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W C Chan

Publications and source records attributed to W C Chan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cellular origin of nodular lymphocyte-predominant Hodgkin's lymphoma: immunophenotypic and molecular studies.

The lymphocyte-predominant (LP) type of Hodgkin's lymphoma (HL) is a unique subtype with characteristic tumor cells (lymphocytic and/or histiocytic [L&H] cells) in associated macronodular structures that resemble progressively transformed germinal centers (PTGCs). Immunohistochemical studies have provided strong evidence that L&H cells are of B-cell lineage and recent molecular studies suggested they are transformed centroblasts. A major clonal population is detectable at presentation, with the immunoglobulin heavy-chain gene often showing evidence of continued somatic hypermutation. In developed nations, Epstein-Barr virus (EBV) is infrequently associated with L&H cells and is probably not involved in the pathogenesis of this disease. L&H cells are frequently surrounded by CD3+, CD4+, CD57+, and CD40L- T cells, but the significance of this T-cell rosetting is unclear. LPHL may be associated with concurrent or subsequent large B-cell lymphoma, and there is evidence of a clonal relationship between the two entities. LPHL may also have nodules or large areas that resemble histiocyte-rich B-cell lymphoma (HRBCL). It is likely that at least some cases of HRBCL arise from LPHL. The same may be true of T-cell-rich B-cell lymphoma. Little is known about cytogenetic abnormalities, the cytokine expression profile, and the expression of several functionally important molecules that have been demonstrated in the Reed-Sternberg (RS) cells of classical HL. The challenge for the future is to obtain a more comprehensive molecular profile of L&H cells and their associated T lymphocytes, so as to provide a framework for eventual elucidation of the pathogenesis of this type of HL.

B-Lymphocytes↗
PubMed1998

Quantum dot bioconjugates for ultrasensitive nonisotopic detection.

Highly luminescent semiconductor quantum dots (zinc sulfide-capped cadmium selenide) have been covalently coupled to biomolecules for use in ultrasensitive biological detection. In comparison with organic dyes such as rhodamine, this class of luminescent labels is 20 times as bright, 100 times as stable against photobleaching, and one-third as wide in spectral linewidth. These nanometer-sized conjugates are water-soluble and biocompatible. Quantum dots that were labeled with the protein transferrin underwent receptor-mediated endocytosis in cultured HeLa cells, and those dots that were labeled with immunomolecules recognized specific antibodies or antigens.

Cadmium Compounds↗
PubMed1998

Histologic and biologic patterns of microscopic pancreatic ductal adenocarcinomas detected incidentally at autopsy.

BACKGROUND: The major clinical problems with pancreatic carcinoma are its silent course and late, fatal clinical manifestation. The results of treatments of small pancreatic carcinomas (<2 cm in greatest dimension) have led to the assumption that the detection of these cancers at earlier stages would lead to better survival and possible cure. Currently, there is no information about the histologic and biologic patterns of early stage pancreatic carcinoma, and the available data on incidentally detected tumors are fragmentary. The authors observed two incidental microscopic pancreatic ductal adenocarcinomas in female patients who died of advanced gastric carcinoma (Case 1) and renal carcinoma (Case 2). METHODS: The pancreatic lesions were examined histologically in serial sections and immunocytochemically for islet cells. Microdissection was performed so that the lesions could be examined for c-Ki-ras mutation. RESULTS: In Case 1, the pancreatic lesion was composed of cystic and solid components. The cystic component consisted of four small cysts compatible with a mucinous cystic tumor and showed no invasion. The solid component was a well-differentiated adenocarcinoma that occupied a 4 x 2 mm area. In Case 2, the pancreatic lesion contained two small, separate cysts, one of which was surrounded by two apparently separate, invasive adenocarcinomas 2.6 x 0.7 mm and 1.2 x 0.5 mm in greatest dimension. There was invasion of pancreatic islets and perineural spaces in both cases; and in Case 2, there was invasion of peripancreatic fatty tissue. In both cases, the epithelia of the cystic components and tumors showed mutation of the c-Ki-ras oncogene at codon 12, with GGT-to-GAT transition. CONCLUSIONS. Pancreatic carcinoma seems to occur under occult circumstances and maintain a silent course. Even in its early developmental stage, the cancer is invasive, primarily affects islets and nerves, and exhibits mutation of the c-Ki-ras oncogene. These findings call for urgency in the development of preventive modalities.

