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Biomedical subjects

H K Wu

Publications and source records attributed to H K Wu.

At least 19 recordsLinked to original sources

Voxel-based detection of white matter abnormalities in mild Alzheimer disease.

OBJECTIVE: To detect white matter abnormalities in patients with mild Alzheimer disease (AD) by diffusion tensor imaging and to determine their topographic relationship with gray matter atrophy. METHODS: Thirteen patients with mild AD and 16 normal age-matched volunteers underwent diffusion tensor imaging and three-dimensional spoiled gradient-recalled sequence scanning. Voxel-based morphometry was conducted to detect regions of gray matter atrophy in the AD group relative to the control group. Fractional anisotropy (FA) maps were processed using SPM2 to make voxel-wise comparison of anisotropy in whole brain between the two groups. The relationship between locations of abnormalities in the white and gray matter was examined. RESULTS: Significant reductions in anisotropy were found in the white matter of both medial temporal lobes, bilateral temporal stems, bilateral superior longitudinal fasciculi, bilateral internal capsules, and cerebral peduncles, as well as the white matter of left middle temporal gyrus and right superior parietal lobule, the body and genu of the corpus callosum, and the right lateral capsule in patients with AD. Although the decrease in FA was consistent with cortical volumetric reduction in both temporal lobes, the widespread involvement of bilateral superior longitudinal fasciculi was dominant in these white matter findings. CONCLUSIONS: Voxel-wise comparison of whole-brain anisotropy revealed widely distributed disintegration of white matter in mild Alzheimer disease (AD). The white matter shows a different pattern of degeneration from gray matter and may be an independent factor in the progress of AD.

Aged↗

Bilateral retrocaval ureters with IVC duplication.

We report a rare case of bilateral retrocaval ureters associated with duplicated inferior renal cava. A 69-year-old woman was sent to our emergency room for abdominal pain. Multidetector computed tomogram with multiplanar reconstruction revealed duplicated inferior renal cavae and the bilateral ureters were positioned behind the duplicated inferior vena cava. To our knowledge, coexistence of bilateral retrocaval ureters and duplicated inferior renal cavae has not been reported in the literature.

Aged↗

Shaping ability of progressive versus constant taper instruments in simulated root canals.

AIM: To compare the shaping ability of progressive versus constant taper shaft designed instruments in simulated root canals. METHODOLOGY: Simulated L- and S-shaped resin canals were prepared by ProTaper (progressive taper) and high elasticity in rotation 642 (Hero 642) (constant taper) instruments (n = 10 canals in each case). The pre- and post-instrumentation images were recorded and assessment of the canal shape was completed with image pro plus 5.0. The width of resin removed was measured at 9 measuring points. Incidence of canal aberrations, instrument fracture, preparation time and change of working length were recorded. In addition, the change of curvature and centring ability were also assessed. The data were analysed statistically using Student's t-test or Fisher's exact-test. RESULTS: In both canal types, Hero 642 instruments prepared canals more rapidly (P < 0.01) and maintained working length significantly more accurately than ProTaper instruments (P < 0.05). In canals prepared with Hero 642 instruments, there was less change in curvature. Instrumentation with ProTaper results in transportation towards the outer aspect of the L-shaped curved canals in the apical part and the inner aspect of the S-shaped canals at the curve. Hero 642 instruments had a better centring ability in the apical part of the canal, but resulted in shapes with a poor taper. CONCLUSIONS: ProTaper and Hero 642 instruments prepared curved canals rapidly, maintained working length well and were relatively safe without creating perforations and danger zones. In both canal types, Hero 642 instruments maintained the original canal curvature better, and had a better centring ability in curved canals because of its constant taper design. The taper prepared by Hero 642 instruments in the coronal part of the canal was generally poor.

Dental Alloys↗

Image segmentation feature selection and pattern classification for mammographic microcalcifications.

