An efficient preparation of TIPS-halofluoropropyne and its application to the diastereoselective synthesis of propargylic fluorohydrins
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Biomedical subjects
Publications and source records attributed to Y Lan.
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Plasma retinol-binding protein (RBP) concentrations have been suggested as surrogate indicators for plasma retinol concentrations in the assessment of vitamin A status in less technologically developed settings. Plasma RBP was measured by radial immunodiffusion and plasma retinol by high performance liquid chromatography in a cross-sectional study of 900 pregnant women at the Queen Elizabeth Central Hospital, Blantyre, Malawi. The Spearman correlation coefficient between plasma RBP and retinol concentrations was 0.95 (p<0.0001). By linear regression, 0.70 micromol l(-1) retinol was equivalent to 21.1 mg l(-1) RBP. With these cut-off points for defining vitamin A deficiency, there was high concordance between categorical descriptions of deficiency using retinol and RBP by chi-square analysis (p<0.001). Measurement of plasma RBP by radial immunodiffusion is simple, inexpensive, and does not require expensive instrumentation. Plasma RBP concentrations measured by radial immunodiffusion are highly correlated with plasma retinol and can be used as a simple surrogate measure for vitamin A concentrations in large field studies.
BACKGROUND: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear. OBJECTIVE: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness). DESIGN: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk. RESULTS: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins. CONCLUSIONS: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.
OBJECTIVE: To study trabecular meshwork induced glucocorticoid response protein (TIGR) gene mutation in Chinese patients with primary open-angle glaucoma (POAG). METHODS: (1) From 70 patients with POAG and 20 normal controls, TIGR gene which consists of three exons (7 pairs of primer) was amplified by polymerase chain reaction (PCR). The mutation of PCR amplification products was evaluated by single-stranded conformation polymorphism (SSCP). (2) After the above PCR products were cloned into the PT-Adv vectors, the construction plasmids were evaluated by Ecor I endonuclease and direct sequence was performed. RESULTS: (1) With SSCP screening, the single strand band abnormality was found in the middle fragments of the third exon (the sixth pair of primer) of TIGR gene in two patients with POAG, but the control group appeared normal. (2) The two samples using clone and sequence showed that one had a 'GAT'- to- 'AAT' transition at amino acid Asp 338 Asn mutation; the base sequence of another one had no change. These results suggested that mutation rate of TIGR gene in Chinese patients with POAG be only 1.4% (1/70), being lower than that of foreigners. CONCLUSION: The pathogenesis of Chinese patients with POAG may be related with TIGR gene mutation, but the mutation rate is lower than that in foreigners, indicating that the mechanism of POAG in China and aboard is different and the pathogenesis of POAG has difference in regions and races.
OBJECTIVE: To understand the relationship between vegetable intake and risk of lung cancer in the Tin Corporation (YTC) miners in Yunnan. METHODS: The reproducibility and validity of frequency of vegetable intake in Food Frequency Questionnaire (FFQ) were studied and the correlations between different vegetable intake and frequency and lung cancer relative risk among high risk population of lung cancer by Chi-square, single- and multi-Cox regression were analyzed. RESULTS: Results showed that the reproducibility and validity of wax gourd, cucumber, spinach, wild celery, fresh bush pepper, fresh soybean, sweet potatoes, asparagus, fresh bamboo shoot were good (r = 0.20 - 0.33, P < 0.05); There were significantly different incidences of lung cancer in different frequencies of wax gourd, cucumber, wild celery, fresh bush pepper out of 11 vegetables intake, and also in different total vegetable intakes (chi(2) = 8.83 - 30.64, P < 0.05). 11 vegetables and total vegetable intake were significantly negatively correlated with risks of lung cancer (RR < 1, P < 0.05). Only 2 vegetable frequencies were negatively correlated with risk of lung cancer by adjusting confounders such as age, occupational history, and smoking (P < 0.05). CONCLUSION: This suggested that vegetables intake may have a role in decreasing the incidence of lung cancer.
