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Biomedical subjects

K Y Yeung

Publications and source records attributed to K Y Yeung.

At least 19 recordsLinked to original sources
PubMed2001

RP1 in Chinese: Eight novel variants and evidence that truncation of the extreme C-terminal does not cause retinitis pigmentosa.

Heterozygous truncating mutations in the RP1 gene cause approximately 7% of autosomal dominant retinitis pigmentosa (RP) cases. To examine the role of RP1 mutations in RP, we screened 101 unrelated Chinese RP patients (unselected for mode of inheritance) and 190 elderly normal control subjects for sequence changes in the coding exons for the 2156 amino acid RP1 protein. One patient had a mutation, thus RP1 mutations cause about 0.0% to 5.4% (95% confidence interval) of all RP among Chinese. The mutation was R677X, the most common found in Americans. Five other known sequence changes were found. In addition, nine novel sequence alterations were identified: 746G>A (R249H), 1437G>T (M479I), 2116G>C (G706R), 3024G>A (Q1008Q), 3188G>A (Q1063R), 5797C>T (R1933X), 6423A>G (I2141M), and the variants 6542C>T and 6676T>A, both in the 3' untranslated region. One control subject and three members of a non-RP family were heterozygous for R1933X, which is therefore likely to be a non-disease-causing variant. The most C-terminal truncation previously reported was due to Tyr1053 (1-bp del) and occurred in RP patients. Thus the presence of a normal level of at least part of RP1 between amino acids 1052 and 1933 appears necessary to prevent RP. Hum Mutat 17:436, 2001.

3' Untranslated Regions↗
PubMed2001

Molecular diagnostics for retinitis pigmentosa.

BACKGROUND: At least 1 million people worldwide have retinitis pigmentosa (RP), making it relatively common among the inherited forms of blindness. Mutations in many genes may cause RP. The most common known mutation, Pro347Leu in rhodopsin, is found in no more than about 1% of unrelated patients, implying the impracticality of a diagnostic test which would screen only for a few, common mutation sites. CONCLUSIONS: Ongoing discovery and study of RP genes makes it feasible to consider a molecular diagnostic test which would screen coding regions of all known RP genes by a mutation detection method such as conformation-sensitive gel electrophoresis followed by sequencing. The parallel development of RP genetic knowledge and treatments such as gene therapy will make such tests both possible and necessary.

China↗
PubMed2001

Model-based clustering and data transformations for gene expression data.

MOTIVATION: Clustering is a useful exploratory technique for the analysis of gene expression data. Many different heuristic clustering algorithms have been proposed in this context. Clustering algorithms based on probability models offer a principled alternative to heuristic algorithms. In particular, model-based clustering assumes that the data is generated by a finite mixture of underlying probability distributions such as multivariate normal distributions. The issues of selecting a 'good' clustering method and determining the 'correct' number of clusters are reduced to model selection problems in the probability framework. Gaussian mixture models have been shown to be a powerful tool for clustering in many applications. RESULTS: We benchmarked the performance of model-based clustering on several synthetic and real gene expression data sets for which external evaluation criteria were available. The model-based approach has superior performance on our synthetic data sets, consistently selecting the correct model and the number of clusters. On real expression data, the model-based approach produced clusters of quality comparable to a leading heuristic clustering algorithm, but with the key advantage of suggesting the number of clusters and an appropriate model. We also explored the validity of the Gaussian mixture assumption on different transformations of real data. We also assessed the degree to which these real gene expression data sets fit multivariate Gaussian distributions both before and after subjecting them to commonly used data transformations. Suitably chosen transformations seem to result in reasonable fits. AVAILABILITY: MCLUST is available at http://www.stat.washington.edu/fraley/mclust. The software for the diagonal model is under development. CONTACT: kayee@cs.washington.edu. SUPPLEMENTARY INFORMATION: http://www.cs.washington.edu/homes/kayee/model.

Algorithms↗
PubMed2001

Validating clustering for gene expression data.

MOTIVATION: Many clustering algorithms have been proposed for the analysis of gene expression data, but little guidance is available to help choose among them. We provide a systematic framework for assessing the results of clustering algorithms. Clustering algorithms attempt to partition the genes into groups exhibiting similar patterns of variation in expression level. Our methodology is to apply a clustering algorithm to the data from all but one experimental condition. The remaining condition is used to assess the predictive power of the resulting clusters-meaningful clusters should exhibit less variation in the remaining condition than clusters formed by chance. RESULTS: We successfully applied our methodology to compare six clustering algorithms on four gene expression data sets. We found our quantitative measures of cluster quality to be positively correlated with external standards of cluster quality.

Algorithms↗
PubMed2001

Principal component analysis for clustering gene expression data.