Since microcalcifications in X-ray mammograms are the primary indicator of breast cancer, detection of microcalcifications is central to the development of an effective diagnostic system. This paper proposes a two-stage detection procedure. In the first stage, a data driven, closed form mathematical model is used to calculate the location and shape of suspected microcalcifications. When tested on the Nijmegen University Hospital (Netherlands) database, data analysis shows that the proposed model can effectively detect the occurrence of microcalcifications. The proposed mathematical model not only eliminates the need for system training, but also provides information on the borders of suspected microcalcifications for further feature extraction. In the second stage, 61 features are extracted for each suspected microcalcification, representing texture, the spatial domain and the spectral domain. From these features, a sequential forward search (SFS) algorithm selects the classification input vector, which consists of features sensitive only to microcalcifications. Two types of classifiers-a general regression neural network (GRNN) and a support vector machine (SVM)--are applied, and their classification performance is compared using the Az value of the Receiver Operating Characteristic curve. For all 61 features used as input vectors, the test data set yielded Az values of 97.01% for the SVM and 96.00% for the GRNN. With input features selected by SFS, the corresponding Az values were 98.00% for the SVM and 97.80% for the GRNN. The SVM outperformed the GRNN, whether or not the input vectors first underwent SFS feature selection. In both cases, feature selection dramatically reduced the dimension of the input vectors (82% for the SVM and 59% for the GRNN). Moreover, SFS feature selection improved the classification performance, increasing the Az value from 97.01 to 98.00% for the SVM and from 96.00 to 97.80% for the GRNN.

Breast Neoplasms↗

Primary tumour volume delineation in nasopharyngeal carcinoma and correlation with 1997 AJCC tumour stage classification.

OBJECTIVE: To investigate the variability in primary tumour volume in nasopharyngeal carcinoma and compare it with the tumour staging of the 1997 American Joint Committee on Cancer. DESIGN: Prospective study. SETTING: Tertiary care centre. METHOD: A series of 33 newly diagnosed patients who were treated with high-dose radiotherapy participated in the study. MAIN OUTCOME MEASURES: Using computed tomographic scans, primary tumour volumes were measured using the summation-of-areas technique, and the variability in tumour volume was determined. The Mann-Whitney test was used for statistical analysis. RESULTS: A large variation in primary tumour volume was observed, especially in advanced-stage cases. CONCLUSIONS: Nasopharyngeal carcinoma shows considerable variability in primary tumour volume. Incorporation of primary tumour volume may lead to further refinement of the 1997 tumour staging system.

Adult↗

Identification of genes expressed in the epithelium of porcine oviduct containing early embryos at various stages of development.

As a first step toward elucidation of the action of factors secreted by the epithelium of oviduct, differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was used in this study to identify transcripts of such oviductal factors in gilts carrying various stages of early embryo development post hormone-induced ovulation. A total of 13 differentially expressed transcripts were identified between 50 and 120 hr post-hCG injection (between 1- and 8-cell embryonic stages). Twelve of these transcripts were found to be initially expressed at 96 hr post-hCG injection (at 4-cell embryonic stage) and beyond. Three of such genes were shown by sequence analysis to be the porcine transforming growth factor-alpha, the porcine transforming growth factor-beta-binding protein II and a porcine astral natriuretic factor receptor-like transcript. Only one differentially expressed gene was detected between 50-60 and 85 hr post-hCG injection, and this gene turned out to be the porcine follicle-stimulating hormone receptor. The remaining eight transcripts detected by DDRT-PCR were novel. Moreover, most of these newly expressed genes were found to be turned on at a time coincidental with that of the 4-cell block of porcine embryos cultured in vitro. Our results demonstrate that DDRT-PCR is a feasible approach for rapid identification of genes that are differentially expressed in oviductal epithelium. Some of the genes thus identified may be important for unhindered development of embryos in the oviduct.

Animals↗

Effects of radiotherapy for nasopharyngeal carcinoma on the paranasal sinuses: study based on computed tomography scanning.

