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Biomedical subjects

Y J Lu

Publications and source records attributed to Y J Lu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cloning and mapping of members of the MYM family.

Tandem repeats of a novel, putative, zinc-binding motif (MYM) have been described within the products of two, highly homologous genes: ZNF198/RAMP/FIM and ZNF261/DXS6673E. ZNF198, mapping to 13q11-q12, was recently shown to fuse to the fibroblast growth factor receptor 1 gene in the t(8;13)(p11;q11-q12) rearrangement associated with a stem cell leukemia/lymphoma syndrome. ZNF261 at Xq13.1 is disrupted by a t(X;13)(q13.1;q32) rearrangement in a mentally retarded patient and is a candidate gene for nonspecific X-linked mental retardation. Here we have cloned another member of this family, designated ZNF258, and mapped it to chromosome band 14q12. In addition, ZNF262/KIAA0425 was identified as a further member of the family and mapped to 1p32-p34. The predicted protein products of ZNF258 and ZNF262 maintain the repeats of the MYM motif. Isolation of these new members will facilitate the functional characterization of the MYM family and motif.

Amino Acid Motifs↗
PubMed1999

Synovial sarcoma specific translocation associated with both epithelial and spindle cell components.

The biphasic subtype of synovial sarcoma consists of both epithelial and spindle cell components. To address the relationship between the different cellular components found in synovial sarcoma, we deduced the presence of the synovial sarcoma-specific der(X)t(X;18)(p11.2;q11.2), and involvement of the SSX1 gene in both the epithelial/glandular and spindle cell components of 3 biphasic synovial sarcomas with wide ranging proportions of each of the 2 elements. This has been achieved using a 2-color fluorescence in situ hybridization (FISH) methodology that we had developed recently for analysis paraffin-embedded material. The presence of the rearrangement could be deduced in histologically defined regions and the results showed clearly that the rearrangement was present in both cellular components. This finding provides direct genetic evidence for biphasic synovial sarcomas being clonal and truly biphasic.

Adult↗
PubMed1999

A comparative molecular field analysis study on several bioactive peptides using the alignment rules derived from identification of commonly exposed groups.

A 3D convex hull computation algorithm designed by us previously is used as a tool to align a series of structures randomly generated for eleven bioactive tachykinin peptides. There are 10 random structures generated for each peptide. A random structure is selected for each peptide to form a structural set of eleven structures. The total number of structural sets generated is 100. The convex hull computation algorithm is applied to each peptide structure generated. We count the frequency of atoms lying on the vertices of each hull computed. Vertices of the same atom type are gathered together as a set of commonly exposed atoms for a structural set generated. Structures are then aligned by treating the set of commonly exposed atoms as a set of correspondences using the FIT option of the SYBYL 6.4 program. All the structure sets are also aligned by using the coordinates of the backbone C alpha atoms as a set of correspondences through the same program. It is found that while a smaller degree of structural similarity for structures aligned by the convex hull alignment rule is detected, the overall SYBYL comparative molecular field analysis (CoMFA) statistics computed for the aligned structures using the alignment rule is better than that computed for the aligned structures using the C alpha atoms alignment rule. A similar conclusion is drawn for a subset of structures selected and probed by a different type of atoms using the SYBYL CoMFA program. These results indicate that computation of 3D convex hulls is a feasible way that one can use to align structures generated for highly flexible molecules of this kind.

Algorithms↗
PubMed1999

Dual colour fluorescence in situ hybridization to paraffin-embedded samples to deduce the presence of the der(X)t(X;18)(p11.2;q11.2) and involvement of either the SSX1 or SSX2 gene: a diagnostic and prognostic aid for synovial sarcoma.

