PubMed Health⌕ Search

Biomedical subjects

G W Lin

Publications and source records attributed to G W Lin.

At least 19 recordsLinked to original sources
PubMed2001

Genetic modification of hematopoietic progenitor cells for combined resistance to 4-hydroperoxycyclophosphamide, vincristine, and daunorubicin.

AIM: To investigate whether human peripheral blood hematopoietic progenitor cells (PBPC) modified with human aldehyde dehydrogenase class-3 gene (ALDH-3) and multidrug resistance gene 1 (MDR1) would increase chemotherapy resistance to 4-hydroperoxycyclophosphamide (4-HC) and -glycoprotein effluxed drugs. METHODS: A bicistronic retroviral vector G1Na-ALDH3-IRES-MDR1 cDNA was constructed and used to transfect the packaging cell lines PA317 by electroporation. CD34+ PBPC were isolated with a high-gradient magnetic cell sorting system (MACS), and then were transfected with supernatant of retrovirus containing human ALDH-3 and MDR1 cDNA. PCR, RT-PCR, Southern blot, Northern blot, FACS, and MTT assay were used to evaluate the transfection and expression of the transgene in target cells. RESULTS: The bicistronic retroviral vector construction was verified by PCR and restriction endonuclease analysis. Dual drug resistance genes were integrated into the genomic DNA of CD34+ PBPC and expressed efficiently. The efficiency of gene transfection in CD34+ PBPC was tested to be 18 % on colonies. Nested PCR and Neor rescue assay indicated that no helper virus was present in this system. Compared with the untransduced cells, transgene recipient cells conferred 4.5-fold resistance to 4-HC, 6.6-fold and 7.8-fold resistance to P-glycoprotein effluxed drug, vincristine and daunorubicin, respectively. CONCLUSION: Efficient transduction of two different types of drug resistance genes into human peripheral blood hematopoietic progenitor cells and the co-expression may decrease cumulative myelosuppression of combination chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

[A bicistronic retroviral vector containing MGMT and MDR1 drug resistance genes transfer into human umbilical cord blood CD34+ cells to improve combination chemotherapy tolerance].

To explore whether human umbilical cord blood hematopoietic progenitor cells transduced with human O6-methylguanine-DNA-methyltransferase (MGMT) and multidrug resistance gene (MDR1) increase resistance to 1,3-Bis(2-Chloroethy1)-1-Nitrosourea (BCNU) and P-glycoprotein effluxed drugs, the present authors obtained a full length cDNA fragment encoding MGMT from liver tissue of a patient with cholelithiasis by RT-PCR. A bicistronic retroviral vector G1Na-MGMT-IRES-MDR1 cDNA was constructed and transfected the packaging cell lines GP + E86 and PA317 by electric performation method, using the medium containing VCR and BCNU for cloning selection and ping-ponging supernatant infection between ecotropic producer clone and amphotropic producer clone, cord blood CD34+ cells were enriched with a high-gradient magnetic cell sorting system (MACS), and then transfected repeatedly with supernatant of retrovirus containing human MGMT and MDR1cDNA under stimulation of hemapoietic growth factors. PCR, RT-PCR, Southern blot, Northern blot, Western blot, FACS and MTT assay were used to evaluate the transfer and expression of the double genes in cord blood CD34+ cells. The cDNA encoding MGMT was verified by DNA sequencing and the bicistronic retroviral vector was confirmed by restriction endonuclease analysis. The purity of cord blood CD34+ cells was approximately 92% and recover rate was 75%, the highest titer of recombinant amphotropic retrovirus in the supernatant was up to 5.8 x 10(5) cfu/ml. The efficiency of gene transduction was 18% and 20% tested by colony formation and PCR, respectively. No helper virus was found by both nested PCR and rescue assay. The results showed that dual drug resistance genes have been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The MTT analysis showed a 4.5 to 7.8-fold increase of resistance of transducted cells to BCNU and P-glycoprotein effluxed drug as compared with the nontransduced cells. This study provided a foundation for ameliorating combination chemotherapy toxicity in tumor clinical trial.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

[POEMS syndrome--a report of eight cases and review of literature].

POEMS syndrome is an unusual multisystem disorder associated frequently with polyneuropathy, organomegaly, endocrinopathy, M-protein change and skin lesion. POEMS is the acronym the above-mentioned clinical manifestations. The patients who were diagnosed must have at least three of the manifestations; polyneuropathy and plasmagenic disorders are almost always present. We present in this paper eight patients, their clinical symptoms, laboratory tests and treatment were analysed and discussed.

Adult↗
PubMed1990

Gestational ethanol consumption on tissue amino acid levels: decreased free histidine and tryptophan in fetal tissues with concomitant increase in urinary histamine excretion.

