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Biomedical subjects

P Tan

Publications and source records attributed to P Tan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Two patients with novel BCR/ABL fusion transcripts (e8/a2 and e13/a2) resulting from translocation breakpoints within BCR exons.

We have identified novel BCR-ABL mRNA fusions by RT-PCR in two patients with Philadelphia (Ph) chromosome positive leukaemia. Sequencing revealed in-frame fusions consisting of part of BCR exon e8 spliced to ABL exon a2 in one patient and part of BCR exon e13 spliced to ABL exon a2 in the other. The breaks within BCR exons e8 and e13 did not conform to consensus splice sites, suggesting that the aberrant fusion mRNAs may have arisen as a result of translocation breakpoints at these sites. This was confirmed by genomic DNA bubble PCR for the second patient. These data show that BCR-ABL translocation breakpoints can occasionally occur within coding exons.

Adult↗
PubMed1999

Establishment of animal models using experimental rats for allogeneic tissue transplantation and quantitative flow cytometric detection of immunochimera.

Establishment of animal models used for allogeneic tissue transplantation, MHC phenotyping as well as quantitative detection of immunochimera were carried out in this study. Both Buffalo (BUF) and Lewis (LEW) rats were chosen as the target animals. The rats were treated with single dose cyclophosphamide (Cy) of 25 to 100 mg/kg to mimic the standard conditioning therapy. Total white blood cells (WBC) were monitored daily for up to 8 days: WBC reached the nadir by day 4 and started to recover by day 5 with an obvious rebounce at day 7 of Cy treatment. Flow cytometric techniques were used to determine the haplotypes of the major histocompatibility complex (MHC) as well as quantitative detection of immunochimerism in unfractionated rat WBC. Monoclonal antibodies against the rat class-I MHC antigens RT1Aab and RT1Au were used to label the class-I MHC antigens on total rat WBC. The results showed that the BUF rats were positive for both RT1Aab and RT1Au antigens, whilst the LEW rats were negative for both. Immunochimera was mimicked in vitro by serial dilution, ranging from 1/1 to 1/10(5) of (BUF/LEW) WBC. A sensitivity of 1/10(4) (BUF/LEW WBC) was achieved. The results showed that there were at least 2 major MHC mismatched loci between BUF and LEW rats and flow cytometry provided a sensitive method for the detection of immunochimera in unfractionated rat WBC. We concluded from this study that both strains of rats could be used as models for allogeneic tissue transplantation across at least two major MHC-mismatches. The sensitivity of flow cytometric method was satisfactory for the detection of immunochimera.

Animals↗
PubMed1998

A comparison of central venous pressure and common iliac venous pressure in critically ill mechanically ventilated patients.

OBJECTIVE: To investigate the possibility of using common iliac venous pressure (CIVP) as an alternative to superior vena cava pressure (SVCP) in mechanically ventilated, critically ill, adult patients. DESIGN: A randomized, blinded comparison. SETTING: Multidisciplinary intensive care unit at a university teaching hospital. PATIENTS: Twenty mechanically ventilated, critically ill, adult patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients had a catheter in situ for measuring the SVCP. A new triple-lumen catheter, with a length ranging from 15 to 20 cm, was placed into the common iliac vein via the femoral route. The SVCP and CIVP were simultaneously measured at hourly intervals for 6 hrs. Positive end-expiratory pressure, mean airway pressure, and intra-abdominal pressure were measured at the same time intervals. For 140 paired measurements of CIVP and SVCP in 20 patients, the mean difference was 0.1 +/- 1.06 (SD) mm Hg (95% confidence interval -0.10 to 0.25); the limits of agreement were -2.04 to 2.20 mm Hg (95% confidence interval -2.34 to 2.50). Mean airway pressure, intra-abdominal pressure, and positive end-expiratory pressure had no measurable effect on the difference between SVCP and CIVP. Serious complications arising from insertion of the catheter through the femoral route were not observed. CONCLUSION: For clinical purposes, CIVP measured by a catheter of 15 to 20 cm placed through the femoral route is interchangeable with SVCP in mechanically ventilated adult patients. This finding provides an alternative route for assessment of central venous pressure when other routes are not appropriate.