Identification of the t(X;18)(p11.2;q11.2) and the fusion gene products, SYT-SSX1 and SYT-SSX2, associated with a high proportion of synovial sarcomas, has been shown to be a useful diagnostic aid. This study demonstrates the application of dual colour fluorescence in situ hybridization to paraffin-embedded samples to deduce the presence of the derivative X chromosome and also the position of the breakpoint on chromosome X at either the SSX1 or the SSX2 gene. This used region specific markers from chromosomes X and 18 and an optimized protocol involving microwave exposure. Novel and rapid scoring criteria were validated which circumvented potential problems of nuclear truncation and defining cell boundaries. This involved blind analysis of two negative sarcoma samples and three synovial sarcomas in which corresponding frozen material had been previously shown to have the translocation involving different SSX genes. Six new cases diagnosed as synovial sarcoma were also analysed; two monophasic and two biphasic case were deduced to have a breakpoint in the SSX1 gene, one monophasic case an SSX2 breakpoint, and one case did not show rearrangement of the region. The ability to analyse formalin-fixed, paraffin-embedded samples in this way has practical implications for aiding the diagnosis of difficult cases, recently ascribed prognostic relevance, and allows further retrospective studies to be carried out. The methodology is also applicable to the identification of other tumour specific translocations in paraffin-embedded material.

Adult↗
PubMed1999

Chromosome 3 imbalances are the most frequent aberration found in non-small cell lung carcinoma.

The chromosomal imbalances in nine cases of primary non-small cell lung cancer (NSCLC) and two cell lines derived from normal human bronchial epithelial (HBE) tissue were identified by comparative genomic hybridization (CGH). Gain of material from 3q and loss of 3p material were the most frequent changes in the primary tumors. Other commonly found imbalances included gain of material from 1q, 7p, 8q, 9q, 17q and 20q, and losses involving 4, 5q, 8p, 10 and 13q. High level gain was found in two cases, both encompassing the 3q23-q27 region. Loss of 3p was also found in both of the HBE cell lines suggesting that loss of one or more tumor supressor genes on 3p may be important for epithelial transformation and could be involved in the earlier stages of lung cancer development.

Adult↗
PubMed1999

Laparoscopic treatment of isolated tubal torsion in a premenarchal girl.

Tubal torsion in a premenarchal girl was diagnosed by pelvic ultrasonography and laparoscopy. A laparoscopic approach was used to resect the twisted tube. To our knowledge, this is the first reported case of laparoscopically managed torsion of a fallopian tube occurring in the absence of torsion of the ovary in a patient of this age group. Video-assisted minimally invasive surgery appears to be suitable for treatment of tubal torsion in children; hospitalization is short, cosmetic results are excellent, and return to normal activity is rapid. (J Am Assoc Gynecol Laparosc 6(2):209-211, 1999)

Child↗
PubMed1999

Relationship of the human cumulus-free oocyte maturational profile with in vitro outcome parameters after intracytoplasmic sperm injection.

PURPOSE: We investigated whether the human oocyte maturational profile at the removal of cumulus/corona cells affects the fertilization rate and subsequent embryo quality after intracytoplasmic sperm injection. METHODS: A total of 1011 oocytes from 150 cycles was included in this retrospective analysis. Cumulus-free oocytes that were in prophase or metaphase I of meiosis at the removal of cumulus/corona cells were incubated in vitro until they reached metaphase II (in vitro-matured oocytes) and were then immediately injected with a single spermatozoa. Oocytes that were in metaphase II at the removal of cumulus/corona cells (MII oocytes) received sperm injection after 3-4 hr of preinjection incubation. RESULTS: The fertilization rate of the MII oocytes was significantly higher than that of in vitro-matured oocytes (81 vs 62%; P < 0.001). The cleavage rates were similar in the two groups (MII oocytes, 94%; in vitro-matured oocytes, 91%). However, MII oocytes had significantly higher percentages of good-quality embryos (grade 1-3 embryos, 87 vs 58%, P < 0.001) and embryos with high cumulative embryo scores (score 10-32 embryos, 62 vs 33%, P < 0.001). The mean cumulative embryo score of MII oocytes after fertilization was also higher than that of in vitro-matured oocytes (12.1 +/- 3.8 vs 8.8 +/- 3.4; P = 0.014). CONCLUSIONS: MII oocytes that extruded the first polar body at the removal of cumulus/corona cells had better fertilization rates and embryo morphology than in vitro-matured oocytes that extruded the first polar body following the removal of cumulus/corona cells and in vitro culture.