OBJECTIVE: The purpose of this study was to determine if radiotherapy for nasopharyngeal carcinoma causes mucosal disease of the paranasal sinuses. DESIGN: This study was a retrospective study. SETTING: This study was conducted at a tertiary care centre. METHOD: A series of 69 newly diagnosed patients, without pre-existing sinus disease, who were treated with high-dose radiotherapy participated. MAIN OUTCOME MEASURES: The prevalence, severity, and time course of mucosal abnormalities were analyzed, as judged by consecutive computed tomographies (CTs). RESULTS: The CT study revealed that 58.8% of the postirradiation scans had mucosal disease of the sinuses. The maxillary sinus had the highest prevalence (42.3%) without statistical significance (p = .10). The difference by McNemar test for two follow-up scans was not significant (p = .48) and by Kappa test was significant (p = .04). The relationship between the prevalence and the time course post radiotherapy revealed that it remained a high prevalence until after the 4-year follow-up scans. CONCLUSIONS: The results of this study confirm that chronic sinus disease is a common late complication of radiotherapy and it persists for years. Thus, aggressive treatment is indicated.

Adolescent↗

Gender determination in single bovine blastomeres by polymerase chain reaction amplification of sex-specific polymorphic fragments in the amelogenin gene.

A sensitive technique for the sexing of bovine embryos was developed using polymerase chain reaction (PCR) amplification of the bovine amelogenin (bAML) gene on the X- and Y-chromosomes of Holstein dairy cattle. Cloning and DNA sequencing showed a 45.1% homology between the fifth intron of the bAML-X and bAML-Y gene with multiple deletions. A pair of sex-specific primers was designed to allow amplification of a single fragment of 467-bp from the X-chromosome of female cattle and two fragments of 467-bp and 341-bp from the X- and Y-chromosomes of male cattle. The primers were successfully applied to bovine sexing from single blastomeres isolated from day-6 to day-7 cow embryos by direct cell lysis and PCR. Our protocol of embryo sexing should be applicable to the diagnosis of defective genes in vitro in human embryos and in other domestic or recreational animals.

Amelogenin↗

Comparison of mitomycin C trabeculectomy, glaucoma drainage device implantation, and laser neodymium:YAG cyclophotocoagulation in the management of intractable glaucoma after penetrating keratoplasty.

PURPOSE: This study aimed to compare the surgical outcomes of mitomycin C trabeculectomy glaucoma drainage device (GDD) surgery and laser neodymium:YAG (Nd:YAG) cyclophotocoagulation (CPC) in the management of intractable glaucoma after penetrating keratoplasty (PKP) in a retrospective study. DESIGN: Interventional case series. PARTICIPANTS/METHODS: The medical charts of consecutive patients who had pre-existing glaucoma or who developed glaucoma after PKP and underwent a surgical procedure to control the glaucoma at the University Eye Associates of Boston University Medical Center, New England Eye Center, and Massachusetts Eye and Ear Infirmary between January 1991 and July 1995 were reviewed. Follow-up ranged from 6 months to 4 years after the glaucoma procedure. A total of 38 patients were included consisting of 17 patients who underwent mitomycin C, 10 patients who underwent GDD surgery, and 11 patients who had CPC. INTERVENTION: Mitomycin C trabeculectomy, GDDs, or Nd:YAG CPC to control glaucoma after PKP was performed, MAIN OUTCOME MEASURES: Graft status, postoperative intraocular pressure (IOP), and visual acuity were the main outcome measures. RESULTS: There were no differences among the three groups with respect to the follow-up time after the corneal graft operation (P = 0.15) or after the glaucoma operation (P = 0.98). At the final follow-up, the average decrease in the IOP was 17 mmHg (P < 0.001) after mitomycin C, 15 mmHg (P = 0.003) after GDD surgery, and 14.4 mmHg (P = 0.001) after CPC. There were no differences in the proportion of patients who developed postoperative IOP above 20 mmHg (P = 0.50) and in the proportion who developed hypotony (P = 0.10) among the three groups. Two grafts failed after mitomycin C and one failed after CPC. Among the three procedures, there were no differences in the proportion of patients who experienced either an improvement (P = 0.14) or a decrease (P = 0.22) in the visual acuity by more than one line after the glaucoma procedure. One patient each in the GDD group and the CPC group lost light perception after the procedure. The risk of graft failure was almost three times higher for each additional PKP (odds ratio = 2.80, P = 0.02). CONCLUSIONS: No differences were found among the three glaucoma procedures with respect to controlling IOP and graft failure. There was a trend for patients treated with CPC to have a higher incidence of graft failure, glaucoma failure, hypotony, and visual loss by more than one line, although this was not statistically significant. The number of PKPs was associated with graft failure, independent of the surgical procedure.

