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Biomedical subjects

M C Shen

Publications and source records attributed to M C Shen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Human immunodeficiency virus infection in haemophiliacs in Taiwan: the importance of CD4 lymphocyte count in the progression to acquired immunodeficiency syndrome.

From July 1984 to December 1996, we tested and studied 303 haemophilic patients for the infection of the human immunodeficiency virus (HIV). Among the 261 haemophilia A patients 44 were HIV positive (16.9%), while none of the haemophilia B patients was HIV positive. The mean age of the 44 HIV-seropositive patients in 1984 was 20.6 years (2-37 years). Seven who had known seroconversion dates and 29 whose first seropositive dates were known seroconverted before 1986. Acquired immunodeficiency syndrome (AIDS) has developed in 16 patients, nine of whom presented with Pneumocystis carinii pneumonia, three with tuberculosis infection, and 13 had died. The Kaplan-Meier estimate of the progression rate to AIDS after the date of first seropositive test is about 30% at the 10th year. The median survival time after development of AIDS obtained from the Kaplan-Meier estimate of the survival curve was 11.7 months. Statistical analysis for the covariate effects on the risk of developing AIDS by the Cox proportional hazards model revealed that there was a statistically significant negative association of the risk for progression to AIDS with the logarithm of initial CD4 cell counts (P = 0.027) and the rate of decline of CD4 cell counts (P = 0.040), but not with age (P = 0.650). In conclusion, the clinical characteristics of AIDS haemophiliacs in Taiwan were not different from that observed in western countries. Low initial CD4 cell count and sharp decline in CD4 cell counts, but not age, increased the risk of progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Aetiologies and prognosis of Chinese patients with deep vein thrombosis of the lower extremities.

Deep vein thrombosis (DVT) of the lower extremities is not frequently encountered in Oriental patients. We investigated its aetiology and prognosis in 143 patients (65 males, 78 females), presenting to the National Taiwan University Hospital over 4.3 years, diagnosed by colour Doppler ultrasonography. Swelling and pain of the lower extremities were the most frequent presenting symptoms. The left femoropopliteal veins were more frequently involved than other parts of the lower extremities. In these patients, malignancy with or without intravenous catheterization was the most frequent cause (39 patients, 27%). Other common aetiologies included coagulopathy (29 patients, 20%), immobilization (24 patients, 17%) and catheter-related (13 patients, 9%). No definite aetiology could be determined in 37 patients (26%). During follow-up, 27 patients (19%) died, mostly with malignancy. Pulmonary embolism was noted in 16 patients and was not significantly directly related to death. Compared to similar studies in Caucasian patients, there were significant differences in the aetiology of DVT, with malignancy and coagulopathy more common in these Chinese patients.

Adolescent↗
PubMed1998

Familial macrothrombocytopenia with granulocyte inclusion: a clinical and laboratory problem.

The differential diagnosis of familial macrothrombocytopenia and idiopathic thrombocytopenic purpura (ITP) may be difficult owing to the similarities in their clinical and laboratory presentations, but it is important because of dissimilarities in their management and prognosis. We investigated two families with familial macrothrombocytopenia and granulocyte inclusion. The probands of both families presented with mild bleeding tendency, macrothrombocytopenia, normal bone marrow, and increased percentages of platelet-associated immunoglobulin G (IgG) and reticulated platelets. ITP had been misdiagnosed in both patients initially. Both probands failed to respond to steroid therapy. Family study revealed an autosomal dominant pattern of heredity in both families, with absence of Alport's syndrome-like features (hearing impairment, congenital cataract, and interstitial nephritis). All thrombocytopenic family members showed blue cytoplasmic inclusions in neutrophils on peripheral blood smears. Ultrastructurally, distinct granulocyte inclusions comprising clusters of rough endoplasmic reticulum, smooth endoplasmic reticulum, and polysomes were detected, without the presence of parallel filaments. The clinical, laboratory, and hereditary findings were consistent with a diagnosis of Sebastian platelet syndrome in both families. In conclusion, caution should be exercised when interpreting the percentages of platelet-associated IgG in thrombocytopenic patients, as overinterpretation may lead to misdiagnosis of macrothrombocytopenia as ITP. Family history is important, as familial ITP is rare, and careful examination of blood smears is essential.

Adult↗
PubMed1997

High prevalence of antithrombin III, protein C and protein S deficiency, but no factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan.