The effects of ethanol consumption during pregnancy on maternal, placental, and fetal tissue amino acid levels and metabolism were investigated. Pregnant Sprague-Dawley rats were given 35% ethanol-calorie liquid diet, ad libitum, from gestation day 7 to 21. Control rats were pair-fed with isocaloric sucrose substituted for ethanol. Ethanol consumption decreased fetal body weight and increased placental weight. Twenty-four amino acids were determined in six tissues (maternal plasma and liver, placenta, fetal plasma, liver, and brain) by HPLC with orthophthalaldehyde derivatization. The effects of ethanol on free amino acid levels differed from tissue to tissue. In general, ethanol affected more amino acids in maternal plasma, fetal plasma, and liver. Maternal liver, placenta, and fetal brain amino acids were more resistant to ethanol effect. Two essential amino acids, histidine and tryptophan, were consistently decreased in fetal tissues by maternal ethanol consumption. The values (ethanol vs. control, nmole/ml or g, mean +/- SEM, N = 20) of fetal plasma, liver, and brain for histidine were 51.8 +/- 6.0 vs. 85.3 +/- 4.5 (p = 0.001), 269.0 +/- 26.4 vs. 503.7 +/- 47.3 (p = 0.0004), and 117.9 +/- 7.7 vs. 154.6 +/- 8.7 (p = 0.0055), respectively; and for tryptophan were 105.7 +/- 3.1 vs. 132.2 +/- 4.1 (p = 0.0001), 128.8 +/- 3.7 vs. 144.3 +/- 6.0 (p = 0.0407), and 83.4 +/- 7.2 vs. 103.6 +/- 3.2 (p = 0.0198), respectively. Histidine was also decreased in placenta by ethanol (138.1 +/- 6.6 vs. 189.1 +/- 11.8 nmole/g, p = 0.0014).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

[Evaluation of erythrocyte basic ferritin in the diagnosis of anemia].

Erythrocyte basic ferritin (EF) concentration was determined in 64 normal subjects, 123 patients with anemia and 12 patients with leukopenia and thrombocytopenia. There was a significant difference between males and females. Other iron indices, including plasma iron (PI), total iron binding capacity (TIBC), zinc protoporphyrin (ZnPP) and plasma ferritin (PF) were also determined in all the subjects and bone marrow iron stain was determined in the 135 patients. The lowest EF concentration was seen in patients with iron deficiency anemia, being significantly lower than that in normal subjects. EF concentration in patients with iron deficiency erythropoiesis was also lower than that in normal subjects and at the same time significantly different from that in patients with iron deficiency anemia. EF concentration increased prior to PF concentration in patients with iron deficiency anemia who had been treated for a period of 1-8 weeks. EF concentration in patients with anemia of chronic diseases had a significant difference as compared with that in normal subjects and in patients with iron deficiency anemia, but EF concentration in those patients who were accompanied by iron deficiency was similar to that in patients with simple iron deficiency anemia. EF concentration in some iron overloaded patients (aplastic anemia, megaloblastic anemia, MDS etc.) was significantly higher than that in normal subjects. It was demonstrated that there was a good correlation between EF concentration and bone marrow sideroblastic iron in the rank correlation analysis of the iron indices in 135 patients (rs 0.893, P less than 0.01). PF concentration had the best correlation with marrow iron (rs 0.948, P less than 0.01).

Adolescent↗
PubMed1989

Effect of ethanol and vitamin B6 deficiency on pyridoxal 5-phosphate levels and fetal growth in rat.

The effects of chronic ethanol consumption and dietary vitamin B6 levels on tissue pyridoxal 5-phosphate (PLP) contents and rat fetal development were investigated. Pregnant Sprague-Dawley rats were given 35% ethanol-calorie liquid diet with either adequate B6 (1.7 mg/liter) or deficient B6 (0.17 mg/liter), ad libitum, from gestation days 7 to 21. Control groups (adequate control and deficient control) were pair-fed with isocaloric sucrose substituted for ethanol. Rats were killed on gestation day 21. Ethanol groups had smaller fetuses than control groups, regardless of their dietary B6 levels. However, in B6 deficiency, ethanol affected fetal weight more severely than in B6 adequate state. Tissue PLP levels were determined by radioenzymatic method. In B6 deficiency, ethanol feeding reduced maternal liver PLP by 22%. PLP in other tissues were not affected by ethanol. These results confirmed that chronic alcohol consumption affected fetal growth and also provided evidence that B6 deficiency exacerbated ethanol effect.

Animals↗
PubMed1989

Functional relationships and structural determinants of two bacteriophage T4 lysozymes: a soluble (gene e) and a baseplate-associated (gene 5) protein.

