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W C Chan

Publications and source records attributed to W C Chan.

At least 19 recordsLinked to original sources
PubMed2026

Methylation profiling of normal tissue adjacent to breast tumors reveals two distinct groups with divergent tumor microenvironment features.

We previously identified diverse genetic evolutionary patterns in whole-genome sequencing of paired normal tissue adjacent to tumor (NAT) and tumor tissues from Hong Kong breast cancer (HKBC) patients. Here, we investigated whether DNA methylation (DNAm) contributes to NAT heterogeneity and shapes the tumor microenvironment (TME). Genome-wide DNAm profiling was performed on paired NAT and tumor tissues from 188 HKBC patients using the Infinium 850 K array. RNA-seq data were available for 76 NATs and 177 tumors. Cellular composition was inferred using MethylCIBERSORT, CIBERSORTx, and EpiDISH, and histopathologic features were assessed on 115 H&E-stained sections. Unsupervised clustering identified two distinct NAT subtypes with divergent TME characteristics. Cluster 1 (N = 139) showed higher epithelial and fibroblast content and enrichment of estrogen response pathways. Cluster 2 (N = 49) exhibited an immune-metabolic phenotype characterized by increased fat and immune cells, stromal disruption, inflammatory pathway activation, and greater macrophage infiltration. Cluster 2 patients also demonstrated significantly younger epigenetic age estimated using multiple epigenetic clocks. These DNAm-defined NAT subtypes and associated TME features were validated in 97 NAT samples from TCGA breast cancer patients. Overall, our findings identify DNAm-driven NAT heterogeneity with distinct TME landscapes, providing new insights into field cancerization and tumor evolution in breast cancer.

Journal Article↗
PubMed1992

Solution structures of nisin A and its two major degradation products determined by n.m.r.

The conformations of nisin and two major degradation products, nisin-(1-32)-peptide (nisin1-32) and des-delta Ala5-nisin1-32 (where delta Ala is alpha beta-didehydroalanine), in aqueous solution have been determined from n.m.r. data. Sequential assignments of the peptides using correlation spectroscopy ('COSY'), homonuclear Hartmann-Hahn spectroscopy ('HOHAHA'), nuclear Overhauser enhancement spectroscopy (NOESY), relayed NOESY and rotating-frame nuclear Overhauser spectroscopy (ROESY) experiments are presented, including stereospecific assignments of beta-methylene protons of the lanthionine residues. ROESY experiments are also used to detect flexible regions in the polypeptide chain. A dynamic-stimulated-annealing approach is used for structural determination. It can be concluded that all these peptides are flexible in aqueous solution, with no experimental evidence of preferred overall conformations; the only defined conformational features are imposed by the presence of the lanthionine residues. Low-temperature studies also reveal that des-delta Ala5-nisin1-32 adopts conformations similar to those when the ring is intact, suggesting that the loss of activity of this degradation product is due to the absence of the delta Ala5 residue rather than to the conformational consequences of ring-opening.

Amino Acid Sequence↗
PubMed1992

Sequence-specific resonance assignment and conformational analysis of subtilin by 2D NMR.

Subtilin, a 32-amino acid peptide with potent antimicrobial activity, has been isolated from Bacillus subtilis ATCC6633. The chemical structure has been confirmed by the unambiguous sequence-specific assignment of its 1H NMR spectrum. Detailed NMR analysis revealed that subtilin is a rather flexible molecule; the only observed conformational contraints were those imposed by the cyclic structures created by the lanthionine and 3-methyllanthionine residues. These results suggest that in aqueous solution subtilin and the homologous peptide nisin have similar conformations.

Amino Acid Sequence↗
PubMed1992

Plasmacytoid monocyte proliferation associated with myeloproliferative disorders.