Adolescent↗

Relaxation of imprinting of human insulin-like growth factor II gene, IGF2, in sporadic breast carcinomas.

Breast cancer is the most frequent malignancy in women and genetically heterogeneous, and a variety of genetic lesions have been identified that tend to accumulate during the disease progress. In breast cancer, loss of heterozygosity (LOH) has been described in the critical regions of chromosomes 11p15 and 11q22-23. Genomic imprinting is defined as gamete specific modification causing differential expression of the two alleles of a gene, in somatic cells. Human insulin like growth factor II gene (IGF2), located on chromosome 11p15, the same region on which LOH frequently occurred in breast cancer, has been recently identified as a genomic imprinting gene expressing preferentially paternal allele. To determine whether loss of IGF2 imprinting was common in breast cancer we studied 30 patients with sporadic breast carcinoma. A new strategy for detecting intragenic Apa I polymorphism in the exon of IGF2 was used to examine allele-specific expression in the breast cancer specimens by reverse-transcription polymerase chain reaction (RT-PCR). Forty percent (12/30) of the breast cancer samples were identified as heterozygous for IGF2 and studied further. Nine of the 12 heterozygous patients showed biallelic expression of IGF2 by cDNA-PCR, indicating relaxation of normal imprinting at this chromosomal locus. Conclusively, aberrant imprinting of IGF2 in 30% of the breast cancer patients tested provides strong evidence that pathological loss or relaxation of IGF2 imprinting plays an important role in either tumorigenesis or cytokine dysregulation for breast cancer cells.

Alleles↗

Transcriptional activation of human LIM-HOX gene hLH-2 in chronic myelogenous leukemia is due to a cis-acting effect of Bcr-Abl.

DNA methylation plays an important role in gene regulation. A human LIM-HOX gene, namely hLH-2, was highly expressed in chronic myelogenous leukemia (CML) and located on chromosome 9q33-34.1, in the same region as the reciprocal translocation that creates the Bcr-Abl chimera of Philadelphia chromosome [Wu et al. (1996) Oncogene 12, 1205]. To elucidate the mechanism of hLH-2 transcriptional activation, we studied the methylation status of hLH-2 in normal bone marrow and CML cells. When blots containing genomic DNA digested with Hpa II or Msp I were hybridized with full-length cDNA probe, it was discovered that hLH-2 was methylated in normal bone marrow cells in which hLH-2 was not expressed; in contrast, both alleles of hLH-2 locus in CML cells were heavily hypomethylated. Furthermore, using the sensitive RT-PCR technique, we examined the expression of LH-2 in mouse x human hybrids and a wide array of mouse cell lines containing Abl or Bcr-Abl and failed to identify a consistent expression pattern in the cell lines tested. These results suggest that the transcriptional activation of hLH-2 in CML is likely due to a cis-acting effect, but not a trans-acting effect of the Bcr-Abl fusion protein. Because hypomethylated genes generally are transcribed more efficiently than hypermethylated genes, the high level of hLH-2 mRNA in CML cells probably is a consequence of the low level of methylation of the gene in the leukemic cells.

Animals↗

Transcriptional activation of human LIM-HOX gene, hLH-2, in chronic myelogenous leukemia is due to a cis-acting effect of Bcr-Abl.

