Search PubMed⌕ Search

Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 145 records · Page 8Linked to original sources

Identification and characterization of variable-number tandem repeats in the Yersinia pestis genome.

Yersinia pestis, the infamous plague-causing pathogen, appears to have emerged in relatively recent history. Evidence of this fact comes from several studies that document a lack of nucleotide diversity in the Y. pestis genome. In contrast, we report that variable-number tandem repeat (VNTR) sequences are common in the Y. pestis genome and occur frequently in gene coding regions. Larger tandem repeat arrays, most useful for phylogenetic analysis, are present at an average of 2.18 arrays per 10 kbp and are distributed evenly throughout the genome and the two virulence plasmids, pCD1 and pMT1. We examined allelic diversity at 42 chromosomal VNTR loci in 24 selected isolates (12 globally distributed and 12 from Siskiyou County, Calif.). Vast differences in diversity were observed among the 42 VNTR loci, ranging from 2 to 11 alleles. We found that the maximum copy number of repeats in an array was highly correlated with diversity (R = 0.86). VNTR-based phylogenetic analysis of the 24 strains successfully grouped isolates from biovar orientalis and most of the antiqua and mediaevalis strains. Hence, multiple-locus VNTR analysis (MLVA) appears capable of both distinguishing closely related strains and successfully classifying more distant relationships. Harnessing the power of MLVA to establish standardized databases will enable researchers to better understand plague ecology and evolution around the world.

Animals↗

Francisella tularensis strain typing using multiple-locus, variable-number tandem repeat analysis.

Francisella tularensis, the etiological agent of tularemia, is found throughout the Northern hemisphere. After analyzing the F. tularensis genomic sequence for potential variable-number tandem repeats (VNTRs), we developed a multilocus VNTR analysis (MLVA) typing system for this pathogen. Variation was detected at six VNTR loci in a set of 56 isolates from California, Oklahoma, Arizona, and Oregon and the F. tularensis live vaccine strain. PCR assays revealed diversity at these loci with total allele numbers ranging from 2 to 20, and Nei's diversity index values ranging from 0.36 to 0.93. Cluster analysis identified two genetically distinct groups consistent with the current biovar classification system of F. tularensis. These findings suggest that these VNTR markers are useful for identifying F. tularensis isolates at this taxonomic level. In this study, biovar B isolates were less diverse than those in biovar A, possibly reflecting the history of tularemia in North America. Seven isolates from a recent epizootic in Maricopa County, Ariz., were identical at all VNTR marker loci. Their identity, even at a hypervariable VNTR locus, indicates a common source of infection. This demonstrates the applicability of MLVA for rapid characterization and identification of outbreak isolates. Future construction of reference databases will allow faster outbreak tracking as well as providing a foundation for deciphering global genetic relationships.

Animals↗

Activation of NF-kappaB by double-stranded RNA (dsRNA) in the absence of protein kinase R and RNase L demonstrates the existence of two separate dsRNA-triggered antiviral programs.

Double-stranded RNA (dsRNA) of viral origin triggers two programs of the innate immunity in virus-infected cells. One is intended to decrease the rate of host cell protein synthesis and thus to prevent viral replication. This program is mediated by protein kinase R (PKR) and by RNase L and contributes, eventually, to the self-elimination of the infected cell via apoptosis. The second program is responsible for the production of antiviral (type I) interferons and other alarmone cytokines and serves the purpose of preparing naive cells for the viral invasion. This second program requires the survival of the infected cell and depends on the expression of antiapoptotic genes through the activation of the NF-kappaB transcription factor. The second program therefore relies on ongoing transcription and translation. It has been proposed that PKR plays an essential role in the activation of NF-kappaB by dsRNA. Here we present evidence that the dsRNA-induced NF-kappaB activity and the expression of beta interferon and inflammatory cytokines do not require either PKR or RNase L. Our results indicate, therefore, that the two dsRNA-activated programs are separate and can function independently of each other.

