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Biomedical subjects

M Chan

Publications and source records attributed to M Chan.

At least 19 recordsLinked to original sources
PubMed1995

Expression of GPI-anchored complement regulatory proteins CD55 and CD59 differentiates two subpopulations of human CD56+ CD3- lymphocytes (NK cells).

CD55 and CD59 are both glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins found on the surface of most hemopoietic cells. Using three-color cytofluorographic analysis with antibodies recognizing CD56, CD3, and CD59 or CD55 we determined that CD56+CD3- lymphocytes (NK cells) expressed both CD55 and CD59 but at lower levels than CD3+ lymphocytes. Since the CD56+CD3- lymphocyte population is heterogeneous, we examined expression of CD55 and CD59 on selected CD56+CD3- lymphocyte populations by depleting peripheral blood leukocytes of T cells, B cells, and monocytes. Dual staining of the selected CD56+CD3- cells, which were > 95% CD56+, permitted the distiction of two subpopulations: a major CD16brightCD56dimCD55dimCD59dim subpopulation and a minor CD16dim/negCD56brightCD55brightCD59bright subpopulation. Treatment with phosphatidylinositol-specific phospholipase C released both the CD55 and CD59 antigens from the surface of CD56+CD3- cells, indicating that both are GPI-anchored, as they are on other lymphocytes. CD56+CD3- cell subpopulations were individually isolated by anti-CD55 or anti-CD16 negative selection and were functionally compared to the parent CD56+CD3- cell population. The CD16brightCD56dimCD55dimCD59dim cells killed NK targets well but did not proliferate well in response to rIL-2, whereas CD16dim/negCD56brightCD55brightCD59bright cells proliferated well in response to rIL-2 but did not kill NK targets efficiently. We conclude that all CD56+CD3- cells express some levels of the GPI-anchored proteins, CD55 and CD59, and that two CD56+CD3- subpopulations with different functional characteristics can be distinguished by the level of expression of these two antigens.

CD3 Complex↗
PubMed1995

Preliminary cryocrystallographic study of the mitochondrial cytochrome bc1 complex: improved crystallization and flash-cooling of a large membrane protein.

Ubiquinol-cytochrome c reductase is a crucial integral membrane protein in the mitochondrial respiratory cycle. Eleven subunits containing three cytochrome heme groups and a 2Fe-2S Rieske center make up this 240 kDa enzyme complex. Previously, many different crystal forms of the bc1 complex have displayed diffraction to as far as 4.5 A. However, rapid degradation of the protein in the X-ray beam at room temperature has obstructed the collection of a full data set from a single crystal. As slight heterogeneities between crystals severely hampered merging of data from different crystals, we sought a method to stabilize the protein crystal in the X-ray beam in order to collect a full data set from one crystal sample. To this end, water soluble protein crystals are frequently flash-cooled to cryogenic temperatures; however, there is no report of cryocrystallography for membrane proteins. In this communication, we report on a successful experiment in which flash-cooled bc1 membrane protein crystals have given rise to sustained diffraction over a 60 hour data collection period at a synchrotron source. Furthermore, we present an improved purification and crystallization protocol yielding crystals readily diffracting out to 3.3 A. These results should greatly aid in the future realization of the molecular structure of the bc1 complex as well as other membrane proteins.

Animals↗
PubMed1995

Resection of hepatocellular carcinoma with diaphragmatic invasion.

Fourteen consecutive patients with hepatocellular carcinoma (HCC) and diaphragmatic invasion found during operation and confirmed histopathologically were studied. They were treated by resection of the liver tumour en bloc with part of the diaphragm. Eight of the 14 patients had a diaphragmatic hump on chest radiography. Preoperative ultrasonography, computed tomography and hepatic angiography were unable to diagnose diaphragmatic invasion in these patients. A control group of 14 closely matched patients were selected from 98 undergoing curative resection for HCC during the period of the study. No evidence of a diaphragmatic hump was found in the control patients (P < 0.001). There was no significant difference in survival, operative morbidity or mortality rates between the two groups. In patients with HCC situated in the dome of the liver, the presence of a diaphragmatic hump on chest radiography strongly suggests invasion of the diaphragm. There was no difference in outcome in patients with or without diaphragmatic invasion; the tumour should be resected if the patient is fit for operation.

