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P Lin

Publications and source records attributed to P Lin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cactin, a conserved protein that interacts with the Drosophila IkappaB protein cactus and modulates its function.

Rel transcription factors function in flies and vertebrates in immunity and development. Although Rel proteins regulate diverse processes, the control of their function is conserved. In a two-hybrid screen for additional components of the pathway using the Drosophila I-kappaB protein Cactus as a bait, we isolated a novel coiled-coil protein with N-terminal Arg-Asp (RD)- like motifs that we call Cactin. Like the other components of this pathway, Cactin is evolutionarily conserved. Over-expression of cactin in a cactus(A2) heterozygous background results in the enhancement of the cactus phenotype. Both the embryonic lethality and ventralization are strongly increased, suggesting that cactin functions in the Rel pathway controlling the formation of dorsal-ventral embryonic polarity.

Amino Acid Sequence↗
PubMed2000

DNA adduct level in lung tissue may act as a risk biomarker of lung cancer.

Lung cancer is a leading cause of mortality in Taiwan. We hypothesised that high susceptibility to DNA damage in the target organ acts as a risk biomarker for the development of lung cancer. To verify this hypothesis, the aromatic/hydrophobic DNA adduct levels of non-tumorous adjacent lung tissues from 73 primary lung cancer patients and 33 non-cancer controls were evaluated by 32P-postlabelling assay. Wilcoxon rank sum test showed that DNA adduct levels in lung cancer patients (49.58+/-33.39 adducts/10(8) nucleotides) were significantly higher than those in non-cancer controls (18.00+/-15.33 adducts/10(8) nucleotides, P<0.001). The DNA adduct levels among lung cancer and non-cancer samples were not influenced by smoking behaviour and cigarette consumption. Our data also showed that the polymorphisms of cytochrome P4501A1 (CYP1A1) Msp1, glutathione S-transferase M1 (GSTM1) and the combination of both genetic polymorphisms were not related to the DNA adduct levels. Interestingly, positive association between CYP1A1 protein expression and DNA adduct levels was found when CYP1A1 protein expression in lung specimens from lung cancer patients was examined by immunohistochemistry. Multivariate linear regression analysis indicated that the DNA adduct level was not associated with gender, smoking behaviour, or genetic polymorphisms of CYP1A1 and GSTM1. Moreover, multivariate logistic regression analysis showed that persons with high DNA adduct levels (>48.66 adducts/10(8) nucleotides) had an approximately 25-fold risk of lung cancer compared with persons with low DNA adduct levels (</=48.66 adducts/10(8) nucleotides). In conclusion, DNA adduct levels in lung tissue may be a more reliable lung cancer susceptibility biomarker than DNA adduct levels in leucocytes. In addition, higher susceptibility to DNA damage in lung cancer patients may partly play a role in the development of lung cancer.

Adenocarcinoma↗
PubMed2000

Association of CYP1A1 and microsomal epoxide hydrolase polymorphisms with lung squamous cell carcinoma.

Lung cancer is the leading cause of death among cancers in Taiwan. Although the etiology of lung cancer has yet to be defined, genetic variability in activities of metabolic enzymes has been correlated with lung cancer. In the present study, the possibility of association of CYP1A1 and microsomal epoxide hydrolase (HYL1) genetic polymorphisms with lung cancer was examined among 132 lung cancer patients and 259 controls in Taiwan. No significant association was observed for either CYP1A1 or HYL1 polymorphism alone and the overall incidence of lung cancer after adjusting for age, gender and smoking status. When cases were stratified according to histological type, there was significant association between CYP1A1*2A homozygote and squamous cell carcinoma (SCC) (odds ratio (OR) 2.86; 95% confidence interval (CI) 1.33-6.12). Similarly, the proportion of HYL1 genotypes corresponding to high or normal enzyme activities was higher in SCC than in controls (OR 1.96; 95% CI 1.04-3.70). A combination of susceptible CYP1A1 and HYL1 genotypes was found to be highly associated with lung cancer, especially with SCC (OR 6.76; 95% CI 2.29-19.10). Our results suggest that the combination of CYP1A1 and HYL1 polymorphisms is an important risk factor for lung SCC.

