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Biomedical subjects

L L Chiu

Publications and source records attributed to L L Chiu.

11 recordsLinked to original sources
PubMed2004

Lactacystin-induced apoptosis of cultured mouse cortical neurons is associated with accumulation of PTEN in the detergent-resistant membrane fraction.

The tumor suppressor function of PTEN is attributed to its phospholipid phosphatase activity that dephosphorylates the plasma membrane phosphatidylinositol-(3,4,5)-triphosphate [PtdIns(3,4,5)P3]. Implicit in this notion is that PTEN needs to be targeted to the plasma membrane to dephosphorylate PtdIns(3,4,5)P3. However, the recruitment of PTEN to the plasma membrane is not fully understood. Here, we demonstrate PTEN accumulation in the detergent-insoluble fraction of neuronal cells in response to treatment by the proteasome inhibitor lactacystin. First, lactacystin induces apoptosis and the activation of caspase-3 in cultured cortical neurons. Second, PTEN undergoes proteolysis to form a truncated 50-kDa form that lacks parts of its C-terminal tail. Third, the truncated PTEN is stably associated with the detergent-insoluble fraction in which the plasma membrane marker protein flotillin-1 resides. Taken together, our results suggest that truncation and accumulation of PTEN to the detergent-insoluble membrane fraction are two events associated with the apoptotic signals of the proteasome inhibitor in cortical neurons.

Acetylcysteine↗
PubMed2003

Sequence confirmation of the EWS-WT1 fusion gene transcript in the peritoneal effusion of a patient with desmoplastic small round cell tumor.

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated neoplasm. The prognosis is poor, even if therapy is instituted promptly, and thus it is important to differentiate it from other histologically and cytologically similar-looking malignancies of the young adult. We present a case of DSRCT in a 17-yr-old male with disseminated peritoneal disease and peritoneal effusion. The cytology sample showed a malignant small round cell tumor, the classical cytological features of DSRCT, and immunohistochemistry performed in the prepared cell block exhibited an antibody expression profile in keeping with DSRCT. Further material from the effusion was prepared for RNA extraction, following which a reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing of the t(11;22)(p13;q11 or q12) were carried out. The result showed the presence of the reciprocal translocation and thus confirmed the diagnosis of DSRCT. This case shows how molecular techniques (including sequencing) can be applied to cytology in clarifying and confirming certain difficult diagnosis of undifferentiated neoplasms, DSRCT in this particular case.

Adolescent↗
PubMed2003

Immunocytochemistry versus molecular fingerprinting of metastases.

Examination of cytological samples of cancer to suggest a possible primary site of origin is one of the commonest and most difficult tasks of diagnostic cytopathologists. Currently, both cytomorphology and immunocytochemistry are the main approaches to this diagnostic dilemma. We report the application of microsatellite analysis in cytological samples in a patient with a primary colonic tumour and two subsequent lung nodules, which were suspected on CT scans of the chest, and compared the findings with those obtained with conventional immunocytochemistry. The molecular results were in agreement with the radiological impression and conflicted with the immunocytochemistry. We conclude that immunocytochemical and molecular biology approaches to the diagnosis of tumours may give rise to contradictory results.

Adenocarcinoma↗
PubMed1999

Glutathione S-transferase (GST) M1 and GST T1 genotypes and hematopoietic effects of benzene exposure.

This study investigated whether or not the genotypes glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with low white blood cell (WBC) count found in benzene exposed workers. We found that individuals with genotypes positive for both GST T1 and GST M1 showed the highest prevalence of low WBC [odds ratio (OR) = 4.67, P = 0.046, 95% confidence interval (CI) = 1.02-24.15] when the benzene exposure was high. Multiple logistic regression showed that benzene exposure (OR = 2.81, P = 0.062, 95% CI = 0.96-8.30) was associated with increased OR on low WBC and interactions between the benzene exposure and the genotype of GST T1 were also observed. These observations suggest that GST T1 and GST M1 may play important roles in the biotransformation of benzene, the effect which leads to its hematotoxicity.

Benzene↗
PubMed1997

Molecular studies of loss of heterozygosity in retinoblastoma.