Aged↗
PubMed1998

Origin of the Hodgkin/Reed-Sternberg cells in chronic lymphocytic leukemia with "Hodgkin's transformation".

A lymphoma with the characteristic features of Hodgkin's disease (HD) occasionally develops in patients with B-cell chronic lymphocytic leukemia (CLL), and has been called Richter's syndrome with HD features. In such cases, large tumor cells have the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (H-RS) cells. However, it is not known whether the H-RS cells arise from transformation of the underlying CLL cells or from a different pathological process. We report herein a study of the clonal relationship between the CLL cells and the H-RS cells in three cases of Richter's syndrome with HD features by using a single cell assay. We isolated single CLL cells and H-RS cells from immunostained tissue sections by micromanipulation. The immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of each cell was amplified by the polymerase chain reaction (PCR). The products were then compared by gel electrophoresis and nucleotide sequencing. The IgH CDRIII sequences from the H-RS cells were identical to those from the CLL cells in two cases. In one case, the clonal relationship between the two types of cells could not be determined because PCR products could not be obtained from any of the H-RS cells. This study shows that the H-RS cells and the CLL cells belong to the same clonal population in some cases of Richter's syndrome with HD features. Furthermore, our findings indicate that mature B cells can undergo transformation to cells with the features of H-RS cells, in association with a cellular background typical of HD. This study also supports recent findings suggesting that the H-RS cells in classical HD are derived from transformed B cells.

Cell Transformation, Neoplastic↗
PubMed1998

Prediction of pathological stage and clinical outcome in prostate cancer: an improved pre-operative model incorporating biopsy-determined intraductal carcinoma.

OBJECTIVE: To relate the predictive value of serum prostate specific antigen (PSA) levels, histological grade and intraductal carcinoma (IDC-P, a possible marker of poor prognosis) to pathological stage and subsequent clinical outcome, and thus derive an improved predictive model to aid the decision to initiate potentially curative therapy in localized prostate cancer. MATERIALS AND METHODS: Fifty-nine radical prostatectomy specimens were histologically graded, allocated a pathological stage and the tumour volume determined by image analysis. Pre-operative (needle biopsy) tumour grade, the presence or absence of IDC-P, and serum PSA levels were correlated with the pathological stage. This was used to define the sequence and values that would be incorporated into a predictive model for pathological stage and clinical outcome. RESULTS: There were close correlations between cancer volume and tumour grade (P = 0.004) and between cancer volume and serum PSA level (P = 0.003). However, in tumours with IDC-P, serum PSA level did not correlate with tumour volume of IDC-P (P > 0.9). IDC-P was an independent variable that significantly improved the prediction of pathological stage and tumour volume, and furthermore, was closely related to (r = 0.53, P = 0.001) and accurately predicted treatment failure. CONCLUSION: The model which best predicted pathological stage and clinical outcome involved first identifying those cancers with IDC-P as having the poorest outcome. Cancers without IDC-P were then separated into low- and high-risk groups on the basis of serum PSA levels below and above 10 ng/mL, and those in the high-risk group further stratified using Gleason grading. Furthermore, the use of a sequential consideration of pre-operative variables including IDC-P allowed cases to be grouped which, after radical surgery, closely correlated with clinical outcome.

Biopsy, Needle↗
PubMed1998

Potential role of epithelial cell-derived histone H1 proteins in innate antimicrobial defense in the human gastrointestinal tract.

