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Biomedical subjects

Y Q Yu

Publications and source records attributed to Y Q Yu.

At least 19 recordsLinked to original sources

Association study of neuregulin 1 gene with schizophrenia.

A number of studies have indicated that 8p22-p12 is likely to harbor schizophrenia susceptibility loci. In this region, the candidate gene of interest, neuregulin 1 (NRG1), may play a role in the pathogenesis of schizophrenia. Then in the present study, we performed the linkage disequilibrium to determine the association between three genetic variants (SNPs: rs3924999, rs2954041, SNP8NRG221533) on NRG1 gene and schizophrenia in 246 Chinese Han schizophrenic family trios using PCR-based restriction fragment length polymorphism method and denaturing high-performance liquid chromatography. The transmission disequilibrium test analysis for each variant showed a significant difference between two transmitted alleles even after Bonferroni correction (rs3924999, P=0.007752; rs2954041, P=0.0009309; SNP8NRG221533, P=0.012606). The global chi(2) test for haplotype transmission also revealed a strong association (chi(2)=46.068, df=7, P&<0.000001). Our results suggest that the NRG1 gene may play a role in conferring susceptibility to the disease.

Adult↗

Naloxone increases vascular responsiveness in chronic morphine treated rats and facilitates intracellular signaling in cultured vascular cells.

AIM: To probe the changes of vascular responsiveness and intracellular signaling during opiate withdrawal syndrome. METHODS: Morphine withdrawal syndrome in rats was precipitated by iv naloxone following daily injection of increasing dose of morphine for 2 weeks, the changes in mean arterial blood pressure (MBP) caused by acetylcholine (ACh) were recorded. Isolated mesenteric vascular beds were perfused with Kreb's solution containing different concentration of drugs. The cytoplasmic Ca2+ ([Ca2+]i) in Fura 2-loaded cultured bovine aortic endothelial cells (aec) and smooth muscle cells (smc) were assayed. The positive immunoreaction to the phosphorylated cyclic AMP responsive element-binding protein (phospho-CREB) in cultured smc was calculated. RESULTS: Naloxone 2 mg/kg iv following chronic morphine treatment precipitated severe opiate withdrawal signs in company with blunted hypotensive effect of Ach that was the same as chronic morphine treated rats before withdrawal. In the mesenteric vascular beds from chronic morphine treated rats, the EC50 of pressor effect of norepinephrine (NE) was decreased from (2.06 +/- 0.38) to (1.14 +/- 0.21) micromol/L (n = 8, P < 0.01) after the perfusion solution containing morphine 20 micromol/L was replaced by Kreb's containing naloxone 25 micromol/L. Furthermore, NE-induced perfusion pressure increases were completely prevented by Kreb's contained morphine 40 micromol/L. Morphine acutely applied to control smc produced some variable and naloxone-reversible [Ca2+]i changes, but naloxone did not. However, naloxone increased [Ca2+]i in two thirds of smc preincubated with morphine 0.1 or 0.5 mmol/L for 48 h from (97 +/- 20) to (167 +/- 29) nmol/L (n = 9, P < 0.01) and from (106 +/- 19) to (225 +/- 48) nmol/L (n = 10, P < 0.01), respectively, and it also increased the ratio of positive immunoreaction to phospho-CREB from (7.7 +/- 3.2) % to (19.6 +/- 4.7) % (n = 6, P < 0.01) in smc preincubated with morphine 0.5 mmol/L. In addition, naloxone decreased [Ca2+]i from (146 +/- 34) to (78 +/- 24) nmol/L in one third morphine-preincubated aec (n = 10, P < 0.01). CONCLUSION: That naloxone enhances vascular responsiveness to NE in chronic morphine treatment rats may be relevant to [Ca2+]i transient facilitation in company with cAMP-dependent phosphorylation enhancement.

Animals↗

[Pharmacokinetics and bioavailability of clinafloxacin in rats].

