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Biomedical subjects

W C Wang

Publications and source records attributed to W C Wang.

At least 109 records · Page 6Linked to original sources

Postcoital use of anordrin and RU 486 for prevention of implantation in the rat.

Because RU 486 synergizes with anordrin and its dihydroxylated metabolite to terminate established pregnancy in the rat and rabbit, the interactions of these agents were studied at two days postcoitally in the rat. RU 486 at a dose of 4 mg/kg did not prevent pregnancy when the animals were killed 12 days post insemination. A 2.5 mg/kg dose of anordrin prevented pregnancy in 14% of animals. By contrast, none of the animals became pregnant when treated with 2.5 mg/kg of anordiol. A non-effective dose of RU 486 (2 or 4 mg/kg) combined with a non-effective dose of anordrin (1.25 or 2.5 mg/kg) prevented pregnancy in all animals treated; there was no evidence of implantation sites or embryos when the animals were killed on day 12 post insemination. The same synergistic effect was observed when a small dose of RU 486 (e.g., 1 mg/kg) was combined with 0.6 mg/kg anordiol. To investigate the mechanism of pregnancy prevention, animals were treated two days postcoitally with 4 mg/kg of RU 486 plus 2.5 mg/kg of anordrin or 2 mg/kg of RU 486 plus 0.6 mg/kg of anordiol and were killed short intervals after treatment. These drugs had no effect by 6 h, but the numbers of embryos in oviducts were significantly reduced 12 h after treatment. By 24 h following treatment, no embryos were recovered from either the oviduct or the uterus. Progesterone and estradiol levels in serum collected 24 h after treatment were not significantly different from those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Disposition of recombinant human granulocyte colony-stimulating factor in children with severe chronic neutropenia.

The disposition of recombinant human granulocyte colony-stimulating factor (G-CSF) was studied in 11 children with severe chronic neutropenia given 6 to 48 micrograms G-CSF per kilogram subcutaneously. Serum concentrations of G-CSF were measured by bioassay. Peak serum G-CSF concentrations were proportional to dosage and occurred 2 to 8 hours after subcutaneous administration. Nine of the eleven children had a significant increase in absolute neutrophil count (ANC). The median ANC in responding patients was 6.7 x 10(9)/L on day 14 versus 0.17 x 10(9)/L on day 1 of therapy (p < 0.01). The G-CSF clearance increased as ANC increased, and the relationship was well described by a sigmoid model. Maximal clearance approached 2 ml/min per kilogram at ANCs > 17.0 x 10(9)/L; minimal clearance was 0.29 ml/min per kilogram at ANCs of 0. The half-life of G-CSF was inversely related to ANC; mean half-life was 4.7 hours at ANCs of 0 but < 2 hours at ANCs greater than 17.0 x 10(9)/L. The two patients who failed to achieve a clinical response had no change in G-CSF clearance or half-life, nor did they have an increase in ANC when G-CSF dosages were escalated to 18 or 48 micrograms/kg twice a day. These results indicate that G-CSF pharmacokinetics are directly influenced by ANC; higher serum concentrations, slower clearances, and longer half-lives are associated with low ANCs.

Adolescent↗

Developmental screening in young children with sickle cell disease. Results of a cooperative study.

PURPOSE: The goal of the study was to assess development in young children with sickle cell disease as part of the Cooperative Study of Sickle Cell Disease (CSSCD). PATIENTS AND METHODS: The Denver Developmental Screening Test (DDST) was administered to children younger than 6 years at 12 participating institutions of the CSSCD. Trained examiners administered tests to 344 children. RESULTS: Tests were scored as normal in 90.4%, questionable in 6.4%, and abnormal in 1.5%; 1.7% of children were considered untestable. There was no relationship between DDST results and sickle cell genotype. Questionable and abnormal (Q/A) scores were more common in children ages 3-5 years than in younger children (12.6% versus 3.8%; P = 0.002). CONCLUSIONS: Because the DDST is a screening test, it should be interpreted cautiously. However, the more numerous Q/A scores in our "older" group agree with the findings of recent reports of neuropsychological impairment in school-age children with sickle cell disease. Our data suggest that development is relatively normal before age 3 years; deficits seen in older children may reflect subsequent ischemic insults.