Carcinoma, Hepatocellular↗
PubMed1995

Detection and assessment of intracranial aneurysms: value of CT angiography with shaded-surface display.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of circle of Willis CT angiography with shaded-surface display in the detection and assessment of suspected intracranial aneurysms. MATERIALS AND METHODS: Twenty-three patients who had clinical or radiologic suspicion of intracranial aneurysms were studied prospectively with CT angiography and conventional angiography. The images were obtained and interpreted in a double-blind fashion by different radiologists. Conventional angiography, which was the reference standard in this study, diagnosed 17 aneurysms in 15 patients. The usefulness of the two types of images for surgical planning was evaluated by two neurosurgeons. RESULTS: No aneurysms were detected with either technique in eight patients. Both techniques showed 15 aneurysms in 14 patients. The maximum dimensions were less than 3.0 mm in three cases, 3.0-5.0 mm in four cases, and greater than 5.0 mm in eight cases. With conventional angiography used as the reference standard, CT angiography has one false-positive and two false-negative findings, resulting in a sensitivity of 88% (15/17) and a specificity of 89% (8/9). For 12 of 15 aneurysms, CT angiography was rated equal or superior to conventional angiography in depicting all aspects (shape, orientation, neck, and parent vessel) of the aneurysms. CONCLUSION: We were able to detect aneurysms of the circle of Willis as small as 2 mm in size. Using conventional angiography as the reference standard, CT angiography has a sensitivity of 88% and a specificity of 89% for the detection of aneurysms in the circle of Willis. In almost all cases, CT angiography was equal or superior to conventional angiography in characterizing the aneurysms for surgical planning.

Adolescent↗
PubMed1995

[Diagnostic score for acute appendicitis].

Scoring systems seem to be ideal for supporting diagnosis of acute appendicitis because they are non invasive, require no special equipment and can be used in clinical routine. Several scores for appendicitis have been developed with good results in the original publications. Unfortunately these good results could not be reproduced on a German data base. Therefore we developed a new score using multivariate statistics and a quality controlled prospective data base. The score covers 8 variables: tenderness, rebound tenderness, micturition, type of pain, leucocytes, age, relocation of pain, rigidity. Independent evaluation of the score on a Dutch database resulted in a negative appendicectomy rate of 21% and a missing appendicitis rate of 2%. The results are encouraging, so that further testing and clinical application can be recommended.

Acute Disease↗
PubMed1994

Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses.

Echoviruses are human pathogens belonging to the picornavirus family. Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol (GPI)-anchored surface protein that protects cells from lysis by autologous complement. Anti-DAF monoclonal antibodies prevented echovirus 7 attachment to susceptible cells and protected cells from infection. HeLa cells specifically lost the capacity to bind echovirus 7 when treated with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from the cell surface, indicating that the virus receptor, like DAF, is a GPI-anchored protein. Although Chinese hamster ovary cells do not bind echovirus 7, transfectants expressing human DAF bound virus efficiently, and binding was prevented by pretreatment with an anti-DAF monoclonal antibody. Anti-DAF antibodies prevented infection by at least six echovirus serotypes. These results indicate that DAF is the receptor mediating attachment and infection by several echoviruses.

Animals↗
PubMed1994

Selective internal radiation therapy with intra-arterial iodine-131-Lipiodol in inoperable hepatocellular carcinoma.

UNLABELLED: From August 1990 to June 1993, 26 patients with inoperable hepatocellular carcinoma were treated with intra-arterial iodine-131-Lipiodol (131I-L). METHODS: Iodine-131-Lipiodol was given through either an implantable arterial port (9 patients) or during hepatic angiography (17 patients). All 26 patients had multiple lesions, 3 had involved resection margin after surgical resection and 1 had diffuse infiltrative lesions. The median size of the largest tumor among 22 patients with a measurable lesion was 4.5 cm (2-9.5 cm). The end points are tumor response in terms of tumor size, change in serum alpha-fetoprotein level, toxicity of treatment and overall survival. RESULTS: Twenty-three patients received a single treatment of 1.11-2.22 GBq (30-60 mCi)131I-L. Three patients received 2.22-4.44 GBq (60-120 mCi)131I-L in three fractions. Considering both radiological regression and reduction in serum alpha-fetoprotein level as objective response criteria, the overall response rate was 52% (13 out of 25 patients with evaluable disease). Ten out of 15 patients who had raised alpha-fetoprotein levels had more than 50% reduction and 8 patients had more than 90% reduction in alpha-fetoprotein level. Since analysis, 19 patients have died and 7 remain alive, giving a minimum median survival of 6 mo (range 1.2-16.6 mo), with 4 surviving more than 1 yr calculated from the day of treatment. There was only one patient who had late deterioration of liver function compatible with radiation hepatitis. There was no bone marrow toxicity documented in any patients. CONCLUSION: Treatment with intra-arterial 131I-L was well tolerated in patients with inoperable hepatocellular carcinoma and produced an objective response of 52% with median survival of 6 mo. A fractionated dose of 131I-L was feasible and the radiation dose could be escalated safely.