Active Transport, Cell Nucleus↗

Soluble E-cadherin is a valid prognostic marker in gastric carcinoma.

BACKGROUND: Gastric cancer remains a major cause of cancer mortality globally but no good prognostic tumour marker is available. Soluble fragment of E-cadherin protein has been reported to increase in the sera of patients with cancer and recently was found to be elevated in 67% of patients with gastric cancer. AIMS: To investigate if serum soluble E-cadherin is a valid prognostic marker in gastric cancer. METHODS: Concentrations of soluble E-cadherin from 116 patients with histologically confirmed gastric adenocarcinoma and 40 healthy subjects were measured using an immunoenzymometric method with a commercially available sandwich ELISA kit based on monoclonal antibodies. RESULTS: The logarithm of the means of soluble E-cadherin concentration was significantly higher in patients with gastric cancers (mean 3.85 (SD 0.28)) than in healthy subjects (3.71 (0.18)) (p=0.001), and in palliative/conservatively treated cancers (3.91 (0.35)) than in operable cancers (3.78 (0.19)) (p=0.015). The logarithm of the concentrations correlated with tumour size (p=0.032) and carcinoembryonic antigen concentrations (p=0.001). The cut off value calculated from discriminant analysis on operability and inoperability/palliative treatment was 7025 ng/ml. Soluble E-cadherin concentrations higher than this cut off value predicted tumour (T4) depth invasion (p=0.020, confidence interval (CI) 1.008-1.668) and palliative/conservative treatment (p=0.023, CI 1.038-2.514). In contrast, the relative risks for lymph node (N2) metastasis, distant metastasis, and stage III/IV disease were 1.41, 1.33, and 1.55 respectively, despite not reaching statistical significance. CONCLUSION: Serum soluble E-cadherin is a potential valid prognostic marker for gastric cancer. A high concentration predicts palliative/conservative treatment and T4 invasion.

Adenocarcinoma↗

Hemodynamic characterization of arterialized and nonarterialized liver transplants in the rat.

Persistent hyperkinetic circulation after liver transplantation has been described in humans, but similar changes have not been well characterized in the rat model. This study aimed to investigate the hemodynamics of the systemic and splanchnic circulations in both arterialized and nonarterialized hepatic allografts. Orthotopic liver transplantation was performed in four groups of Sprague-Dawley rats. Group A comprised sham-operated rats with hepatic artery ligation that did not receive transplants; group B comprised rats that received transplants without arterialization; group C comprised sham-operated rats with intact hepatic artery that did not receive transplants; and group D comprised rats that received transplants with arterialization. Blood flow measurements were performed three weeks after the surgical procedure, using the radioactive microsphere method. The results showed that rats that received transplants exhibited a significantly higher cardiac index and lower systemic vascular resistance than the control rats. Splanchnic hyperemia was also present with increased mesenteric blood flow. However, there was no difference in hemodynamics between rats that received arterialized transplants and those that received nonarterialized transplants. Arterial collateral vessels from adjacent tissues were observed in the nonarterialized grafts; this was confirmed histologically. It is concluded that rats that undergo orthotopic liver transplantation exhibit hyperdynamic circulation, regardless of the arterial reconstruction procedure, possibly due to extensive collateral formation in the hepatosplanchnic circulation.

Animals↗

Laparoscopic versus open bowel resection for Crohn's disease.

