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Biomedical subjects

H Yee

Publications and source records attributed to H Yee.

At least 19 recordsLinked to original sources
PubMed2005

Proteasome inhibition with bortezomib (PS-341): a phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle.

PURPOSE: We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. PATIENTS AND METHODS: Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m2 on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. RESULTS: On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses > or = 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m2; 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. CONCLUSION: Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea.

Adult↗
PubMed2004

Fourier transform infrared (FTIR) spectral mapping of the cervical transformation zone, and dysplastic squamous epithelium.

OBJECTIVES: This paper is aimed at establishing infrared spectral patterns for the different tissue types found in, and for different stages of disease of squamous cervical epithelium. Methods for the unsupervised distinction of these tissue types are discussed. METHODS: Fourier transform infrared (FTIR) maps of the squamous and glandular cervical epithelium, and of the cervical transformation zone, were obtained and analyzed by multivariate unsupervised hierarchical cluster methods. The resulting clusters are correlated to the corresponding stained histopathological features in the tissue sections. RESULTS: Multivariate statistical analysis of FTIR spectra collected for tissue sections permit an unsupervised method of distinguishing tissue types, and of differentiating between normal and diseased tissue. By analyzing different spectral windows and comparing the results with histology, we found the amide I and II region (1740-1470 cm(-1)) to be very important in correlating anatomical and histopathological features in tissue to spectral clusters. Since an unsupervised, rather than a diagnostic, algorithm was used in these efforts, no statistical analysis of false-positive/false-negative results is reported at this time. CONCLUSIONS: The combination of FTIR micro-spectroscopy and multivariate spectral processing provides important insights into the fundamental spectral signatures of individual cells and consequently shows potential as a diagnostic tool for cervical cancer.

Cell Transformation, Neoplastic↗
PubMed2004

Identification of gammadeltaT lymphocytes in human periapical lesions.

Endodontic (root canal) therapy is required when the pulp of a tooth becomes necrotic due to a bacterial infection or trauma. A proportion of patients who receive endodontic therapy subsequently have periapical (around the tooth root) lesions detected by radiolucency. Currently, there are no means to identify susceptible patients. Although tissue from periapical lesions has been described as inflammatory, inflammatory cell types and their functions have been poorly characterized. For example, T lymphocytes were identified using pan specific anti-CD3 mAb, which recognizes both alphabeta and gammadeltaT cells. Using the current model of gammadeltaT cells as immunoregulatory cells; gammadeltaT cells can mediate protective or destructive milieus. We postulated that patients who have a periapical lesion, as identified by radiographic bone loss, mount a gammadeltaT cell response. We collected specimens removed by surgery from both periapical lesions and other oral tissues, generated total RNA and performed reverse-transcriptase polymerase chain reaction to identify rearranged delta genes. Results were confirmed with semi-nested polymerase chain reaction. In addition, we demonstrate that these lesions contain a population of CD3+ cells that are alphabetaT cell receptor negative, implying that these cells are gammadeltaT cells. Here we show that 36/37 of periapical lesions and only 2/11 of other lesions contain gammadeltaT cells (P<0.0001). Vdelta2+ T cells were the most common subtype identified (30/36) in these samples. This is the first report in the literature of the presence of gammadeltaT cells in human periapical lesions.

Adult↗
PubMed2004

Toxic epidermal necrolysis-like reaction secondary to colchicine overdose.

Colchicine is a microtubule-inhibiting drug used to treat gout, familial Mediterranean fever and many other skin diseases. Intoxication with colchicine affects multiple organs, often fatally. Cutaneous sequelae of colchicine toxicity are rare. We describe the clinical and histological features of a toxic epidermal necrolysis-like exanthem in a patient who lethally overdosed on colchicine.

Apoptosis↗
PubMed2002

Molecular mechanisms of nickel carcinogenesis.

Humans are exposed to carcinogenic nickel (Ni) compounds both occupationally and environmentally. In this paper, molecular mechanisms of nickel carcinogenesis are considered from the point-of-view of the uptake of nickel sulfide particles in cells, their dissolution and their effects on heterochromatin. Molecular mechanisms by which nickel induces gene silencing, DNA hypermethylation and inhibition of histone acetylation, will be discussed.

Acetylation↗
PubMed2002

Enhanced expression of a novel protein in human cancer cells: a potential aid to cancer diagnosis.