In the human gastrointestinal tract, microorganisms are present in large numbers in the colon but are sparse in the proximal small intestine. In this study, we have shown that acid extracts of fresh human terminal ileal mucosal samples mediate antimicrobial activity. Following cation-exchange chromatography, one of the eluted fractions demonstrated antibacterial activity against bacteria normally resident in the human colonic lumen. This activity was further fractionated by reverse-phase high-performance liquid chromatography and identified as histone H1 and its fragments. We have also shown that in tissue sections, immunoreactive histone H1 is present in the cytoplasm of villus epithelial cells. In vitro culturing of detached (from the basement membrane) villus epithelial cells led to the release of antimicrobial histone H1 proteins, while the cells demonstrated ultrastructural features of programmed cell death. Our studies suggest that cytoplasmic histone H1 may provide protection against penetration by microorganisms into villus epithelial cells. Moreover, intestinal epithelial cells released into the lumen may mediate antimicrobial activity by releasing histone H1 proteins and their fragments.

Amino Acid Sequence↗
PubMed1998

Characteristics of radiology groups and of diagnostic radiologists and radiation oncologists in different types of practices.

PURPOSE: To describe the characteristics of U.S. radiology groups and of radiologists in different types of practices in 1995. MATERIALS AND METHODS: A survey was distributed to 3,024 radiologists; the response rate was 75%. Responses were weighted to represent all U.S. groups or radiologists. RESULTS: There were 3,285 groups; 340 were academic, and 356 were multispecialty. Fifty percent of groups had two to four members; 39% of radiologists were in groups with fewer than eight members, and 8% were solo practitioners. Seventy percent of all radiologists were in practices owned entirely by physicians in the practice, and 80% of these were themselves owners. Eight percent of radiologists were in government-owned practices, and 15% (primarily academic) were in privately-owned practices in which all physicians were employees. Sixty-nine percent of academic diagnostic radiologists worked primarily in one field, but this was true of only 22% of those in nonacademic groups. Solo diagnostic practitioners also typically had a broad practice but excluded high-cost modalities. Radiologists in nonacademic groups averaged more vacation days (30 d/yr) than academic (19 d/yr) or solo (12 d/yr) practitioners. Solo and locum tenens practitioners were relatively old; academic radiologists, relatively young. CONCLUSION: Through 1995, average group size has grown slowly. There are important differences among practice types, especially between academic and nonacademic practices.

Academic Medical Centers↗
PubMed1998

Effect of follicularity on autologous transplantation for large-cell non-Hodgkin's lymphoma.

PURPOSE: This study evaluated the outcomes of patients who received high-dose chemotherapy (HDC) and autologous hematopoietic stem-cell transplantation (ASCT) for large-cell non-Hodgkin's lymphoma (NHL) and the effect of a follicular versus a diffuse histology. PATIENTS AND METHODS: The prognostic factors in 289 patients who underwent HDC and ASCT for large-cell NHL between May 1983 and December 1996 were analyzed. RESULTS: With a median follow-up duration of 24 months for surviving patients (range, 3 to 131 months), 112 of 289 (39%) were alive and 82 of 289 (28%) were failure-free. In a multivariate analysis, the factors associated with a poorer failure-free survival (FFS) included a lactic dehydrogenase (LDH) level greater than normal (P < .0001), three or more prior chemotherapy regimens received (P < .01), a mass > or = 10 cm at transplant (P < .01), and diffuse histology at the time of transplant (P = .026). Patients who received HDC and ASCT for large-cell NHL in the good-prognosis category (normal LDH, < three prior chemotherapy regimens, no large mass, and not chemotherapy-resistant) had a 5-year survival rate of 45%. Within the good-prognosis group, patients with diffuse large-cell NHL had a 5-year survival rate of 42% compared with 58% for patients with follicular large-cell (FLC) lymphoma (P = .05). CONCLUSION: Good-prognosis patients with FLC histology who receive HDC and ASCT have an improved survival compared with good-prognosis patients with a diffuse large-cell histology.

Adolescent↗
PubMed1998

Women in the radiology profession: data from a 1995 national survey.