BACKGROUND: Laparoscopic bowel resection is an alternative to open surgery for patients with Crohn's disease requiring surgical resection. The present report describes a seven-year experience with the laparoscopic treatment of Crohn's disease compared with the open technique in a tertiary Canadian centre. PATIENTS AND METHODS: A retrospective analysis of 61 consecutive patients undergoing elective resection for Crohn's disease was carried out between October 1992 and June 1999. This analysis included 32 laparoscopic resections (mean age 33 years) and 29 open resections (mean age 42 years). Patient demographics were compared, as well as short and long term outcomes after surgery (mean follow-up 39 months). RESULTS: Patients in the laparoscopic group were younger and had fewer previous bowel surgeries than patients who had open resections. Indications for surgery and operative times were similar between the groups. Patients who underwent laparoscopic resections required fewer doses of narcotic analgesics. The resumption of bowel function after surgery, and tolerance of a clear liquid and solid diet was quicker in the laparoscopic group. Patients who underwent laparoscopic resections had significantly shorter hospital stays than those who underwent open resections. Fifteen patients (48.4%) in the laparoscopic group experienced recurrence of disease compared with 13 patients (44.8%) in the open group. In both groups, the most common site of recurrence was at the anastomosis. The disease-free interval was the same length for both groups (23.9+/-17.3 months for the laparoscopic resection patients compared with 23.9+/-20.2 months for the open resection patients; P=1.00). CONCLUSIONS: Laparoscopic resection for Crohn's disease can be performed safely and effectively. Quicker resumption of oral feeds, less postoperative pain and earlier discharge from hospital are advantages of the laparoscopic method. No differences in the recurrence rate or the disease-free interval were noted.

Adolescent↗

Novel demonstration of a physiologic/pharmacologic role of insulin-like growth factor-1 in ovulation in rats and action on cumulus oophorus.

Gonadotropins are well known to be the most important stimulus for ovarian follicular development. More recently, there is indirect evidence that insulin-like growth factor-1 (IGF-1) is also a very important autocrine/paracrine factor in folliculogenesis. We had access to an analog of IGF-1, LR3IGF-1, which binds very poorly to IGF-1 binding proteins and therefore was shown by previous investigators to have biologic effects. We studied rats that were superovulated with the use of gonadotropins. We showed that the addition of LR3IGF-1 by infusion further increased the ovulation rate (statistically significant) and increased the ovarian weight in two of three strains of rats. We demonstrated that infusion of LR3IGF-1 or injection of equine chorionic gonadotropin or a combination of these two were associated with oocytes with reduced number of cumulus cells (statistically significant). We conducted an experiment to determine whether in vitro culturing with varying dosage of IGF-1 may stimulate cumulus cell replication to improve the quality of oocyte cumulus complex. IGF-1 did not show any change in this respect. Through these physiologic (pharmacologic) studies, we have shown that IGF-1 (analog) can further increase the ovulation rate induced by gonadotropins.

Animals↗

Recent discoveries in physiology of insulin-like growth factor-1 and its interaction with gonadotropins in folliculogenesis.

Ovarian follicular development is under the influence of gonadotrophins. The manner by which gonadotrophins achieve their role in cell replication and hormone production is through other specialized molecules. Insulin-like growth factor-1 (IGF-1) is considered to be one of the most important of these molecules. IGF-1 is present in relatively large amounts in the ovary and the IGF-1 gene is expressed in the graafian follicle. IGF-1 binding proteins modulate the action of IGF-1 and are influenced by gonadotrophins. Null mutations of genes encoding IGF-1 and type-1 IGF receptor have demonstrated the obligatory role of IGF-1 in folliculogenesis. It was proposed that IGF-1 may be an obligatory mediator of gonadotrophin-induced folliculogenesis and that the interaction is synergistic. From this point, one group embarked on a series of physiological studies to further elucidate the interaction of these molecules. We discovered that, according to circumstances, follicle stimulating hormone (FSH) may act with IGF-1 synergistically (as was postulated before), additively, independently, or even antagonistically. We discovered that granulosa cells must first be exposed to FSH and then they respond well to IGF-1. All previous studies of granulosa cells were done on mural granulosa cells. We subsequently showed that cumulus type of granulosa cells (adjacent to the oocyte) behave differently in their responses to gonadotrophins and IGF-1.

Animals↗

Sleep disorders.

Explore the source record for details and available documents.

Adolescent↗

Effect of cloud on UVA and exposure to humans.