Age Factors↗

Laparoscopic splenectomy.

Splenectomy is easily amenable to laparoscopic technique. Compared with the open technique, its advantages include improved exposure, decreased pain, improved pulmonary function, shortened hospitalization, rapid return to unrestricted activities, and improved cosmetic appearance. These advantages are at the expense of prolonged operative time that, with experience and improved instruments, should diminish.

Adolescent↗

[The diagnosis and the treatment on lingual thyroid]

Lingual thyroid is a rare example of ectopic thyroid.This paper reported three cases of lingual thyroid(all female,aged between 16 and 61 years) were discussed with diagnosis and treatment.A transoral excision using the median total glossotomy and precervical excision was performed through a transsuprahyoid approach.Postoperative complications is not developed.The approach above mention is better than that of median labiomandibular glossotomy.

Journal Article↗

[Effect of Salvia miltiorrhizae in the treatment of 36 infantile acute toxic myocarditis].

Control observation of infantile acute toxic myocarditis treated by Salvia miltiorrhizae (SM) showed that 36 cases were clinically cured through SM treatment. The total effects have obvious advantages over Western Medicine control group, P < 0.01. The period of hospitalization and ECG normalization, of control group was significantly longer than that of SM treated group, P < 0.001 respectively.

Child↗

Atypical Wiskott-Aldrich syndrome in a girl.

Wiskott-Aldrich syndrome (WAS) is a fully penetrant X-linked recessive disorder characterized by thrombocytopenia with small platelets, eczema, and defects of both T-cell and B-cell immunity. Obligate carriers of this disorder show no signs of the gene defect because in the cell lineages primarily affected by the disorder they demonstrate preferential use of the normal, nonmutant X as the active X. This can be explained by the selective disadvantage in proliferation and/or survival experienced by the cells with the mutant X as the active X. We have recently evaluated an 8-year-old girl with a disorder phenotypically identical to WAS. Cytogenetic studies did not show any structural abnormalities of the X chromosome and X chromosome inactivation analysis showed that both of her X chromosomes could function as the active X. These findings suggest that there is an autosomal recessive disorder that is very similar to classic WAS.

Antigens, CD↗

Factors controlling variability in measurements of the transient gene expression in electroporated protoplasts of wheat callus.

Factors controlling variability in enzyme transient expression assays have been investigated in electroporated protoplasts isolated from wheat embryogenic and nonembryogenic calli. The level of variation was reduced to a minimum through the optimization of the beta-glucuronidase measurements in the pellet and the supernatant of the homogenized protoplasts, by expressing the data on the basis of the number of protoplasts found to be viable immediately before the assay and on the amount of protein in the pellet and supernatant. Protoplast separation on the basis of size was also useful in eliminating some of the variation resulting from the heterogeneity of the callus used. Efforts to partially synchronize the callus tissue by auxin starvation have not resulted in a significant decrease of this variation. Our results indicate that the level of variation in enzyme transient activity in protoplasts resulting from calli can be reduced by implementation of the experimental techniques presented here.

Cell Membrane Permeability↗

Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials.

Changes in the glycosylation of asparagine-linked oligosaccharides have been shown in various tumor cells, including human colon cancer. Attempts were made to elucidate the difference in Asn-linked oligo-saccharides attached to lysosomal membrane glycoproteins isolated from sublines of human colon carcinoma exhibiting high and low metastatic potentials in nude mice. Lysosomal membrane glycoproteins (lamp) 1 and 2 were immunoprecipitated from the cells after labeling with radioactive sugars, and the glycopeptides prepared were fractionated by serial lectin affinity chromatography employing immobilized concanavalin A, Datura stramonium agglutinin, and tomato lectin. Comparison of Asn-linked oligosaccharides from the different colonic carcinoma cells revealed the following features. First, the highly metastatic carcinoma cells express more poly-N-acetyllactosaminyl side chains with branched galactose residues than cells with low metastatic potential. Second, sialylation is more significant in the highly metastatic carcinoma cells than in the poorly metastatic ones. Conversely, N-acetyllactosamine units are less fucosylated in the highly metastatic cells than in poorly metastatic cells. These structural changes were apparently caused by the increase in sialyltransferase and the decrease in alpha 1----3 fucosyltransferase in the highly metastatic cells. The results also suggest that highly metastatic carcinoma cells express more sialyl Lex structures at the termini of poly-N-acetyllactosaminyl side chains than poorly metastatic carcinoma cells. Further, highly metastatic cells were found to express more lamp-1 and lamp-2 on the cell surface. These results were found to be correlated to the increased expression of sialyl Lex structures with high affinity binding of anti-sialyl Lex antibody on highly metastatic cells. Increased expression of sialyl Lex in the poly-N-acetyllactosamines of the cell surface may contribute to the metastatic behavior of the cells, assuming that this structure can serve as a better ligand for selectins present on endothelial cells and platelets.