Base Sequence↗
PubMed2000

Precursor B-cell lymphoblastic lymphoma: a predominantly extranodal tumor with low propensity for leukemic involvement.

Precursor B-cell lymphoblastic lymphoma (B-LBL) is uncommon and accounts for less than 10% of cases of lymphoblastic lymphoma. We collected 25 cases of B-LBL, occurring in children and adults, and report the clinical and histologic features. Patients with concurrent precursor B-cell acute lymphoblastic leukemia (B-ALL) or a history thereof were excluded. There was no evidence of bone marrow disease at the time of diagnosis in 23 patients; two patients had focal (<5%) involvement. Immunophenotypic analysis was performed in all cases using flow cytometry or immunohistochemical methods. The treatment and survival data available for a subset of patients with B-LBL were compared with those from a series of patients with B-ALL at our institution. The median age was 20 years (range, 5-68 yrs); 22 (88%) patients were younger than 35 years of age. There were 17 males and 8 females. The primary sites of disease were skin (nine cases), bones (five cases), soft tissue (four cases), lymph nodes, (three cases), breast (two cases), stomach and colon (one case), and mediastinum (one case). Clinical stage was stage I in 13 cases, stage II in seven cases, stage III in three cases, and stage IV in two cases. Histologically, each neoplasm was diffuse and composed of small to medium-sized lymphoid cells with blastic nuclear chromatin and a high mitotic rate. All cases were positive for B-cell antigens and terminal deoxynucleotidyl transferase. Thirteen (76.4%) of 17 cases analyzed were positive for CD10 and 13 (54.1%) of 24 cases assessed were positive for CD20. Of 14 patients with available survival data, all achieved complete clinical response after combination chemotherapy (13 patients) or surgical excision followed by local irradiation (one patient). Five (35.7%) patients subsequently relapsed, including the patient who had received only irradiation, and four of these patients died after a median survival time of 60 months. None of the patients had leukemia, although one patient developed extensive bone marrow involvement. Nine patients remained in complete remission and were alive at the last follow up (range, 6-144 months). Unlike precursor T-cell lymphoblastic lymphoma, which commonly involves lymph nodes and the mediastinum, B-LBL usually involves extranodal sites, most often the skin, and rarely presents as a mediastinal mass. With aggressive chemotherapy, patients with precursor B-LBL rarely develop leukemia and appear to have a better prognosis than do patients with B-ALL.

Adolescent↗
PubMed2000

Fluorine-18 FDG dual-head gamma camera coincidence imaging of radiation pneumonitis.

A 69-year-old man with inoperable stage I squamous cell carcinoma of the lung underwent a radical course of radiotherapy combined with platinum-based chemotherapy. Fluorine-18 fluorodeoxyglucose (FDG) imaging with a dual-head coincidence gamma camera system (Co-PET) diagnosed radiation pneumonitis 1 month after completion of radiotherapy, when the clinical and radiographic signs were atypical and more suggestive of carcinomatous lymphangitis. Treatment with oral steroids was begun based on FDG scan findings, with prompt clinical benefit as would be expected for radiation pneumonitis.

Aged↗
PubMed1999

NAD(P)H: quinone oxidoreductase polymorphism and lung cancer in Taiwan.