We studied the prevalence of antithrombin III (AT III), protein C (PC) and protein S (PS) deficiencies and factor V Leiden mutation in thrombophilia in Taiwan. Eighty-five consecutive and unrelated patients with otherwise unexplained venous thrombophilia were studied. Both antigen and activity of inhibitors were determined using commercial kits (Stago), activated PC sensitivity ratio (APC SR) by Coatest (Chromogenix), and factor V mutation by polymerase chain reaction with sequence specific primer. Of 85 patients, 41 were male, 44 female, and mean age 49.4 years (17-82 years). None had factor V mutation, or APC SR of less than 2; 50 (58.8%) showed a deficiency of inhibitor proteins; 34 (68.0%) were hereditary, 16 (32.0%) non-hereditary; 3 had an AT III deficiency, 16 a PC deficiency, 28 a PS deficiency, and 3 a combined deficiency. Thirty-five were non-deficient without a known cause. The average age at the first thrombotic episode was 48.5 years (13-81 years). Thrombosis occurred spontaneously in 39 (78.0%) of 50 deficient patients. In conclusion, a relatively higher prevalence of AT III, PC and PS deficiency (59%), but no factor V Leiden mutation, was found in venous thrombophilic Chinese patients in Taiwan compared to that in western countries. Screening for inhibitor protein deficiency in Chinese thrombophilic patients is highly recommended.

Adolescent↗
PubMed1997

GB virus-C/hepatitis G virus infection in an area endemic for viral hepatitis, chronic liver disease, and liver cancer.

BACKGROUND & AIMS: GB virus-C/hepatitis G virus (GBV-C/HGV) is a newly identified flavivirus, and little is known about its clinical significance. GBV-C/HGV was investigated in different populations, and its coinfection was investigated in patients with liver disease in Taiwan where hepatitis B and C are endemic. METHODS: Viral RNA was studied in 70 high-risk individuals, 20 patients with chronic non-B, non-C hepatitis, 13 with non-A-E fulminant hepatitis, 100 with asymptomatic hepatitis B surface antigen carriage, 120 with hepatitis B surface antigen-positive chronic liver disease and hepatocellular carcinoma, 100 patients with chronic hepatitis C, and 100 healthy adults. RESULTS: GBV-C/HGV infection was more frequent in high-risk groups (15%-30%) and hepatitis C virus carriers (10%) than in healthy adults (1%) and hepatitis B virus carriers (3.2%). Eighty-three percent of those infected had undergone blood transfusions previously. The prevalence in hepatitis B virus carriers increased with the severity of liver disease, being 1% in asymptomatic carriers and 10% in hepatocellular carcinoma. In chronic hepatitis C, clinical and virological data were comparable between those with and without coinfection. CONCLUSIONS: In Taiwan, GBV-C/HGV infection is common in high-risk groups, and its coinfection seems to not aggravate the course of chronic hepatitis B or C.

Adult↗
PubMed1997

Clinical and biological characteristics of acute promyelocytic leukemia in Taiwan: a high relapse rate in patients with high initial and peak white blood cell counts during all-trans retinoic acid treatment.

Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML-RAR alpha fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.

Adolescent↗
PubMed1997

PIG-A gene mutations in four Taiwanese patients with paroxysmal nocturnal haemoglobinuria following aplastic anaemia.

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder caused by deficient biosynthesis of the glycosyl phosphatidylinositol (GPI) anchor in haemopoietic stem cells. PIG-A, an X-linked gene that participates in the first step of GPI-anchor synthesis, is responsible for PNH. Various abnormalities of the PIG-A gene have been demonstrated in all patients with PNH so far examined. In this study we characterized the somatic mutations in PIG-A gene in four Taiwanese patients with PNH. We identified five novel mutations in the PIG-A gene, three single nucleotide substitution mutations (-342, C-->G, codon 335, GGT-->AGT and codon 405, GCT-->GTT) and two frameshift mutations (codon 22, GGA-->G-A and codon 356, TGT-->TGTT) in the PIG-A gene. The -342 mutation was judged to be a polymorphism. Furthermore, three patients had previous clinicopathologic evidence which suggested aplastic anaemia (AA), before the development of PNH. One of these was found to have thrombocytopenia during follow-up. We suggest that the somatic PIG-A gene mutations highlight a subgroup of AA having a pathogenetic link with PNH.

Anemia, Aplastic↗
PubMed1997

Synergistic transactivation of HNF-1alpha, HNF-3, and NF-I contributes to the activation of the liver-specific protein C gene.

