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Biomedical subjects

T Mok

Publications and source records attributed to T Mok.

11 recordsLinked to original sources

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

Adult↗

Fatal Penicillium citrinum pneumonia with pericarditis in a patient with acute leukemia.

We report here a case of fatal Penicillium citrinum infection. The patient, who suffered from acute myeloid leukemia, developed signs and symptoms typical of fungal pneumonia and pericardial tamponade after undergoing standard induction chemotherapy. Despite attaining complete remission of her leukemia, the patient succumbed 8 weeks after presentation. At autopsy, multiple nodular cavitary pulmonary lesions with invasion by fungal hyphae were found. Pericardial and lung tissue obtained at autopsy grew P. citrinum, a fungus ubiquitous in the environment but seldom reported as a pathogen. The microbiological findings were consistent with the histopathological features and confirmed this as a case of true P. citrinum infection causing fatal pulmonary and pericardial complications in an immunocompromised host.

Acute Disease↗

Immunochemistry and localization of the enzyme disaggregatase in Methanosarcina mazei.

The enzyme disaggregatase (Dag) from Methanosarcina mazei was studied immunochemically. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified Dag under reducing and nonreducing conditions revealed a single band with a 94-kDa molecular mass. Dag was found to be immunogenic in rabbits; a polyclonal antibody probe was prepared and used to detect the enzyme by slide immunoenzymatic assay, immunofluorescence, and immunoblotting in various species of Methanosarcina known to convert from packets to single cells, including M. mazei. The enzyme could not be detected in other members of the family Methanosarcinaceae that do not convert. By immunogold electron microscopy, Dag was mapped to the cell wall of packets and to the cell membrane of single cells of two M. mazei strains.

Antibodies, Bacterial↗

The development of protein A-gold electron microscopy for immunological studies of Haemophilus somnus.

Two separate experiments were conducted using modifications of protein A-gold immunoelectron microscopy (PAGIEM) to evaluate the ability of sera from calves vaccinated against Haemophilus somnus to bind virulent organisms (experiment I) and to detect differences in the antibody accessible antigenic sites on the outer membrane of selected strains of H. somnus having different virulence attributes using a high IgG2 titre specific bovine hyperimmune serum (experiment II). The results of experiment I demonstrated that the direct opsonisation of H. somnus by specific antisera was related to its IgG2 titre. In experiment II, strain-dependent differences in the labelling of antigenic sites by specific IgG2 antibodies were observed. The virulent strains of both septicaemic and genital isolates of H. somnus showed higher protein A-gold labelling than their non-virulent counterparts. The results from a comparison of pathogenic and non-pathogenic respiratory isolates did not reveal the same difference in labelling intensity. The studies demonstrated the PAGIEM technique to be a sensitive, versatile and a reliable laboratory method to analyse antigen-antibody interactions of H. somnus.

Animals↗

Physicochemical studies of two major subpopulations of low density lipoproteins by differential scanning calorimetry and n.m.r. spectroscopy.

Two subpopulations, layer 2 (density 1.025-1.029 g/ml) and layer 3 (density 1.032-1.043 g/ml) of low density lipoproteins (LDL) were isolated from fresh human plasma of normal lipidaemic subjects by density gradient ultracentrifugation. Chemical analyses demonstrated the ratios of triglyceride/cholesterol ester decreased with increasing densities of subfractions. These subfractions together with triglyceride-rich lipoproteins (layer 1, density less than 1.019 g/ml) were subjected to physicochemical studies by differential scanning calorimetry (d.s.c.) and nuclear magnetic resonance (n.m.r.) spectroscopy. The average transition temperature (Tt) of layer 2 was 34.20 +/- 0.83 degrees C and that of layer 3 was 37.25 +/- 0.35 degrees C. In addition, many of the layer 3, but not layer 2 and layer 1, samples showed structural alteration and gave rise to an average Tt of 39.18 +/- 1.24 degrees C. The structural alteration could be detected with polarizing light microscopy showing birefringent spherulites at body temperature. The peak Tt values obtained by d.s.c. were in good agreement with those by n.m.r. spectroscopy. These results demonstrate the physicochemical heterogeneity within the LDL density region and suggest that layer 3 subpopulation is much more labile than the others.

Adult↗

Concentrations and compositions of plasma lipoprotein subfractions of Lpb5-Lpu1 homozygous and heterozygous swine with hypercholesterolemia.