AIM: To study the pharmacokinetics and bioavailability of clinafloxacin in rats. METHODS: The drug concentration was determined by HPLC. The main pharmacokinetic parameters were obtained by 3P87 program. An RP-C18 was used as the stationary phase. The mobile phase was a mixture of acetonitrile-0.05 mol.L-1 citric acid triethylamine (pH 2.5) (20:80). The flow rate was 1.0 mL.min-1. The UV absorbance detector was set at 300 nm. RESULTS: A good linearity was obtained from 0.03-20 micrograms.mL-1 of clinafloxacin in rat plasma with gamma = 0.9998. The plasma concentration--time curve of clinafloxacin conformed to one compartment open model. After ig administration of 50 mg.kg-1 and 100 mg.kg-1 dose of clinafloxacin in six rats, mean Cmax and AUC values increased in proportion to dose. Mean T1/2 appeared to be independent of dose. Mean AUC was 65 +/- 6 and 27 +/- 4 micrograms.h.mL-1 respectively after i.v. and ig administration of 100 mg.kg-1 dose. The extent of bioavailability (F) of clinafloxacin was 42%. CONCLUSION: The results of the pharmacokinetic study of clinafloxacin showed that it exhibited first order kinetic characteristics and the bioavailability is low.

Animals↗

Plasticity of cadherin-catenin expression in the melanocyte lineage.

Cadherins are calcium-dependent cell adhesion receptors with strong morphoregulatory functions. To mediate functional adhesion, cadherins must interact with actin cytoskeleton. Catenins are cytoplasmic proteins that mediate the interactions between cadherins and the cytoskeleton. In addition to their role in cell-cell adhesion, catenins also participate in signaling pathways that regulate cell growth and differentiation. Cadherins and catenins appear to be involved in melanocyte development and transformation. Here, we investigated the function of cadherin-catenin complexes in the normal development and transformation of melanocytes by studying the patterns of expression of the cell-cell adhesion molecules, E-, N- and P-cadherin, and the expression of their cytoplasmic partners, alpha-, beta- and gamma-catenin during murine development. Similar analyses were performed in vitro using murine melanoblast, melanocyte, and melanoma cell lines in the presence and absence of keratinocytes, the cells with which melanocytes interact in vivo. Overall, the results suggest that the expression of cadherins and catenins is very plastic and depends on their environment as well as the transformation status of the cells. This plasticity is important in fundamental cellular mechanisms associated with normal and pathological ontogenesis, as well as with tumorigenesis.

Animals↗

Radiation-induced arrest of cells in G2 phase elicits hypersensitivity to DNA double-strand break inducers and an altered pattern of DNA cleavage upon re-irradiation.

PURPOSE: To determine how radiation-induced arrest in G2 affects the response of mammalian cells to a challenging dose of radiation or to antitumour drugs producing DNA double-strand breaks. MATERIALS AND METHODS: V79 fibroblast survival to 5 Gy gamma-rays followed at intervals by 3 Gy irradiation or by contact with an equitoxic dose of neocarzinostatin or etoposide, was measured by clonogenic assays. The pattern of radiation-induced DNA double-strand breaks was determined by filter elution and CFGE (continuous field gel electrophoresis) or PFGE (pulsed-field gel electrophoresis) in G2-arrested cells as well as in nonpre-irradiated asynchronous or synchronized cells. The cell-cycle phase specificity of drug susceptibility was determined in synchronized HeLa cells. RESULTS: Cell kill by radiation-drug combined treatment varied markedly with the time elapsed after priming irradiation. Pre-irradiated, G2-arrested V79 fibroblasts demonstrated excess double-stranded DNA cleavage upon re-irradiation and hypersensitivity to drugs and radiation, although maximum resistance to both neocarzinostatin and etoposide in synchronized HeLa cells was in G2. This effect occurred in the megabase range only, with a peak around 4 Mbp; no change in the electrophoretic migration profile of DNA was observed below 1 Mbp. Moreover, the DNA migration profile and the yield of DNA cleavage in G2-arrested cells were close to those expected from S-phase cells. CONCLUSION: The available data suggest that mechanisms operating within the radiation-induced G2 block promote susceptibility to DNA double-strand break inducers at this stage. It is also proposed that the conformation of DNA in cells accumulated in G2 following irradiation bears resemblance to that for cells in S phase, due either to active repair mechanisms or to inhibition of chromosome disentanglement at the S-G2 transition.

Animals↗

Reactivity of Cl-P(+)-Cl toward cyclic organic ethers.