We have previously characterized the functional cis elements of the protein C promoter. One hepatocyte nuclear factor-1 (HNF-1) site, three HNF-3 sites, and at least two NF-I sites have been identified within the 140-bp basal transcriptional unit of this promoter. Here we present evidence that either HNF-1alpha or HNF-3 can cooperate with each other in binding to their cis elements. The results from the co-transfection assays in HeLa cells showed a novel synergistic transactivation between HNF-1alpha and HNF-3. Our data further indicate that the unique overlapping of the HNF-3 sites, the specific spatial relationship of the sites, and the co-activator C/EBP all contributed to the synergistic interaction. Although NF-I itself has a weak transactivating effect, it apparently coordinates the transactivation complex formation. NF-I can synergistically enhance the transactivation of HNF-1alpha or HNF-3. Taken together, the combinatorial interplay of HNF-1alpha, HNF-3, and NF-I make a significant contribution to the activation of the liver-specific protein C gene.

Animals↗
PubMed1996

Characterization of human protein C gene promoter: insights from natural human mutants.

Human protein C is a liver-produced plasma anticoagulant. Four heterozygous point mutations located in the promoter region have been identified in families with type I protein C deficiency and recurrent venous thrombosis. However, detailed analysis of regulatory elements and their interacting factors remains to be undertaken. This report presents results of biochemical and functional characterizations of several cis-elements located in the 5'-upstream regulatory region and the trans-acting factors that interact with them. A cloned DNA fragment from nucleotides (nt) -418 to +45 could confer tissue specificity, whereas nt -88 to +45 was sufficient for basal promoter activity of protein C gene. Five cis-elements corresponding to HNF-1, HNF-3, and NF-I/CTF binding sites have been identified. Four heterozygous mutations have been shown to disrupt HNF-3 [mutants of A(-32)G and T(-27)A] and HNF-1 [T(-14)C and C(-10)T] binding. Mutation in the NF-I-binding site also significantly impairs the promoter activity. Viewed as a whole, these results indicate that HNF-1, HNF-3, and NF-I/CTF play critical roles in transcriptional regulation of the protein C gene.

Base Sequence↗
PubMed1996

Leptomeningeal seeding with acute hydrocephalus--unusual central nervous system presentation during chemotherapy in Ki-1-positive anaplastic large-cell lymphoma.

An unusual central nervous system (CNS) manifestation in a 18-year-old male with Ki-1- positive anaplastic large-cell lymphoma is presented. The diagnosis of Ki-1 lymphoma was first confirmed by the distinct pleomorphic morphology, expression of Ki-1 (CD30) antigen on neoplastic cells and the specific chromosome translocation, t(2;5)(p23;q35). Although young age is thought to be a good prognostic factor in this disease, the course in our patient was very aggressive. At presentation, there was already extensive extranodal involvement, with malignant cell found in the pleural cavity and bone marrow. In spite of rapid shrinkage of whole-body lymph nodes and a decrease in malignant pleural effusion soon after starting chemotherapy, headaches and vomiting ensued in the following days. A computerized tomography scan of the brain showed poor corticomedullary differentiation without definite mass lesions, and numerous malignant cells were found in the cerebrospinal fluid (CSF). Although intrathecal methotrexate was given, the patient died following the sudden onset of acute hydrocephalus. CNS involvement in Ki-1 anaplastic large-cell lymphoma is very rare and most cases present as focal mass lesions in the brain parenchyma. Leptomeningeal seeding of the lymphoma cells with acute hydrocephalus contributing directly to death has never been reported. The experience from this case suggests that CNS involvement may present in variable forms in Ki-1 lymphoma and may be an important cause of mortality in young patients, especially those in advanced stages of the disease. Early detection of CNS involvement by CSF investigation or even prophylactic CNS therapy may be mandatory in these patients.

Adolescent↗
PubMed1996

Clinical and hematological characteristics of hepatosplenic T gamma/delta lymphoma with isochromosome for long arm of chromosome 7.

