Search PubMed⌕ Search

Biomedical subjects

W C Chan

Publications and source records attributed to W C Chan.

At least 73 records · Page 4Linked to original sources
PubMed1997

Profile of U.S. radiologists at middecade: overview of findings from the 1995 survey of radiologists.

PURPOSE: To profile the demographic, professional, and practice characteristics of diagnostic radiologists and radiation oncologists in the United States. MATERIALS AND METHODS: Questionnaires mailed to a national stratified random sample of 3,024 diagnostic radiologists, radiation oncologists, and nuclear medicine specialists yielded a 75% response rate. Weighted data reflect what responses would be if all radiologists had been surveyed and had responded. RESULTS: Among professionally active, posttraining radiologists in 1995, 14% were women; 12% were radiation oncologists, 62% diagnostic generalists, and 26% diagnostic subspecialists; 92% were board certified in radiology; 48% had postresidency fellowship training; 69% were in a position where practice ownership was a potential, and of these, 80% were practice owners. Enjoyment of work was less the greater the perceived effect of managed care on a radiologists practice, but average work satisfaction was unchanged from 1990. Among radiologists aged 55 years or older, the percentage who were retired was unchanged from 1990. Average hours worked by professionally active radiologists aged 65 years or older increased since 1990. CONCLUSION: Despite the spread of managed care and other trends that affect radiologists, surprisingly, few changes were evident in the demographic or professional characteristics of U.S. radiologists in 1995 compared with 1990.

Adult↗
PubMed1997

Molecular studies on single cells harvested by micromanipulation from archival tissue sections previously stained by immunohistochemistry or nonisotopic in situ hybridization.

Molecular analysis of isolated single cells is a powerful tool for analyzing heterogeneity within a population of cells and for clarifying issues of cell origin and clonality. Current techniques are limited by the availability of suitable fresh tissue. To broaden the applicability of molecular techniques at single-cell level, we have developed an approach that uses routinely processed archival tissue. Immunoglobulin heavy chain (IgH) gene rearrangement was analyzed in large tumor cells from four cases of diffuse large cell B-non-Hodgkin's lymphoma and in small reactive T and B lymphocytes from three cases of lymphocytic predominance Hodgkin's disease. One case of Epstein-Barr virus (EBV)-encoded RNA (EBER)-positive angiocentric pulmonary T-cell lymphoma was assayed for the presence of the BamHI-W multiple-copy fragment of the EBV genome. T- and B-lymphoid cells were immunostained with anti-CD3 and CD20, respectively. The tissue sections from the EBER-positive T-cell lymphoma were stained by nonisotopic in situ hybridization. Single cells were mobilized after proteolytic treatment under an inverted microscope using a hydraulic micromanipulator at a magnification of 400 x. Isolated cells were aspirated into a micropipette fixed to a second micromanipulator and transferred into a PCR tube. The IgH complementarity determining region (CDR)3 was successfully amplified in 17 of 52 (33%) small B-lymphocytes from lymphocytic predominance Hodgkin's disease using a previously reported semi-nested PCR method, and the products from each case differed in size as expected of a polyclonal population. None of the 49 small T lymphocytes demonstrated any amplifiable IgH CDR3 products, indicating no significant cellular contamination. The IgH CDR3 sequence analysis of the PCR products indicated a clonal relationship among harvested cells. In the T-cell lymphoma case, the harvested EBER-positive cells were amplifiable for the multiple-copy fragment BamHI-W of the EBV genome. Our study indicates that single-cell analysis can be performed on paraffin-embedded archival tissue after being subjected to immunoperoxidase and in situ hybridization procedures.

Antigens, CD20↗
PubMed1997

Laparoscopic management of ruptured pyogenic liver abscess.

Intraperitoneal rupture of pyogenic liver abscess is a rare but potentially fatal disease, often involving the elderly, who are commonly of poor surgical risk with background of significant medical illness. Accurate preoperative diagnosis is difficult and often necessitates exploratory laparotomy for peritonitis. We report a case of ruptured cryptogenic solitary liver abscess presented with acute peritonitis that was successfully treated laparoscopically. The laparoscopic approach obviated the access trauma, confirmed the diagnosis, was able to drain the abscess, as well as provided microbiology and histology samples. A thorough peritoneal lavage could be also performed. The use of laparoscopic ultrasound could also localize concomitant abscesses and detect associated biliary tract pathology.

