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G C Chan

Publications and source records attributed to G C Chan.

At least 19 recordsLinked to original sources
PubMed2001

Human endothelin converting enzyme-2 (ECE2): characterization of mRNA species and chromosomal localization.

Generation of the functionally pleiotropic members of the endothelin vasoactive peptide family is critically catalyzed by unique type II metalloproteases, termed endothelin converting enzymes (ECE). Isolation of human ECE-2 (EC 3.4.24.71) cDNAs revealed deduced open reading frames of 787 and 765 amino acids with approximately 60% identity with human ECE-1. Characterization of mRNA variants revealed mRNA structural diversity at the 5'-terminus. Two mRNA species exist containing distinct first and second exons. Furthermore, in one of these species, an in-frame deletion of the intracytoplasmic domain removed 29 amino acids. Because of the previously reported human genetic diseases ascribed to germline mutations of member genes of the endothelin family, ECE2 was localized in human chromosomes with fluorescence in situ hybridization and radiation hybrid mapping to 3q28-q29 and SHGC-20171/D3S1571, respectively.

Adrenal Glands↗
PubMed2001

Solid-cystic papillary tumor of the pancreas in children.

Solid-cystic papillary tumor (SCPT) of the pancreas is a rare neoplasm in children. The current study attempted to estimate the incidence and possible pathological origin of the tumor. Clinicopathologic features of the children under the age of 16 years with pancreatic tumors managed in a single institution between January 1993 and November 1999 were reviewed. Representative blocks of SCPT specimens were immunostained for neuron-specific enolase (NSE) chromogrannin, synaptophysin, insulin, glucagon, somatostatin, and gastrin. There were three SCPTs, two pancreatic endocrine tumors, and one acinar cell carcinoma during the study period. The estimated yearly incidence in the referral area of 2 million population is about 0.01 pediatric SCPT per year per 100,000 population. The children underwent surgical removal of the tumors. Postoperatively, they were followed up for 6 months to 4 years and were well. Immunostaining for NSE, chromogranin, synaptophysin, insulin, somatostatin, and gastrin was negative in all cases. SCPT may thus be the most common pancreatic tumor in the Asian pediatric population. The pathological origin of the tumor remains unclear and requires further investigations.

Adolescent↗
PubMed2001

Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia.

t(1;22) is the principal translocation of acute megakaryoblastic leukemias. Here we show this chromosomal rearrangement to result in the fusion of two novel genes, RNA-binding motif protein-15 (RBM15), an RNA recognition motif-encoding gene with homology to Drosophila spen, and Megakaryoblastic Leukemia-1 (MKL1), a gene encoding an SAP (SAF-A/B, Acinus and PIAS) DNA-binding domain.

Chromosomes, Human, Pair 1↗
PubMed2001

Successful mismatched sibling cord blood transplant in Hb Bart's disease.

A 20-month-old girl with Hb Bart's disease, who had survived neonatal complications, underwent HLA-DR antigen mismatched sibling cord blood transplantation successfully. Immune thrombocytopenia, which occurred around 2.5 months after transplant, responded to intravenous gamma-globulin. The fetal hemoglobin level rose to a peak of 52.3% on day +69 post transplant and declined gradually during the following year. Ten percent of hemoglobin Bart's was detected 2 months after transplant and this reflects the alpha-thalassemia trait of the donor.

Female↗
PubMed2001

Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study.

TEL/AML1 gene fusion that results from a cryptic t(12;21) is the most common genetic aberration in childhood B-lineage acute lymphoblastic leukemia (ALL). While the translocation may initiate the leukemic process, critical secondary genetic events are currently believed to be pivotal for leukemogenesis. We investigated 12 cases of childhood ALL with TEL/AML1 gene fusion by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) and documented additional or secondary genetic changes in seven patients (58%). Three patients showed extra copies of chromosome 21 including a case in which the trisomy 21 (+21) clone was distinct from the one harboring TEL/AML1 gene fusion. Interestingly, one patient without +21 showed amplification of the AML1 gene on chromosome 21q, supporting the contention that AML1 amplification may be an important additional genetic event. Gene expression study by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) in two of these four patients showed an increase in AML1 transcripts that paralleled the increase in gene copy number. Deletion of the normal TEL allele was detected in two patients, with one of them showing loss of chromosome 12 together with duplication of the der(12)t(12;21). Finally, one patient showed duplication of the fusion signal. Our findings confirm that additional or secondary genetic changes including AML1 amplification are commonly encountered in childhood ALL with TEL/AML1 gene fusion, which are envisaged to play significant roles in disease progression.