The dichlorophosphenium ion (Cl-P(+)-Cl) undergoes a variety of reactions with cyclic organic ethers in the gas phase in a Fourier-transform ion cyclotron resonance mass spectrometer. Most of the reactions are initiated by Cl-P(+)-Cl-induced heterolytic C-O bond cleavage. However, the observed final products depend on the exact structure of the ether. For saturated ethers, e.g., tetrahydropyran, tetrahydrofuran, and 2-methyltetrahydrofuran, the most abundant ionic product corresponds to hydroxide abstraction by Cl-P(+)-Cl. This unexpected reaction is rationalized by a multistep mechanism that involves an initial heterolytic C-O bond cleavage accompanied by a 1,2-hydride shift, and that ultimately yields a resonance-stabilized allyl cation and HOPCl2. The process is estimated to be highly exothermic (AM1 calculations yield delta H = -(33-38) kcal mol(-1) for the ethers mentioned above). However, the adducts formed from most of the unsaturated ethers are unable to undergo hydride shifts and hence cannot react via this pathway. In some of these cases, e.g., for 2,5-dihydrofuran and 2,5-dihydro-3,4-benzofuran, the C-O bond heterolysis is followed by oxygen/chlorine exchange to yield the O=PCl radical and a resonance-stabilized carbocation (AM1 calculations yield delta H = -14 kcal mol(-1) for the reaction of 2,5-dihydro-3,4-benzofuran). Hydride abstraction by Cl-P(+)-Cl also yields an abundant product for these two ethers. On the other hand, the ethers with low ionization energies, such as 2,3-dihydrofuran and 2,3-dihydrobenzofuran, react with Cl-P(+)-Cl by electron transfer. Finally, a unique pathway, addition followed by elimination of HCl, dominates the reaction with furan. The observed reactions are rationalized by thermochemical data obtained from semiempirical molecular orbital calculations.

Benzofurans↗

Improved survival with resection after transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma.

AIM: This retrospective study was undertaken to analyze the outcome of hepatic resection in hepatocellular carcinomas (HCCs) that shrunk after transcatheter hepatic arterial chemoembolization (TACE) in 65 patients with unresectable HCCs between June 1987 and September 1996. MATERIALS AND METHODS: Among these 65 patients, the median diameter of the tumor was 9.9 cm (5.6-20.0) prior to the first TACE, after 1-6 times of TACE (median 3) the median tumor diameter reduced to 3.7 cm (1.9-12.5) prior to resection. The duration between the last TACE treatment and sequential resection varied from 1 to 9 months (median 2.5). Serum alpha-fetoprotein (AFP) levels were abnormal in 39 out of the 65 patients. In AFP producing HCCs, the AFP level returned to normal (</=20 microgram/l) in 14 out of 39 patients (35.9%). Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in 61 patients, right hemihepatectomy in 1, left trisegmentectomy in 2, and left hemihepatectomy in 1. RESULTS: Tumor necrosis ranged from 40 to 100% and pathologically and complete tumor necrosis occurred in 11 patients (16.9%). Of 14 patients with AFP levels decreased to normal, 10 still had microscopic living tumor foci. The 1-, 3- and 5-year survival rates of the 65 patients were 80.0, 65.0 and 56.0% respectively. CONCLUSION: TACE treatment can provide a chance of tumor resection for those patients with initially judged unresectable HCCs, and liver resection should be performed when the tumor has shrunk to be resectable, even when the AFP level has returned to normal.

Adult↗

Progress and prospects in hepatocellular carcinoma surgery.

Hepatocellular carcinoma (HCC), the second cause of cancer death in China, is responsible for 130,000 deaths every year. However, as a result of efforts in early detection and small HCC resection, re-resection for subclinical recurrence, cytoreduction and second-stage resection for unresectable HCC, and aggressive palliative surgery other than resection (hepatic artery ligation/cannulation, cryosurgery, etc.), and encouraging improvemental of long-term survival of inpatients has been observed in the authors' institution. In the entire series of 2672 HCC inpatients, the 5-year survival was 4.8% in 1958-70, 12.2% in 1971-83, and 46.7% in 1984-95. The 5-year survival rates were: 61.3% for small HCC resection (n = 645), 33.6% for large HCC resection (n = 950), 48.9% for re-resection (n = 147) calculated from the first resection, 67.9% for second-stage resection (n = 73), and 19.8% for palliative surgery (n = 574, including 73 with second-stage resection). By 1995, 239 HCC patients survived for more than 5 years. Recurrence and metastasis remained the major obstacles to more prolonged survival after HCC surgery. Molecular studies of HCC invasiveness, experimental intervention in the newly established highly metastatic model of human HCC in nude mice in the authors' institution have also been delineated. It is concluded that early detection and small HCC resection remain the major approach to improve survival. Aggressive surgical treatment, such as re-resection and second-stage resection, are also important, and invasiveness-related recurrence will be the next target to be studied.

