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Biomedical subjects

S Zheng

Publications and source records attributed to S Zheng.

13 recordsLinked to original sources

Clinical trial on termination of early pregnancy with RU486 in combination with prostaglandin.

Termination of early pregnancy was performed in 1572 healthy women with RU486 (mifepristone, 600mg orally once), followed 36-60 hours later by administration of methyl ester of dl-15-methyl-PGF2 alpha (PG05, 1mg vaginal suppository). Complete abortion was accomplished in 91.2% (1433/1571), incomplete abortion in 4.8% (76/1571), and continued pregnancy in 3.9% (62/1571). The time elapsed between RU486 intake and complete expulsion was 2.4 +/- 1.3 days. Expulsion took place on the third day in 935 women (72%), and on the 4th day in 273 women (21.0%). Uterine bleeding occurred on the second or third day after RU486 intake in 1256 women (88.8%), and lasted 11.7 +/- 6.4 (SD) days, range 2-55 days. One subject had blood transfusion due to excessive bleeding. The main side effects were nausea/vomiting (22.3%), abdominal pain (10.2%), headache/dizziness (4.1%) and diarrhea (2.8%). Fatal side effects have not been reported in this study. About 73% of subjects with complete abortion assessed the treatment as good to excellent. Even in the failed cases, 25-42% of subjects considered the treatment as good. Further studies are needed to determine the optimal dose of the RU486 regimen. It should be emphasized that the treatment must be used under close medical supervision in order to monitor the uterine bleeding.

Abortion, Incomplete

Physical map of the genome of Rhodobacter capsulatus SB 1003.

A map of the chromosome of Rhodobacter capsulatus was constructed by overlapping the large restriction fragments generated by endonucleases AseI and XbaI. The analyses were done by hybridization of single fragments with the restriction fragments blotted from pulsed-field gels and by grouping cosmids of a genomic library of R. capsulatus into contigs, corresponding to the restriction fragments, and further overlapping of the contigs. A technical difficulty due to a repeated sequence made it necessary to use hybridization with cloned genes and prior knowledge of the genetic map in order to close the physical circle in a unique way. In all, 41 restriction sites were mapped on the 3.6-Mb circular genome and 22 genes were positioned at 26 loci of the map. Cosmid clones were grouped in about 80 subcontigs, forming two groups, one corresponding to the chromosome of R. capsulatus and the other corresponding to a 134-kb plasmid. cos site end labeling and partial digestion of cosmids were used to construct a high-resolution EcoRV map of the 134-kb plasmid. The same method can be extended to the entire chromosome. The cosmid clones derived in this work can be used as a hybridization panel for the physical mapping of new genes as soon as they are cloned.

Blotting, Southern

Immunolocalization and expression of functional and nonfunctional cell-to-cell channels from wild-type and mutant rat heart connexin43 cDNA.