PURPOSE: To investigate the results of the interferon-gamma (IFN-gamma) gene transfer and transient expression in human Tenon's capsule fibroblast in vitro in order to find a way to gene therapy in vivo. METHOD: Using LipofectAMINE, IFN-gamma gene was transferred in human Tenon's capsule fibroblasts with plasmid pcDNA3 IFN-gamma. Its mRNA transcription and protein expression were determined by RT-PCR and flow cytometry assay respectively. RESULT: The human Tenon's capsule fibroblasts transferred the IFN-gamma gene can express the IFN-gamma in transcription and protein level transiently. CONCLUSION: IFN-gamma gene can be transferred successfully and expressed expressed efficiently in human tenon's capsule fibroblast in vitro.
OBJECTIVE: To culture astrocytes of optic nerve and to establish the cell lines for further study of healing process after optic nerve trauma. METHODS: Optic nerve astrocytes of infantile and adults with sudden death were cultured by tissue inoculation or tissue digestion with 0.25% Trypsin and 0.06% EDTA. The second and fourth passage cells were stained with HE and anti-GFAP, S-100 protein, Vimentin, and CD34 antibodies. RESULTS: The trypsinized astrocytes of infantile optic nerve reached confluence in 7 days, but the astrocytes of adults weren't successfully cultured. The cultured cells were in polygonal shape with processes; the cytoplasm was abundant and pink; the cells had light-blue nuclei. These cells were positive in GFAP, S-100 protein and vimentin staining, and negative in CD34 staining. CONCLUSIONS: The results showed that astrocytes of infantile optic nerve can be successfully cultured and trypsinization is a better method than tissue inoculation. The culture of infantile astrocytes is easier than that of adult astrocytes. Immunohistochemistry were used to determine the source and type of those cultured cells.
PURPOSE: To study the effect of human IFN-gamma on in vitro cultured human fibroblasts from Tenon's capsule. MATERIALS AND METHODS: The effect of different concentrations of human IFN-gamma and mitomycin-C (MMC), 5-fluorouracil (5-Fu) on cultured human Tenon's capsule fibroblasts (HTCF) was measured using a MTT [3-(4, 5-dimethylthiazo-2-yl)]-2, 5-diphenyltetrazolium bromide; Thiazolyl blue) colorimetric assay. The results were analyzed using ANOVA of the statistical package for social sciences (SPSS) 9.0 version. The difference was considered to be significant if P < 0.05. RESULTS: The effects of MMC and 5-Fu on the growth of HTCF were negative, while the effects of IFN-gamma on the growth of HTCF were both negative (10(2)-10(4) units/ml in two experiments) and positive (10(6), 10(5), 10 units/ml in two experiments). The inhibition rate of MMC ranged from 5.73% to 46.9%, which was similar to the inhibition rate of 5-Fu ranged from 12.49% to 38.92% (P = 0.351). The inhibition rate of IFN-gamma in two experiments was smaller than MMC and 5-Fu (P < 0.05). CONCLUSION: IFN-gamma has bifunctional effect (both enhancement and inhibition) on proliferation of cultured HTCF. The antiproliferative effect of IFN-gamma was weaker than MMC and 5-Fu. Further study has to be carried out to document the inhibition of scar formation of filtration bleb by IFN-gamma and the molecular mechanisms of its bifunctional effect on HTCF proliferation.
OBJECTIVE: To study the clinical application of Hopkins rod-lens coupled with gasping forceps sheaths in the extraction of tracheobronchial foreign bodies. METHODS: Sixty-two patients with tracheobronchial foreign bodies were operated on with Hopkins rod-lens coupled with grasping forceps sheaths under direct telescopic view or TV watching. High frequency jet ventilation was used and BPs ECGs SaO2 were monitored in all cases. RESULTS: Sixty-two patients were all successfully operated on. The extraction was primarily successful in 90% of the cases; and secondarily successful in 7% of the cases. No death and serious complication occurred. CONCLUSION: Compared with conventional bronchoscopic foreign body extraction, this new instrument and technique make it possible for the operator to clamp and extract foreign body under direct telescopic view or TV watching. It has increased the accuracy and safety of bronchoscopic extraction of tracheobronchial foreign bodies.