Lung cancer is one of the leading causes of death in Taiwan since 1996. Genetic variation in metabolic activation or detoxification enzymes has been associated with the occurrence of lung cancer. NAD(P)H:quinone oxidoreductase (NQO1) enzyme is a cytosolic two-electron reductase thought to be involved in bioactivation and detoxification of environmental carcinogens. The possible association between NQO1 genetic polymorphism and lung cancer risk was examined among 95 male smokers without cancer and 100 male smokers with lung cancer in Taiwan. There was no significant difference in the proportion of wild-type NQO1 among all cancer cases and controls. When cases were stratified according to histological subtypes, the wild-type NQO1 was more common in adenocarcinoma than in controls. The odds ratio was 2.93 (95% confidence interval, 1.23-7.02; p = .02). This is the first observation for the positive association of this locus with lung cancer in an Asian population. These results suggest that NQO1 polymorphism is an important genetic risk factor for lung adenocarcinoma among smokers in Taiwan.

Adenocarcinoma↗
PubMed1999

Identification of a novel actin binding motif in smooth muscle myosin light chain kinase.

Phosphorylation of the 20-kDa regulatory light chain of myosin catalyzed by a Ca(2+)/calmodulin-dependent myosin light chain kinase is important in the initiation of smooth muscle contraction and other contractile processes in non-muscle cells. It has been previously shown that residues 1-142 of smooth muscle myosin light chain kinase are necessary for high-affinity binding to actin-containing filaments in cells (1). To further localize the region of the kinase required for binding, a series of N-terminal deletion mutants as well as several N-terminal glutathione S-transferase fusion proteins were constructed. Cosedimentation assays showed that a peptide containing residues 1-75 binds to purified smooth muscle myofilaments. Furthermore, the N-terminal peptide was sufficient for high-affinity binding to actin stress fibers in smooth muscle cells in vivo. Alanine scanning mutagenesis in the fusion protein identified residues Asp-30, Phe-31, Arg-32, and Leu-35 as important for binding in vitro. There are two additional DFRXXL motifs located at residues 2-7 and 58-63. The DFR residues in these three motifs were individually replaced by alanine residues in the full-length kinase. Each of these mutations significantly decreased myosin light chain kinase binding to myofilaments in vitro, and each abolished high-affinity binding to actin-containing filaments in smooth muscle cells in vivo. These results identify a unique structural motif comprised of three repeat consensus sequences in the N terminus of myosin light chain kinase necessary for high-affinity binding to actin-containing filaments.

Actin Cytoskeleton↗
PubMed1999

Overexpression of CALNUC (nucleobindin) increases agonist and thapsigargin releasable Ca2+ storage in the Golgi.

We previously demonstrated that CALNUC, a Ca2+-binding protein with two EF-hands, is the major Ca2+-binding protein in the Golgi by 45Ca2+ overlay (Lin, P., H. Le-Niculescu, R. Hofmeister, J.M. McCaffery, M. Jin, H. Henneman, T. McQuistan, L. De Vries, and M. Farquhar. 1998. J. Cell Biol. 141:1515-1527). In this study we investigated CALNUC's properties and the Golgi Ca2+ storage pool in vivo. CALNUC was found to be a highly abundant Golgi protein (3.8 microg CALNUC/mg Golgi protein, 2.5 x 10(5) CALNUC molecules/NRK cell) and to have a single high affinity, low capacity Ca2+-binding site (Kd = 6.6 microM, binding capacity = 1.1 micromol Ca2+/micromol CALNUC). 45Ca2+ storage was increased by 2.5- and 3-fold, respectively, in HeLa cells transiently overexpressing CALNUC-GFP and in EcR-CHO cells stably overexpressing CALNUC. Deletion of the first EF-hand alpha helix from CALNUC completely abolished its Ca2+-binding capability. CALNUC was correctly targeted to the Golgi in transfected cells as it colocalized and cosedimented with the Golgi marker, alpha-mannosidase II (Man II). Approximately 70% of the 45Ca2+ taken up by HeLa and CHO cells overexpressing CALNUC was released by treatment with thapsigargin, a sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) (Ca2+ pump) blocker. Stimulation of transfected cells with the agonist ATP or IP3 alone (permeabilized cells) also resulted in a significant increase in Ca2+ release from Golgi stores. By immunofluorescence, the IP3 receptor type 1 (IP3R-1) was distributed over the endoplasmic reticulum and codistributed with CALNUC in the Golgi. These results provide direct evidence that CALNUC binds Ca2+ in vivo and together with SERCA and IP3R is involved in establishment of the agonist-mobilizable Golgi Ca2+ store.