Adolescent↗
PubMed2001

DNA elements of the type 1 adenylyl cyclase gene locus enhance reporter gene expression in neurons and pinealocytes.

The Ca2+-stimulated type 1 adenylyl cyclase (AC1) contributes to several forms of synaptic plasticity and is the only known neurospecific adenylyl cyclase. Furthermore, the protein and mRNA levels of AC1 undergo a circadian oscillation in the pineal gland, and AC1 may play a pivotal role in regulating nocturnal melatonin synthesis. To better understand the expression of AC1, we isolated mouse genomic DNA clones of AC1. The transcription and translation start regions of mouse AC1 share extensive homologies with the bovine counterpart. The upstream proximal region has potential binding sites for transcription factors, including the steroid receptor family, the E-box factors, and Sp1. A 280-bp fragment that contains the transcription start site directed reporter gene expression in cultured cortical neurons and pinealocytes functioning as a basal neuro- and pineal-directed promoter. Interestingly, pinealocyte expression of the reporter gene was inhibited by increases in cAMP. This cAMP sensitivity may explain why AC1 mRNA in the pineal is low at night when cAMP is elevated and high during the day when cAMP signals drop. An adjacent 330-bp fragment interacted specifically with nuclear factor(s) that we designate binary E-box factor (BEF). Methylation interference and DNase I footprinting identified the BEF-binding site sequence as 5'-CCAAGGTCACGTGGC-3'. When linked to the basal tissue-directed promoter, this 15-bp sequence further enhanced reporter expression in neurons and pinealocytes. We propose that this 15-bp sequence may contribute to increased expression of AC1 in neurons and pinealocytes relative to other cells.

Adenylyl Cyclases↗
PubMed2001

Ewing sarcoma of the small intestine.

This report describes a rare case of Ewing sarcoma (ES) of the small intestine. The patient was a 9-year-old girl with progressive abdominal distension. Computed tomography showed a large mass in the small bowel. Histopathologic examination of the resected tumor showed ES with typical histologic, immunohistochemical, and ultrastructural features. The tumor recurred in the pelvic cavity 18 months after the original surgery. Molecular study of the recurrent tumor confirmed a diagnostic EWS-FLI1 gene fusion. This patient illustrates the unique occurrence of ES in the small intestine.

Child↗
PubMed2001

Primitive small round cell tumour of the adrenal gland presenting with fever of unknown origin and t(12;22)(q13;q12) cytogenetic finding.

This report describes a left adrenal tumour in a 16 year old Chinese girl who presented with fever of unknown origin. The histological and ultrastructural features of the adrenal tumour were those of a primitive small round cell tumour with neuroendocrine differentiation. Cytogenetic analysis of cultured tumour cells showed a reciprocal translocation t(12;22)(q13;q12). This is the first example of such a tumour being reported in the adrenal gland. The adrenal tumour was also the cause of the fever, which subsided after the removal of the tumour.

Adolescent↗
PubMed2000

Complex cytogenetic abnormalities in T-lymphoblastic lymphoma: resolution by spectral karyotyping.

We describe a case of T-lymphoblastic lymphoma (T-LBL) in a 13-year-old boy in which conventional cytogenetic analysis of lymph node tissue showed complex karyotypic aberrations including add(1p), add(2q), and multiple chromosomal deletions involving 5q, 7p, 7q, 13q, and 16q. Analysis by spectral karyotyping (SKY) refined add(1p) to a paracentric inversion of 1p, and add(2q) to an unbalanced translocation between chromosomes 2 and 4. The chromosomal deletions were simple deletions except del(5q), which was confirmed by SKY to be a cryptic unbalanced translocation between chromosomes 5 and 18. The present report illustrates that SKY technology is useful in identifying subtle translocations and resolving complex karyotypic aberrations in neoplastic disorders.