Plasmacytoid T-cell (PTC) lymphoma is a rare clinicopathologic entity characterized by generalized lymphadenopathy in association with a myeloproliferative disorder. Hepatosplenomegaly and weight loss frequently are present. Nodal T-zone expansion by mononuclear cells with ultrastructural and immunohistochemical features typical of PTC is diagnostic. All of the five previously reported cases of PTC lymphoma coincided with or heralded the onset of a clinically aggressive myeloid leukemia. This strong association and recent immunohistochemical findings in reactive or neoplastic PTC favored a monocyte/macrophage derivation of these cells, and it has been suggested that they be renamed plasmacytoid monocytes (PM). Two additional cases of PTC lymphoma were studied at the institutions of the authors, and the findings supported the concept that PTC belong to the monocytic lineage. The disease presentation was generalized lymphadenopathy with constitutional symptoms. One patient also had hepatosplenomegaly and bilateral renal enlargement concomitantly with myelofibrosis with myeloid metaplasia that progressed within months to acute myelogenous leukemia. Similar rapid evolution of acute monoblastic leukemia occurred in the other patient. Tumor cells within subtotally effaced lymph nodes had positive findings for CD45, CD4, CD7, and LN2 and negative findings for CD3, CD8, and beta F1. Occasional cells had positive findings for CD2. One case demonstrated CD5, HLA-DR, CD71, and CD43 (Leu-22)-positive cells. The myeloid/monocyte-associated antigens CD14 and CD68 were identified in both. The tumor cells lacked the B-cell markers LN1, CD20 (L26), CD19, and CD22 and did not rearrange immunoglobulin heavy chain genes and T-cell receptor beta, gamma, and delta chain genes. The term plasmacytoid T-zone lymphoma or PM proliferation is more appropriate for this rare disease. The close association of the PM proliferation with a myeloproliferative disorder indicates that the two entities are related.

Acute Disease↗
PubMed1992

Large granular lymphocyte proliferation with the natural killer-cell phenotype.

Lymphoproliferated disorders involving large granular lymphocytes (LGL) can be divided into a common T-cell subset (CD3+, CD8+) and a rarer natural killer (NK)-cell subset (CD2+, CD3-). The immunophenotype, clinical pathologic features, and cytogenetic and molecular genetic analyses are reported for seven patients with NK-cell-LGL proliferation. The typical immunophenotype was CD2+, CD3-, CD4-, CD11b+, and CD16+ or CD56+. A low but variable percentage of cells were CD8+ or CD57+. Unusual phenotypes with CD2- (1 of 7), CD11b- (1 of 7), or CD16-/CD56- (1 of 7) cells were seen. Strong NK-cell activity was observed in all cases, indicating that none of the NK-cell markers (CD11b, CD16, CD56, CD57) is essential for NK-cell activity. One patient died shortly after diagnosis from coexistent refractory multiple myeloma and another patient died within 1 month from the LGL proliferation. The other patients had been followed for 12 to 70 months, with a median follow-up period of 38 months. There was no progression of their LGL proliferation. Lymphocyte counts varied from 3.3 x 10(3)/microL to 58.4 x 10(3)/microL at the time of diagnosis. Unexplained anemia and neutropenia were observed in one patient. Cytogenetic abnormalities were detected in two of four patients studied with t(6;12) in one and der(5), der(6), and der(11) in the other. The approximately T gamma and T beta genes were in the germline configuration and Epstein-Barr virus DNA was undetectable in five of five patients studied. Natural killer-cell LGL proliferations were morphologically indistinguishable from T-cell LGL proliferations. However, the two were immunophenotypically and genotypically distinct and NK-cell activity was consistently observed in the former. Most of the NK-cell proliferations also were chronic indolent disorders and the incidence of associated cytopenias seemed to be lower than T-cell LGL proliferations.

Adult↗
PubMed1992

Acute megakaryoblastic leukemia in infants with t(1;22)(p13;q13) abnormality.

Six infants with acute megakaryoblastic leukemia and a translocation (1;22)(p13;q13) were studied. There were five female infants and one male infant, and the age at initial examination varied from 0.8 to 6.5 months (median, 2.3 months). All the patients had hepatosplenomegaly and anemia (6 to 8.3 g/dL), and four patients had thrombocytopenia (9,000 to 63,000/mm3). The bone marrow showed prominent fibrosis in five cases and reticulin fibrosis in one patient at presentation. Crush artifact often made the histologic sections difficult to interpret, but typical megakaryoblasts could be identified in the smears. Biopsy specimens of the liver and lymph node were suggestive of a nonhematopoietic malignant condition because of the cohesiveness of the tumor cells, stromal fibrosis, and the prominent sinusoidal and vascular pattern of infiltration. Immunophenotyping of peripheral blood mononuclear cells was helpful in identifying the blasts as belonging to the megakaryoblastic lineage. Using a panel of mononclonal antibodies, it was also possible to confirm the nature of the infiltration in paraffin sections and to differentiate it from other childhood small round cell tumors, especially neuroblastoma in paraffin sections (typical staining pattern: CD45-, CD43+, vW Factor, Ulex europeus I+, CD20-, CD45RO-, synaptophysin-, chromogranin-, cytokeratin-, desmin-). This special type of infantile acute leukemia can be recognized with confidence if one is aware of its clinical features, peculiar pathologic characteristics, the morphologic features and immunophenotype of the megakaryoblasts, and the unique cytogenetic abnormality.