Hepatosplenic T gamma/delta lymphoma is a rare entity of peripheral T cell lymphoma. Three of 386 patients with non-Hodgkin's lymphoma in our institute were found to have this subtype of lymphoma. All had chromosomal abnormalities of isochromosome 7q and trisomy 8. The clinical and hematological features of these three patients are reported. All were males with ages ranging from 23 to 29 years. Initial presentation comprised purpura and variable degree of hepatosplenomegaly. None had superficial lymphadenopathy. Hematologically, they showed pictures resembling immune related thrombocytopenia and/or hemolytic anemia. Examination of the bone marrows revealed hypercellularity with increased number of megakaryocytes and erythroid cells and various degrees of abnormal lymphoid cell infiltration. The histopathologic section of the spleen from one patient who underwent splenectomy revealed abnormal cell infiltration in the sinusoids of the red pulp. Lymphoma cells showed T gamma/delta lymphoid immunophenotype (CD3+ CD2+ CD4- CD8-, TCR delta-1+, and beta F1-). The platelet counts were elevated transiently after initial treatment with corticosteroids, but the condition soon deteriorated. All died of refractory lymphoma five to nine months after diagnosis. Review of the literature, showed that only four other cases have been reported until now and although no cytogenetic data were available for these patients, they had very similar clinical pictures as those in this series. It is suggested that hepatosplenic T gamma/delta lymphoma represents a rare, but distinct, clinicopathological and cytogenetic entity.

Adolescent↗
PubMed1995

Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan.

Of 235 consecutive patients with de novo acute myeloid leukemia (AML), clonal chromosomal abnormalities were detected in 151 (64%) of them. Twenty-four of the 71 patients with M2 AML had t(8;21), 35 of the 36 M3 patients had t(15;17), and 11 of the 45 M4 leukemia disclosed inv(16). Six of the eight patients with 11q23 abnormality had M4 or M5 subtype of leukemia. The incidence of t(15;17) and t(8;21) was higher in our patients than in patients from most Western countries. Immunophenotyping was performed on 197 patients. Patients with t(15;17) were associated with negativity to HLA-DR, CD11b, and CD34. Patients with t(8;21) expressed CD13 and CD33 less frequently than other patients, but all showed CD15 positivity. Coexpression of lymphoid-associated antigens on the leukemic blasts was detected in 52 patients (26%), including all 7 patients with t(9;22), 3 of the 8 patients with t/del(11)(q23), 2 of the 25 patients with t(15;17), and 2 of the 22 patients with t(8;21). Seven (35%) of the 20 patients coexpressing lymphoid markers showed immunoglobulin heavy chain or T-cell receptor beta-chain gene rearrangements, while only 2 (4%) of the 53 patients without lymphoid antigen expression did so. Patients with inv(16), t(8;21), and t(15;17) had a better prognosis than other patients. Of all surface antigens tested, only CD15, CD11b, and HLA-DR were of prognostic value: CD15 with a higher complete remission (CR) rate and CD11b or HLA-DR with a shorter CR duration. N-ras mutations were detected in 7 (18%) of the 40 patients in the study, including two of the three patients with inv(16). This study demonstrated differences in clinical features, immunophenotypes, and genotypes among different cytogenetic subgroups.

Adolescent↗
PubMed1995

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗
PubMed1995

Consistent presence of isochromosome 7q in hepatosplenic T gamma/delta lymphoma: a new cytogenetic-clinicopathologic entity.

Peripheral T-cell lymphoma (PTL), which is characterized by hepatosplenic presentation and the gamma/delta T-cell receptor (TCR) phenotype on the malignant cells, is a rare but distinct subtype of non-Hodgkin's lymphomas. Little is known about the chromosomal changes in these lymphomas. We report the cytogenetic analysis of three patients who had neoplastic proliferation of T gamma/delta cells in the spleen, bone marrow, and liver, but not in lymph nodes or skin. Isochromosome 7q and trisomy 8 were observed in all three patients. Isochromosome 7q as the sole abnormality has been previously reported in one patient with similar clinicopathologic features. It is suggested that i(7q) is a primary, nonrandom chromosomal abnormality in hepatosplenic T gamma/delta PTL.

Adult↗
PubMed1995

Acute leukemic transformation of myelodysplastic syndrome--immunophenotypic, genotypic, and cytogenetic studies.