Embryo, Mammalian↗
PubMed1999

Seven novel methylation guide small nucleolar RNAs are processed from a common polycistronic transcript by Rat1p and RNase III in yeast.

Through a computer search of the genome of the yeast Saccharomyces cerevisiae, the coding sequences of seven different box C/D antisense small nucleolar RNAs (snoRNAs) with the structural hallmarks of guides for rRNA ribose methylation have been detected clustered over a 1.4-kb tract in an inter-open reading frame region of chromosome XIII. The corresponding snoRNAs have been positively identified in yeast cells. Disruption of the nonessential snoRNA gene cluster specifically suppressed the seven cognate rRNA ribose methylations but did not result in any growth delay under the conditions of yeast culture tested. The seven snoRNAs are processed from a common polycistronic transcript synthesized from an independent promoter, similar to some plant snoRNAs but in marked contrast with their vertebrate functional homologues processed from pre-mRNA introns containing a single snoRNA. Processing of the polycistronic precursor requires nucleases also involved in rRNA processing, i.e., Rnt1p and Rat1p. After disruption of the RNT1 gene, the yeast ortholog of bacterial RNase III, production of the seven mature snoRNAs was abolished, while the polycistronic snoRNA precursor accumulated. In cells lacking functional Rat1p, an exonuclease involved in the processing of both pre-rRNA and intron-encoded snoRNAs, several processing intermediates of the polycistronic precursor accumulated. This allowed for the mapping in the precursor of the presumptive Rnt1p endonucleolytic cuts which provide entry sites for subsequent exonucleolytic trimming of the pre-snoRNAs. In line with known properties of double-stranded RNA-specific RNase III, pairs of Rnt1p cuts map next to each other on opposite strands of long double-helical stems in the secondary structure predicted for the polycistronic snoRNA precursor.

Base Sequence↗
PubMed1999

Multiple pregnancy with adnexal torsion after in vitro fertilization: case report.

Assisted reproductive techniques (ART) are widely accepted procedures for infertile couples. Rare complications, like heterotopic pregnancy, bilateral tubal pregnancy, and adnexal torsion during pregnancy, have been diagnosed with increasing frequency after ART. We present a case of an early triplet pregnancy complicated with adnexal torsion. The patient was pregnant through in vitro fertilization. Early ultrasound examination revealed a triplet pregnancy within the uterine cavity. At 7 weeks' gestational age, an acute onset of lower abdominal pain, progressive abdominal distension, and massive internal bleeding prompted emergency laparotomy. The right ovary was enlarged, twisted, necrotic and hemorrhagic. Attempts to preserve the ovary failed because of the friable nature of the affected ovary, and an oophorectomy had to be performed. Although the removed ovary contained a corpus luteum, the pregnancy continued smoothly after only short luteal support. A precise pre-surgery diagnosis in our case was difficult based on the patient's initial clinical presentation. However, with high clinical suspicion in addition to color Doppler ultrasound, the physician should be able to make an early decision for an exploratory laparotomy or laparoscopy, gaining the benefit of more conservative treatment.

Adnexal Diseases↗
PubMed1998

cDNA cloning of a third human C2-domain-containing class II phosphoinositide 3-kinase, PI3K-C2gamma, and chromosomal assignment of this gene (PIK3C2G) to 12p12.

Phosphoinositide (PI) 3-kinases have been shown to have critical roles in signaling pathways that regulate proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. We have previously used reverse-transcription polymerase chain reaction methods to identify novel PI 3-kinase isoforms in normal human breast and in lymph nodes containing metastatic breast cancer. Here we report the cDNA cloning of a Class II PI 3-kinase found in normal breast tissue. This gene (PIK3C2G) encodes the third distinct protein of the human Class II PI 3-kinase family, PI3K-C2gamma. PIK3C2G was mapped to chromosome 12 at 12p12 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1998

Comparative genomic hybridization analysis of lobular carcinoma in situ and atypical lobular hyperplasia and potential roles for gains and losses of genetic material in breast neoplasia.

Lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) of the breast are cytologically similar breast lesions that reportedly carry different relative risks of subsequent development of invasive carcinoma. They are frequently multifocal and bilateral. We have identified the chromosomal copy number changes in 31 LCIS and 14 ALH lesions from 28 cases and also the 7 invasive carcinomas that subsequently developed in 6 of these cases. This was achieved by comparative genomic hybridization analysis of microdissected formalin-fixed, paraffin-embedded material. There was no significant difference between the aberrations found in the unilateral versus the bilateral cases of LCIS. Loss of material from 16p, 16q, 17p, and 22q and also gain of material from 6q were found at a similar high frequency in LCIS and ALH. Loss of these genomic regions may indicate the locations of genes that predispose to the development of the lesions, and the results are consistent with LCIS and ALH representing the same genetic stage of development. Comparison of the comparative genomic hybridization results from LCIS/ALH with those from ductal carcinoma in situ and invasive cancer showed some similarities at the chromosomal level, but it also showed significant differences, including gain of 1q and 8q and evidence for genomic amplification, which were not found in LCIS/ALH. A genetic model is postulated for the possible relationships between noninvasive lobular lesions and invasive breast carcinoma, delineating potential roles for specific chromosome copy number changes.

Adult↗
PubMed1998

Experimental pathology and breast cancer genetics: new technologies.

The goal is to understand the critical events in tumour development and to apply this understanding to new approaches to diagnosis, prevention and treatment. It is clear that breast cancer is a heterogeneous disease at the molecular level, raising the possibility of a future functional classification based on mechanisms rather than morphology. These molecular phenotypes will also confer predictive value on the potential of the tumour to invade, metastasise and respond to or resist new therapeutic strategies. Studies of the genome in individuals are predicted also to enable the identification of polymorphisms that are associated with increased susceptibility to environmental factors, in addition to possibly explaining de novo variations in responses to drugs and radiation. The difficulty is how to identify which, of the approximately 30,000 genes expressed by a typical cancer cell alone or in combination, are the ones involved in these processes. The majority of breast cancers have such a multitude of molecular changes that it is difficult to distinguish between those that are critical to tumour progression and those that are epiphenomena of genetic instability and abnormalities in DNA repair. The identification of the earliest events in carcinogenesis must be the best hope, as it will then be possible to target the events that predispose to other secondary changes before they occur. Genomics and proteomics is the current hope to take us forward. This involves the application of a number of new technologies to facilitate the profiling of individual tumours, including laser-guided microdissection of microscopic lesions, comparative genomic hybridisation and loss of heterozygosity analysis of DNA using microarray technology to study DNA and expressed RNAs and protein profiling using 2D gel mass spectroscopy. With over 100,000 mRNAs and proteins to examine in complex tissues and in various combinations, there is obviously going to be a requirement for a large investment in computing power (bioinformatics) to facilitate the analysis of these data in relation to the clinical characteristics of the individual tumour and the patient.

Bacteriophages↗
PubMed1998

Establishment and characterization of a SV40T-transformed human bronchial epithelial cell line.

The majority of human lung cancers originate from the carcinogenesis of bronchial epithelial cells. To study the malignant progression of human bronchial epithelial cells, we established a SV40T-transformed human bronchial epithelial cell line, and observed some biological and genetic changes of the cell line at different passages. In a 2-year culture, this cell line was approaching malignancy without obvious senescence. Cells in a later passage proliferated faster and required less growth factors than those of an early passage. After continued passaging, these cells were resistant to the terminal squamous differentiation effects of serum, and many of the cells grew anchorage independently. However, no tumor formed after cells were injected into nude mice. Some genetic alterations were found accompanying those morphological changes, such as 3p- and activation of c-myc, c-erbB-2 and bcl2, suggesting that those genetic alterations may contribute to the carcinogenesis of human bronchial epithelial cells at an early stage. This cell line should be particularly useful for studying the progression of human lung cancers.