DNA methylation plays an important role in gene regulation. A human LIM-HOX gene, namely hLH-2, was highly expressed in chronic myelogenous leukemia (CML) and located on chromosome 9q33-34.1, in the same region as the reciprocal translocation that creates the Bcr-Abl chimera of Philadelphia chromosome (H.-K. Wu et al., 1996, Oncogene 12, 1205-1212). To elucidate the mechanism of hLH-2 transcriptional activation, we studied the methylation status of hLH-2 in normal bone marrow and CML cells. When blots containing genomic DNA digested with Hpa II or Msp I were hybridized with full-length cDNA probe, it was discovered that hLH-2 was methylated in normal bone marrow cells in which hLH-2 was not expressed; in contrast, both alleles of the hLH-2 locus in CML cells were heavily hypomethylated. Furthermore, using a sensitive RT-PCR technique, we examined the expression of LH-2 in mouse x human hybrids and a wide array of mouse cell lines containing Abl or Bcr-Abl, and we failed to identify a consistent expression pattern in the cell lines tested. These results suggest that the transcriptional activation of hLH-2 in CML is likely due to a cis-acting effect, but not a trans-acting effect, of the Bcr-Abl fusion protein. Because hypomethylated genes generally are transcribed more efficiently than hypermethylated genes, the high level of hLH-2 mRNA in CML cells probably is a consequence of the low level of methylation of the gene in the leukemic cells.

Animals↗

Promoter-dependent tissue-specific expressive nature of imprinting gene, insulin-like growth factor II, in human tissues.

The insulin-like growth factor II (IGF2) is a polypeptide with structure homology to insulin which possesses mitogen activity, and imprinted with paternal allele. In order to elucidate the distribution of imprinting pattern and relationship between allele- and tissue-specific expression of IGF2 in growth and maturation of human tissues, we investigated allele-specific expression of IGF2 in a wide spectrum of normal maturated human tissues by a PCR-based assay and found monoallelic expression in all eight-type tissues tested except human adult liver. Moreover, when a RT-PCR based sensitive allele-specific primer extension for an Apa I polymorphism within exon 9 of IGF2 was used, the analysis revealed the gene was normally imprinted in placenta; in contrast to the finding with placenta, IGF2 transcripts were biallelically expressed in human adult liver. Our results have clearly demonstrated preferential paternal expression and tissue-specific imprinting pattern of IGF2 in all human tissues tested in this study. Collectively, since IGF2 expression in developing fetal and adult liver is specified by distinct promoters, these extensive observations definitively indicate that transcriptional imprinting of IGF2 is more likely a promoter dependent manner.

Adult↗

Loss of imprinting of human insulin-like growth factor II gene, IGF2, in acute myeloid leukemia.

Genomic imprinting is a non-Mendelian form of gene regulation resulting in differential allelic expression of a gene and plays an important role in the development of certain types of cancer and genetic diseases. Imprinting of IGF2 was demonstrated in normal placenta and fetal kidney by showing monoallelic paternal expression. In contrast, several kinds of tumor showed biallelic expression of IGF2, suggesting that relaxation of the normal imprinting of this growth cytokine may be a feature of some tumors. In this study we wished to determine whether relaxation of IGF2 imprinting was also common in human leukemias. An intragenic Apa I polymorphism within the 3' untranslated region of the gene was used to examine allele-specific transcription in leukemic blasts derived from 24 primary patients with acute myeloid leukemia by RT-PCR. Leukemic samples from 12 of the 24 leukemia patients were identified as heterozygous for IGF2 and potentially informative for the RT-PCR assay. RNA-PCR from these informative leukemia samples studied showed biallelic expression of IGF2, indicating loss of normal imprinting of this gene to be very frequent. In conclusion, constitutional loss of monoallelic expression in 50% of the leukemia samples tested suggests that abnormal imprinting of IGF2 could play an important role in either leukemogenesis or cytokine dysregulation for leukemic cells.

Alleles↗

Capillary electrophoretic determination of the constituents of paeoniae radix.

A method combining the techniques of capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) has been developed to separate a total of eight peony constituents. The CZE method was used to determine the content of paeonol, oxypaeoniflorin, benzoic acid, pentagalloylglucose and gallic acid, and MEKC technique based on sodium cholate was applied to analyze albiflorin, paeoniflorin, benzoyla biflorin, paeonol and oxypaeoniflorin. Linearity around two orders of magnitude of concentration was generally obtained and limits of detection for these compounds were in the range of 2.6-23.7 micrograms/ml. The relative standard deviations of migration times were less than 1.43% (n = 6). Contents of peony constituents in an ethanol-water extract of Paeonia lactiflora Pall. sample could easily be determined by this method.

Chromatography, Liquid↗

Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1.

We describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease.

Amino Acid Sequence↗