OBJECTIVE: This report provides an in-depth picture of similarities and differences in the professional and practice characteristics of women and men who are radiologists in the United States, with specific attention to whether gender differences are less pronounced among younger radiologists. MATERIALS AND METHODS: Data were taken from a national stratified random sample survey of radiologists. The response rate was 75%. The 1731 men and 294 women responding included diagnostic radiologists, radiation oncologists, and radiology-related nuclear medicine specialists. RESULTS: Seven percent of respondents who completed their radiology residency before 1970 were women, compared with 9% in 1970-1979, 19% in 1980-1989, and 27% in 1990-1995. Gender differences were smaller among posttraining radiologists younger than 40 years old than among those 40 years old or older for the following questions: when the respondent decided to specialize in radiology, whether the respondent is a subspecialist within diagnostic radiology, whether the respondent's practice is primarily academic, whether the practice is privately owned, and whether the respondent is a practice owner (partner, shareholder). Women who were residents and fellows more frequently indicated problems with unwanted sexual attention occurring in the past 2 years than did women who were not in training positions. However, posttraining women were more likely to have encountered discrimination in salary, hiring, or promotion at some time in their careers. CONCLUSION: Women's professional roles in radiology are changing slowly. A narrowing gender gap among younger radiologists on some professional and practice characteristics may indicate a further diminishing of gender differences in radiology in the future. It may also reflect greater gender equality at earlier rather than later stages of one's career.

Adult↗
PubMed1998

The clonal relationship between nodular sclerosis Hodgkin's disease with a clonal Reed-Sternberg cell population and a subsequent B-cell small noncleaved cell lymphoma.

We evaluated the clonal relationship between a case of nodular sclerosis Hodgkin's disease (NSHD) and a small noncleaved cell (SNC) lymphoma that subsequently developed. Single Hodgkin and Reed-Sternberg (H-RS) cells were isolated from immunostained sections of the NSHD by micromanipulation, and the immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of the cells was amplified by the polymerase chain reaction (PCR). A clonal population of H-RS cells was found in the NSHD tumor. The nucleotide sequence of the clonal H-RS cells was compared with the clonal IgH CDRIII sequence from the SNC lymphoma. The two sequences were found to be unrelated. In addition, clone-specific primers and probes were designed from the two clonal IgH CDRIII sequences and used to investigate the presence of the respective clonal population in the NSHD tumor. The latter studies confirmed the presence of a major clonal H-RS cell population, as detected by the single cell assay, but cells corresponding to the SNC clone were not demonstrable by this highly sensitive technique. These findings suggest that the SNC arising in this case represents the development of the second neoplasm clonally unrelated to the preceding NSHD. They also support the recent findings that the H-RS cells in classical HD consist of a clonal population of B cells.

Adult↗
PubMed1997

Clonality in nodular lymphocyte-predominant Hodgkin's disease.

BACKGROUND: There is general agreement that lymphocytic and histiocytic (L&H) cells, the variants of Reed-Sternberg cells in nodular lymphocyte-predominant Hodgkin's disease, belong to the B-cell lineage. However, the clonality of L&H cells remains controversial. METHODS: We used complementarity-determining region 3 (CDR3) of the immunoglobulin heavy-chain gene as a clonal marker to study individual L&H cells isolated by micromanipulation from tissue sections of five patients with nodular lymphocyte-predominant Hodgkin's disease. The heavy-chain CDR3 of each cell was amplified by the polymerase chain reaction. The products were analyzed by gel electrophoresis, and representative amplification products from each patient were sequenced. RESULTS: L&H cells whose heavy-chain CDR3 was related, indicating the presence of a clonal population, were detected in all five patients and were the dominant population in three. In four of the five patients, members of the clone were found in different nodules in the tissue section, different tissue blocks from the same tumor, or different lymph nodes from the same patient. The CDR3 sequences in each clone frequently contained nucleotide substitutions indicative of intraclonal mutation. CONCLUSIONS: Clonal populations of L&H cells occur in nodular lymphocyte-predominant Hodgkin's disease. Intraclonal variation in nucleotide sequences suggests that hypermutation of the heavy-chain CDR3 continues to occur among the clonal progeny.

B-Lymphocytes↗
PubMed1997

p16 tumor suppressor gene mutations in Chinese esophageal carcinomas in Hong Kong.

