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Biomedical subjects

Y F Liu

Publications and source records attributed to Y F Liu.

At least 55 records · Page 3Linked to original sources
PubMed1996

Molecular characterization of primary mediastinal B cell lymphoma.

Primary mediastinal B cell lymphoma (PMBL) is a diffuse large B cell lymphoma (DLCL) postulated to arise from noncirculating thymic B lymphocytes. Because of its distinctive clinical and morphological features and putative unique cellular origin, PMBL is generally considered a distinct clinicopathological entity. Little is known, however, about the molecular characteristics of PMBL. Therefore, we analyzed 16 PMBLs for molecular alterations involving the bcl-1, bcl-2, bcl-6, c-myc, H-ras, K-ras, N-ras, and p53 genes and for Epstein-Barr virus infection, which are commonly involved in lymphoid neoplasia. Employing a combination of Southern blotting and/or polymerase chain reaction and single-strand conformation polymorphism assays, we detected genetic alterations in 7 of the 16 (44%) PMBLs. Whereas the bcl-6 gene is rearranged in up to 45% of DLCLs, rearrangement of the bcl-6 gene was detected in only 1 of these 16 (6%) PMBLS. Point mutations of the 5' noncoding region of the c-myc gene were demonstrated in 3 other cases (19%), although c-myc gene rearrangements were not seen by Southern blotting. Missense point mutations of the p53 gene were identified in 3 additional PMBLs (19%). Alterations of the bcl-1, bcl-2, or ras genes and evidence of Epstein-Barr virus infection were not observed. In conclusion, a variety of molecular lesions occur in PMBLs and may be involved in their pathogenesis. This molecular genetic pattern bears little resemblance to that known for other B cell malignancies, including DLCL. In particular, the infrequent occurrence of bcl-6 gene rearrangement in PMBLs distinguishes them from other DLCLs of B cell origin, suggesting that PMBLs do not represent a distinct subtype of DLCL.

Adolescent↗
PubMed1995

Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms.

BACKGROUND: Posttransplantation lymphoproliferative disorders (PT-LPDs) are a clinicopathologically heterogeneous group of lymphoid proliferations of varied clonal composition, the majority of which are associated with Epstein-Barr virus (EBV) infection. The clonal content and clonal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. METHODS: Twenty-four separate PT-LPD lesions from the colon and mesentery of a 15-year-old male, developing 4 months after cardiac transplantation, were studied for clonality based on immunoglobulin heavy chain (IgH) gene rearrangements for the presence, clonality, and type of EBV infection and for the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformation polymorphism assays were employed. RESULTS: All 24 lesions were histologically similar (polymorphic B-cell lymphomas) but exhibited varied clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV type A. Structural alterations of oncogenes or tumor suppressor genes were not identified. CONCLUSIONS: Separate PT-LPD lesions occurring synchronously in a single organ or patient may be clonally distinct, suggesting that they represent multiple distinct primary lymphoid proliferations rather than metastatic disease as in conventional malignant lymphomas. This may explain partially the rapid development in some patients of a large PT-LPD tumor burden that may regress rapidly after reduction of immunosuppression.

Adolescent↗
PubMed1995

Posttransplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus.

Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are seen in immunocompromised hosts and in many lymphoid neoplasms associated with immunocompromise. The posttransplantation lymphoproliferative disorders (PT-LPDs) are a heterogeneous group of B-cell neoplasms that arise in the setting of immunosuppressive therapy, and are associated with EBV infection. Whether type A and/or type B EBV are associated with PT-LPDs is unknown. Therefore, we investigated 27 PT-LPD lesions from 22 solid-organ transplant recipients by polymerase chain reaction (PCR) at the EBNA-2 and EBNA-3c loci to detect sequence deletions that distinguish the two EBV families. Another locus, EBER, was examined by single-strand conformation polymorphism analysis (SSCP), in conjunction with direct sequencing in selected cases. Type A EBV was found in 24 of 27 cases (89%) as seen by amplification of the EBNA-2 and EBNA-3c regions. Four different EBER polymorphisms were detected, confirming the presence of different type A EBV isolates among these cases. Three cases were negative for infection by EBV. Surprisingly, despite the immunocompromised state of the hosts, none of the 27 PT-LPD lesions harbored type B EBV. Thus, although type B EBV may commonly infect peripheral blood lymphocytes in immunocompromised individuals, they do not appear to induce readily PT-LPD formation.