The daily autumn and winter ultraviolet-A (320-400 nm) (UVA) exposures and 6 min UVA irradiance data for a southern hemisphere subtropical site (Toowoomba, Australia, 27.6 degrees S, 151.9 degrees E) are presented. This data is used to quantify the effect of cloud on UVA using an integrated sky camera and radiation system. Additionally, an estimate of the effect of enhanced UVA exposure on humans is made. The measurement system consisted of broad-band visible-infrared and UVA sensors together with a sun tracking, wide-angle video camera. The mean daily June exposure was found to be 409 kJ m-2. Under the constraints of the uncertainty of both the UVA measurement system and clear-sky model, one case of enhanced UVA irradiance was found. Three cases of cloud enhancement of daily UVA exposure, approaching clear-sky levels, were also determined using a calculated clear-sky envelope. It was also determined that for a fulltime outdoor worker the additional UVA exposure could approach approximately that of one third of a full winter's day. For indoor workers with an outside lunch break of 12:00-1:00 P.M. the additional UVA exposure was on an average 6.9 kJ m-2 over three cloud-enhanced days. To the authors' knowledge this is the first paper to present some evidence of cloud-enhanced UVA human exposure.

Environmental Exposure↗

Treatment of inguinodynia after laparoscopic herniorrhaphy: a combined laparoscopic and fluoroscopic approach to the removal of helical tackers.

Laparoscopic inguinal herniorrhaphy has become a popular operation for the treatment of inguinal hernia. However, injury and entrapment of the cutaneous nerves of the lumbar plexus by the staples or tackers used for mesh fixation have been described. Laparoscopic removal of the staples or tackers in the inguinal region has been attempted with variable success. The success of the laparoscopic approach for removal of helical tackers in particular is sometimes limited by the fact that the offending tackers are deeply embedded in the preperitoneal tissues and not readily located with a simple laparoscopic view. The authors report a case in which fluoroscopy was used to help identify tackers that could not be visualized laparoscopically. The neuralgia disappeared after successful removal of the offending tackers with no neurologic deficit. Liberal use of fluoroscopic guidance in the laparoscopic removal of helical tackers in similar cases is recommended.

Fluoroscopy↗

Detection of genetic alterations in esophageal squamous cell carcinomas and adjacent normal epithelia by comparative DNA fingerprinting using inter-simple sequence repeat PCR.

In this study, we screened 19 esophageal squamous cell carcinomas (ESCCs) for the detection of genetic alterations using inter-simple sequence repeat PCR, a DNA fingerprinting approach. Three simple repetitive unanchored primers representing tri- and tetranucleotide repeats [(GTG)(5), (GACA)(4), and (GATA)(4)] were used, and evidence of gains and losses of chromosomal sequences were detected in all tumors (19 of 19 cases) for at least one of the primers. In 13 of these cases, apparently normal marginal epithelia adjacent to the tumors were also collected and examined. Eight of the 13 (62%) patients showed matching somatic mutations in the marginal epithelia adjacent to the tumors. Five of these 8 (63%) marginal epithelial samples were histologically normal, two were dysplastic, and one had extremely rare tumor cells. In 3 of these 13 (23%) cases, the profile bands were also seen to quantitatively increase in intensity, progressing from normal epithelia to marginal epithelia to tumors. Ten profile bands showing gains and one profile band showing loss in tumors compared with the corresponding normal epithelia were cloned, and their origins were determined by sequencing. The DNA sequence of one of the profile bands showing gain in the tumor could be matched to an expressed sequence tag sequence that has been mapped to the 7q22 region, a genomic amplification novel to ESCC. The sequence of the other profile band showing gain in the tumor could be matched to a nonexonic sequence of chromosome 20, whereas the sequences of the remaining profile bands could not be matched with any known sequences after comparison with the genomic sequence data in the European Molecular Biology Laboratory and GenBank databases. The bona fide nature of the gains or losses of 11 profile bands in the original cases was confirmed by direct genomic PCR amplification. The frequencies of these specific gene alterations in tumors were then analyzed in a total of 60 ESCCs, which included 41 additional cases of ESCC. Significantly, 26 of 60 (43%) tumors showed the DNA amplification for the expressed sequence tag sequence of chromosome 7, whereas the frequency of other individual gene alterations ranged from 7% to 15%. It is concluded that the inter-simple sequence repeat PCR strategy is adequate for the detection of somatic mutations in tumors, most of which are quantitative alterations in anonymous genomic sequences. This approach is also suitable for detection of somatic mutations preceding the onset of morphologically detectable neoplasia in ESCC.