Aged↗
PubMed1996

Structure-activity relationships in the peptide antibiotic nisin: antibacterial activity of fragments of nisin.

The post-translationally modified peptide antibiotic nisin has been cleaved by a number of proteases and the fragments produced purified, characterised chemically, and assayed for activity in inhibiting the growth of Lactococcus lactis MG1614 and Micrococcus luteus NCDO8166. These results provide information on the importance of different parts of the nisin molecule for its growth-inhibition activity. Removal of the C-terminal five residues leads to approximately a 10-fold decrease in potency, while removal of a further nine residues, encompassing two of the lanthionine rings, leads to a 100-fold decrease. There are some differences between analogous fragments of nisin and subtilin, suggesting possible subtle differences in mode of action. Cleavage within, or removal of, lanthionine ring C essentially abolishes the activity of nisin. The fragment nisin1-12 is inactive itself, and specifically antagonises the growth-inhibitory action of nisin. These results are discussed in terms of current models for the mechanism of action of nisin.

Amino Acid Sequence↗
PubMed1996

p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis.

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.

Base Sequence↗
PubMed1996

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma.

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.

Adolescent↗
PubMed1996

Clonality analysis of B-lymphoid proliferations using the polymerase chain reaction.

BACKGROUND: Polymerase chain reaction (PCR) based assays are becoming more reliable, simpler, and faster alternatives to traditional Southern blot hybridization (SBH) analysis for the detection of clonal immunoglobulin heavy chain (IgH) gene rearrangements. However, a variety of technical approaches have been reported with markedly different results. METHODS: We analyzed the frozen tissue of 147 neoplastic and hyperplastic lesions on which SBH had previously been performed. Semi-nested and single-step PCR methods were compared. Consensus primers to the joining segments and the framework region (FR) III of the variable segments of the IgH gene were used. All PCR products were analyzed by polyacrylamide gel electrophoresis (PAGE). Thirteen samples were re-analyzed using a denaturing gradient gel electrophoresis (DGGE) system. RESULTS: The overall concordance between SBH and semi-nested PCR assays was 80.2%. In the non-Hodgkin's lymphoma (NHL) group, 75% of the cases with IgH rearrangements by SBH were found to be monoclonal by PCR. Regardless of type of lesion, 71.7% of the cases with IgH rearrangements by SBH were found to be clonal by PCR. The concordance between the semi-nested and single-step procedures was 87.1%. DGGE was helpful in clarifying the results for cases in which the PAGE analysis was difficult to interpret. CONCLUSIONS: PCR analysis of IgH gene rearrangements was found to be an efficient technique for the initial determination of clonality in lymphoid proliferations. The single-step method had an advantage over the semi-nested method because of its simplicity and speed. The DGGE system was useful for the assessment of clonality in cases with equivocal results after PAGE. However, a combination of these techniques in specific cases may achieve higher specificity and sensitivity.

B-Lymphocytes↗
PubMed1996

Phenotype, genotype and clonality of Reed-Sternberg cells in nodular sclerosis Hodgkin's disease: results of a single-cell study.

The genotype and clonality of Reed-Sternberg (RS) cells in Hodgkin's disease (HD) has remained a controversial issue, largely due to the scarcity of RS cells in tissues and the limitations of the techniques used to resolve this issue. Southern hybridization and polymerase chain reaction (PCR) assays using DNA extracted from tissues can only document clonal gene rearrangements, but do not indicate which cellular population is responsible for such rearrangements. To overcome the limitations of these previous techniques for studying the genotype and clonality of RS cells, we analysed single RS cells with a single-cell PCR assay to detect immunoglobulin heavy chain gene (IgH) rearrangements and X-chromosome inactivation. Six cases of nodular sclerosis (NS) HD were studied. The RS cells displayed a B-cell phenotype in three cases and a null-cell phenotype in the other three cases. IgH rearrangements were detected in the RS cells of the three cases with a B-cell phenotype, but not in the other cases. In these three cases the IgH rearrangements in the RS cells were polyclonal, although a subpopulation of clonal RS cells was documented in one case. The finding that the RS cells with IgH rearrangements were not monoclonal was supported in one case by studying the pattern of X-chromosome inactivation in single RS cells by a single-cell human androgen receptor gene (HUMARA) PCR assay. Our results indicate that NSHD begins as a polyclonal process in which a clonal RS cell population may arise; and that the RS cells in a subset of NSHD show evidence of B-lineage differentiation.