Cap43 is a protein whose RNA is induced under conditions of severe hypoxia or prolonged elevations of intracellular calcium. Cap43 protein is expressed at low levels in normal tissues; however, in a variety of cancers, including lung, brain, melanoma, liver, prostate, breast, and renal cancers, Cap43 protein is overexpressed in cancer cells. The low level of expression of Cap43 in some normal tissues compared to their cancerous counterparts combined with the high stability of Cap43 protein and mRNA makes the Cap43 gene a new, important cancer marker. We hypothesize that the mechanism of Cap43 overexpression in cancer cells involves a state of hypoxia characteristic of cancer cells where the Cap43 protein becomes a signature for this hypoxic state.

Blotting, Western↗
PubMed2001

Microphthalmia transcription factor: a sensitive and specific marker for malignant melanoma in cytologic specimens.

BACKGROUND: The diagnosis of melanoma can be difficult because of shared cytomorphology with other malignant neoplasms. The most commonly used melanocytic markers, anti-S-100 protein and HMB-45 antigen, have limited specificity and sensitivity, respectively. Microphthalmia transcription factor (Mitf) is a nuclear transcription factor critical for the development and survival of melanocytes and has been shown as a sensitive and specific marker for melanoma in histologic specimens. METHODS: To evaluate the efficacy of Mitf as a marker for melanoma in cytologic preparations, 81 cell blocks from 44 patients with melanoma and 37 patients with nonmelanoma malignancies (29 patients with carcinoma, 4 patients with mesotheliomas, 2 patients with lymphoma, and 2 patients with islet cell tumors) were stained with monoclonal antibodies against Mitf (clone D5), S-100 protein, and HMB-45 antigen. The staining was evaluated blindly by three independent observers. The presence of nuclear staining for Mitf and cytoplasmic staining for S-100 protein or HMB-45 antigen in > 10% of tumor cells was considered positive staining for each antigen. RESULTS: Forty-four melanomas (100%), including all 3 spindle-cell melanomas, were positive for Mitf. All nonmelanoma neoplasms were negative with only one exception: One mammary carcinoma showed rare (< 10%), weak nuclear staining with Mitf. The sensitivity and specificity of Mitf as a marker for melanoma were both 100%, whereas the sensitivity of HMB-45 antigen was 90.4%, and the specificity of S-100 protein was 70.3%. CONCLUSIONS: Mitf is a sensitive and specific marker for malignant melanoma, including the spindle-cell variant, in cytologic specimens and may be superior to the current standard melanocytic markers, S-100 protein and HMB-45 antigen.

Antibodies, Monoclonal↗
PubMed2001

Protein sizing on a microchip.

We have developed a microfabricated analytical device on a glass chip that performs a protein sizing assay, by integrating the required separation, staining, virtual destaining, and detection steps. To obtain a universal noncovalent fluorescent labeling method, we have combined on-chip dye staining with a novel electrophoretic dilution step. Denatured protein-sodium dodecyl sulfate (SDS) complexes are loaded on a chip and bind a fluorescent dye as the separation begins. At the end of the separation channel, an intersection is used to dilute the SDS below its critical micelle concentration before the detection point. This strongly reduces the background due to dye molecules bound to SDS micelles and also increases the peak amplitude by 1 order of magnitude. Both the on-chip staining and SDS dilution steps occur in the 100-ms time scale and are approximately 10(4) times faster than their conventional counterparts in SDS-PAGE. This represents a much greater speed increase due to microfabrication than has been obtained in other assay steps such as electrophoretic separations. We have designed and tested a microchip capable of sequentially analyzing 11 different samples, with sizing accuracy better than 5% and high sensitivity (30 nM for carbonic anhydrase).

Carbonic Anhydrases↗
PubMed2001

Effect of HIV-1 infection on lymphocyte proliferation in gut-associated lymphoid tissue.

OBJECTIVE: To determine the change in the percentage of proliferative and activated lymphocytes in gut-associated lymphoid tissue (GALT) in HIV-1-infected subjects compared with that in uninfected controls. METHODS: We measured the percentage of proliferative (Ki-67+) and activated (CD-69+, HLA-DR+, CD45RO+) lymphocytes from GALT and peripheral blood in chronically HIV-1-infected (12) and uninfected (9) individuals. RESULTS: The percentage of proliferative GALT CD4+ T cells was increased in HIV-1-infected control subjects compared with that in uninfected controls (p <.007). Based on immunohistochemical staining, proliferative T cells were principally located in the parafollicular area surrounding lymphoid aggregates. The percentage of activated GALT lymphocytes, however, was not significantly different in HIV-1-infected individuals, whereas it was significantly increased in the peripheral blood of HIV-1-infected individuals. The percentage of peripheral blood lymphocytes trafficking to the intestine was also not significantly different in HIV-1-infected individuals compared with that in uninfected controls. CONCLUSIONS: CD4+ T cell proliferation in GALT is increased in HIV-1 infection without a significant alteration in the percentage of peripheral blood T cells trafficking to the gastrointestinal mucosa.