Animals↗

Three decades' experience in surgery of hepatocellular carcinoma.

In the author's institution, 2254 patients with hepatocellular carcinoma (HCC) have been treated during 1958-1994. The overall 5-year survival increased from 5.4% (1958-1970), to 11.9% (1971-1982), to 46.2% (1983-1984), which correlated well with the increasing proportion of small HCC in the series (2.6%, 12.1%, and 33.4%, respectively); with the increasing percentage of limited resection (3.1%, 32.2%, and 58.3%); with the increasing number of re-resections for recurrence (0, 27, and 114 patients); and with the increasing number of second stage resections (0, 5, and 67 patients). In our institution, surgical approaches that resulted in significantly prolonging survival included: small HCC resection, re-resection, and cytoreduction followed by sequential resection for initially unresectable HCC. Experience in these 3 aspects suggests: (a) Small HCCs are mainly found by screening using AFP and ultrasonography (US) in a high risk population, and limited resection is the best treatment in patients with compensated liver cirrhosis, the 5-year survival after resection being 62.9% (n = 549). (b) Postoperative monitoring using AFP/US every 2-3 months for 5-10 years after curative resection is needed to detect subclinical recurrence. Limited re-resection is indicated for liver recurrence less than 3 nodules, and lung lobectomy is of proven merit to prolong survival for solitary lung metastasis. Re-resection of subclinical recurrence has resulted in a 10-20% further increase in 5-year survival after curative resection. (c) Palliative surgery other than resection such as hepatic artery ligation (HAL) and cannulation with arterial infusion (HAI), cryosurgery, etc. are superior to palliative resection with residual cancer. (d) Cytoreduction and sequential resection have provided hope for localized unresectable HCC, particularly in the right cirrhotic liver. Multimodality combination treatments such as HAL+HAI+radioimmunotherapy/regional radiotherapy are acceptable cytoreductive therapies. Repeated transcatheter hepatic arterial chemoembolization (TACE) is an alternative nonsurgical approach. Sequential resection is important to eradicate residual cancer after cytoreduction. The 5-year survival of 72 patients with cytoreduction and sequential resection for initially unresectable HCC was 62.1% and resulted in improving 5-year survival in the entire series of unresectable HCC over the 3 periods from 0% to 7.4% to 25.7%, respectively. However, multicentric origin and tumor invasiveness are two major targets to be studied in the control of recurrence and metastasis.

Carcinoma, Hepatocellular↗

Long-term results of surgery for small primary liver cancer in 514 adults.

During 1958-1993, 2030 patients with pathologically proven primary liver cancer (PLC) were retrospectively reviewed. Comparison between small PLC (< or = 5 cm, n = 514) and large PLC (> 5 cm, n = 1516) revealed that small PLC had a higher resection rate (92.4% versus 49.1%), lower operative mortality (1.7% versus 5.2%), a higher percentage of single tumour nodules (78.0% versus 53.4%), a higher percentage of well encapsulated tumour (74.5% versus 35.8%) and higher survival rates after resection (5-year, 63.8% versus 36.6%; 10-year, 46.8% versus 28.5%). No significant difference was found between survival following limited resection (n = 440) and lobectomy (n = 34) in patients with small PLC. Re-resection of any subclinical recurrence or solitary pulmonary metastasis after small PLC resection was done in 70 cases. These results indicate that resection is still the modality of choice for treatment of small PLC; limited resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality; re-resection of subclinical recurrence was important to prolong survival further.

Adult↗

Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens.