Retinoblastoma (Rb) is a paediatric intraocular tumour in which predisposition can be inherited. Cases of Rb tumours can be divided into three types: familial cases, sporadic bilateral cases and sporadic unilateral cases. Familial and sporadic bilateral cases are usually categorised as hereditary while sporadic unilateral cases as non-hereditary. In both familial and non-familial forms of Rb, loss of heterozygosity of the Rb locus has been reported although its frequency in tumours has not so far been accurately determined. The cloning of the gene responsible for retinoblastoma (Rb1) has facilitated DNA studies and genetic counselling of patients. We have examined forty-five cases of retinoblastoma at five intragenic sites of the Rb1 locus, namely intron 1/BamH1, intron 17/Xba1, intron 24/TthIII1, intron 25/Dra1 and Rb1.20 VNTR. Thirty-six out of the forty-five cases (80%) were informative for these markers. Comparison of results between genomic DNA from peripheral blood and from tumours revealed that loss of heterozygosity of alleles could be detected in 50% of cases studied in which tumour samples were available. Investigation of parental origin of retained alleles showed that in all these cases, the paternal alleles were preferentially retained. The analysis of the genetic origin of mutations predisposing to retinoblastoma can facilitate new approaches for identifying recessive mutant genes that lead to cancer as well as to provide a conceptual basis for accurate prenatal predictions of cancer predisposition.

Genetic Markers↗
PubMed1997

Detection of low numbers of neuroblastoma cells in vitro.

Neuroblastoma is a tumour derived from the sympathoadrenal progenitors of the neural crest. It is one of the most malignant solid tumours in childhood with an annual incidence of 9.4 per 10(6) children under 15 years of age. Recent studies suggest that immunocytological detection of neuroblastoma cells in bone marrow and circulating neuroblasts during treatment may predict clinical outcome and correlate with tumour relapse. The present methods of diagnosing metastasis in neuroblastoma include histological, biochemical and immunohistological analysis. Morphological distinction between tumour cells and primitive lymphoblasts in bone marrow is often difficult, and these methods may also not always be sensitive enough for early detection of the residual and minimally circulating tumor cells. A sensitive assay for detection of such residual cells using two tissue-specific markers, NFM and SYN, by reverse transcriptase-polymerase chain reaction (RT-PCR) is reported here. Analysis of the specificity of this assay in three neuroblastoma cell lines, namely IMR 32, SK-N-SH and SY5Y showed positive expression while control peripheral blood mononuclear cells (HL 60) were negative. In reconstituted cell spiking tests, this method has the ability to detect 1-10(3) neuroblastoma cell in 10(7) normal peripheral blood mononuclear cells (PBMC), as shown by serial dilution and limiting dilution. The NFM marker was found to be a more sensitive marker. The specificity and sensitivity of this technique makes it suitable for future application in detection of minimally disseminated tumour cells in neuroblastoma patients.

Base Sequence↗
PubMed1996

p53 gene mutation in cerebral primitive neuroectodermal tumor in Taiwan.

p53 mutation has been rarely reported in cerebral primitive neuroectodermal tumors (PNET). To determine the significance of p53 mutations in the development of cerebral PNET, we studied cerebral PNET samples from 14 patients, 8 females and 6 males with a mean age of 38 years (range 10 months to 77 years) who had total or subtotal surgical resection. Histological typing of PNET with neuronal (N) and non-neuronal (NN) differentiation groups revealed 8 and 6 cases, respectively. Six (43%) of the 14 patients had p53 mutation. The p53(+) and p53(-) groups had an age range of 19-77 with a mean of 49 years and 10 months to 57 years with a mean of 30 years, respectively. p53 expression between the PNET-N and PNET-NN groups was 5 of 8 (62.5%) and 1 of 6 (16.7%), respectively. The mutations contained 3 transitions, 2 transversions and 1 frameshift; none of them occurred at the site of 'hot-spot' residues (codons 175, 248, 273). The results suggest that: (1) p53 mutation in cerebral PNET tends to show a higher incidence of neuronal differentiation and occurs in the older age group in Taiwan, (2) there was no difference in survival time between the PNET-N and PNET-NN groups (7 months and 6 months) (P = 0.54), and between p53(+) and p53(-) groups (6 months and 7 months) (P = 0.57), and (3) PNET may be an entity of a heterogenous group of tumors with different genetic mechanisms controlling their trends of differential lineage. Further studies are needed to determine the significance of p53 mutations in PNET development, especially the role of carcinogens in the genesis of PNET in Taiwan.