Adult↗
PubMed2001

Increased matrix metalloproteinase expression and activation following experimental acute pancreatitis.

BACKGROUND: The observation that matrix metalloproteinases (MMPs) are central to tissue remodeling and may contribute to organ failure prompted us to investigate the role of MMPs in acute pancreatitis. We hypothesize that increased expression and activation of MMP-2 and MMP-9 will correlate with organ injury following acute pancreatitis. METHODS: Acute pancreatitis was induced in five male rats by retrograde infusion of 5% sodium taurocholate into the pancreatic duct. Sham laparotomy was performed on five rats serving as a control. Pancreatitis was confirmed by histology and serum amylase levels. MMP-2 and MMP-9 activity and expression were assayed by gelatin zymography in the lungs and ascitic fluid of each animal. Lung permeability was assayed by Evans blue dye extravasation. Lung activity of MMP-2 and MMP-9 was confirmed by a specific fluorogenic MMP substrate assay. RESULTS: Lung permeability increased twofold in the animals with severe pancreatitis compared with sham. Analysis of the zymograms from lung homogenate revealed a threefold increase in active MMP-2 in severe pancreatitis compared with sham and no change in MMP-9 activity. Gelatin zymograms of peritoneal fluid from severe pancreatitis animals demonstrated increased levels of active MMP-2 and MMP-9 compared with the sham group. Increases in MMP activity were confirmed by MMP activity assay using a fluorogenic substrate. CONCLUSIONS: This study demonstrates a correlation between severity of acute pancreatitis and active MMP-2 and MMP-9 levels in the peritoneal fluid and MMP-2 activity in lung homogenate. The MMP-mediated degradation of the basement membrane offers a potential pharmacologic and therapeutic target for halting the final biologic outcome of severe pancreatitis.

Acute Disease↗
PubMed2001

Expression of cell cycle regulators p57(KIP2), cyclin D1, and cyclin E in epithelial ovarian tumors and survival.

The search for new prognostic indicators is especially important in the diagnosis and treatment of ovarian cancer because clinicopathologic criteria currently used to predict survival are largely inadequate. We examined 2 groups of patients with epithelial ovarian cancer, 1 group of long-term survivors (>5 years), and 1 group of short-term survivors (<2 years) for levels of expression of the cell cycle regulators p57(KIP2), cyclin D1, and cyclin E and their relationship with survival. Our findings show that p57(KIP2) is not associated with prognosis, in contrast to p27(KIP1) expression, which is previously shown to be positively associated with long-term survival in univariate analysis (P =.001). Cyclin E expression, in contrast to cyclin D1 expression, is marginally associated with short-term survival in univariate analysis for a group of 53 women. Among the short-term survivors, 15 (65%) of 23 were positive for cyclin E expression, compared with only 11 (37%) of 30 long-term survivors (P = 0.054). This association remained significant (P =.04) in a logistic regression analysis adjusted simultaneously for performance status and extent of residual disease, the 2 strongest predictors of survival in our study. We also found a significant difference in the frequency of the cyclin E staining pattern between nonserous and serous ovarian tumor subtypes (P =.0002). Immunostaining for levels of cyclin E and p27(KIP1) expression may have potential as prognostic markers in the management of ovarian cancer.

Adenocarcinoma↗
PubMed2001

Motility-related proteins as markers for head and neck squamous cell cancer.