Abdomen↗
PubMed1997

The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas.

Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospective series of 202 patients with stage T1a,b invasive breast carcinomas was evaluated. The clinicopathological features (age, histological grade, extensive in situ carcinoma, hormone receptor status, and nodal metastasis) as well as microvessel density and the expression of c-erb-B2, p53, MIB-1/Ki-67, and cdc25B were assessed. In addition, expression of the cell cycle inhibitor p27 was evaluated. Nineteen patients (18% of patients who had axillary dissection) had locoregional lymph node metastases. Forty-two % of them died of disease (median survival, 112 months), whereas mortality was 11% in node-negative patients (median survival, 168 months; P = 0.0055). Patients with low p27 expression had a median survival of 139 months (17% mortality) versus 174 months (9% mortality) in the group with high p27 expression (P = 0.0233). Lack of p27 was associated with poor prognosis when node-positive patients were excluded (P = 0.0252). Nodal status and low p27 were found to be the only independent prognostic parameters by both univariate and multivariate analysis, with relative risks of dying of disease of 4.9 (P = 0.001) and 3.4 (P = 0.0306), respectively. Assessment of p27, which yields prognostic information in node-negative patients, could be useful to identify patients with small, invasive breast carcinomas who might benefit from adjuvant therapy.

Age Factors↗
PubMed1997

A splice-site mutation causing ovine McArdle's disease.

McArdle's disease is an autosomal recessive myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme muscle glycogen phosphorylase which releases glucose for contraction during exercise. The human cDNA has been sequenced and disease-causing mutations identified. An ovine equivalent of McArdle's disease has been diagnosed and the mutation responsible identified by PCR-amplification of the ovine glycogen myophosphorylase cDNA in six overlapping fragments followed by single strand conformation polymorphism (SSCP) analysis. Two fragments showed SSCPs in the glycogen myophosphorylase cDNA from affected sheep. The SSCP in fragment one was a silent polymorphism, while that in fragment six, was an eight base deletion at the 5' end of exon 20. This deletion will cause a frame-shift, a premature stop codon and remove the last 31 amino-acid residues from the protein. The cDNA deletion suggested that the genomic mutation most likely involved a splice-site. Sequencing intron 19 identified the mutation as an adenine for guanine substitution at the intron 19 3' splice-site. This eliminated an XbaI site present in normal sheep allowing diagnosis of normal, affected and carrier sheep. This ovine model of McArdle's disease is now available for therapeutic trials.

Amino Acid Sequence↗
PubMed1997

[The effect of protheo on pulmonary function and the change of its plasma concentration in patients with chronic asthmatic bronchitis].

OBJECTIVE: In order to study the effect of protheo on pulmonary function and the change of its plasma concentration in patients with chronic asthmatic bronchitis. METHOD: 31 patients with chronic asthmatic bronchitis were treated by taking protheo 400 mg once a day orally for 6 weeks. The pulmonary functions, including FEV1, FVC, FEV1/FVC and PEFR, and the plasma concentrations of theophylline were measured respectively before and after the administration. RESULTS: The results showed that the pulmonary functions after the therapy were greatly improved compared with that before the therapy, even after the administration for two weeks. In the second, fourth, sixth week of the therapy, the plasma levels of theophylline after taking protheo for 4 hours and 12 hours were both within the effective concentration. CONCLUSION: Protheo is a kind of medicine with good effect, steady plasma concentration and less side effect for the patients with chronic asthmatic bronchitis.

Asthma↗
PubMed1997

Gastrointestinal lymphoma--a review of 54 patients in Singapore.