MOTIVATION: There is a great need to develop analytical methodology to analyze and to exploit the information contained in gene expression data. Because of the large number of genes and the complexity of biological networks, clustering is a useful exploratory technique for analysis of gene expression data. Other classical techniques, such as principal component analysis (PCA), have also been applied to analyze gene expression data. Using different data analysis techniques and different clustering algorithms to analyze the same data set can lead to very different conclusions. Our goal is to study the effectiveness of principal components (PCs) in capturing cluster structure. Specifically, using both real and synthetic gene expression data sets, we compared the quality of clusters obtained from the original data to the quality of clusters obtained after projecting onto subsets of the principal component axes. RESULTS: Our empirical study showed that clustering with the PCs instead of the original variables does not necessarily improve, and often degrades, cluster quality. In particular, the first few PCs (which contain most of the variation in the data) do not necessarily capture most of the cluster structure. We also showed that clustering with PCs has different impact on different algorithms and different similarity metrics. Overall, we would not recommend PCA before clustering except in special circumstances.

Algorithms↗
PubMed2001

Rhodopsin mutations in Chinese patients with retinitis pigmentosa.

AIM: To determine the pattern of rhodopsin mutations in Chinese retinitis pigmentosa (RP) patients. METHODS: The rhodopsin gene was examined in 101 RP patients and 190 controls from Hong Kong. RESULTS: Three coding changes were identified: Pro347Leu, Ala299Ser, and 5211delC. Each protein sequence alteration was found in one patient. Ala299Ser also existed in two controls. CONCLUSION: The C-terminal nonsense mutation may cause mis-sorting of rhodopsin protein. The finding of controls with Ala299Ser suggests this is only the third missense alteration reported that does not cause RP. The expected frequency of rhodopsin mutations in RP is <7% (2/101=2.0%, 95% confidence interval: 0.2%-7.0%).

Adult↗
PubMed1993

Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program.

PURPOSE: To evaluate the efficacy of three hormonal manipulations in the palliation of chemoresistant ovarian cancer, and to analyze the results in the light of other clinical trials. PATIENTS AND METHODS: Three sequential phase II trials were performed in patients with refractory epithelial ovarian carcinoma, using high-dose megestrol acetate (800 mg/d for 30 days, then 400 mg/d), high-dose tamoxifen (80 mg/d for 30 days, then 40 mg/d), and aminoglutethimide (1 g/d plus tapering doses of hydrocortisone). Results were compared with those described in the world literature from trials of the same or similar agents. RESULTS: No responses were seen among 30 assessable patients treated with megestrol acetate, and most (but not all) similar trials have reported low response rates. Five responses (17%) were seen among 29 patients treated with tamoxifen. Two responses exceeded 5 years in duration. No responses were seen among 15 patients treated with aminoglutethimide. CONCLUSION: Antiestrogen therapy may offer the possibility of useful and, occasionally, long-term palliation of refractory epithelial ovarian carcinoma, with little toxicity. There may be a trend toward a dose-response effect, which represents a suitable topic for a future prospective trial.

Adenocarcinoma↗
PubMed1991

Methods for enumerating Escherichia coli in subtropical waters.

The standard membrane filtration method of the UK has been modified in order to improve its specificity for enumerating Escherichia coli in the subtropical waters of Hong Kong. This involves incorporating into the membrane lauryl sulphate (mLS) method either an in situ urease test (the mLS-UA method), or an in situ beta-glucuronidase test (the mLS-GUD method). The false-positive errors of the mLS-UA and mLS-GUD methods are low, ranging from 3-5%. A comparison between the membrane filtration (mLS-UA) method and the multiple tube technique in testing E. coli in subtropical beach-waters has demonstrated that the former can give much more precise counts, and is the method of choice for such a purpose. The mLS-GUD method, for which automated counting of E. coli colonies is possible, is a good alternative to mLS-UA in routine enumeration of this bacterial indicator in environmental waters.

Colony Count, Microbial↗
PubMed1988

Alcohol-induced vacuolization in bone marrow cells: ultrastructure and mechanism of formation.

Vacuolization has been known for two decades to occur in the cytoplasm and over the nuclei of the erythroid and myeloid precursors in bone marrows of patients with acute alcoholism. Electron microscopic examination of the marrows from four acute alcohol-intoxicated subjects disclosed that the vacuoles are present only in the cytoplasm and free of organized structure. Surface invagination of the cell membrane of erythroblasts leads to endocytosis and consequent vacuole formation. Cytoplasmic vacuolization of bone marrow cells was reproduced in vitro in 8 of 12 bone marrows from normal individuals when incubated for 6 hours or more in nutrient medium containing alcohol. The critical alcohol concentration for vacuolization was 62.5 mg/dl. The proportion of cells developing vacuoles appeared to correlate with the concentration of alcohol particularly above levels of 250 mg/dl.

Adult↗
PubMed1985

The cyclophosphamide, hexamethylmelamine, 5 fluorouracil (CHF) regimen in the treatment of advanced and recurrent ovarian cancer.