Antigens, Viral↗
PubMed1995

Zonal differences in DNA synthesis activity and cytochrome P450 gene expression in livers of male F344 rats treated with five nongenotoxic carcinogens.

Both increased cell proliferation and "altered" CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. To further characterize these two responses, groups of rats were kept on powdered rat chow diet containing 0.05% phenobarbital (PB) or 0.025% ciprofibrate (Cip) for 8 days or given 8 daily doses by gavage of pregnenolone 16 alpha-carbonitrile (PCN, 150 mg/kg/ml corn oil), 3,3',4,4'-tetrachlorobiphenyl (PCB-MC, 3 mg/kg/ml corn oil) or 2,2',4,4'-tetrachlorobiphenyl (PCB-PB, 7.5 mg/kg/ml corn oil). A minipump was implanted in the rat abdominal cavity to release bromodeoxyuridine (BRDU) 5 days after the start of nongenotoxic carcinogen treatment and the experiment was terminated 3 days later. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CYP gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a unique composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, 3A1, 3A2, and 4A1, which were variably increased or decreased relative to the untreated control livers, depending on the treatment. Similarly, the rate and pattern of CYP enzyme-mediated hydroxylation toward testosterone, 17 beta-estradiol, corticosterone, and lauric acid were greatly altered by nongenotoxic carcinogen treatment. According to the zonal distribution patterns of CYP immunoproteins, each hepatocyte in the cell plate from the periportal triad to the central vein has a characteristic and nongenotoxic carcinogen-specific composition of CYP enzymes. Because many endogenous substrates are modulators of DNA and RNA synthesis, intracellular kinetics of endogenous substrates of CYP enzymes in the corresponding hepatocytes could contribute, at least in part, to the differences in gene expression, differentiation, and cell proliferation among the hepatocytes in the cell plate.

Animals↗
PubMed1994

Inhibition of cell proliferation by ciprofibrate in glutathione S-transferase P1-1-positive rat hepatic hyperplastic nodules.

Previous studies have demonstrated that short-term treatment with a peroxisome proliferator (PP) decreased the size and number of genotoxic carcinogen-induced hepatic hyperplastic lesions identified by gamma-glutamyl transpeptidase (GGT) or glutathione S-transferase P1-1 (rGSTP1-1) staining. However, longer-term PP treatment of animals bearing similar hepatic hyperplastic lesions produced an increase in both the size and number of liver tumors. To characterize the hepatic hyperplastic lesions which are inhibited or promoted by PP, a unique double labeling technique was developed to determine the relative rate of cell division (e.g., DNA synthesis) in rGSTP1-1-positive nodules before and after ciprofibrate (Cip) treatment. rGSTP1-1-positive nodules were induced with the Solt-Farber resistance protocol (diethylnitrosamine-2-acetylaminofluorene partial hepatectomy). Eleven weeks after diethylnitrosamine initiation, 3 groups of rats were maintained on a control chow diet or switched to a powdered chow diet containing 0.025% Cip or 0.05% phenobarbital (PB) for the last 8 days of the experiment. A minipump implanted in the abdominal cavity released [methyl-3H]thymidine continuously for 72 h and was then removed prior to CIp or PB treatment. A second minipump was then implanted which released bromodeoxyuridine to the abdominal cavity 5 days after the start of Cip or PB administration and lasted for 72 h until the termination of the experiment. Both the [methyl-3H]thymidine and bromodeoxyuridine labeling indices (LIs) were determined in the same group of cells within individual rGSTP1-1-positive nodules in the right posterior lobes of livers. PB treatment increased both the average number of persistent GGT-positive nodules and the ratio of persistent GGT-positive to rGSTP1-1-positive nodules/cm2. In contrast, Cip treatment greatly decreased the average number and area of persistent GGT-positive nodules, as well as the ratio between persistent GGT-positive and rGSTP1-1-positive nodules/cm2. Cip treatment also resulted in a 40% decrease in the average LI in the rGSTP1-1-positive nodules. In some rGSTP1-1-positive nodules, the LI was decreased from > 40% prior to Cip treatment to < 5% afterward, suggesting that Cip treatment interrupted progression in these nodules. Such drastic changes in the LI before and after treatments were not observed in either PB- or vehicle-treated (control) animals. A number of small nodules with a high bromodeoxyuridine LI but with no or very few [methyl-3H]thymidine-labeled nuclei and negative GGT and rGSTP1-1 staining were detected only in the Cip group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

G protein specificity in receptor-effector coupling. Analysis of the roles of G0 and Gi2 in GH4C1 pituitary cells.