Base Sequence↗
PubMed1996

Single cell analysis of H/RS cells.

The nature of the Hodgkin/Reed-Sternberg (H/RS) cells in Hodgkin's disease (HD) is still unclear. We have studied isolated H/RS cells from four cases of lymphocytic predominance (LP) HD and six cases of nodular sclerosis (NS) HD and assayed the cells for immunoglobulin heavy chain (IgH) gene rearrangement by the polymerase chain reaction (PCR). The H/RS cells in all four cases of LPHD had rearranged their IgH gene in a polyclonal pattern. The H/RS cells of three cases of NSHD where at least a fraction of the cells expressed the B-cell marker CD20 had also rearranged their IgH gene. In two of the cases, the rearrangements were totally unrelated while in one case, two out of six rearrangements were identical in sequence indicating the presence of a clonal subpopulation amid a polyclonal background. Clonality was assessed independently in one NSHD case by determining the pattern of X-chromosome inactivation. This technique also failed to show that the H/RS cells were monoclonal. Our studies suggest that in both LPHD and NSHD, the H/RS cells may be a polyclonal proliferation at presentation and clonal populations may emerge from this polyclonal background. There is also some evidence of a correlation between the immunophenotype and the genotype of the H/RS cells. Single cell assays show great potential in elucidating the cell lineage and clonality of H/RS cells, as well as their in vivo evolution during the disease process.

Gene Rearrangement↗
PubMed1996

Concurrent lymphocyte predominance Hodgkin's disease and T-cell lymphoma. A report of three cases.

Lymphocyte predominance Hodgkin's disease (LPHD) is a B-cell lymphoproliferative disorder; patients with LPHD have an increased risk of developing synchronous or metachronous B-cell non-Hodgkin's lymphoma. The synchronous presence of LPHD and B-cell lymphoma in the same lymph node in some cases lends support to the argument that the B-cell lymphoma arises as a consequence of transformation or progression of LPHD. We have recently identified three cases of LPHD occurring simultaneously with T-cell lymphoma in a series of 76 cases of LPHD in the files of the Nebraska Lymphoma Study Group Registry. In large areas of the lymph nodes, atypical T cells with large, irregular, and hyperchromatic nuclei were admixed with Reed-Sternberg variants characteristic of LPHD (L&H cells). However, in all cases, areas of typical nodular LPHD without obvious T-cell lymphoma were also evident. In one case, frozen-section immunohistochemistry demonstrated the absence of expression of CD5, CD4, or CD8 by the T-cell lymphoma. The L&H cells in all cases expressed CD45 and CD20, as expected. In all three cases, clonal T-cell receptor (TCR)-gamma gene and TCR-beta gene rearrangements were documented by polymerase chain reaction analysis and Southern blotting, respectively. No clonally rearranged immunoglobulin genes were detected by either technique. To our knowledge, this represents the first report of the simultaneous occurrence of LPHD and T-cell lymphoma. Although B-cell lymphoma occurring in the setting of LPHD is a well-recognized phenomenon, previous reports of T-cell lymphoma occurring after a diagnosis of LPHD, as well as our cases with synchronous disease, suggest that the association of T-cell lymphoma and LPHD may not be uncommon as well. Furthermore, our cases indicate that T-cell lymphoma occurring in LPHD is not therapy related. However, the underlying mechanisms by which these composite lymphomas occur remain unknown.

Adult↗
PubMed1996

Lymphomatous polyposis. A neoplasm of either follicular mantle or germinal center cell origin.

Lymphomatous polyposis (LP) is generally thought to be an expression of non-Hodgkin's lymphoma (NHL) of follicular mantle cell (MC) origin. We report nine patients with LP from more than 3,500 cases of NHL studied by the Nebraska Lymphoma Study Group. Our patients differed from those reported previously in that LP represented a follicular center cell (FCC) NHL in two of the nine cases, with the remainder consisting of MC NHL. Three patients developed LP during a relapse of previously diagnosed and treated extraintestinal MC NHL (parotid gland, tonsil, and inguinal lymph node, respectively), whereas the other six patients presented with primary LP. In seven of the nine LP cases, a large mass predominated among a myriad of small polyps. The FCC cases were confined to the small intestine, whereas the MC cases were either pan-intestinal or colonic on their localization. Two MC cases studied by Southern blotting exhibited rearrangement of the bcl-1 locus. Bcl-2 rearrangement was not detected in any of the nine cases when studied by either a polymerase chain reaction-based assay (seven cases) or by Southern blotting (two cases). To date, four patients (three MC, one FCC) have experienced recurrent NHL in gastrointestinal sites. With follow-up ranging from 13 to 147 months, the entire group had a median survival of 41 months (primary MC LP:13, 13, 41, and 77 months; primary FCC LP:45 and 147 months; secondary MC LP:17, 41 and 76 months), and only one patient has died. We conclude that LP is a rare manifestation of NHL of either follicular MC or germinal center cell origin.