Antibodies↗

Recombinant human granulocyte colony-stimulating factor promotes wound healing in a patient with congenital neutropenia.

We report a patient with congenital neutropenia or Kostmann's Syndrome who suffered many complications after presenting with Clostridium septicum enterocolitis, including absence of wound healing. Because of several reports of the use of granulocyte colony-stimulating factor (G-CSF) in patients with various complications of neutropenia, we treated this patient with recombinant human (rh) G-CSF. We found that once rhG-CSF restored neutrophil counts to normal, progressive wound healing followed. Thus, rhG-CSF therapy may be useful in treating neutropenic patients with wound complications.

Adolescent↗

Site-directed mutagenesis of glycosylation sites in the transforming growth factor-beta 1 (TGF beta 1) and TGF beta 2 (414) precursors and of cysteine residues within mature TGF beta 1: effects on secretion and bioactivity.

The transforming growth factor-beta 1 (TGF beta 1) and -beta 2 (414) precursors both contain three predicted sites of N-linked glycosylation within their pro regions. These are located at amino acid residues 72, 140, and 241 for the TGF beta 2 (414) precursor and at residues 82, 136, and 176 for the TGF beta 1 precursor; both proteins contain mannose-6-phosphate (M-6-P) residues. The major sites of M-6-P addition are at Asn (82) and Asn (136), the first two sites of glycosylation, for the TGF beta 1 precursor. We now show that the major site of M-6-P addition within the TGF beta 2 (414) precursor is at Asn241, the third glycosylation site. To determine the importance of N-linked glycosylation to the secretion of TGF beta 1 and -beta 2, site-directed mutagenesis was used to change the Asn residues to Ser residues; the resulting DNAs were transfected into COS cells, and their supernatants were assayed for TGF beta activity. Substitution of Asn (241) of the TGF beta 2 (414) precursor resulted in an 82% decrease in secreted TGF beta 2 bioactivity. Mutation at Asn72 resulted in a 44% decrease, while mutation at Asn140 was without effect. Elimination of all three glycosylation sites resulted in undetectable levels of TGF beta 2. These results were compared with similar mutations made in the cDNA encoding the TGF beta 1 precursor. Mutagenesis of the two M-6-P-containing sites (Asn82 and Asn136) resulted in an 83% decrease in secreted TGF beta 1; replacement of Asn82 and Asn136 with Ser individually resulted in 85% and 42% decreases in activity, respectively. Substitution of Asn176 with Ser was without effect, while substitution of all three sites of glycosylation resulted in undetectable levels of TGF beta 1 activity, similar to the results obtained with TGF beta 2. The nine Cys residues within the mature region of TGF beta 1 were mutated to serine, and their effects on TGF beta 1 secretion were evaluated. Mutation of most Cys residues resulted in undetectable levels of TGF beta 1 protein or activity in conditioned medium. Mutation of Cys (355) led to the secretion of inactive TGF beta 1 monomers, suggesting that this residue is either directly involved in dimer formation or required for correct interchain disulfide bond formation.

Amino Acid Sequence↗

[Effects of anisodamine and atropine on the microvasculature of liver, skeletal muscle and foot-pad skin in anesthetized rats].