Aged↗

Pathological features and BRCA1 mutation screening in premenopausal breast cancer patients.

PURPOSE: Risk calculations for carrying BRCA1/BRCA2 mutations are based on family history and the age of onset of cancers. However, women may carry these deleterious mutations without a strong family history. Additional criteria for risk estimation would be of value. It has been recently established that BRCA1-associated breast cancers are associated with poor tumor differentiation (TD3) and estrogen receptor (ER) negativity. The aim of this study is to determine whether morphological features of breast cancers in premenopausal patients (age < 45 years) could determine additional women who may benefit from BRCA1 screening. EXPERIMENTAL DESIGN: In a prospective, systematic study of 76 consecutive breast cancer patients (age < 45 years), genomic DNA was obtained from peripheral blood, and eight mutations in BRCA1 (10.5%) were found. Archival paraffin-embedded breast cancer specimens were then analyzed for tumor differentiation and ER status. RESULTS: In patients < 45 years of age, 25% (6 of 24) of ER-negative and TD3 breast cancers were found to harbor mutations in BRCA1. Only 5.6% (2 of 36) of BRCA1-associated breast cancers did not have this morphological profile, compared with 94.4% (34 of 36) patients without BRCA1 mutations, giving an odds ratio of 5.67 (95% confidence interval, 1.04-32; P = 0.05). Finally, only one patient with BRCA1 mutations had a significant family history. CONCLUSIONS: In patients with early-onset breast cancer, the use of morphological criteria provides an additional strategy to determine those patients who might benefit from genetic testing.

Adult↗

Identification of differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1, and CDC25B genes in ESCC.

PURPOSE: This study aims to identify differentially expressed genes in esophageal squamous cell carcinoma (ESCC) through the use of a membrane-based cDNA array. EXPERIMENTAL DESIGN: Two newly established human ESCC cell lines (HKESC-1 and HKESC-2) and one corresponding to a morphologically normal, esophageal epithelium tissue specimen, prospectively collected from the HKESC-2-related patient, were screened in parallel using a cDNA expression array containing gene-specific fragments for 588 human genes spotted onto nylon membranes. RESULTS: The results of cDNA expression array showed that 53 genes were up-regulated 2-fold or higher and 8 genes were down-regulated 2-fold or higher in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of a subset of these differentially expressed genes gave results consistent with cDNA array findings. Four of the differentially expressed genes that belong to the categories of oncogenes/tumor suppressor genes (Fra-1 and Neogenin) and cell cycle-related genes (Id-1 and CDC25B) were studied more extensively for their protein expression by immunohistochemistry. The two ESCC cell lines and their corresponding primary tissues, 61 primary ESCC resected specimens and 16 matching, morphologically normal, esophageal epithelium tissues were analyzed. The immunostaining results showed that Fra-1, Neogenin, Id-1, and CDC25B were overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the microarray findings. The results of the clinical specimens showed that the Fra-1 gene was overexpressed in ESCC compared with normal esophageal epithelium in 53 of 61 cases (87%), Neogenin in 57 of 61 cases (93%), Id-1 in 57 of 61 cases (93%), and CDC25B in 48 of 61 cases (79%). Furthermore, the expression of Fra-1, Neogenin, and Id-1 in ESCC correlated with tumor differentiation. CONCLUSIONS: Overall, this study demonstrates that multiple genes are differentially expressed in ESCC and provides the first evidence that oncogenes Fra-1 and Neogenin and cell cycle-related genes Id-1 and CDC25B are overexpressed in ESCC.