Animals↗
PubMed1997

Ion channels formed in planar lipid bilayers by Bacillus thuringiensis toxins in the presence of Manduca sexta midgut receptors.

A purified, GPI-linked receptor complex isolated from Manduca sexta midgut epithelial cells was reconstituted in planar lipid bilayers. CryIAa, CryIAc and CryIC, three Bacillus thuringiensis insecticidal proteins, formed channels at much lower doses (0.33-1.7 nM) than in receptor-free membranes. The non-toxic protein CryIB also formed channels, but at doses exceeding 80 nM. The channels of CrylAc, the most potent toxin against M. sexta, rectified the passage of cations. All other toxin channels displayed linear current-voltage relationships. Therefore, reconstituted Cry receptors catalyzed channel formation in phospholipid membranes and, in two cases, were involved in altering their biophysical properties.

Animals↗
PubMed1997

Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma.

We demonstrate that the cytogenetically defined translocation t(X;1)(p11.2;p34) observed in papillary renal cell carcinomas results in the fusion of the splicing factor gene PSF located at 1p34 to the TFE3 helix-loop-helix transcription factor gene at Xp11.2. In addition we define an X chromosome inversion inv(X)(p11.2;q12) that results in the fusion of the NonO (p54nrb) gene to TFE3. NonO (p54nrb), the human homologue of the Drosophila gene NonAdiss which controls the male courtship song, is closely related to PSF and also believed to be involved in RNA splicing. In each case the rearrangement results in the fusion of almost the entire splicing factor protein to the TFE3 DNA-binding domain. These observations suggest the possibility of intriguing links between the processes of RNA splicing, DNA transcription and oncogenesis.

Adolescent↗
PubMed1997

Phyllodes tumors of the breast analyzed by comparative genomic hybridization and association of increased 1q copy number with stromal overgrowth and recurrence.

Phyllodes tumors are rare neoplasms of the breast. Although they contain both epithelial and stromal components they are considered to be stromally derived lesions. The chromosomal copy number changes were determined in 19 well characterized samples from 18 patients using comparative genomic hybridization. Most chromosomes were involved and generally the gains and losses were similar to those found in breast cancer with the exception that the phyllodes tumors showed no evidence of genomic amplification. The one recurrent sample analyzed had the same imbalances as the original tumor. Frequent changes were gain of 1q (7/18) and loss of 3p (6/18), followed by gain of 7q (4/18) and loss of 6q (4/18) and 3q (3/18). Gain of 1q material was significantly associated with histologically defined stromal overgrowth (P = 0.011). In addition, all the cases with gain of 1q material, without 1p gain, had a clinical history of recurrence. Only one case without 1q gain had a recurrence and this had loss of the X chromosome as the sole abnormality. Increased copy number of 1q material in the phyllodes tumors studied, in one case restricted to 1q24-32, was associated with recurrence (P = 0.00365) and might therefore be considered as an indicator of local aggressiveness requiring more radical treatment.

Adult↗
PubMed1997

Molecular cytogenetic alterations in the early stage at human bronchial epithelial cell carcinogenesis.

Lung carcinogenesis is a multi-step process involving activation of oncogenes and inactivation of tumor suppress genes. Many molecular and cytogenetic alterations occur in the early stages of carcinogenesis. We have developed an effective culture system for human bronchial epithelial cells and lung cancer cells. Four immortalized human bronchial epithelial cell lines were established by transfecting the epithelial cells with plasmid DNA containing the early region of SV40. Some molecular and cytogenetic alterations, such as 3p-, 2q-, 9p-, c-myc translocation t(8;14) (q23; q32), were found in one immortalized bronchial epithelial cell line M when approaching malignant transformation. An increase in cell proliferation and decrease of apoptosis were noted in the late passages of the immortalized cell line M. Some molecular cytogenetic alterations were also observed in human primary non-small cell lung cancers. Molecular cytogenetic alterations during the early stage of carcinogenesis of human bronchial epithelial cells may be useful as biomarkers for both diagnosis and intermediate endpoint of chemoprevention of lung cancer.

Animals↗