OBJECTIVE: To investigate the change of gastric solid emptying at different stages in diabetic rats, and the effect of Chinese traditional medicine(CTM) on gastric emptying. METHODS: 40 Wistar rats were randomly divided into three groups: CTM treated diabetic(15 rats), untreated diabetic(15 rats) and control(10 rats). Diabetes was induced by i.p. of streptozotocin(STZ), 65 mg/kg. CTM, 3.75 g/kg daily (consisting of Dan shen, Fu Ling mainly which functioned as Huo xue hua yu and Bu shen) was administrated in treated diabetic rats. Blood glucose and body weights were measured weekly. 12 and 24 weeks after induction of diabetes, gastric emptying was examined with scintigraphy for 240 min (30 min interval). A test meal (42 kJ) labeled with 99mTc-SC(2.96 x 10(5) Bq) was provided. RESULTS: (1) There were no significant differences in total gastric retention rate and T 1/2 among three groups at 12 weeks. (2) The lag phase of total stomach in DM-B was (41.56 +/- 8.39) min, shorter than in control's (67.50 +/- 9.09) min, (P < 0.05). (3) The proximal gastric retention rate of 12-week diabetes at 90 min were (38.2 +/- 6.2)% (vs control, P < 0.01), (16.0 +/- 7.9)% (vs control, P < 0.01), and (61.9 +/- 3.5)%; and of 24-week at 120 min were (21.3 +/- 6.8)% (vs control, NS), (48.5 +/- 8.2)% (vs control, P < 0.05, vs treated diabetes, P < 0.01), (28.3 +/- 6.4)% in treated, untreated and control group respectively. (4) There was negative correlation between blood glucose and gastric retention rate (r = -0.62, P < 0.05). CONCLUSION: (1) The proximal gastric solid emptying was impaired in diabetic rats, there was significantly accelerated in 12-week and slowed down in 24-week compared with control. (2) CTM could modify these impairment. (3) Hyperglycemia had positive correlation to gastric emptying in animal model, which might explain the clinic presentations of patients with diabetes in early stage.
Fusion proteins between whole antibodies (Abs) and cytokines (immunocytokines) such as interleukin 2 have shown efficacy in several mouse tumor models despite a circulating half-life that is significantly shorter than that of the original Ab. We have examined the potential mechanisms responsible for clearance and shown that an important factor is enhanced binding to Fc receptor (FcR). Improvements in the half-lives of two different immunocytokines were made by changing the isotype of the human heavy chain C region from IgG1 or IgG3 to those with reduced binding to FcR, e.g., IgG4. The same effect could also be achieved through site-directed mutagenesis of the FcR binding site in the IgG1 H chain. In vitro studies using mouse J774 FcR-expressing cells showed increased binding of interleukin 2-based immunocytokines, relative to their corresponding Abs, and that this was reversed in those fusion proteins made with IgG4 or mutated IgG1 H chains. All of the fusion proteins showing reduced FcR binding also had reduced Ab-dependent cellular cytotoxicity activity, as measured in 4-h chromium release assays. A complete loss of complement-dependent cytotoxicity activity was seen with an IgG4-based immunocytokine derived from an IgG1 Ab with potent activity. Despite these reduced effector functions, the IgG4-based immunocytokines with extended circulating half-lives showed equivalent (in the case of severe combined immunodeficiency mouse xenograft models) or better (in the case of syngeneic models) efficacy in mouse tumor models than the original IgG1-based molecules. These novel immunocytokines may show improved efficacy in therapeutic situations where T cell- rather than natural killer- or complement-mediated antitumor mechanisms are involved.