HYPOTHESIS: Increased cell motility is a hallmark of cancer cells. Proteins involved in cell motility may be used as molecular markers to characterize the malignant potential of tumors. METHODS: Molecular biology and immunohistochemistry techniques were used to investigate the expression of a selected panel of motility-related proteins (Rho A, Rac 2, Cdc42, PI3K, 2E4, and Arp2) in normal, premalignant, and squamous cell cancer cell lines of human head and neck origin. To assess the clinical potential of these proteins as molecular markers for cancer, immunohistochemistry was performed on paraffin-fixed head and neck cancer specimens (n = 15). RESULTS: All six motility-associated proteins were overexpressed in the premalignant and squamous cell cancer cell lines relative to normal keratinocytes. Immunohistochemistry with Rho A and Rac 2 showed increased staining in areas of cancer but not in normal tissue. CONCLUSION: Proteins involved in cell motility can be used as markers for head and neck squamous cell carcinoma. The head and neck cell lines used in this study may be used as a model to further investigate cell motility. Molecular markers of motility could have a significant impact on the diagnosis and staging of cancers originating from differentiated non-motile cells.

Biomarkers, Tumor↗
PubMed2001

Adhesion molecules as prognostic factors in nasopharyngeal carcinoma.

OBJECTIVE/HYPOTHESIS: To identify the significance of molecular markers in determining the risk of recurrence and distant metastases in nasopharyngeal carcinoma. STUDY DESIGN: In this retrospective case study, we evaluated archival nasopharyngeal carcinoma specimens for patterns of expression of E-cadherin, beta-catenin, c-erb-B2, and Ki-67, which have been demonstrated to be important in other tumors. METHODS: Fifty-four cases of nasopharyngeal carcinoma were identified, with a maximum follow-up of 13 years. The histopathological sections were stained using an automated immunohistochemical stainer (NexES, Ventana Medical Systems, Tucson, AZ) for E-cadherin (Zymed Laboratories [San Francisco, CA] and Transduction Laboratories [Lexington, KY] clones), beta-catenin (Zymed), c-erb-B2 (Ventana Medical Systems), and Ki-67 (Novocastra, Burlingame, CA). The numbers of positively staining cells were scored as follows: 0%, 1% to 33%, 34% to 66%, or greater than 67%. RESULTS: E-cadherin (Zymed) stained positively in only one case. The Transduction Laboratories clone demonstrated a spectrum of staining in all cases, from complete to disrupted to no identifiable membranous staining. The staining was consistently absent at the advancing tumor border, regardless of stage. The loss of beta-catenin expression did not correlate with that of E-cadherin or with clinical outcomes. No staining was identified for c-erb-B2. Ki-67 staining was variable and did not correlate with clinical outcomes. CONCLUSIONS: Altered expression or loss of E-cadherin, or both, may result in loss of function, particularly at the infiltrating edge, with resultant loss of cell polarity, cell migration, and eventual metastasis. The interpretation of E-cadherin staining depends on antibody source. In contrast to recent studies, beta-catenin expression is not altered and c-erb-B2 expression not identified, suggesting that these markers are not important in the prognosis of nasopharyngeal carcinoma.

Adult↗
PubMed2001

Aplastic anemia in systemic lupus erythematosus: a distinct presentation of acquired aplastic anemia?

Aplastic anemia is a rare but serious complication of systemic lupus erythematosus (SLE) with an often dramatic and unanticipated onset. The peripheral destruction of formed blood elements, which frequently accompanies the syndrome, may obscure or delay the diagnosis of bone marrow suppression, and the number of published cases may be an underestimate of the actual incidence of the disease. Furthermore, the disease course may differ significantly from other forms of acquired aplastic anemia and seems to carry a more favorable prognosis once effectively diagnosed and treated. In addition, aplastic anemia may precede other manifestations of SLE. Therefore, the possibility of bone marrow aplasia should be excluded in all SLE patients with severe pancytopenia, and conversely, the diagnosis of SLE should be explored in cases of aplastic anemia. Two patients with aplastic anemia in SLE, one with aplastic anemia preceding the onset of SLE, are described along with 15 cases reviewed from the English language literature. The presentation, prognosis, treatment, and pathogenesis of aplastic anemia complicating SLE are discussed. Recognition that cytopenias, especially pancytopenia, may occur on the basis of inhibited myelopoesis rather than peripheral destruction as either a harbinger of SLE or as a manifestation of disease flare is important. This knowledge will prompt the astute clinician to obtain screening antinuclear antibodies in the setting of otherwise unexplained bone marrow acellularity or, given the prognosis of SLE associated aplastic anemia, give early consideration to more aggressive immunosuppression.

Journal Article↗
PubMed2001

Risk group-based management of differentiated thyroid carcinoma.