Carcinoma, Hepatocellular↗
PubMed1992

Phosphatidylcholine metabolism in ischemic and hypoxic hearts.

The rates of phosphatidylcholine biosynthesis in the isolated hamster hearts under ischemic and hypoxic conditions were examined. Global ischemia was produced by perfusion of the heart with a reduced flow, whereas hypoxia was produced by perfusion with a N2-saturated buffer. A 51% reduction in the biosynthesis of phosphatidylcholine was observed in the ischemic heart. The reduction was caused by a severe decrease in ATP level which resulted in a diminished conversion of choline into phosphocholine. A 22% reduction in the biosynthetic rate of phosphatidylcholine was also detected in the hypoxic heart. The reduction was caused by a diminished level of CTP which resulted in a decreased conversion of phosphocholine to CDP-choline. No compensatory mechanism was triggered during ischemia, but the CTP: phosphocholine cytidylyltransferase activity was enhanced in the hypoxic heart. Our results demonstrate the possible rate-limiting role of choline kinase and reconfirm the regulatory role of the cytidylyltransferase in the biosynthesis of phosphatidylcholine.

Adenosine Triphosphate↗
PubMed1992

Treatment of inoperable hepatocellular carcinoma by intra-arterial lipiodol and 4'-epidoxorubicin.

A total of 30 patients presenting with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial Lipiodol (5 ml) and 4'-epidoxorubicin (90 mg/m2) once every 4 weeks. The treatment results included no complete response, 2 partial responses, 6 cases of static disease and 19 cases of progressive disease. The median survival was 18.9 weeks. All patients had died by the time of this writing, with survival duration ranging from 4.1 to 87.3 weeks. Toxicities were minimal and included anaemia and alopecia. As compared with a historic control group that had received the same dose of intravenous 4'-epidoxorubicin, the treatment group showed similar response rates but developed fewer toxicities. There was no significant survival benefit over the control group. We concluded that although this form of treatment had comparable activity and produced fewer side effects, it provided no survival benefit over intravenous treatment. The slight prolongation of survival achieved in the treatment group as compared with the control arm might have been due to case selection.

Adult↗
PubMed1992

The effect of amino acids on choline uptake and phosphatidylcholine biosynthesis in mammalian hearts.

The uptake of choline in mammalian hearts in the presence of amino acids was examined. Isolated hamster, guinea pig, rat and rabbit hearts were perfused with labeled choline in the presence and absence of amino acids. Neutral amino acids enhanced choline uptake in the hamster heart, but not in the guinea pig, rat and rabbit hearts. Phosphatidylcholine biosynthesis in these hearts was not affected by the presence of amino acids. Choline uptake in the hamster myocytes was also enhanced by neutral amino acid. The enhancement of choline uptake suggests a direct interaction between the amino acid and the transport of choline into the myocardiac cells. The different responses in choline uptake to neutral amino acids indicate that the regulation of choline uptake in the hearts may be different between mammalian species.

Amino Acids↗
PubMed1991

Expression of inducible membrane-anchored insulin receptor kinase enhances deoxyglucose uptake.

We have transfected mouse L cells with a recombinant membrane-anchored insulin receptor kinase (called MARK), under the transcriptional control of a glucocorticoid-responsive element. The transfected construct includes only 15 extracellular residues, with the transmembrane and intracellular kinase domains of the human insulin receptor cDNA (amino acid residues -27 to 12 and 915 to 1343 (see Ullrich, A., Bell, J. R., Chen, E. Y., Herrera, R., Petruzzelli, L. M., Dull, T. J., Gray, A., Coussens, L., Liao, Y. C., Tsubokawa, M., Mason, A., Seeburg, P. H., Grunfeld, C., Rosen, O. M., and Ramachandran, J. (1985) Nature 313, 756-761), predicted Mr = 56,000 with signal sequence, 53,000 without). Transfected cells which are exposed to dexamethasone express two proteins of approximate Mr = 54,000 which (a) react with anti-peptide antisera raised to human insulin receptor sequences, (b) localize to the membrane fraction, and (c) possess ligand (insulin)-independent tyrosine kinase activity. In extracts of steroid-treated MARK cells, a phosphotyrosine-containing protein of Mr = 185,000 is detected, which corresponds in size to a known endogenous substrate for the insulin receptor. Control studies were performed with the nontransfected parent line, and with L cells transfected with an inactive human insulin receptor protein tyrosine kinase. Dexamethasone induced no change in the proteins detected by an anti-phosphotyrosine antibody in the two control lines. In studies of deoxyglucose uptake, dexamethasone stimulated increase in deoxyglucose uptake 2-fold in the MARK cells compared to the same cells studied in the absence of dexamethasone. Dexamethasone had no effect in the control cell lines. These studies demonstrate that a membrane-anchored insulin receptor kinase, devoid of virtually the entire extracellular domain of the insulin receptor, is sufficient to induce enhanced deoxyglucose uptake.