Fifty-one patients with advanced ovarian carcinoma were treated with a combination of cyclophosphamide, hexamethylmelamine, and 5-fluorouracil, CHF. Compared to the hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (Hexa-CAF) regimen, the omission of methotrexate in CHF did not detract from its antitumor activity and it was well tolerated with only mild to moderate toxicity. The CHF combination was as effective as Hexa-CAF and was particularly active in patients who had nonmeasurable/residual disease, classified as less than 2 cm in its greatest diameter at the initiation of chemotherapy. In future studies, CHF should be prospectively compared to other combination using Adriamycin and cis-platinum that with extended use can cause renal and cardiac damage in long-term survivors.

Adult↗
PubMed1985

Phase I clinical evaluation of oral and intravenous 4-demethoxydaunorubicin.

Thirteen patients were treated with both the oral and intravenous preparations of 4-demethoxydaunorubicin (DMDR). The drug was well tolerated in both forms. Neutropenia was the dose-limiting side-effect. Approximately 30% of the compound was absorbed when given orally. The maximum tolerated dose was 12.5 mg/m2 intravenously or 50 mg/m2 (10 mg/m2 q d X 5) orally, given every 21-28 days.

Administration, Oral↗
PubMed1979

Asbestos-associated neoplasms of B cell lineage.

Three different neoplasms of B cell lineage, chronic lymphocytic leukemia, immunoglobulin A (IgA) myeloma and immunoglobulin G (IgG) myeloma were detected in three patients who had heavy occupational exposure to asbestos dust. Two of the patients had coexistent pulmonary asbestosis, whereas the third patient had a pleural mesothelioma subsequent to his initial presentation with myeloma. Defective cell-mediated immunity and hyperactivity of B cell function have previously been noted in patients with asbestosis. We suggest the possibility that these asbestos-related immunologic derangements may predispose to the development of immunoproliferative and lymphoproliferative neoplasms, since such tumors have been observed in a variety of other settings, characterized by protracted hyperactivity of the immune system.

Aged↗
PubMed1979

Metastasis-induced acute pancreatitis in small cell bronchogenic carcinoma.

Despite frequent metastatic involvement of the pancreas at postmortem examination in patients with small cell lung cancer, clinically observed pancreatitis due to metastatic pancreatic tumor rarely has been reported. This communication describes three cases of clinical acute pancreatitis occurring in a consecutive series of 40 patients with oat cell lung cancer. This complication may appear either as the initial manifestation of the neoplasm or during a recrudescent phase of the malignant growth. The diagnosis should be suspected in the presence of the clinical, laboratory, and radiologic features of acute pancreatitis in patients with known small cell carcinoma of the lung, especially if there is evidence of progression of the neoplastic disease elsewhere and no response to conservative medical management. Aggressive treatment with polychemotherapy can produce rapid clinical improvement and useful prolongation of survival.

Acute Disease↗
PubMed1978

Rapid development of keratoacanthoma and accelerated transformation into squamous cell carcinoma of the skin: a mutagenic effect of polychemotherapy in a patient with Hodgkin's disease?

A 59-year-old white man developed keratoacanthoma of the nose immediately following one course of MOPP polychemotherapy for clinical state IV B mixed cellularity Hodgkin's disease. Despite the dramatic response of Hodgkin's disease to intensive chemotherapy, the skin lesion was rapidly transformed into squamous cell carcinoma in 10 weeks. The immunosuppressive effect of intensive polychemotherapy may play a significant role in accelerating the malignant transformation. We report here our results concerning this complication which may occur in any patient with Hodgkin's disease undergoing intensive therapy.

Antineoplastic Agents↗
PubMed1977

Bronchogenic carcinoma presenting as spontaneous pneumothorax: case reports with review of literature.

Six months after right-sided spontaneous pneumothorax developed in a 56-year-old man, squamous cell carcinoma was discovered in the ipsilateral lung. Fifteen cases of bronchogenic carcinoma presenting as spontaneous pneumothorax have been reported in the English language literature. Possible pathogenetic mechanisms include: direct tumor invasion of pleura; rupture of a subpleural bleb (in an area of obstructive emphysema) or an emphysematous bulla (in an overexpanded portion of the lung associated with lobar or segmental collapse); or unknown. Patients with spontaneous pneumothorax who fail to achieve complete expansion after three weeks of therapy or who have persistent roentgenographic pulmonary infiltration should undergo further investigation for bronchogenic carcinoma.

Adult↗
PubMed1977

Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Case report with ultrastructural study.

An unusual case of mucinous adenocarcinoma of the sweat glands originating from the right axilla is described. Despite complete control of the primary tumor after local excision, diffuse metastatic lesions continued to appear in the scalp, face, upper and lower extremities, sacral and pelvic bones, and left posterior iliac bone marrow space. The tumors were radioresistant. Multiple trials of various chemotherapeutic regimens, including alkylating agents, antifolates, antipyrimidines, vinca alkaloids, and antineoplastic antibiotics, were ineffective. The cutaneous neoplasms were grossly round, smooth, red, glistening, and cystic and were filled with a gelatinous mucinous material. Microscopic and ultrastructural findings are described.

Adenocarcinoma, Mucinous↗