The clinical and biological characteristics of myelodysplastic syndrome (MDS) in acute leukemic transformation were studied in 23 patients. All had myeloid transformation according to FAB criteria, but coexpression of lymphoid-associated antigens was detected in five of the 20 patients who underwent an immunophenotypic study. Rearrangement of the immunoglobulin heavy chain gene was also observed in one of the five patients who coexpressed lymphoid markers and that of the T-cell receptor beta chain gene in another one. None had pure lymphoid transformation. Clonal chromosomal abnormalities were noted in 12 (63%) of the 19 patients who underwent cytogenetic study, most commonly - 7 (six patients or 32%). In the 18 patients who underwent serial analyses both at MDS diagnosis and at acute transformation, seven (39%) underwent karyotypic evolution. The most common new or additional aberrations were +8 and +21. N-ras gene mutation was detected in two of the nine patients at acute leukemic transformation. The median interval from diagnosis of MDS to onset of acute transformation was 10 months (1-36 months). Patients with a normal karyotype at diagnosis had a significantly longer chronic phase duration than those with chromosomal abnormalities (median of 20 months vs. 5 months). However, all had a short survival time after diagnosis of acute leukemia, whether chromosomal anomalies were present or not.

Adolescent↗
PubMed1995

Genetic diagnosis of haemophilia A of Chinese origin.

Genetic diagnosis of haemophilia A has been studied in two aspects. One is to directly identify the mutations in the factor VIII genes of the affected probands, and the other is to examine the usefulness of several intragenic factor VIII markers for gene tracking. Direct mutational analysis by PCR-SSCP (polymerase chain reaction--single-strand conformation polymorphism) has been accomplished previously in 87 haemophilia A patients, accounting for nearly 10% of cases in Taiwan. Of the 87 cases, 46% were with point mutations, short deletions or insertions, and most of the remaining were with gene inversion readily identified by Southern blotting. Further examination of 112 patients has estimated a 33% incidence for gene inversion in all the patients with haemophilia A, or 37% in severe cases. Since the direct mutational detection described above cannot be used in all Chinese families with haemophilia A, genetic markers were also investigated. The two CA repeat markers located at intron 13 (CA-13) and intron 22 (CA-22), respectively, were amplified and analysed simultaneously. Seven different alleles with 18-24 CAs have been identified for CA-13. Alleles of 20 and 21 CAs are the most common and their population frequency was 0.68 and 0.24, respectively. The CA-22 marker contained a repetition of (GT)n(AG)n as was identified in the white European but not in the Canadian population. Alleles with 25 and 26 GT/AGs account for 18% and 75% of this group of samples, respectively. The expected rate of heterozygosity for either CA markers was 68%, although a value of 57% was observed by haplotype analysis, indicating an association of the two repeat markers. Nevertheless, the study of 62 females showed that with the combined use of CA-13 and CA-22 with BclI, approximately 71% would be informative for these markers. This number may increase to 81% if XbaI polymorphism is added. We propose that a better genetic diagnosis procedure for Chinese individuals would be first to look for the inversion mutation, secondly for one of the intragenic markers, and then at the PCR-SSCP analysis.

Blotting, Southern↗
PubMed1994

Characterization of a factor IX variant with a glycine207 to glutamic acid mutation.

Factor IXTaipei9 is a factor IX variant from a hemophilia B patient with reduced levels of circulating protein molecules (cross-reacting material reduced, CRM). This variant contained a glycine (Gly) to glutamic acid (Glu) substitution at the 207th codon of mature factor IX. The functional consequences of the Gly-->Glu mutation in factor IXTaipei9 (IXG207E) were characterized in this study. Plasma-derived IXG207E exhibited a mobility similar to that of normal factor IX on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its specific activity was estimated to be 3.5% that of the purified normal factor IX in a one-stage partial thromboplastin time assay (aPTT). Cleavage of factor IXG207E by factor XIa or factor VIIa-tissue factor complex appeared to be normal. When the calcium-dependent conformational change was examined by monitoring quenching of intrinsic fluorescence, both normal factor IX and IXG207E exhibited equivalent intrinsic fluorescence quenching. Activated factor IXG207E (IXaG207E) also binds antithrombin III equally as well as normal factor IXa. However, aberrant binding of the active site probe p-aminobenzamidine was observed for factor XIa-activated factor IXG207E, indicating that the active site pocket of the heavy chain of factor IXaG207E was abnormal. Moreover, the rate of activation of factor X by factor IXaG207E, as measured in a purified system using chromogenic substrates, was estimated to be 1/40 of that of normal factor IXa. A computer-modeled heavy-chain structure of factor IXa predicts a hydrophobic environment surrounding Gly-207 and this Gly forms a hydrogen bound to the active site serine-365. The molecular mechanism of the Gly-->Glu mutation in factor IXTaipei9 might result in the alteration of the microenvironment of the active site pocket which renders the active site serine-365 inaccessible to its substrate.

Benzamidines↗