Biopsy↗
PubMed1992

How accurate was GMENAC?--A retrospective review of supply projections for diagnostic radiologists.

In 1982, the Graduate Medical Education National Advisory Committee (GMENAC), a prominent national panel, predicted there would be 25,650 full-time equivalent (FTE) diagnostic radiologists, a 34% oversupply, by 1990. The radiologists involved in GMENAC, however, using models developed by the American College of Radiology, projected 19,800 FTE diagnostic radiologists in 1990, which was similar to the GMENAC estimate of need. The disagreement arose principally from different assumptions about residents entering the specialty. Recent data show there actually were approximately 21,900 FTE diagnostic radiologists in 1990. The radiologists' projection was 10% below this figure; the GMENAC projection was 17% above it. GMENAC erred principally in assuming diagnostic radiology residencies would not replace general radiology residencies, but rather be an addition to them. The radiologists erred principally in their assumption about the effects of the financial problems of hospitals on the number of residency positions. Accurate long-term projection of physician supply in individual specialties may well not be feasible.

Forecasting↗
PubMed1991

Lymphomatous polyneuropathy. Biopsy of clinically involved nerve and successful treatment.

We present a patient with large-cell lymphoma in remission who, over several weeks, developed widespread multifocal polyneuropathy. There was involvement of all four limbs, most severely the left upper extremity that had become useless. Biopsy of the left saphenous nerve within an area of sensory loss showed lymphoma in the endoneurium. There was no other evidence of recurrent lymphoma despite extensive investigation, including bone marrow, lumbar puncture, magnetic resonance imaging of the spine, and computed tomography of the abdomen and pelvis. Intensive systemic chemotherapy was accompanied by nearly complete recovery. Biopsy of a symptomatic nerve is preferable to routine sural nerve biopsy in this condition because of its patchy distribution. Treatment with systematic chemotherapy can be effective.

Adult↗
PubMed1991

Extrachromosomal human immunodeficiency virus type-1 DNA can initiate a spreading infection of HL-60 cells.

In this report, we describe a human immunodeficiency virus type-1 (HIV-1)-infected promyelocytic cell line, OM, derived from HL-60 cells. Although the OM cell line was biologically cloned twice, the pattern of HIV-1 expression during culture appeared analogous to a classical acute spreading infection and was inhibited by both azidothymidine and recombinant soluble CD4 treatment. The number of OM cells actually expressing HIV-1 at the beginning of culture was 0%, reached a peak of nearly 100% at 6 weeks, and then fell to less than 10% HIV-1+ cells by 10 weeks. Clonal analysis of the surviving cells verified that stable HIV-1+ OM cells resulted from the spreading infection. Southern analysis confirmed the transmission of HIV-1 through these OM cultures and the occurrence of stable clones which resulted. The initial percentage of OM cells actually harboring the HIV-1 genome was less than 0.1%, indicating nonfaithful transmission of an unintegrated HIV-1 genome during clonal expansion. These results demonstrate that extrachromosomal HIV-1 DNA can contribute to the spread of HIV-1 infection and give rise to cells which have stably integrated HIV-1 provirus.

Blotting, Southern↗
PubMed1991

Radiology practices and their contracts with hospitals, 1989-1990: a representative sample survey.