The mammalian cochlea contains an invariant mosaic of sensory hair cells and non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster. The sensory epithelium in the mammalian cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a single row of inner hair cells and three rows of outer hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends the length of the cochlear duct. Previous results suggest that determination of cell fates in the cochlear mosaic occurs via inhibitory interactions between adjacent progenitor cells (lateral inhibition). Cells populating the cochlear epithelium appear to constitute a developmental equivalence group in which developing hair cells suppress differentiation in their immediate neighbours through lateral inhibition. These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates. Here we show that genes encoding the receptor protein Notch1 and its ligand, Jagged 2, are expressed in alternating cell types in the developing sensory epithelium. In addition, genetic deletion of Jag2 results in a significant increase in sensory hair cells, presumably as a result of a decrease in Notch activation. These results provide direct evidence for Notch-mediated lateral inhibition in a mammalian system and support a role for Notch in the development of the cochlear mosaic.
The orientation of the particles in an electrorheological fluid under an electric field has been studied. Triglycine sulfate (TGS)-wax mixtures were applied in this study. Here the TGS particles are in the ferroelectric phase with spontaneous polarization p(s) in the <010> direction at below the Curie temperature T(C) and become paraelectric without a permanent electric moment at above T(C). By measuring x-ray-diffraction intensities of TGS/wax samples under an electric field at below and above T(C), respectively, it is found that the particles with spontaneous polarization turn their p(s) vectors to the direction of the external electric field in addition to forming chains or columns. However, the particles without permanent moment only form chains or columns, in which no preferred orientation of the particles can be observed. The preferred orientation degree is determined by comparing the diffraction intensity in these two cases.
Although an elevated sodium concentration in human milk is suggested to be an indicator of mastitis, it is unclear whether elevated sodium concentrations are associated with immunological and inflammatory mediators in human milk. We conducted a cross-sectional study to evaluate the relationships between elevated breast milk sodium concentrations and levels of lactoferrin, lysozyme, secretory leukocyte protease inhibitor (SLPI), interleukin-8 (IL-8), and RANTES (regulated on activation normal T cell expressed and secreted) in human milk at 6 weeks postpartum in 96 lactating women in Blantyre, Malawi. Mastitis, as indicated by an elevated breast milk sodium concentration, was present in 15.6% of the women. Women with and without mastitis had respective median levels of other factors as follows: lactoferrin, 1,230 versus 565 mg/liter (P < 0. 0007); lysozyme, 266 versus 274 mg/liter (P = 0.55); SLPI, 76 versus 15 microg/liter, (P < 0.0002); IL-8, 339 versus 25 ng/liter (P < 0. 0001); and RANTES, 82 versus 3 ng/liter (P < 0.0001). Elevated sodium concentrations in breast milk are associated with an increase in levels of some immunological and inflammatory factors in breast milk.
Human milk contains important immunological factors that protect the breast from infection and are thought to protect infants from infection, including human immunodeficiency virus (HIV) infection. Human milk immunological factors have not been well characterized in HIV-infected lactating women. Lysozyme, secretory leukocyte protease inhibitor (SLPI), sodium (an indicator of mastitis), and HIV were measured in breast milk of 334 HIV-infected women at 6 weeks postpartum. Women with mastitis, as indicated by elevated breast milk sodium concentrations, had higher median levels lysozyme (290 vs 221 mg/L, p < 0.04), SLPI (38 vs 19 mg/L, p < 0.0001) and HIV (920 copies/mL vs undetectable, p < 0.0001) compared with women without mastitis. Lower total plasma carotenoid levels (p < 0.02) and higher maternal HIV load (p < 0.006) by quartile were risk factors for mastitis. Mastitis, as indicated by elevated breast milk sodium levels, is associated with high concentrations of immunological factors and higher HIV load in breast milk.