Adolescent↗
PubMed2000

Cytotoxic chemotherapy has minimal direct effect on gastric myoelectric activity in children with 5HT(3) antagonist prophylaxis.

BACKGROUND: Cancer patients receiving cytotoxic chemotherapy frequently develop nausea and vomiting. The direct effect of chemotherapy on gastric pacemaker is not clear. The objective of this study was to assess the direct interference of gastric electrical activity by chemotherapeutic agents as a possible cause of vomiting using electrogastrography (EGG). PROCEDURE: Fasting surface EGGs were recorded in 24 children with malignancy and 24 age-matched controls. All oncology patients received the intravenous prophylatic ondansetron. According to the known emetic potential of the medications they received, the children were divided into mild, moderate, and severe groups. The EGG recordings of oncology patients were segmented into prechemotherapy period, chemotherapy period, and emetic period. The EGG data from each period were collected and analyzed (paired t-test and Mann-Whitney U test). RESULTS: There were 24 children (M:F ratio: 14:10), with a mean age of 9.6 years. Eight children vomited during the course of recording (0/3 from the mild group, 2/6 from the moderate group, and 6/15 from the severe group). The average duration of intravenous medication infusion was 7.8 hr (range 2 min to 24 hr). There was no difference between the EGG of normal control and the prechemotherapy EGG of the oncology patients. No difference was detected between the EGG data from the prechemotherapy period and the chemotherapy period. A statistically significant increase in tachygastria was detected in emetic periods (28 episodes, mean duration 5 min; P = 0.01). CONCLUSIONS: Insignificant EGG changes during chemotherapy suggest that chemotherapy has a minimal direct effect on gastric pacemaker. Tachygastria seemed to be a secondary effect of vomiting rather than the cause of it. These preliminary findings suggest that efforts to modify gastric electrical rhythm as a means of management of chemotherapy-induced vomiting may be futile. Further studies to identify factors responsible for vomiting are warranted.

Adolescent↗
PubMed2000

Analysis of MLL-derived transcripts in infant acute monocytic leukemia with a complex translocation (1;11;4)(q21;q23;p16).

It has been proposed, on the basis of cytogenetic studies and molecular analysis of MLL-derived transcripts in acute leukemia with 11q23 rearrangement, that only one fusion gene transcript present on the der(11) chromosome is critical for leukemogenesis. This view is challenged by a recent observation in a case of leukemia with a complex translocation that results in MLL being fused in-frame to two different partner genes. We investigated a case of infant monocytic leukemia with a complex translocation, (1;11;4)(q21;q23;p16). Molecular studies revealed MLL rearrangement by both fluorescence in situ hybridization and Southern blot analysis, and MLL/AF1q, but not the reciprocal message (i.e., AF1q/MLL), was amplified by polymerase chain reaction. Sequence analysis of MLL/AF1q revealed an in-frame fusion between MLL exon 6 and the breakpoint located six bases upstream of the ATG start site for AF1q. Our data suggest that only one form of MLL fusion gene is implicated in leukemogenesis in our case to t(1;11;4).

Base Sequence↗
PubMed2000

Cytogenetic characterization of childhood hepatoblastoma.

We describe the cytogenetic abnormalities in two cases of childhood hepatoblastoma. The first case was of fetal histology with squamous metaplasia, and cytogenetic study showed an add(5)(q31). Although an association between hepatoblastoma and familial adenomatous polyposis is recognized, the breakpoint in this case is distal to 5q21 and most probably does not involve the APC gene at that location. The second case was of macrotrabecular histology, and cytogenetic study showed an unbalanced translocation in the form of der(4)t(1;4)(q12;q34) in a hyperdiploid clone. Including our case, der(4)t(1;4)(q12;q34) has been recognized in four cases of hepatoblastoma, and it may be the first recurrent translocation in this tumor. Understanding the molecular mechanism and clinical significance of this translocation awaits analysis of more cases.

Child, Preschool↗