Adolescent↗
PubMed1995

Usefulness of dinucleotide polymorphism markers in genetic analysis of Duchenne's muscular dystrophy cases in Singapore.

Dinucleotide polymorphisms are short tandem repeat sequences that can be used as probes for haplotype analysis in Duchenne's muscular dystrophy (DMD). There are approximately a total of 50,000 to 100,000 such loci in the human genome, and they are highly informative due to the variability of allele lengths at these loci. Primers can be designed to amplify across such repeats located in the dystrophin gene to provide diagnostic information when RFLP analysis is uninformative. We report the usefulness of three such loci for analysis of DMD families in Singapore. The STR50 marker consists of (CA)n repeats located in intron 50 of the dystrophin gene while DYS1 marker is located upstream to the transcriptional start site for the brain dystrophin promoter and BSTRH marker is identified in the 3' untranslated region of the gene. End-labeled PCR products were resolved on 6% denaturing polyacrylamide sequencing gel. Alleles were identified by comparison with sequencing markers. PCR product typically ranged between 174 bp to 255 bp with five to six alleles observed. The heterozygosity rates estimated from 50 X chromosomes of unrelated individuals were 76.0% (BSTRH), 86.6% (DYS1) and 93.3% (STR50). In 38 DMD families studied, the results obtained show that these markers were highly informative and reveal Mendelian mode of inheritance. They were useful for linkage analysis, identification of deletion mutations, confirmation of paternity and mapping of gene recombination.

Alleles↗
PubMed1984

Purification and some properties of a protein obtained from normal human plasma which inhibits the platelet aggregation induced by thrombotic thrombocytopenic purpura plasma.

Plasma from patients with thrombotic thrombocytopenic purpura (TTP) caused the aggregation of washed human platelets, which was inhibited by preincubation with normal plasma. Using salt fractionation, ion exchange chromatography, and preparative agarose gel electrophoresis, we purified a protein from normal plasma which inhibited the platelet aggregation caused by TTP plasma. On SDS polyacrylamide gel, the purified inhibitor gave a single band with a M.W. of 150,000. The antiserum against the purified protein neutralized the activity of the inhibitor and formed an identical precipitin line against normal and TTP plasma.

Blood Coagulation Factors↗
PubMed1984

Inhibition of platelet-aggregating activity in thrombotic thrombocytopenic purpura plasma by normal adult immunoglobulin G.

Plasma from patients with thrombotic thrombocytopenic purpura (TTP) caused the aggregation of autologous and homologous platelets, and effect which was inhibited by normal plasma. IgG purified from seven normal adults at a concentration of 0.7 mg/ml completely inhibited the platelet aggregation induced by plasma obtained from two TTP patients with active disease. The inhibition of platelet aggregation by human adult IgG was concentration dependent, and the inhibitory activity of human IgG was neutralized by rabbit antihuman IgG. Fab fragments inhibited the TTP plasma-induced platelet aggregation as well as intact IgG, whereas Fc fragments had no effect. Platelet aggregation caused by ADP, collagen, epinephrine, or thrombin was not affected by purified human IgG. The prior incubation of IgG with TTP plasma caused a significantly greater reduction of platelet aggregation by TTP plasma than that of IgG and platelet suspension, suggesting that the IgG inhibits TTP plasma-induced platelet aggregation through direct interaction with platelet aggregating factor in TTP plasma. IgG obtained initially from five infants and young children under the age of 4 yr did not possess any inhibitory activity. When one of the children reached 3 yr of age, his IgG inhibited the aggregation induced by one TTP plasma, but not that caused by another plasma. The IgG procured from the same boy at 4 yr of age inhibited the aggregation induced by both TTP plasmas. The IgG purified from the TTP plasma during active disease failed to inhibit the aggregation caused by the same plasma. After recovery, however, the IgG effectively inhibited aggregation. These observations suggest that platelet-aggregating factors present in the TTP plasma are heterogeneous in nature and that the IgG present in the normal adult plasma, which inhibits the TTP plasma-induced platelet aggregation, may be partially responsible for the success of plasma infusion therapy in TTP.

Adult↗