Animals↗
PubMed1990

Sonographic diagnosis of portal vein invasion in patients with hepatocellular carcinoma: comparison with arterial portography.

The results of sonographic assessment of the main portal vein were compared with arterial portography in 65 patients with documented hepatocellular carcinoma. When compared with fully-diagnostic angiograms, obtained in 54 patients, sensitivity of ultrasound was 64% with a specificity of 98%. We conclude that ultrasound is a valuable first-line method of detecting portal vein invasion in the preoperative assessment of patients with hepatocellular carcinoma.

Adolescent↗
PubMed1990

Characterization of the high and low affinity components of the renal Ca2(+)-Mg2+ ATPase.

The purpose of this study was to characterize the interrelationship between free calcium (Ca2+) and magnesium (Mg2+) in the Ca2+ ATPase enzyme cycle of kidney membranes. Experiments were performed with basolateral membranes from rat renal cortex and microdissected proximal and distal tubules from mice. Results were similar in the three types of preparations. We first investigated the effect of ATP concentration on Ca2(+)- and Mg2(+)-dependent ATP hydrolysis. With 0.2 microM Ca2+, the enzyme activity, as a function of ATP concentration, showed two saturable components: a high affinity component with a Km of 33 microM ATP and a low affinity component with a Km of 0.63 mM ATP. These components may represent either two distinct sites of ATP binding or two forms of the same site. For the sake of simplicity, it was assumed that the two components correspond to a high affinity and a low affinity substrate site. At the high affinity site (ATP = 50 microM), the Ca2+ dependence of ATP hydrolysis followed a single Michaelis-Menten kinetics with Km for Ca2+ of 0.08 microM. The addition of 1 mM Mg2+ resulted in a relatively constant increase in ATP hydrolysis at all Ca2+ concentrations, indicating that the effects of the two cations were additive. With high ATP concentration (ATP = 3 mM), Ca2+ also induced an ATP hydrolysis according to a saturable process, with a Km for Ca2+ of 0.2 microM. In contrast with what occurred with low concentrations of ATP, addition of millimolar Mg2+ completely curtailed the sensitivity of the enzyme to Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Hepatocellular carcinoma in Hong Kong: clinical study on 340 cases.

Three hundred and forty cases of hepatocellular carcinoma in Hong Kong were studied for their clinical features, and various factors were analysed for their prognostic values. The clinical presentation was often vague and rather non-specific and a majority of patients were presented late and often unresectable. The overall median survival was 8 weeks. The Karnofsky performance scale and bilirubin level were the most important prognostic factors. The treated group survived longer than the untreated group.

Adolescent↗
PubMed1990

Twelve years' experience of computer-aided diagnosis in a district general hospital.

This paper describes experience in a modern district general hospital with a small desktop system for computer-aided diagnosis of acute abdominal pain, over a 12-year period involving 5512 cases. When compared with a baseline year (1973) in which unaided performance was monitored, during an initial study period (1974-76) the diagnostic accuracy of junior staff rose by between 10 and 15%. This higher performance level was then maintained for a decade (1976-86) despite changes in staff. The perforation rate among appendicitis cases fell from 27% to 12.5%, accompanied by a smaller fall in negative laparotomy rates. The saving in surgical bednights devoted to acute abdominal pain was approximately 15%, and the notional cost of resources saved during the first 6 years of operation was 120,000 pounds. Other hospitals have shown--in the short term--benefits similar to those obtained at Airedale District General Hospital. The long-term benefits of the system at Airedale reinforce the conclusions of the earlier short-term trials that a comparable system should probably be offered to all DGHs in the UK, not as an exercise in 'artificial intelligence' but as an effective continuing stimulus to good clinical practice.

Abdominal Pain↗