Amino Acid Sequence↗
PubMed1999

Properties of filament-bound myosin light chain kinase.

Myosin light chain kinase binds to actin-containing filaments from cells with a greater affinity than to F-actin. However, it is not known if this binding in cells is regulated by Ca2+/calmodulin as it is with F-actin. Therefore, the binding properties of the kinase to stress fibers were examined in smooth muscle-derived A7r5 cells. Full-length myosin light chain kinase or a truncation mutant lacking residues 2-142 was expressed as chimeras containing green fluorescent protein at the C terminus. In intact cells, the full-length kinase bound to stress fibers, whereas the truncated kinase showed diffuse fluorescence in the cytoplasm. After permeabilization with saponin, the fluorescence from the truncated kinase disappeared, whereas the fluorescence of the full-length kinase was retained on stress fibers. Measurements of fluorescence intensities and fluorescence recovery after photobleaching of the full-length myosin light chain kinase in saponin-permeable cells showed that Ca2+/calmodulin did not dissociate the kinase from these filaments. However, the filament-bound kinase was sufficient for Ca2+-dependent phosphorylation of myosin regulatory light chain and contraction of stress fibers. Thus, dissociation of myosin light chain kinase from actin-containing thin filaments is not necessary for phosphorylation of myosin light chain in thick filaments. We note that the distance between the N terminus and the catalytic core of the kinase is sufficient to span the distance between thin and thick filaments.

Actin Cytoskeleton↗
PubMed1999

Prevention of glucocorticoid-induced osteoporosis: provider practice at an urban county hospital.

PURPOSE: We sought to determine the frequency and types of prophylaxis for osteoporosis that were prescribed to outpatients who were receiving chronic glucocorticoid treatment and to identify the patient and provider characteristics that were associated with the use of prophylaxis. SUBJECTS AND METHODS: We identified 215 adult outpatients at San Francisco General Hospital who had received a prescription for prednisone (or its equivalent) at a daily dose of at least 5 mg for at least 1 month. Patient demographic characteristics, the diagnosis for which glucocorticoids were prescribed, comorbid illnesses, and medications were determined by chart review. Characteristics of the patients who were prescribed prophylaxis were compared with those of patients who were not prescribed prophylaxis. RESULTS: Prophylaxis for glucocorticoid-induced osteoporosis was prescribed to 58% of patients. Patients prescribed prophylaxis were older (mean [+/-SD] age of 50.0 +/- 13.9 versus 44.5 +/- 13.6 years, P = 0.004), more likely to be female (69% versus 40%, P <0.0001), postmenopausal if female (84% versus 56%, P = 0.002), have more comorbid illnesses (63% versus 29%, P = 0.001), and take multiple medications (66% versus 45%, P = 0.002). Patients attending the rheumatology clinic were 1.6 times more likely to receive prophylaxis than those attending other clinics (P <0.0001). The strongest predictor of prophylaxis was postmenopausal state. In premenopausal women, the independent predictors of prophylaxis were being treated in the rheumatology clinic and the presence of comorbid illnesses, whereas comorbid illnesses was the only independent predictor of prophylaxis in men. CONCLUSIONS: Educational efforts should be directed toward increasing awareness of the importance of glucocorticoid-induced osteoporosis and its prevention.

Adult↗
PubMed1999

Loss of retinoic acid receptor-beta expression is an early event during esophageal carcinogenesis.