Carcinoma, Squamous Cell↗

Rosai-Dorfman disease presenting with isolated bilateral orbital masses: report of two cases.

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is a rare benign idiopathic proliferative disease of phagocytic histiocytes. Approximately 80% of patients present with painless massive cervical lymphadenopathy. Isolated extranodal involvement is relatively uncommon. Two cases of Rosai-Dorfman disease are reported: one with isolated bilateral orbital involvement and one with marked cervical lymphadenopathy and multiple dural-based and intraventricular masses.

Adult↗

Universal screening of human immunodeficiency virus infection in pregnant women in Hong Kong: prospective study.

OBJECTIVE: To evaluate universal screening with an opt-out approach of pregnant women for human immunodeficiency virus infection. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: All women booked or delivered in Kwong Wah Hospital from 1 January 1999 to 30 November 1999 were recruited. MAIN OUTCOME MEASURES: Numbers of women who received the human immunodeficiency virus antibody screening test, refused the test (and the reasons why), tested positive, and tested positive with confirmation by immunoblot study. RESULTS: A total of 5597 women were recruited and 5459 screening tests performed in this study. Of the 16 screened positive cases, three were confirmed by immunoblot study. The overall acceptance rate for the test was 97.5%. The acceptance rate among the 5191 women recruited through the hospital's booking clinic was not significantly different from that among the 406 women who did not go through the hospital's booking clinic (97.6% versus 96.6%). CONCLUSION: Universal screening of pregnant women for human immunodeficiency virus infection with an opt-out approach is practical, feasible, and clinically acceptable in Hong Kong.

Female↗

Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC.

PURPOSE: To examine the global gene expression of cancer-related genes in esophageal squamous cell carcinoma (ESCC) through the use of Atlas Human Cancer Array membranes printed with 588 well-characterized human genes involved in cancer and tumor biology. EXPERIMENTAL DESIGN: Two human ESCC cell lines (HKESC-1 and HKESC-2) and one morphologically normal esophageal epithelium tissue specimen from the patient of which the HKESC-2 was derived were screened in parallel using cDNA expression arrays. The array results were additionally validated using semiquantitative PCR. The overexpression of oncogene MET was studied more extensively for its protein expression by immunohistochemistry in the two ESCC cell lines and their corresponding primary tissues and 61 primary ESCC resected specimens. Sixteen of these 61 ESCC cases also had available the corresponding morphologically normal esophageal epithelium tissues and were also analyzed for MET expression. The clinicopathological features associated with overexpression of the MET gene were also correlated. RESULTS: The results of cDNA arrays showed that 13 cancer-related genes were up-regulated > or =2-fold (CDC25B, cyclin D1, PCNA, MET, Jagged 2, Integrin alpha3, Integrin alpha6, Integrin beta4, Caveolin-2, Caveolin-1, MMP13, MMP14, and BIGH3) and 5 genes were down-regulated > or =2-fold (CK4, Bad, IGFBP2, CSPCP, and IL-1RA) in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of 9 of these differentially expressed genes, including the MET gene, gave results consistent with cDNA array findings. The immunostaining results of the expression of MET gene showed that MET was overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the cDNA arrays findings. The results of the clinical specimens showed that the MET gene was overexpressed in ESCC compared with normal esophageal epithelium in 56 of 61 cases (92%). Moreover, the overexpression of MET protein was more often seen in well/moderately differentiated than in poorly differentiated ESCC. CONCLUSIONS: Multiple cancer-related genes are differentially expressed in ESCC, the oncogene MET is overexpressed in ESCC compared with normal esophageal epithelium, and its protein overexpression correlates with tumor differentiation in ESCC.

Aged↗