Because of concern about pressures from hospitals for changes in their contracts with radiology practices, the American College of Radiology undertook a stratified sample survey of radiology practices and their contracts with hospitals in late 1989 and early 1990. After three remailings, the survey obtained 904 valid responses for a 64% response rate. It found (weighting data to represent all radiology practices in the nation) that 91% of radiology practices provide services in hospitals. There are contracts at 57% of these hospital sites, and hospitals use tax-exempt bond financing in 54% of the sites with contracts. One year is the most common duration of contracts, and 90 days is the most common cancellation period (89% of contracts can be canceled during the contract's term). Eighty-six percent of contracts are exclusive; 73% are automatically renewable ("evergreen"). Separate billing exists in well over 90% of hospitals with contracts. Two percent of contracts require radiologists to provide equipment; 4% require them to provide support staff. There are fixed-fee arrangements in 9% of contracts and percent compensation arrangements in 3%. Hospitals share in radiologists' fees as a charge for contractual privileges in 5% of contracts. Twenty-seven percent of contracts require hospital approval for radiologists' fee increases; 19% require radiologists to participate with Blue Shield or Medicare. If a contract characteristic is predominant nationally, it is predominant in every region, for solo, small, medium, and large practices, and whether or not hospitals use tax-exempt bond financing. There is, however, some modest variation in frequency of contract provisions. Multivariate analysis shows that most such variation reflects true effects of region and other variables, not statistical artifacts. Region was a statistically significant determinant of 11 of 17 contract characteristics studied. Practice size was a statistically significant determinant of only about half as many characteristics. The survey found some interference in the independence of radiology practices (e.g., required hospital approval of fee increases), questionable clauses (e.g., mandated provision of equipment), and even illegal ones (hospitals charging a fee for contract privileges). Knowledge of the survey findings can make individual radiology practices more effective in negotiations with hospitals and assist the profession in forming a strategy to oppose disadvantageous and illegal provisions.

Capital Financing↗
PubMed1991

Mature B-cell acute leukemia: a clinical, morphological, immunological, and cytogenetic study of nine cases.

Nine patients who presented with acute lymphoid leukemia of mature B-cell phenotype without FAB-L3 morphology are discussed. All patients were male with a median age of 69 years. All patients had extensive bone marrow involvement at presentation with lymphoid leukemic cells in the peripheral blood. Six patients had extramedullary disease and 3 developed meningeal involvement sometime during the course of their illness. The leukemic cells were negative for terminal deoxynucleotidyl transferase in all 9 cases, and monoclonal surface immunoglobulin was demonstrated in all 8 cases evaluated with a lambda light chain predominance. Clonal chromosomal abnormalities were detected in 4 of 6 cases studied with no specific pattern identified, although abnormalities involving chromosome 8 were present in all 4 cases. Despite aggressive chemotherapy, only 2 patients achieved complete remission which was of short duration (1 month) in 1 patient. Eight patients died of their disease 1 week to 20 months after diagnosis with a median survival of 5.5 months. Mature B-cell acute leukemias that are not of the FAB-L3 type have a very aggressive clinical course and poor prognosis.

Adult↗
PubMed1990

Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a recently recognized, relatively rare atypical lymphocytosis characterized by the presence of over 2000 lymphocytes with cytoplasmic azurophilic granules/mm3 in the peripheral blood. The clinical course is heterogeneous, varying from spontaneous regression to progressive, malignant disease. As a consequence, clinical intervention is not standardized. In a worldwide multicenter study, the authors observed 151 patients with LDGL for a mean follow-up time of 29 months. Forty-three patients were asymptomatic at the time of diagnosis. In the remaining cases, clinical symptoms included fever (41 cases), infections (58), neutropenia (47), anemia (17), and thrombocytopenia (12). In 69 cases, LDGL coexisted with an associated disease. Most patients had a nonprogressive clinical course despite the presence of severe symptoms. In 19 patients, death related to LDGL occurred within 48 months. The authors investigated which features at diagnosis were significantly associated with increased mortality. In the univariate analysis, lymph node and liver enlargement, fever at presentation, skin infiltration, a low (less than or equal to 5000/mm3) or high (greater than 20,000/mm3) peripheral leukocyte count, relatively low (less than or equal to 3000) or high (greater than 7000/mm3) absolute peripheral granular lymphocyte (GL) count, and a low (less than or equal to 15%) percentage of HNK-1-positive cells were found to be predictors of increased mortality. In the multivariate analysis, significant independent predictors were fever at diagnosis, a low (less than or equal to 15%) percentage of HNK-1-positive peripheral blood mononuclear cells (PBMC) and a relatively low (less than or equal to 3000) GL count. These results showed that about 25% of the patients with LDGL were diagnosed after a routine blood count and had no clinical symptoms. The remaining patients were symptomatic, with some experiencing a fatal clinical course. The author's analysis of the significant prognostic features of LDGL may help in understanding the heterogeneous nature of this syndrome.

Adolescent↗
PubMed1990

Chromosomal localization of the human myeloperoxidase gene by in situ hybridization using oligonucleotide probes.