OBJECTIVE: To characterise the major plasma carotenoids in pregnant women with and without HIV infection attending antenatal clinic in Blantyre, Malawi. DESIGN: A cross sectional study. SETTING: Antenatal clinic of Queen Elizabeth Central Hospital, Blantyre, Malawi. SUBJECTS: Nine hundred women (697 HIV-positive and 203 HIV-negative women) in their second trimester of pregnancy. MAIN OUTCOME MEASURES: Plasma carotenoid levels as related to HIV status and level of disease progression. RESULTS: There were no significant differences in plasma carotenoid levels between HIV-positive and HIV-negative women. Median (25th, 75th percentiles) plasma levels of carotenoids for all women in the study were alpha-carotene, 0.040 (0.23, 0.071) mumol/L; beta-carotene, 0.350 (0.192, 0.595) mumol/L; beta-cryptoxanthin, 0.050 (0.029, 0.091) mumol/L; lutein/zeaxanthin 0.646 (0.426, 0.976) mumol/L; lycopene, 0.088 (0.055, 0.138) mumol/L, and total carotenoids 1.321 (0.884, 1.874) mumol/L. Mothers had higher mean plasma concentrations of alpha-carotene (p < 0.04), beta-carotene (p < 0.0001), lutein/zeaxanthin (p < 0.0001), and total carotenoids (p < 0.0001) in the wet season than the dry season. No seasonality was observed for beta-cryptoxanthin, lycopene, or retinol. CONCLUSION: This study suggests that pregnant women with and without HIV infection in Blantyre, Malawi have relatively low plasma carotenoid levels and poor dietary intake of provitamin A carotenoids.
IL-12 is a complex cytokine in both its structure and its range of biologic activities. Fusions of this heterodimeric molecule with an intact antitumor Ab were made to test the feasibility and efficacy of targeting IL-12 to tumors to elicit a local immune response. Fusion proteins composed of the human p35 and p40 subunits had IL-12 bioactivities that were nearly as potent on human immune cells as the rIL-12 standard, but were inactive on mouse cells. Hybrid IL-12 fusion proteins composed of mouse p35 and human p40, fused to Ab, were capable of inducing IFN-gamma, but were much less active on mouse spleen cells than a mouse IL-12 standard. Despite this relatively low activity, the hybrid fusion protein was as effective in a SCID mouse model as a fully active Ab-IL-2 fusion protein in eliminating established pulmonary metastases of CT26 colon carcinoma. Specific targeting of a human IL-12 fusion protein to metastatic prostate carcinoma xenografts was also shown to be effective in SCID mice transplanted with human lymphocyte-activated killer cells. These results demonstrate the importance of directing this potent cytokine to the tumor microenvironment and suggest an important alternative to systemic IL-12 administration or gene therapy for increasing its therapeutic index.
The Slug gene encodes a zinc finger protein, homologous to the product of the Drosophila Snail gene, that is implicated in the generation and migration of both mesoderm and neural crest cells in several vertebrate species. We describe here the cloning and genetic analysis of the mouse Slug (Slugh) gene. Slugh encodes a 269-amino-acid protein the shares 92% amino acid identity with the product of the chicken Slug gene. We have characterized Slugh gene expression during early mouse embryogenesis by whole mount in situ hybridization of Slugh mRNA and through detection of beta-galactosidase expression from an in-frame SlughIacZ allele generated through homologous recombination. Slugh expression is first detected in extraembryonic mesoderm and is later detected in many mesodermal subsets, although it is not detected in the primitive streak. In contrast to many other vertebrates, the mouse Slug gene is not expressed in premigratory neural crest cells but is expressed in migratory neural crest cells. Analysis of a targeted null mutation that deleted all Slugh coding sequences revealed that Slugh is not required for mesoderm formation or for neural crest generation, migration, or development in mice. These results indicate that neither the expression pattern nor the biological function of the Slug gene is conserved among all vertebrates. These data also raise interesting questions about the regulation of neural crest generation, which is one of the distinguishing characteristics of the vertebrate subphylum.