In rat pituitary GH4C1 cells, activation of transfected dopamine D2 receptors (long, D2L, or short, D2S, form) and endogenously expressed somatostatin and muscarinic M4 receptors induced inhibition of cAMP synthesis and of Bay K 8644-induced calcium entry via pertussis toxin-sensitive G proteins. To analyze the role of alpha 0 and alpha i2 in relaying of these signals, alpha 0 or alpha i2 antisense constructs were separately and stably transfected into GH4C1 cells. Reverse transcription-polymerase chain reaction and Western blot analyses indicated specific ablation of alpha 0 or alpha i2 in the antisense transfectant clones. Elimination of alpha 0 selectively abolished receptor-mediated inhibition of calcium entry. Notably, the action of dopamine D2L receptor was partially (about 30%) retained. By contrast, depletion of alpha i2 selectively impaired receptor-mediated inhibition of cAMP accumulation. Inhibition of basal cAMP synthesis by any of the four receptors studied was blocked in alpha i2-depleted clones. Additionally, dopamine D2L, somatostatin and muscarinic M4 receptor-mediated inhibition of vasoactive intestinal peptide-stimulated cAMP formation was also abolished. Remarkably, somatostatin even potentiated (by 30%) the action of vasoactive intestinal peptide in alpha i2-antisense clones. In contrast, the action of dopamine D2S receptor on stimulated cAMP synthesis remained largely unaltered. The results demonstrate that alpha 0 specifically triggers receptor-induced closure of calcium channels, whereas alpha i2 specifically mediates inhibition of adenylyl cyclase in GH4C1 cells. Furthermore, the data suggest that G1 protein specificity in receptor coupling to inhibition of adenylyl cyclase depends critically on the activity state of the enzyme. Moreover, the results indicate an essential difference in coupling of dopamine D2L and D2S receptors to G proteins.

Animals↗
PubMed1994

Inhibition of human HL-60 cell responses to chemotactic factors by antisense messenger RNA depletion of G proteins.

Chemotactic factors bound to receptors of the seven-transmembrane domain family signal leukocytes through associated guanine nucleotide-binding (G) proteins. Human leukocytes of the HL-60 line, which express G protein-coupled receptors for leukotriene B4 (LTB4) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) after differentiation with vitamin D3 and transforming growth factor-beta, were transfected with expression plasmids containing antisense-oriented cDNAs encoding the alpha-chains of Go, Gi1, Gi2, and Gi3. Antisense mRNA for Go and Gi2 alpha-chains suppressed by over 80% the level of the respective G protein. Go-deficient HL-60 cells had depressed functional and intracellular calcium responses to LTB4 and fMLP, but no alterations in the responses of cyclic adenosine 3',5'-monophosphate (cAMP). In contrast, HL-60 cells deficient in Gi2 lost only responses of the intracellular concentration of cAMP. Antisense mRNA suppression of distinct G proteins thus may delineate some transductional requirements for cellular responses.

Cell Line↗
PubMed1994

Expression of insulin-like growth factor II in hepatitis B, cirrhosis and hepatocellular carcinoma: its relationship with hepatitis B virus antigen expression.

Expression of insulin-like growth factor II in two human hepatocellular carcinoma cell lines and in hepatitis B, cirrhosis and hepatocellular carcinoma in 419 cases were investigated, and its relationship with the expression of hepatitis B virus X gene was studied by means of immunohistochemical and electron microscopic techniques. The results demonstrated that hepatocellular carcinoma cells (SMMC 7721 and QGY 7703) in culture could express insulin-like growth factor II. Expression seemed to be regulated by cell density, which was suggested as the molecular basis of the contact inhibition of cell proliferation. In tissue sections, cells with high expression of insulin-like growth factor II were observed not only in hepatocellular carcinoma (93%) but also in 95% of the pericancerous liver tissues, 72% of cirrhotic livers, 64% of chronic active hepatitis and 37% of chronic persistent hepatitis. In most cases of hepatocellular carcinoma, insulin-like growth factor II was localized in the cytoplasm of the cancer cells. In the benign liver disorders, four types of cells that highly expressed insulin-like growth factor II were observed: (a) a kind of small liver cell we named the small polygonal liver cell; (b) multinuclear giant hepatocytes; (c) hepatocytes in most of hyperplastic and neoplastic nodules, small hepatocyte nodules and some of regenerative nodules; and (d) some proliferating ductular cells. Even more interestingly, insulin-like growth factor II expression was shown to be closely related to the expression of hepatitis B virus X gene product. We suggest that the activation of insulin-like growth factor II gene and its overexpression may be a crucial step in the processes of hepatitis B virus-associated hepatocarcinogenesis and that the X gene product may activate the insulin-like growth factor II gene through a transactivation mechanism. In addition, we studied the characteristics of small polygonal liver cells, and the roles they may play in the regeneration and carcinogenesis of hepatitis B virus-infected liver are discussed.