In this study of orthotopic implantation of histologically intact surgical specimens, the authors constructed metastatic models of human hepatocellular carcinoma (HCC) in nude mice. Histologically intact human liver cancer specimens, derived from patients, were implanted directly into the liver of nude mice, and their orthotopic growth and metastases were observed. The transplantability and metastatic rate of two specimen groups (primary and metastatic lesions) were analysed. alpha-Fetoprotein (AFP) was also determined in transplanted tumours by an immunohistochemical method. Orthotopic growth was observed in 14 of 30 transplanted specimens and formation of metastases in 7 cases, which exhibited the variety of clinical behaviours seen in patients with HCC. These behaviours included local growth, regional invasion, spontaneous intrahepatic, lymph node and lung metastasis and peritoneal seeding. In two groups the growth rate of metastatic lesions following implantation was clearly higher than that of primary tumours. Chromosome analysis from locally growing tumours confirmed their morphologically human origin. An immunohistochemical study showed that implanted tumours originating from AFP-positive specimens maintained AFP expression. These results indicated that the animal models should prove valuable for developing new treatment modalities and studying the mechanism of metastasis of human HCC.

Animals↗

Ablative approach for primary liver cancer: Shanghai experience.

This article summarizes the results of 2018 patients receiving surgical treatment for pathologically proven primary liver cancer (PLC). Special references are made to the role of cryosurgery and cytoreduction for unresectable PLC.

Antineoplastic Combined Chemotherapy Protocols↗

MRI of a pituitary cryptococcoma simulating an adenoma.

We describe a rare pituitary cryptococcoma in an immunocompetent patient, with radiological features similar to those of a pituitary macroadenoma. Although unusual, it should be added to the list of differential diagnosis of pituitary masses. Contrast enhancement of adjacent meninges differentiated the lesion from an adenoma.

Adenoma↗

Characteristics and prognosis of primary liver cancer in young patients in China.

To investigate the clinicopathologic characteristics of primary liver cancer (PLC) in young adults, 77 patients aged 35 or younger were compared with 603 patients older than 35 years during the same period. In the young patients, PLC showed: (1) a low incidence detected at mass survey (young 15.6% vs older 28.7%, P < 0.05); (2) a low level of history of hepatitis (young 36.8% vs older 66.3%, P < 0.01); (3) a high incidence of positivity for hepatitis B surface antigen (HBsAg) (young 79.2% vs older 67.6%, P < 0.05); (4) a relatively low incidence of associated cirrhosis (young 64.9% vs older 90.7%, P < 0.01); (5) larger tumor size (PLC > 5 cm; young 87.0% vs older 73.0%, P < 0.01); and (6) a more advanced stage of the disease according to the TNM classification (stage III; young 29.9% vs older 18.2%, P < 0.05). It is suggested that hepatitis B virus (HBV) may play an important role in the development of PLC without associated liver cirrhosis in young patients. Close periodic surveillance of young adults who are positive for HBsAg is important to detect PLC at an early stage.

Adult↗

Observation of changes in peripheral T-lymphocyte subsets by flow cytometry in patients with liver cancer treated with radioimmunotherapy.

An analysis of lymphocyte subsets was performed in 24 patients with surgically verified unresectable hepatocellular carcinoma (HCC). In all cases, the hepatic artery was cannulated and ligated and a single dose of 131I-Hepama-1 monoclonal antibody (MAb) was infused through a hepatic artery catheter. Blood samples were obtained before infusion and 1 month post-infusion. The results indicated that the CD3+ T-cells (pan T-cells) were normal, whereas the CD4+ T-cells (T-helper/inducer cells) decreased and the CD8+ T-cells (T-suppressor/cytotoxic cells) increased significantly in comparison with the control group. So the CD4+:CD8+ ratio declined markedly. One month post-radioimmunotherapy (RIT), the T-cell subsets did not change, but CD4+, CD8+ and the CD4+:CD8+ ratio differed significantly between patients with and without sequential resection. The changes in the T-cell subsets were closely related to tumour capsule status and the human anti-murine antibody (HAMA) response, but no relationship was found between the tumour and administration of a moderate dose of radioimmunoconjugate. Therefore, determination of changes in the T-lymphocyte subsets and the CD4+:CD8+ ratio could be used as clinical and prognostic indicators in patients who have received RIT. Furthermore, RIT did not affect the distribution of T-cell subsets in patients with HCC.

Animals↗