Primary gastrointestinal (GI) lymphoma accounts for 2% to 5% of all GI malignancies. Primary therapy in uncomplicated GI lymphoma remains controversial. Fifty-four patients (male to female ratio of 4:3, median age 56 years) with GI lymphoma were studied to evaluate complications and results of therapy. The sites involved were the stomach (31), small bowel (12), large bowel (4), gallbladder (1) and multifocal (6). Distribution by stage and grade (Working Formulation or Kiel) were: IE-30%, IIE-43%, IIIE-6%, IV-20% and unknown-1%; low grade-33%, intermediate grade-59% and high grade-8%. Majority (54%) had diffuse large cell lymphoma. Twenty-three patients (43%) underwent primary resection of the tumour followed by chemotherapy in 14 or radiotherapy in 3. Seventeen patients (31%) had primary chemotherapy and 3 (6%) had primary radiotherapy. Of the 48 patients who underwent therapy, 52% had complete response. At the last follow-up (median 21 months), 25 patients were disease-free. Overall survival was 67% at two years. Treatment strategies employing surgery, radiotherapy and chemotherapy, alone or in combination, do not appear to influence outcome. Surgical resection plus chemotherapy appear to be effective in the control of local and distant disease.

Adolescent↗
PubMed1996

L- and P-selectins, but not CD49d (VLA-4) integrins, mediate monocyte initial attachment to TNF-alpha-activated vascular endothelium under flow in vitro.

Monocyte adhesion to the vascular endothelium is a pivotal step during their egress to tissues at sites of inflammation and immune reactions, and during atherogenesis. In this study, an in vitro flow model and blocking mAb were used to define the role of adhesion molecules in monocyte interactions with activated HUVEC under flow conditions. By videomicroscopy, freely flowing monocytes abruptly halted (initial attachment) on 6-h TNF-alpha-activated HUVEC under flow via L- and P-selectin, whereas E-selectin was not involved. CD49d/CD29 integrin (VLA-4), which can mediate initial attachment of certain T cells to VCAM-1 under flow, did not support monocyte initial attachment. Once initially attached, a small number of monocytes began rolling at 9 microns/s through a mechanism involving L-selectin, as well as CD49d and CD11/CD18 integrins, while the remaining monocytes became firmly adherent, or released to the flow stream. Monocyte stable arrest and subsequent transendothelial migration occurred rapidly and efficiently through either CD49d or CD18 integrin adhesion pathways. Transendothelial passage was also dependent on PECAM-1 (CD31). These data reveal monocytes initially attach to activated endothelium via an L-selectin-dependent mechanism, with a smaller contribution from P-selectin and no contribution by CD49d. Subsequent monocyte rolling, arrest, and transmigration require overlapping functions between multiple members of the selectin, integrin, and Ig gene families.

Animals↗
PubMed1996

Exacerbation of hepatitis in hepatitis B carriers following chemotherapy for haematological malignancies.

We describe nine asymptomatic chronic carriers of hepatitis B virus, four males and five females, with a mean age of forty-six years and all were Chinese, who developed exacerbation of hepatitis following chemotherapy for haematological malignancies. Seven patients had non-Hodgkin's lymphoma of whom three were treated with MACOP-B, two with BCEPP, one with PROMACE-CYTABOM and one with CHOP. Two patients had acute myeloid leukaemia and were treated with daunorubicin and cytosine arabinoside. Exacerbation of hepatitis occurred between one to four weeks following the last course of chemotherapy in eight patients. Two patients developed exacerbation of hepatitis when the dosage of prednisolone was reduced after they had ten weeks of high dose prednisolone. The outcome was fatal in six patients; all of whom developed hepatic encephalopathy. In four of these patients, alanine transaminase levels exceeded 1000 iu/l. Cytotoxic and immunosuppressive therapy permit enhanced viral replication. Withdrawal of the drugs results in partial restoration of immunocompetence and leads to rapid destruction of hepatocytes with consequent hepatic necrosis. Hence, patients who are hepatitis B virus carriers undergoing chemotherapy should be closely monitored. The fatal outcome of reactivation of chronic hepatitis B virus warrants prospective trials addressing preventive measures.