The frequency and nature of genetic alterations in the p16 tumor suppressor gene in 25 esophageal squamous cell carcinoma specimens from Chinese patients were investigated by PCR-SSCP and DNA sequencing techniques. No gross deletions occurred in either exon 1 and 2 of the gene by PCR amplification. However, genetic changes were observed in three cases. These included a point mutation in codon 12 of exon 1 with a resulting Ala --> Thr amino acid substitution, a point mutation at base 91 in the non-coding region of exon 1, and a 1 base pair insertion in codon 116 of exon 2. The low mutation frequency of 12% is consistent with that of three previous studies involving Japanese and Caucasian patients (8, 16 and 21% frequency: Esteve et al., 1996, Igaki et al., 1995 and Zhou et al., 1994). p16 gene mutations do not appear to play a major role in esophageal carcinogenesis.

Aged↗
PubMed1997

CD56+ putative natural killer cell lymphomas: production of cytolytic effectors and related proteins mediating tumor cell apoptosis?

Apoptosis is a regulated form of cell death that may be triggered by natural killer (NK) or cytotoxic T cells, which effect target cell lysis by cytolytic effector and related proteins through complex intracellular signals. This study was aimed to investigate whether there is selective expression of these cytolytic markers in the putative NK-cell lymphomas and whether there is correlation with zonal tumor cell death in these tumors. Expression of the cytolytic effectors perforin, granzyme B9, and the granule membrane protein TIA1 were examined in 24 putative NK-cell lymphomas, 18 postthymic T-cell lymphomas (one case CD8+ CD56+ and three anaplastic large cell lymphomas (ALCL), three T-lymphoblastic lymphomas, and 20 B-cell lymphomas. Nineteen (79%) putative NK-cell lymphomas expressed perforin, and all 24 cases expressed granzyme B9 and TIA1. The only CD8+ CD56+ postthymic T-cell lymphoma also expressed all three cytolytic markers, two CD8- ALCL expressed TIA1; other postthymic T-cell, T-lymphoblastic, and B-cell lymphomas were consistently negative. There was strong correlation between percentage perforin-positive cells and zonal tumor cell death. Angioinvasion, in contrast, was present only in a proportion (37%) of these lymphomas despite the frequent presence of zonal tumor cell death (71%). We propose that cytolytic effector and related proteins produced by putative NK and some CD8+ CD56+ postthymic T-cell lymphomas, probably in conjunction with other mechanisms, may effect massive tumor cell apoptosis. The frequent expression of cytolytic effector markers in the CD2+ surface CD3- CD56+ putative NK-cell lymphomas lends further support to their probable NK cell origin.

Apoptosis↗
PubMed1997

The detection of minimal lymphoma by molecular and combined culture-molecular methods.

Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem cell (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14:18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52%) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100%) and t(14;18)+ B-NHL (86%) but at a lower frequency in B-NHLs without t(14,18) (44%). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of tumour detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.

Base Sequence↗
PubMed1997

Role of transmembrane pH gradient and membrane binding in nisin pore formation.

Nisin is a cationic antimicrobial peptide that belongs to the group of lantibiotics. It is thought to form oligomeric pores in the target membrane by a mechanism that requires the transmembrane electrical potential delta psi and that involves local pertubation of the lipid bilayer structure. Here we show that nisin does not form exclusively voltage-dependent pores: even in the absence of a delta psi, nisin is able to dissipate the transmembrane pH gradient (delta pH) in sensitive Lactococcus lactis cells and proteoliposomes. The rate of dissipation increases with the magnitude of the delta pH. Nisin forms pores only when the delta pH is inside alkaline. The efficiency of delta psi-induced pore formation is strongly affected by the external pH, whereas delta pH-induced pore formation is rather insensitive to the external pH. Nisin(1-12), an amino-terminal fragment of nisin, and (des-deltaAla5)-(nisin(1-32) amide have a strongly reduced capacity to dissipate the delta psi and delta pH in cytochrome c oxidase proteoliposomes and L. lactis cells. Both variants bind with reduced efficiency to liposomes containing negatively charged phospholipids, suggesting that both ring A and rings C to E play a role in membrane binding. Nisin(1-12) competes with nisin for membrane binding and antagonizes pore formation. These findings are consistent with the wedge model of nisin-induced pore formation.

Animals↗