Oligonucleotide probes have been used to map the myeloperoxidase (MPO) gene locus to chromosome bands 17q21-22. This is in agreement with results reported using conventional cDNA probes. No evidence for the existence of a second MPO gene locus was obtained. Six synthetic 72-base oligonucleotides, corresponding to different exon regions of the MPO gene, were tritium-labeled and used as in situ hybridization probes. Synthetic oligonucleotide probes offer a useful alternative to conventional DNA probes for gene mapping.

Chromosome Banding↗
PubMed1990

C595--a monoclonal antibody against the protein core of human urinary epithelial mucin commonly expressed in breast carcinomas.

Urinary mucins which express determinants for the anti-breast carcinoma monoclonal antibody, NCRC-11 (IgM), closely resemble the mammary mucins found in milk fat globules and carcinomas. An IgG3 monoclonal antibody, C595, was prepared against urinary mucins isolated on a NCRC-11 antibody affinity column, and this 'second generation' antibody was shown to have a very similar pattern of reactivity to the original NCRC-11 antibody. By immunohistology, the profile of reactivity of both antibodies with tumour and normal tissue specimens was virtually identical. Both antibodies reacted with epithelial mucins isolated from breast tumours or normal urine using an NCRC-11 antibody affinity column, although the antibodies were unreactive with other antigen preparations. Heterologous immunoradiometric assays ('sandwich' tests) confirmed that NCRC-11 and C595 epitopes were co-expressed on the same molecule. C595 antibodies inhibited the binding of radiolabelled NCRC-11 antibodies to antigen, suggesting that the two epitopes were in close topographical proximity. The protein core of the mammary mucins has recently been shown to consist predominantly of a repeated 20 amino acid sequence (Gendler et al., 1988). Peptides with this complete sequence and small fragments were synthesised, and the C595 antibody was found to recognise an epitope within this repeat. The ability to identify and synthesise monoclonal antibody-defined determinants, as well as those in the adjacent or overlapping sequences within the protein core of epithelial mucins, is viewed as a strategy for facilitating the production of antibodies of new and novel specificity to complement the panels of existing anti-breast cancer reagents.

Antibodies, Monoclonal↗
PubMed1990

Early detection of left ventricular mural thrombi after acute Q wave myocardial infarction using 111In oxine-labelled autologous platelets.

Autologous 111In oxine-labelled platelet scintigraphy was used to detect left ventricular thrombi in 20 patients with anterior and 18 patients with inferior Q wave myocardial infarction within 48-72 h. Left ventricular thrombi were found in 8/20 patients with anterior myocardial infarction and in 1/18 patients with inferior myocardial infarction, giving a total incidence of 24%. Patients with left ventricular thrombi were older (64.3 versus 58.2 years), had higher peak creatinine kinase (CK) levels (4523 versus 2749 IU 1-1), lower ejection fraction (19.5 versus 37.8%, P less than 0.005) and were more likely to have an enlarged left ventricle than those without left ventricular thrombi (87.5 versus 54.5%, P less than 0.001). Left ventricular thrombi were found overlying sites of myocardial infarction in 8 out of 9 patients. Apical left ventricular thrombi were 1.7 times more common than septal left ventricular thrombi. All patients received minidose heparin for prevention of deep venous thrombosis. This technique is complementary to echocardiography and may provide additional information in the difficult cases where the decision about full-dose anticoagulation is in doubt.

Adult↗
PubMed1990

Studies of myeloperoxidase gene expression at the cellular level by in situ hybridization.

Recent studies have demonstrated myeloperoxidase (MPO) gene expression during granulocytic differentiation. Since these studies have been done exclusively by Northern and dot blot analysis and frequently with mixed populations of cells, quantitative changes in gene expression for particular populations of cells are difficult to assess. We therefore examined MPO expression at the cellular level in various normal and malignant hematopoietic cells by the in situ hybridization (ISH) technique. Using this approach, we demonstrated that inducing the promyelocytic HL-60 cell line to differentiate along either monocytic or granulocytic pathways decreases MPO mRNA expression. Similarly, when ISH was performed on normal bone marrow, relatively high levels of MPO mRNA were detected in myeloblasts, promyelocytes, and early eosinophilic precursors, whereas the expression was markedly decreased in more advanced stages of myeloid differentiation. These findings agree with the known decrease in MPO protein synthesis observed during granulocytic differentiation and suggest that regulation of MPO protein synthesis occurs at the level of MPO mRNA expression. We conclude by showing that ISH can detect MPO mRNA in myeloblasts of patients with acute leukemia and can be a potentially useful technique in the study of myeloid differentiation in acute leukemias.

Adolescent↗