We recently observed that growth inhibition of esophageal cancer cells by retinoic acid (RA) was associated with both constitutive expression and RA-induced up-regulation of RA receptor beta (RAR-beta). Cell lines that did not express RAR-beta were also resistant to RA. To explore the expression of RAR-beta mRNA in vivo, we analyzed esophageal tissue specimens from 16 normal mucosae, 30 dysplastic lesions, and 157 esophageal tumors by in situ hybridization. RAR-beta was detected in 88% (14/16) of normal esophageal tissues and in 96% (96/100) of distant normal esophageal mucosa from cancer specimens. In contrast, RAR-beta was expressed in only 57% (17/30) of dysplastic lesions and in 54% (84/157) of carcinomas. Among esophageal carcinomas RAR-beta mRNA was expressed in 62% (26/42) of well-differentiated, 54% (27/50) of moderately differentiated, and only 29% (4/14) of poorly differentiated SCCs. Our data suggest that the loss of RAR-beta expression is an early event associated with esophageal carcinogenesis and the status of squamous differentiation.

Aged↗
PubMed1999

Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium.

OBJECTIVE: Transmyocardial laser revascularization (TMR) is emerging as a potential treatment option for patients with end-stage CAD, and adjuvant gene therapy may be helpful in further improving the results of the procedure. However, the effects of TMR on gene transfer are unknown. METHODS: Swine underwent left thoracotomy. TMR was performed to create five channels at 2-cm intervals in the anterolateral free wall of the left ventricle (LV) followed by injection of 1 x 10(9) plaque-forming units (pfu) of a replication-deficient adenovirus vector carrying the reporter gene beta-galactosidase (Ad.Pac beta-gal). An additional five direct injections of 1 x 10(9) pfu Ad.Pac beta-gal were made at 2-cm intervals in the posterolateral LV of each heart. Control animals underwent TMR alone/vehicle alone (n = 3) or empty virus alone/no treatment (n = 3) of the anterolateral/posterolateral LV, respectively. RESULTS: ELISA revealed significantly greater transgene expression in the direct Ad.Pac beta-gal injection versus TMR plus Ad.Pac beta-gal inject regions at both 3 (n = 6) (273.0 +/- 58.5 vs. 133.4 + 28.1 pg beta-gal/g protein, P = 0.02) and 7 days (n = 6) (180.0 + 59.9 vs. 56.7 + 18.1 pg beta-gal/g protein, P = 0.02) postoperatively. At 14 days postoperatively (n = 2), no transgene expression was detected in either region. No transgene expression was detected in any of the control regions at 3 days postoperatively. CD-18 staining revealed significantly greater inflammation in the TMR plus Ad.Pac beta-gal and TMR alone regions as compared to Ad.Pac beta-gal or vehicle (P < 0.001). CONCLUSIONS: Adenoviral-mediated gene transfer in conjunction with TMR is possible, although TMR appears to limit the degree of transgene expression attained as compared to direct intramyocardial injection alone, likely due to the greater immune response observed with the former. These findings may have important implications for therapeutic strategies aimed at combining TMR with gene therapy for CAD.

Adenoviridae↗
PubMed1999

Differential response to benzo[A]pyrene in human lung adenocarcinoma cell lines: the absence of aryl hydrocarbon receptor activation.

Benzo[a]pyrene (B[a]P) has been shown to produce DNA adducts and to initiate pulmonary carcinogenesis in animals. We observed differential susceptibility to B[a]P in two human lung adenocarcinoma cell lines, A427 and CL3. DNA adducts were induced by B[a]P treatment in CL3 cells, however, A427 cells were much less responsive to B[a]P treatment. Cytochrome P450 1A1 (CYP1A1) is involved in bioactivation of B[a]P in nonhepatic tissues. Cotreatment with alpha-naphthoflavone, a CYP1A1 inhibitor, abolished DNA adduct formation by B[a]P in CL3 cells. Nevertheless, CYP1A1 inducer beta-naphthoflavone, enhanced DNA adduct formation by B[a]P in both A427 and CL3 cells. Both enzyme activity and mRNA levels of CYP1A1 were highly induced by 1 or 10 microM B[a]P treatment for 24 hr in CL3 cells but not in A427 cells. Protein levels of AhR and aryl hydrocarbon receptor nuclear translocator (Arnt) were similar in A427 and CL3 cells before B[a]P treatment. However, B[a]P induced a retarded band with the [32P]-dioxin responsive element in CL3 cells, but not in A427 cells. This study demonstrated that variation in AhR-mediated CYP1A1 induction contributes to differential susceptibility to B[a]P-DNA adduct formation in human lung cells. Since AhR and/or Arnt function is impaired in A427 cells, this cell line offers a model for investigating the repression mechanisms of CYP1A1 induction by B[a]P in lung cells.