Carcinoma, Hepatocellular↗
PubMed1994

Detection of borreliacidal antibody by using acridine orange and flow cytometry.

Borreliacidal antibody has been shown to be important for the serodiagnosis of Lyme disease and determination of immune status. Our results show that borreliacidal antibody can be rapidly and accurately detected by flow cytometry. Acridine orange was added to normal and immune sera containing Borrelia burgdorferi organisms in the presence and absence of complement prior to data acquisition by flow cytometry. The flow cytometric parameters of side scatter and detection of acridine orange fluorescence were used to determine events per minute (number of labeled spirochetes), percent shift in fluorescence (number of dead spirochetes), and mean channel fluorescence (intensity of fluorescence-labeled spirochetes) of acridine orange-labeled spirochetes. Borreliacidal antibody was detected as early as 4 h, with optimal detection 16 to 24 h after incubation of B. burgdorferi organisms with immune serum and complement. Our results also showed that complement was necessary for detection of borreliacidal antibody. Flow cytometry with acridine orange-labeled spirochetes provides a rapid means for detection of borreliacidal antibody.

Acridine Orange↗
PubMed1994

Differentiation of borreliacidal activity caused by immune serum or antimicrobial agents by flow cytometry.

We demonstrated that borreliacidal activity caused by immune serum and complement can easily be differentiated by flow cytometry from killing activity caused by antimicrobial agents that are commonly used for the treatment of Lyme disease. Assay suspensions containing normal or immune serum were incubated with Borrelia burgdorferi in the presence or absence of ceftriaxone, doxycycline, penicillin, and phosphomycin for 2, 8, 16, and 24 h. Samples containing killing activity were identified by using flow cytometry and acridine orange. In 30 min, the effects of immune serum and complement were easily distinguished from the killing of spirochetes by antimicrobial agents by adding fluorescein isothiocyanate-conjugated goat anti-hamster immunoglobulin. This simple procedure greatly enhanced the usefulness of the borreliacidal assay by eliminating a major source of false-positive reactions.

Acridine Orange↗
PubMed1994

Immunohistochemical demonstration of CCAAT/enhancer binding protein (C/EBP) in human liver tissues of various origin.

C/EBP is a sequence-specific DNA-binding protein. In order to identify its distribution and localization, immunohistochemical technique (ABC method) was done using anti-C/EBP polypeptide antibodies 1103#, 425# in liver specimens from 20 normal adults, 5 neonates, 6 patients with hepatitis, 25 with liver cirrhosis, 80 with hepatocellular carcinoma (40 cases were associated with surrounding nontumorous tissues) and 26 patients with cholangiocarcinoma (15 cases were associated with surrounding nontumorous tissues). The results showed that C/EBP was diffusely distributed in nuclei and cytoplasm of differentiated liver cells and very low or undetectable in liver cancer cells. The manifestation of C/EBP correlated with degree of differentiation of tumour cells, and was obviously weaker than that in surrounding nontumorous tissues. C/EBP positive staining has also been found in regenerating epithelial cells of bile ductules. The results suggested that C/EBP should play an important role in establishing and maintaining the differentiation of liver cells.

CCAAT-Enhancer-Binding Proteins↗
PubMed1994

[Sequence of light chain variable region gene of a monoclonal antibody to human hepatocarcinoma].

The isolation of the rearranged immunoglobulin genes from a hybridoma cell line, which is a prerequisite for the construction of a recombinant antibody, can easily be achieved by PCR. We have determined the nucleotide sequence of the variable region of L chain of a high affinity monoclonal antibody HAb27 directed to human hepatocarcinoma. Analysis of the nucleotide sequence of the light chain V region of HAb27 revealed that the V kappa sequence was 85% identical to germline V kappa Ox1 sequence.

Amino Acid Sequence↗
PubMed1994

[Comparative study of the expression of IGF-2 and HBxAg in human hepatocellular carcinoma and liver cirrhosis].