Adult↗
PubMed1996

High-resolution analysis of immunoglobulin heavy-chain gene rearrangements using denaturing gradient gel electrophoresis.

The detection of clonality in B-cell lymphomas has been facilitated by polymerase chain reaction (PCR) analysis of the immunoglobulin heavy-chain gene (IgH) complementarity determining region 3 (CDR3) and size fractionation by polyacrylamide gel electrophoresis (PAGE). However, the detection of minor clonal populations and biallelic rearrangements and the isolation of monoclonal products from gels are sometimes problematic. This study evaluated whether denaturing gradient gel electrophoresis (DGGE), a technique that separates DNA based on nucleotide sequence rather than length, could alleviate these problems. A total of 32 selected cases was studied with a diagnosis of monoclonal (n = 10), polyclonal (n = 9), and indeterminate (n = 13) IgH gene rearrangements, which were determined by analysis of seminested IgH CDR3 PCR products in 8% PAGE. These cases were evaluated using DGGE of seminested IgH CDR3 PCR products that included a 40-bp GC clamp on the Jh primer. DGGE allowed the discrimination of monoclonal populations in 9 of 13 cases where 8% PAGE results were indeterminate. In addition, DGGE demonstrated biallelic IgH rearrangements in three cases where 8% PAGE revealed only one predominant product. DGGE facilitated the purification and isolation of clonal IgH CDR3 products for sequencing without prior cloning. As an adaptation of current IgH PCR protocols, DGGE can enhance the construction of tumor-specific CDR3 primers/probes for investigations of minimal residual disease.

Antibodies, Monoclonal↗
PubMed1996

Molecular analysis of the regulation of nisin immunity.

The genetic determinants controlling immunity to nisin are coordinately regulated, along with biosynthesis genes, in response to an environmental signal, nisin or a nisin analogue. The nisR gene product, the putative response regulator of nisin biosynthesis, was found to be a vital component of this induction mechanism. This protein forms part of a two-component regulatory system which controls the expression of genes involved in nisin immunity and biosynthesis. Analysis of the structural requirements of the external signal, using nisin fragments and engineered nisin variants, indicated that the 12 amino-terminal residues of the molecule are a minimum requirement for induction, with an intact ring A being an essential component. Changes throughout the molecule also affected its induction capacity. The production of certain variant nisins by engineered lactococcal strains is reduced in parallel with the strains' immunity to nisin. This can be attributed to inefficient induction by the variant molecule. Treating growing cultures with nisin restored full immunity and maximized the yields of nisin variants by the producer strains.

Chromosome Mapping↗
PubMed1996

Structure-activity relationships in the peptide antibiotic nisin: role of dehydroalanine 5.

A mutant of the peptide antibiotic nisin in which the dehydroalanine residue at position 5 has been replaced by an alanine has been produced and structurally characterized. It is shown to have activity very similar to that of wild-type nisin in inhibiting growth of Lactococcus lactis and Micrococcus luteus but is very much less active than nisin as an inhibitor of the outgrowth of spores of Bacillus subtilis. These observations, which parallel those of W. Liu and J. N. Hansen (Appl. Environ. Microbiol. 59:648-651, 1993) on the corresponding mutant of the related antibiotic subtilin, are discussed in terms of the mechanism(s) of action of these antibiotics.

Alanine↗
PubMed1996

Hiring by radiology groups in 1994.