The carboxyl terminal cytoplasmic domain of distinct gap junction proteins may play an important role in assembly of functional channels as well as differential responsiveness to pH, voltage, and intracellular second messengers. Oligonucleotide-directed site-specific mutagenesis in a paired Xenopus laevis oocyte expression system was used to examine the expression of mRNAs encoding wild-type and carboxyl terminal mutant connexin43 (Cx43) proteins. Oocytes were stripped, injected with mRNA or distilled water (dH2O), preincubated for 16-20 hours, and then paired for 5-10 hours; this process was followed by electrophysiological recording using the dual voltage-clamp technique. Initial experiments compared the relative junctional conductances (Gjs) in oocyte pairs expressing Cx43 (382 amino acid residues) and two truncated mutants lacking most or a portion of the cytoplasmic carboxyl terminal. The shortest mutant (M241) contained 240 amino acid residues and was devoid of all phosphorylatable serine residues in the cytoplasmic tail; its length approximated the length of liver connexin26. The longest mutant (M257) tested contained 256 amino acid residues, including two serine residues. Oocyte pairs expressing M241 yielded a Gj similar to that of oocytes injected with dH2O, whereas M257 yielded a Gj similar to that of oocytes injected with Cx43. Immunoprecipitation studies showed that Cx43, M257, and M241 proteins were readily detectable in oocytes injected with their respective mRNAs, indicating that the lack of Gj observed with the M241 mRNA was not due to reduced translation. Immunocytochemical studies revealed that wild-type and both truncated mutants were localized to the area of cell-to-cell contact between the paired oocytes, indicating that protein targeting to the membrane was not inhibited in oocytes injected with M241 mRNA. Oocyte pairs expressing mutants in which serine residues were replaced with nonphosphorylatable amino acids (serine codon No. 255 AGC was converted to GCC, alanine, designated as M255S----A, and serine codon No. 244 AGC was converted to GGC, glycine, designated as M244S----G) showed Gjs similar to M257, indicating that these serine residues and, by inference, their phosphorylation state are not critical for expression of functional channels. The importance of the length of the carboxyl terminus was assessed by comparing the Gjs in a series of mutants that were intermediate in length between M257 and M241. Gradual shortening of the carboxyl terminus produced a gradual reduction of Gj relative to M257. However, simple deletion of amino acid residues 241-257 from the wild-type Cx43 did not affect Gj relative to M257.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Liposome-encapsulated hemoglobin processing methods.

An effective and safe red blood cell substitute is being developed based on double emulsion/evaporation techniques followed by high pressure homogenization to form liposome-encapsulated hemoglobin (LEH). Formulations are made up of hydrogenated phosphatidylcholine (PC, soy or egg), cholesterol, phosphatidylinositol (PI), and alpha-tocopherol in a molar ratio of 1:1:0.2:0.02, respectively. Resulting LEH-encapsulated hemoglobin (Hb) concentrations are greater than 80% of precursor Hb solutions. Met-Hb generation accompanying LEH processing appears to be small with only a 3% increase for encapsulated over precursor. These results correspond to an oxygen content for an LEH suspension sample (50% by volume LEH) of 15 volume% oxygen. Oxygen affinity and cooperativity values for LEH suspensions appear to be near the normal values expected for whole blood. The viscosity of LEH suspension samples (50% by volume LEH in phosphate-buffered saline containing 7.5 wt% albumin) were slightly higher than that of whole blood. The effect of shear rate on leakage of encapsulated Hb from LEH was small, i.e. 0.5% or less. Nearly total isovolemic exchange transfusion using a cannulated rat model demonstrates efficacy of LEH suspension samples. There appears to be no difference in rat internal organ weights between rats exchanged with control compared to rats exchanged with LEH. Circulation half-life following 50% isovolemic exchange-transfusion is about 15 to 18 hours.

Animals

[Effects of four adrenergic drugs on electroacupuncture analgesia].

The role of central nor-epinephrine (NE) in electroacupuncture (EA) analgesia is a controversial question., it is probably due to the complication of adrenergic receptors. The present results show: (1) Clonidine 30 micrograms/2ml/kg ip had no significant effect on the pain threshold, but decreased the analgesic effect of EA. Clonidine 1.5 and 3 micrograms were injected into the lateral cerebral ventricles. After 45 minutes, the analgesic effect of EA was lowered as compared with the saline controls respectively. (2) Yohimbine had no significant effect on the basal pain threshold, but (icv Yoh 50 micrograms) elevated the analgesic effect of EA. (3) 2-adrenoceptor agonist methoxamine decreased the analgesic effect of EA. (4) Another 2-adrenoceptor antagonist prazosin (icv 16 micrograms) enhanced the analgesic effect of EA. These results suggest that an activation of alpha 1- or alpha 2-adrenoceptors would decrease the analgesic effect of EA.

Acupuncture Analgesia

[Thin layer chromatographic studies on radix Ginseng, fructus Schisandrae and radix Salviae miltiorrhizae in yixinfumai granules].