60 Cases of hepatocellular carcinoma (HCC) and 47 cases of liver cirrhosis (LC) were examined with immunocytochemistry methods using antibodies against IGF-2 and HBxAg on paraffin embedded sections. 32 HCC and 37 LC were found to be positive to HBxAg, in which the positive rates of IGF-2 were 100% (32/32) and 94.6% (35/37) respectively. 28 HCC and 10 LC were found to be HBxAg negative, IGF-2 was positive in 23 HCC (82.1%) and 6 LC (60%). The positive expression rates of IGF-2 in the HBxAg positive tissues were significantly higher than those in the HBxAg negative tissues (P < 0.05). There were three types of IGF-2 distribution in HCC and LC: (1) perinucleus; (2) diffuse in cytoplasm; (3) in nucleus. Small polygonal liver cells (SPLC) were found in the liver tissue surrounding the tumor or cirrhosis, the SPLC were positive to both IGF-2 and HBxAg. The positive rates of IGF-2 in SPLC were 86.4% (38/44) in HBxAg positive group and 40.5% (15/37) in the HBxAg negative group. The above findings suggest that IGF-2 plays an important role in abnormal proliferation of HCC and SPLC. The relation of IGF-2 and HBxAg and the nature of SPLC were also discussed.

Carcinoma, Hepatocellular↗
PubMed1994

Characteristics of immunocomplex in autopsy tissues of hemorrhagic fever with renal syndrome.

Using repeated PAP or repeated PAP and ABC immunocytochemical methods, we were able to demonstrate viral antigens, Ig and Clq in the tissues of 20 autopsy materials that had been preserved for 3-30 years. Serial paraffin sections were stained with the first antibodies against both viral antigens (G2 and Np) and human IgG, IgM, C3 and Clq. Immunocomplex, composed of viral antigen, IgG and Clq were found diffusely in the cells of each organ and extracellularly in the sera, various secretions and exudates. When stained by A25 etc, coarse granular antigen or inclusion bodies were found without demonstrable Ig and Clq. It was concluded that the immunocomplex in tissues of epidemic hemorrhagic fever in Shaanxi Province, China was both intracellular and extracellular and was perhaps soluble due to antigens in excess, with characteristics quite different from that of other immune diseases.

Animals↗
PubMed1994

The effect of Isoptin SR on blood pressure, heart function and hypertrophy of left ventricle of hypertensive patients.

Isoptin SR was used in 65 essential hypertensive patients. 240mg Isoptin SR (German Knoll Pharmaceutical company) per day was used in group A (35 cases) for 6 weeks, and in group B (30 cases) for 24 weeks, BP in group A and B decreased obviously in the first and second week after treatment. Marked effective rate and total effective rate were 65.7% and 74.3% respectively in group A, and 70.0% and 83.3% in group B. There were no significant changes of HR in group A before and after treatment while there was a decrease of HR in group B (P < 0.001). Left atrium (LA) decreased after 6 weeks in group A with an obvious increase of E/A ratio. There was significant decrease in LA, increase in E/A ratio, regression of IVS, LVPW and LVMI, but no changes in SV, CO, LVEF after 24 weeks of treatment of Isoptin SR in group B. E/A ratio was very sensitive and occurred earliest both in group A and group B. Side effects such as headache, dizziness, constipation, insomnia, peripheral oedema, sinus bradycardia occurred mainly in the first week of treatment. These symptoms disappeared gradually in the course of continued administration of Isoptin SR.

Adult↗
PubMed1993

Maxon is an optimal suture for bile duct anastomoses in pigs.

BACKGROUND: Three commonly used sutures were tested in a pig model of bile duct anastomosis to assess their relative contributions to inflammation and scarring. METHODS: Thirty pigs were randomised to bile duct division and anastomosis with either polyglyconate (Maxon), polyglactin 910 (Vicryl) or polypropylene (Prolene). Half the animals were sacrificed at two weeks and the remainder at 23 weeks. Anastomoses were assessed by cholangiography, scanning electron microscopy and light microscopy. RESULTS: There was less short term histological reaction with the two monofilament materials, Prolene and Maxon, compared to the braided suture Vicryl. Maxon was associated with less long term inflammation than Prolene, was found to handle better, and has an advantage over Prolene by being absorbable. CONCLUSION: Maxon is an optimal suture for bile duct anastomoses. Its long term absorption characteristics make it suitable for situations where bile duct healing may be delayed.

Anastomosis, Surgical↗