PURPOSE: To assess the hiring activities of radiology groups in 1994 and changes between 1991 and 1994 in the employment market for diagnostic radiologists and radiation oncologists. MATERIALS AND METHODS: Questionnaires about recruitment and hiring were mailed to a stratified random sample of radiology groups in the United States; 92% (341 groups) responded. Data were compared with a 1991 telephone survey that included responses from 150 radiology groups. RESULTS: In 1994, radiology groups sought candidates for approximately 1,600 positions, a 29% decline from 1991. Fifteen percent of positions were in radiation oncology, 52% in general diagnostic radiology, and 33% in diagnostic subspecialties. As in 1991, groups filled three-fourths of their openings. The percentage of openings filled did not differ statistically significantly from one field or subspecialty to another. CONCLUSION: Available positions declined sharply. However, approximately 400 positions remained vacant at the end of the hiring season, with groups still actively recruiting for 75% of them. Employment is about equally difficult regardless of field.

Employment↗
PubMed1996

The demand side of the job market for diagnostic radiologists and radiation oncologists: hiring by physician groups in 1995.

OBJECTIVE: The American College of Radiology sought to assess the hiring activities of radiology groups in 1995, the 1995 employment market for diagnostic radiologists and radiation oncologists, and changes in the employment market since 1991. MATERIALS AND METHODS: We mailed surveys about recruitment and hiring to a stratified random sample of 600 radiology groups in the United States; 85% responded. The responses were weighted to show what they would have been if all of the approximately 3150 radiology groups in the United States had answered the survey. The findings were compared with similar surveys conducted in 1994 and 1991. RESULTS: In 1995, 31% (+/- 1% [SE]) of radiology groups actively recruited diagnostic radiologists or radiation oncologists, seeking to fill 1423 (+/- 119) openings. These figures represent a progressive decline from the 50% of groups recruiting and 2255 positions offered in 1991. In 1995, radiology groups filled 85% of available positions, compared with 76% in 1994 and 71% in 1991. In 1995, positions available because of expansion of radiology groups numbered 613 (+/- 73), considerably fewer than the estimated 720-position increase that takes place each year in the number of posttraining diagnostic radiologist and radiation oncologists in practice. In 1995, general diagnostic radiology accounted for approximately 48% of the full time-equivalent radiologists sought; radiation oncology, 11%; and the diagnostic subspecialties, 41%. We found few statistically significant differences among specialty and subspecialty fields in the percentage of available positions filled. Private, nonacademic groups offered 77% of their positions on a partnership track basis. Groups strongly affected by managed care recruited fewer radiologists and offered fewer expansion positions than similar groups that were less affected by managed care. However, managed care did not influence whether positions were offered on a partnership basis. CONCLUSION: Available positions continued to decline, and the shortfall of expansion positions relative to the annual growth in the workforce may generate serious employment problems. Managed care is having a negative effect on employment opportunities for radiologists. Gaining employment remains about equally difficult, regardless of field. The approximately 200 positions that remained unfilled at the end of the 1995 hiring season did not result from a mismatch between radiologists' skills and the qualifications that radiology groups were seeking.

Data Collection↗
PubMed1996

p53 mutational spectrum of esophageal carcinomas from five different geographical locales in China.

A mutational spectrum for exons 5-8 of the p53 tumor suppressor gene in esophageal carcinomas in mainland China and Hong Kong was established. This study involved 209 squamous cell carcinoma specimens obtained from five different geographical locales in China: Zhengzhou, Taiyuan, Shantou, Guangzhou, and Hong Kong. Zhengzhou and Shantou were high-incidence regions for esophageal cancer, whereas the other three regions had low or intermediate incidence of the disease. Analysis by single-strand conformation polymorphism and DNA sequencing showed that 87 specimens (41.6%) contained mutations in exons 5-8 of the p53 gene compared to 163 cases (78%) that had accumulation or aberrant expression of the protein, as detected by immunohistochemical staining. Point mutations accounted for 80.4% (87/107) of all genetic changes. The specimens from northern China exhibited fewer p53 gene aberrations and a more even distribution of mutations in exons 5-8 compared to those from southern China in which 60% of all mutations were found in exon 5. A major hot spot was found at codon 176 in exon 5, where 41 samples from Shantou, Guangzhou, and Hong Kong had a G-->T transversion. It is likely that among southern Chinese this codon is susceptible to mutagenesis by carcinogens. Codons 175, 203, 245, 250, 273, and 282 were also shown to be mutational hot spots, with three or more mutations observed at each site. The p53 mutational data obtained in this study showed that Chinese esophageal carcinomas are often associated with some unique genetic alterations, which may be attributed to specific dietary or environmental carcinogens that affect the Chinese but not Caucasians.

Adult↗