. In situ hybridization and immunohistochemical analyses demonstrated that Ron was present in the cells of the ectoplacental cone and trophoblast giant cell regions surrounding the implanting embryo. Ron expression was also observed in SM9-1, SM9-2, and SM-10 murine trophoblast cell lines. To determine the effects of Ron activation on trophoblast function, Matrigel invasion and cell survival assays were performed using the SM9-1 and SM-10 trophoblast cell lines. The HGFL stimulation of these cells increased invasion and enhanced cell survival. These observations suggest that activation of the Ron receptor by HGFL binding may aid in implantation by way of trophoblast function and viability.

Animals↗
PubMed2002

The use of TaqMan PCR assay for detection of Bordetella pertussis infection from clinical specimens.

OBJECTIVE: The routine clinical laboratory detection of Bordetella pertussis is through culture, which can require 5 to 7 days for the bacteria to grow. Using a polymerase chain reaction (PCR) assay can shorten this detection time while increasing the sensitivity of detection with similar specificity. This study compared culture with TaqMan PCR for detection of B pertussis in clinical specimens and the turnaround time for each assay during the pertussis season. MATERIALS AND METHODS: Nasopharyngeal swabs in Regan-Lowe transport media were collected from 1556 persons who had symptoms of whooping cough or who had had contact with infected persons; the swabs were submitted for B pertussis detection during the pertussis season. A single nasopharyngeal swab from each patient was submitted for both culture and TaqMan PCR detection. Upon receipt of the specimens, the swabs were inoculated onto Regan-Lowe agar for culture and incubated for up to 7 days. The same swab was processed for PCR detection using TaqMan PCR assay. A second nested PCR was used on positive specimens for resolution purposes. The TaqMan PCR assay was performed 3 to 5 days a week, whereas the culture was performed 6 days a week. All specimens were processed on the same day or earliest possible working day for TaqMan or culture, and specimens queued for resolution by nested PCR were batched. RESULTS: There were a total of 275 PCR positives and 28 culture positives. After resolution with the second nested PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 97.4%, 87.6%, and 100% for TaqMan PCR and 11.6%, 100%, 100%, and 85.7% for culture. The average turnaround time for positive culture was 5.1 days, and the average turnaround time for PCR was 2.3 days. CONCLUSION: The TaqMan PCR assay has superior sensitivity and shorter turnaround time over culture because it can be finished within one working day. Furthermore, the same swab can be used for culture of the bacteria for antibiotic susceptibility testing. The early detection of pertussis using TaqMan PCR assay allows early intervention on the spread of the disease and the ability to culture the bacteria from the same swab, thereby eliminating the need for a second swab and allowing for detection of antibiotic resistance.

Bordetella pertussis↗