The main constituents of Radix Ginseng, Fructus Schisandrae and Radix Salviae Miltiorrhizae in Yixinfumai Granules were studied by TLC. It was found that ginsenoside got hydrolyzed while the drugs were being boiled together. The main constituents of Fructus Schisandrae were schizandrol A and B; and those of Radix Salviae Miltiorrhizae were tanshinone and protocatechuic aldehyde.

Chromatography, Thin Layer

Immunochemical and biochemical characterization of purified canine interferon-gamma. Production of a monoclonal antibody, affinity purification, and its effect on mixed lymphocyte culture and mixed lymphocyte kidney culture reactions.

We have advanced the hypothesis that the primary autolymphoproliferative response of dog T cells in mixed lymphocyte kidney cultures (MLKC) results from their recognition of tissue-specific (kidney-associated) antigen(s) presented in conjunction with class II MHC antigens. Lymphocyte culture-derived supernatants had been found previously to upregulate class II antigen expression on kidney cells and enhance T cell activation. In the present study we have isolated and characterized dog IFN-gamma, a class II-inducing substance that is secreted in the culture supernatant of activated T lymphocytes. Dog IFN-gamma was induced with A-23187 and PMA and purified stepwise using controlled-pore glass, Mono Q anion exchange chromatography, and Superose 6-gel filtration on FPLC. The purification resulted in two molecules of 42 Kd and 31 Kd molecular weights. An IgG1 monoclonal antibody was engendered to these molecules. With this mAb reagent, in immunochemical experiments, we have developed a sensitive ELISA and a method for purifying dog IFN-gamma by affinity chromatography. Species specificity studies indicated that purified dog IFN-gamma reacted with a polyclonal rabbit antihuman IFN-gamma, but not with a mAb to human IFN-gamma. However, the antidog IFN-gamma mAb that was generated also reacted with recombinant human IFN-gamma. In in vitro biological studies, the purified IFN-gamma (two mol. wt. species) upregulated the expression of canine class II MHC molecules on dog tubular epithelial cells and the dog kidney epithelial cell line (MDCK). The antidog IFN-gamma mAb blocked T cell proliferative response to kidney cell and, by inference, the interaction between endogenously released IFN-gamma in vitro with its cell surface receptor, thus inhibiting the induced upregulation of class II. Interestingly, although antidog IFN-gamma markedly blocked the MLKC (10 micrograms mAb/well), there was no effect on the allogeneic MLC. This observation indicates that the cytokine IFN-gamma may be a uniquely key substance amplifying the immune response of T cells to tissue-associated antigens on surrogate antigen-presenting cells that require induced upregulation of class II MHC antigen expression (MLKC), in contrast to reactions in which these antigens are already constitutively expressed on the antigen-presenting cells (mixed lymphocyte culture).

Animals

Aerobic radioprotection of pBR322 by thiols: effect of thiol net charge upon scavenging of hydroxyl radicals and repair of DNA radicals.

The extent of conversion of supercoiled pBR322 plasmid DNA to the open circular and linear forms can be measured by HPLC on a Waters Gen Pak FAX column following in vitro gamma irradiation of the DNA. This radiation effect has proven to be useful for the study of the radioprotection of DNA by thiols and other drugs. This system was used with gamma irradiation in air at pH 7.0 and physiological ionic strength to compare radioprotection by a series of thiols, disulfides, and thioethers, all having approximately 10(8) s-1 effective hydroxyl radical scavenging rate (10 mm dm-3 drug) and having net charge (Z) ranging from -2 to +3. All sulfur compounds exhibited substantial protection due to scavenging of hydroxyl radicals in bulk solution but thiols exhibited a 24-fold variation in relative ability to protect the plasmid DNA from strand breaks, as assessed from the dose-response curves: mercaptosuccinate (Z = -2), 0.53; GSH (Z = -1), 0.67; 3-mercaptopropionate (Z = -1) 0.80; mercaptoethanol (Z = 0), 1.00; dithiothreitol (Z = 0), 1.5; cysteamine (Z = +1), 3.7; N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065, Z = +2), 6.7; N1-(2-mercaptoethyl)spermidine (WR-35980, Z = +3), 12. Comparison of these results with those obtained using disulfide and thioether radioprotectors indicated that local scavenging of hydroxyl radicals near DNA increases slightly with Z, apparently as a result of variations in thiol concentration near DNA, but this accounts for only a small fraction of the change with Z found for cationic thiols. The marked increase in protection found for cationic thiols was attributed to chemical repair of DNA radicals and was in accord with predictions based upon recently measured rates for chemical repair of DNA radicals and was in accord with predictions based upon recently measured rates for chemical repair of pBR322 radicals. It is concluded that chemical repair of DNA radicals by anionic thiols does not compete with the oxygen fixation reaction in air and that protection by these thiols occurs primarily via the scavenging of hydroxyl radicals. However, chemical repair of DNA radicals is significantly enhanced by counterion condensation for cationic thiols and becomes a significant factor in their ability to protect DNA against radiation damage under aerobic conditions.