Adenocarcinoma↗
PubMed1999

Cytochrome P4502E1 genetic polymorphisms and lung cancer in a Taiwanese population.

Cytochrome P4502E1 (CYP2E1) is involved in metabolic activation of carcinogenic nitrosamines, benzene and low molecular weight halogenated hydrocarbons. In this study, we assessed the association between CYP2E1 RsaI and DraI genetic polymorphisms and lung cancer in a Taiwanese population. The RsaI genotype distribution was significantly different between 119 lung cancer patients and 231 non-cancer controls. The homozygote variants of RsaI genotypes were more common in controls (6.9%) than in lung cancer patients (0.8%). The estimated odds ratio (OR) was 0.11 (95% confidence interval (CI), 0.01-0.87). After adjusting for age, sex, and smoking status, the OR was 0.12 (95%, CI, 0.02-0.95). This is the first observation of a positive association between this locus and lung cancer in an Asian population. No significant differences in CYP2E1 DraI genotype distributions were found between cases and controls. The results of this study indicate that CYP2E1 RsaI polymorphism, but not DraI polymorphism, may contribute to the development of lung cancer in Taiwan.

Cytochrome P-450 CYP2E1↗
PubMed1999

Complications of laparoscopy. Strategies for prevention and cure.

With a detailed knowledge of pelvic anatomy, familiarity with the many laparoscopic instruments, and attention to the details of good technique, many of the complications of laparoscopy described in this article can be avoided. The information presented complements that in the other articles in this issue and briefly summarizes many salient lessons already published in other excellent texts. The focus is on the most common laparoscopic complications, namely, those associated with insufflation and trocar insertion, such as vascular injury and bowel perforation. Other complications that may arise during adhesiolysis, removal of and bleeding from an ectopic pregnancy, and specimen removal from the abdomen are also discussed.

Blood Loss, Surgical↗
PubMed1999

Mutations in the gene encoding 3 beta-hydroxysteroid-delta 8, delta 7-isomerase cause X-linked dominant Conradi-Hünermann syndrome.

X-linked dominant Conradi-Hünermann syndrome (CDPX2; MIM 302960) is one of a group of disorders with aberrant punctate calcification in cartilage, or chondrodysplasia punctata (CDP). This is most prominent around the vertebral column, pelvis and long bones in CPDX2. Additionally, CDPX2 patients may have asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis and atrophoderma. The phenotype in CDPX2 females ranges from stillborn to mildly affected individuals identified in adulthood. CDPX2 is presumed lethal in males, although a few affected males have been reported. We found increased 8(9)-cholestenol and 8-dehydrocholesterol in tissue samples from seven female probands with CDPX2 (ref. 4). This pattern of accumulated cholesterol intermediates suggested a deficiency of 3beta-hydroxysteroid-delta8,delta7-isomerase (sterol-delta8-isomerase), which catalyses an intermediate step in the conversion of lanosterol to cholesterol. A candidate gene encoding a sterol-delta8-isomerase (EBP) has been identified and mapped to Xp11.22-p11.23 (refs 5,6). Using SSCP analysis and sequencing of genomic DNA, we found EBP mutations in all probands. We confirmed the functional significance of two missense alleles by expressing them in a sterol-delta8-isomerase-deficient yeast strain. Our results indicate that defects in sterol-delta8-isomerase cause CDPX2 and suggest a role for sterols in bone development.

Adolescent↗