Pigs with two mutant epitopes, Lpb5 of apolipoprotein B (apoB) and Lpu1 of a yet undefined apolipoprotein, specified by a haplotype Lpb5-Lpu1 and fed a cholesterol-free low fat diet show hypercholesterolemia. The purpose of this study was to establish whether a direct relationship exists between the swine lipoprotein concentration/composition and the genotype for the Lpb5-Lpu1 haplotype; i.e., homozygote versus heterozygote. Lipoproteins of fasted plasma from hypercholesterolemic swine, homozygous (HmHC) and heterozygous (HtHC) for Lpb5-Lpu1, and from normolipidemic (NL) pigs of other Lpb-Lpu haplotypes were separated into five layers by density gradient ultracentrifugation. Layer 1 contained particles of d less than 1.019 g/ml and layer 5 particles of d greater than 1.073 g/ml. Layers 2, 3, and 4 represented subfractions of low density lipoproteins (LDL). The plasma total cholesterol (TC) of the HmHC group (300 +/- 84 mg/dl) was different (P less than 0.05) from the HtHC group (200 +/- 80 mg/dl) and in both HmHC and HtHC, TC was significantly higher (P less than 0.0005 and P less than 0.005, respectively) than that of the NL group (69 +/- 14 mg/dl). The elevation in plasma TC was due to the increased TC in layers 2 and 3: a 13- and 7-fold increase in HmHC and a 7- and 4-fold increase in HtHC in layers 2 and 3, respectively. Parallel increases in unesterified cholesterol were observed in these two layers. Marked increases in apoB were also observed in layers 2 and 3 of HmHC and intermediate increases in apoB in the same two layers of HtHC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Apolipoprotein B-100 is the major form of this apolipoprotein secreted by human intestinal Caco-2 cells.

Although the discovery of stop codon has explained the mechanism for the formation of the intestinal marker, apolipoprotein B-48, the dispute regarding the presence of apolipoprotein B-100 in the intestine is still unsettled. To further investigate the characteristics of intestinal apolipoprotein B, the newly developed human colonic adenocarcinoma Caco-2 cells which express functional properties of the differentiated enterocytes, were used. SDS-polyacrylamide gel electrophoresis analyses of the intact culture medium or its lipoproteins of d less than 1.23 g/ml showed the presence of only a single protein band of apolipoprotein B-100 with no detectable apolipoprotein B-48. After immunoblotting with oligoclonal antibodies to the amino-terminal peptide of apolipoprotein B, a trace amount of apolipoprotein B-48 was observed in the isolated lipoproteins, but not in the intact culture medium. These results suggest that apolipoprotein B-100 is the major form of apolipoprotein B secreted by human intestinal cells.

Adenocarcinoma↗

Apolipoprotein B is a globular protein--morphological studies by electron microscopy.

Water-soluble apolipoprotein B was prepared from fresh plasma by quick isolation of low density lipoproteins and immediate delipidization under non-oxidative conditions. The denatured protein in 6 M guanidine X HCl was reduced and carboxymethylated, dialyzed through 6 M urea/preservatives and to 1% ammonium acetate/0.05% EDTA/0.13% epsilon-amino caproic acid, pH 7.3 under N2 at 4 degrees C. The morphological studies were carried out by electron microscopy with negative staining and freeze fracture. Both these techniques showed that apolipoprotein B is a globular protein with average diameter of 11.48 +/- 1.25 nm (n = 978). The M.W. of apolipoprotein B calculated from this particle size was comparable to that from amino acid sequence.

Apolipoproteins B↗

Apolipoprotein B is a calcium binding protein.

Human hepatocarcinoma Hep G2 cells were grown in culture medium containing [45Ca2+]. The secreted lipoproteins of d less than 1.063 g/ml and d 1.063-1.21 g/ml were isolated from the culture media and analyzed by 3.3% and 7% SDS-polyacrylamide gel electrophoresis. Radioactivity profiles of [45Ca] from the gels showed that the peak of radioactivity corresponded to the apolipoprotein B band. The molar ratio of the incorporated [45Ca2+] and apolipoprotein B was close to unity. No radioactivity was found associated with any other secreted apolipoproteins. To confirm these findings, apolipoprotein B-containing lipoproteins were precipitated with anti-apolipoprotein B and high density lipoproteins were precipitated with anti-apolipoprotein A-I. Only the former precipitate was radioactive. These results suggest that apolipoprotein B is a calcium binding protein.

Animals↗

Presence of B-100 in rat mesenteric chyle.

Molecular forms of apolipoprotein B (ApoB) were studied in the rat intestinal chyle by SDS-polyacrylamide gel electrophoresis, immunoblotting and immunodiffusion. Time studies on intestinal chyle showed the presence of B-100 in all the samples analyzed within 3 hr after drawing. However, the analyses repeated on day 2 or day 3 revealed disappearance of B-100 and appearance of B-48. Addition of 3 mM EDTA, 10 mM diisopropylfluorophosphate, 5 mM chloroquine and 10 mM epsilon-amino caproic acid slowed down but could not prevent the disappearance of B-100. Chylomicrons isolated from chyle in the presence of preservatives immediately after drawing displayed B-100 as a major and B-48 as a minor ApoB form. However, repeatedly washed chylomicrons or those isolated from chyle 18-24 hr after drawing showed B-48 as the only ApoB present. These results suggest that rat intestine synthesizes B-100 which is quickly converted to smaller molecular form.

Animals↗