Chromatography, High Pressure Liquid

Reproductive factors and colorectal cancer risk among Chinese females.

We report results from a population-based case-control study of colorectal cancer among Chinese women in western North America (NA) and the People's Republic of China (China). A common protocol was used to assess reproductive characteristics and hormone use of 395 Chinese women (189 from NA and 206 from China) with cancer of the colon or rectum and of 1112 age-matched Chinese controls (494 from NA and 618 from China). In NA, risks for cancers of both the colon and rectum were lower among parous compared to nulliparous women (odds ratio for colorectal cancer, 0.6, P = 0.08), but the trend in risk was not smooth with increasing number of livebirths. This association with parity was absent for both cancer sites in China. There were no consistent patterns in the relationships between other reproductive factors (including age at menarche, age at first livebirth, menopausal status) and risk of colon and rectal cancer on either continent.

Adult

[The screening model for early diagnosis of colorectal cancer in general population].

In this study, 75,813 asymptomatic individuals above 30 in Jiashan County of Zhejiang Province were recruited in the screening program. Based on results of risk assessment using a mathematical model (expressed as AD value) and Reverse Passive Hemagglutination Fecal Occult Blood test (RPHA FOB). 62,667 subjects (82.7%) who completed two procedures were divided into 4 groups: 1) AD greater than or equal to 0.3 FOB (+) accounts for 1.2% of total; 2) AD less than 0.3 FOB (+) 3.0%; 3) AD greater than or equal to 0.3 FOB (-) 26.8%; 4) AD less than 0.3 FOB (-) 68.9%. Individuals in groups 1 and 2 were subjected to 60 cm fiberoptic colonoscopic examination; and those of group 3 with AD greater than or equal to 0.5 or with AD less than 0.5 but a positive repeated FOB test was also eligible for 60 cm colonoscopy. Out of 4,299 eligible subjects 3,162 were examined with 60 cm sigmoidoscopy (73.6%). 21 cases of colorectal cancer and 331 cases of polyps (including 75 adenomas) were detected. Among 21 cancers known of Dukes' stages 10 were at early stages (10 Dukes' A and 5 Dukes' B) accounting for 71.5%. According to the screening protocol individuals with negative 60 cm colonoscopic findings and consistently positive FOB results indicate that the lesion may be located above the spleen flexure and require a full fiberoptic colonoscopic examination (150 cm) and/or x-ray air-barium enema.

Adenocarcinoma

[Dynamic observation on the incidence and mortality rates of the nasopharyngeal carcinoma (NPC) in Zhongshan City 1970-1984].

The standardized incidence rate of NPC was 14.44/10(5) (male 20.31/10(5), female 8.95/10(5] and the standardized mortality rate was 10.91/10(5) (male 16.00/10(5), female 6.14/10(5] in Zhongshan city during 1970-1984. The fluctuation of incidence and mortality rates were 13.66-18.07/10(5) and 9.02-13.95/10(5) respectively. It was worthy to be mentioned that both the incidence and mortality rate of NPC were relatively stable in 1970-1984.

China