A number of controversies exist in the treatment of differentiated thyroid carcinoma with respect to the extent of surgery, use of radioactive iodine and post-operative thyroxine suppression. Recent recognition of prognostic factors has helped to assign patients, based on their risk profile, as being at high risk of developing recurrence. This has facilitated the development of a selective approach to therapy, thus, avoiding unnecessary treatment and reducing morbidity without compromising treatment outcome. This review attempts to evaluate the current concepts of management of differentiated thyroid carcinoma in the light of these new developments.

Adenocarcinoma, Follicular↗
PubMed2000

Use of E-cadherin and CD44 aids in the differentiation between reactive mesothelial cells and carcinoma cells in pelvic washings.

BACKGROUND: The presence of malignant cells in peritoneal washings is an independent prognostic factor in the evaluation of gynecologic malignancies. The differentiation between reactive mesothelial cells and carcinoma cells can be a diagnostic challenge based on morphology alone. The expression of some cell adhesion molecules may be helpful in the differential diagnosis. METHODS: To evaluate the specificity of 2 transmembrane cell adhesion proteins (E-cadherin and CD44) in the differentiation of mesothelial cells from carcinoma cells in pelvic washings, formalin fixed, paraffin embedded cell blocks of pelvic washings from 19 cases of metastatic ovarian adenocarcinoma and 16 cases of benign peritoneal washings were immunostained with monoclonal antibodies to E-cadherin and CD44. The staining patterns were evaluated blindly by three observers. Positive staining was defined as uniform membranous staining for each marker. RESULTS: Fourteen benign peritoneal washings (87.5%) demonstrated immunoreactivity with anti-CD44. On the contrary, only four adenocarcinomas (21.1%) demonstrated anti-CD44 immunoreactivity. E-cadherin expression was identified in only 2 benign peritoneal washings (12.5%) whereas 16 adenocarcinomas (84.2%) strongly expressed E-cadherin. The differences in immunostaining for both CD44 and E-cadherin between benign and malignant peritoneal washings were statistically significant. The combination of positive staining for E-cadherin and negative staining for CD44 was 100% specific for metastatic adenocarcinoma, whereas a combination of negative staining for E-cadherin and positive staining for CD44 was 100% specific for reactive mesothelial cells. CONCLUSIONS: Both E-cadherin and CD44 reliably distinguish reactive mesothelial cells from adenocarcinoma. The combination of E-cadherin/CD44 is highly specific and is a useful diagnostic adjunct with which to distinguish benign reactive mesothelial cells from adenocarcinoma in pelvic washings.

Adenocarcinoma↗
PubMed2000

Calretinin staining pattern aids in the differentiation of mesothelioma from adenocarcinoma in serous effusions.

BACKGROUND: The differentiation between malignant mesothelioma and adenocarcinoma based on morphology alone can be a diagnostic challenge. The majority of the available antibodies recognize molecules expressed by adenocarcinoma whereas to the authors' knowledge specific markers for mesothelial cells are lacking. Calretinin, a calcium-binding protein, has been reported to be a selective marker for mesothelioma and largely is absent from adenocarcinoma on histologic material. The results with cytologic preparations have been inconsistent. METHODS: To evaluate the specificity of calretinin in differentiating mesothelioma from adenocarcinoma in cytologic preparations, 21 paraffin embedded cells blocks of serous effusions from 15 patients with metastatic adenocarcinoma and 16 cell blocks from 9 patients with malignant mesothelioma were stained with a monoclonal antibody against calretinin. The immunoreactivity was evaluated blindly by two observers. Positive staining was defined as nuclear and cytoplasmic staining with or without intense membranous decoration. The former resulted in a characteristic "fried egg" appearance. RESULTS: Calretinin staining was positive in all but 2 cases of mesothelioma (14 of 16 cases; 87.5%). The latter contained predominantly spindle-shaped neoplastic mesothelial cells in the cell block preparations. All adenocarcinoma specimens were classified as negative for calretinin staining; 9 (42.9%) lacked any immunoreactivity and 12 (57.1%) showed weak, sparse, coarse, granular cytoplasmic staining without nuclear or membranous staining. Benign reactive mesothelial cells, when observed in association with adenocarcinoma, also showed the characteristic "fried egg" appearance. The difference in the staining pattern of calretinin between cells of mesothelial origin and adenocarcinoma cells was statistically significant. CONCLUSIONS: Calretinin is a useful marker in differentiating mesothelioma of the epithelial type from adenocarcinoma in serous effusions. The "fried-egg" appearance or cytoplasmic and nuclear staining pattern is characteristic of cells of mesothelial origin.

Adenocarcinoma↗