Adult↗
PubMed1996

Hepatic manifestation of malignant histiocytosis: a case study.

Malignant histiocytosis, as defined by Rappaport, is now known as a manifestation of malignant lymphoma, the majority of which is the T-cell type. However, unlike the typical presentation of most non-Hodgkin lymphomas, this condition presents with atypical features mimicking acute hepatitis or infectious mononucleosis. The latter diagnosis is often made because of the occurrence of atypical mononuclear cells on the peripheral blood films. This is clearly seen in the seven patients we report where the initial diagnoses were that of viral fever or hepatitis. Some characteristics were found in these patients to differentiate the condition from infectious mononucleosis (IMS) and acute hepatitis (AH): paucity of lymph nodes, cholestasis and prolonged prothrombin time (PT) which is atypical IMS; persistent fever, thrombocytopaenia and disproportionately high aspartate aminotransferase which is unusual in AH in the absence of any drug or alcohol history. The PT is the most important prognosis factor. Early diagnosis and treatment led to improved survival in an otherwise aggressive and rapidly fatal condition.

Acute Disease↗
PubMed1996

Molecular analysis of neurotransmitter transport into secretory vesicles.

Molecular cloning of the transport proteins involved in packaging monoamines and ACh into secretory vesicles has implicated their activity in neural degeneration as well as signaling. Future studies will explore further the mechanism of active transport, its regulation, and the membrane trafficking of the proteins with the long-term goal of understanding how the regulation of transmitter release and, in particular, quantal size influences information processing and behavior. In addition, the bioenergetics of vesicular GABA and glutamate transport suggests that the proteins responsible for these activities may belong to a distinct gene family.

Animals↗
PubMed1995

The Saccharomyces cerevisiae SPT7 gene encodes a very acidic protein important for transcription in vivo.

Mutations in the SPT7 gene of Saccharomyces cerevisiae originally were identified as suppressors of Ty and delta insertion mutations in the 5' regions of the HIS4 and LYS2 genes. Other genes that have been identified in mutant hunts of this type have been shown to play a role in transcription. In this work we show that SPT7 is also important for proper transcription in vivo. We have cloned and sequenced the SPT7 gene and have shown that it encodes a large, acidic protein that is localized to the nucleus. The SPT7 protein contains a bromodomain sequence; a deletion that removes the bromodomain from the SPT7 protein causes no detectable mutant phenotype. Strains that contain an spt7 null mutation are viable but grow very slowly and have transcriptional defects at many loci including insertion mutations, Ty elements, the INO1 gene and the MFA1 gene. These transcriptional defects and other mutant phenotypes are similar to those caused by certain mutations in SPT15, which encodes the TATA binding protein (TBP). The similarity of the phenotypes of spt7 and spt15 mutants, including effects of spt7 mutations on the transcription start site of certain genes, suggests that SPT7 plays an important role in transcription initiation in vivo.

Amino Acid Sequence↗
PubMed1995

Purification and Characterization of a Dipeptidase from Lactobacillus helveticus SBT 2171.

A metal-dependent dipeptidase was purified to homogeneity from a cell extract of Lactobacillus helveticus SBT 2171 by fast protein liquid chromatography. The enzyme was purified 237-fold from the extract, with a yield of 1.8%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single protein band with a molecular weight of 50,000. The dipeptidase hydrolyzes a range of only dipeptides. Dipeptides containing proline, glutamic acid, and aspartic acid are not hydrolyzed. The enzyme was shown to be a metalloenzyme with a pH optimum of 8.0 and a temperature optimum of 55(deg)C. Dithiol-reducing reagents exert strong inhibition on enzyme activity. Kinetic studies indicated that the enzyme has a relative average affinity for leucyl-leucine (K(infm), 0.5 mM). The negative immunoresponse of the purified enzyme with monoclonal antibodies raised against a dipeptidase from Lactococcus lactis subsp. cremoris Wg2 shows that both enzymes can be immunologically distinguished.

Journal Article↗