Lysozymes have proved useful for analyzing the relation between protein structure and function and evolution. In bacteriophage T4, the major soluble lysozyme is the product of the e gene, gpe (gene product = gp). This lysozyme destroys the wall of its host, Escherichia coli, at the end of infection to release progeny particles. Phage T4 contains two additional lysozymes that facilitate penetration of the baseplates into host cell walls during adsorption. At least one of these, a 44-kD protein, is encoded by gene 5. We show here that a segment of the gp5 lysozyme amino acid sequence, deduced from the DNA sequence of gene 5, is remarkably similar to that of the T4 gene e lysozyme. Both T4 lysozymes are somewhat similar to the lysozyme of the Salmonella phage P22, but there is little significant DNA sequence homology among the two T4 lysozyme genes and the P22 lysozyme gene. We speculate that these lysozymes are adapted to differences in the composition of the cell walls of E. coli and S. typhimurium. The cloned gene 5 of the phage T4 directs synthesis of a 63-kD precursor protein that is approximately 19 kD larger than the gene 5 protein isolated from baseplates. Gp5 first associates with gp26 to form the central hub of this structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1984

Effect of ethanol feeding on the urinary histamine level of the pregnant rat.

The influence of ethanol feeding during pregnancy on histamine excretion was studied. Pregnant Sprague-Dawley rats (N = 5) were fed a liquid diet containing 30% ethanol-derived calories from gestation-day 7 to 21; control rats (N = 5) were pair-fed with isocaloric sucrose substituted for ethanol. Twenty-four hour urines were collected for histamine analysis. Rats were killed on day 21 of gestation. Food and ethanol intakes averaged 260 kcal and 11 g/kg/day, respectively. No differences were found between ethanol and control rats in maternal weight gain, litter size or in fetal and placental weights. Although urinary histamine increased in all rats with the advance of pregnancy, on day 16, ethanol rats excreted significantly more (47%) than the controls (199.1 +/- 33.9 vs 135.5 +/- 51.4 ug/24 hr); on day 20, it was 123% more (534.6 +/- 114.4 vs 239.5 +/- 99.3 ug/24 hr). Ethanol enhanced urinary histamine did not reflect the histamine content or histidine decarboxylase activity of fetal liver, presumed site of histamine formation; its physiological significance is discussed.

Animals↗
PubMed1981

Fetal malnutrition: a possible cause of the fetal alcohol syndrome.

The effects of ethanol ingestion during pregnancy on total folate levels in fetal tissues and on the concentrations of free amino acids in fetal and maternal plasma were examined in the rat. No differences were observed between the ethanol-fed and the control groups in total folates in fetal brain and liver. However, the concentration of fetal plasma histidine was reduced by 50% as a result of maternal ethanol consumption; the maternal plasma histidine level was not affected. It is suggested that fetal malnutrition in an essential amino acid, histidine, could impair fetal protein synthesis producing the fetal alcohol syndrome.

Absorption↗
PubMed1981

The effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat.

The distribution of 14C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed.

Amino Acids↗
PubMed1980

Distribution of ethanol between blood and dorsal subcutaneous air of the rat and the feasibility of using this distribution coefficient to estimate blood ethanol.

Equilibration of ethanol between dorsal subcutaneous air and blood is rapid, a steady state being already present in 60 seconds after air injection in the rat. The mean in vivo partition coefficient (blood/air) is 2,875, the linear regression coefficient having a standard error of 112, the high F value of this regression indicating the linearity and reliability of the estimates of calculated blood ethanol; the variance arises mainly from temperature variance of the air bleb. Although the concentration of alcohol in the blood must remain the standard of comparison, the production of the air bleb and its subsequent serial sampling is a virtually noninvasive technique which yields an almost immediate result at a sensitivity and specificity greater than that from the usual enzymatic determination of ethanol in blood.

Air↗
PubMed1980

Significance of the gastrointestinal tract in the in vivo metabolism of ethanol in the rat.

The rate of ethanol metabolism and the extrapolated zero time blood ethanol concentration (C0) were compared in naive and ethanol-fed rats following intracardiac or ingastric administration of a test dose of ethanol (3 g/kg). If the gastrointestinal tract is involved in the disposition of ethanol, intragastric administration should result in a lower C0 and a faster overall rate of metabolism than intracardiac administration, since part of the dose would be metabolized in the gastrointestinal tract without having been absorbed and thereby entering the blood. However, no significant differences were observed in C0. The rate of metabolism was substantially higher in the ethanol-fed rats, but was uninfluenced by route of administration. Thus, the gastrointestinal tract plays no significant role in the metabolism of ethanol.

Alcohol Drinking↗