Rats were urethanised and kept in a constant temperature chamber. The surface temperature of various organs including the liver and the armpit skeletal muscle were monitored with a special mercury thermometer through a narrow hole on the skin cut with scalpel. The temperature of the foot-pad skin were measured using a thermometer as reported previously. After iv of anisodamine or atropine at doses of 12.5-50 micrograms/kg the temperature of the liver and the armpit skeletal muscle were significantly reduced in a dose-dependent manner but the skin temperature was increased. Temperature changes were observed 5 min after drug administration, reaching peak height at about 15 min and maintained for one hour or so. Isoprenaline, dopamine and aminophylline iv showed only a temperature-elevating effect, while serotonin and noradrenaline caused only a temperature-decreasing effect in all the three organs mentioned above. Although the functional significance of the opposite effects on the microcirculation of different tissues remain to be defined, the effects of atropine-like drugs must result in a redistribution of circulating blood and may have beneficial effects on the survival of some vital organs such as brain, lungs, kidneys ... especially in shock.

Animals↗

The poly-N-acetyllactosamines attached to lysosomal membrane glycoproteins are increased by the prolonged association with the Golgi complex.

The poly-N-acetyllactosamines on neutrophils and monocytes have been shown to serve as ligands for various selectins present on endothelial cells and platelets. We have previously shown that only a limited number of glycoproteins contain poly-N-acetyllactosamine and found that lysosomal membrane glycoproteins (lamps) are the major glycoproteins carrying poly-N-acetyllactosamine. In order to understand the reason why only certain glycoproteins can be modified by poly-N-acetyllactosamine, we have utilized 21 degrees C incubation conditions, which were previously shown to cause the accumulation of glycoproteins at the trans-Golgi. HL-60 cells were labeled with [3H]galactose at 21 or 37 degrees C for 6 or 24 h, and lamp-1 and lamp-2 were immunoprecipitated. Upon examination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, each lamp from HL-60 cells incubated at 21 degrees C exhibited a much broader, slower migrating band than that isolated from the cells incubated at 37 degrees C. The number of N-glycans containing poly-N-acetyllactosamine, estimated by their binding to tomato lectin column, increased approximately 30-50% after incubation at 21 degrees C than incubation at 37 degrees C. The analysis of oligosaccharides released by endo-beta-galactosidase digestion demonstrates that the amount of side chains containing three or more N-acetyllactosamine repeats increased about 100% after incubation at 21 degrees C, and methylation analysis confirmed these results. The same analysis and the results obtained by ion-exchange chromatography also provided evidence that the N-glycans of lamps are sialylated at 21 degrees C as much as at 37 degrees C. Pulse-chase experiments using [35S]methionine labeling indicated that the time necessary for processing of lamps is much longer at 21 degrees C than at 37 degrees C. These results therefore indicate that incubation at 21 degrees C causes the lamps to reside longer within the Golgi complex, and such longer residence allows lamps to acquire more polylactosaminoglycan. These results also suggest that the time necessary for moving through the Golgi complex is a critical factor for poly-N-acetyllactosamine formation.

Carbohydrate Sequence↗

Comparison of the actions of some platelet-activating factor antagonists on platelets and aortic smooth muscles.

The pharmacological actions of five platelet-activating factor (PAF) antagonists were compared in rabbit platelets and rat thoracic aorta. In PAF (2 ng/ml)-induced aggregation of washed rabbit platelets, WEB 2086 and WEB 2170 much were more potent inhibitors than BN 52021, kadsurenone and denudatin B, and the IC50 values were calculated to be 0.1, 0.3, 5, 8 and 10 micrograms/ml, respectively. WEB 2086, WEB 2170 and BN 52021 did not affect the platelet aggregation caused by collagen (10 micrograms/ml), ADP (20 microM), arachidonic acid (100 microM) or thrombin (0.1 U/ml). Kadsurenone and denudatin B suppressed ATP release, thromboxane B2 formation and the rise in intracellular calcium of washed rabbit platelets caused by collagen and thrombin, while WEB 2086, WEB 2170 and BN 52021 did not have an effect. Norepinephrine (3 microM) induced a sustained contraction in rat thoracic aorta. Pretreatment with these PAF antagonists (20-100 micrograms/ml) caused inhibition of the aortic contraction in the following order: kadsurenone greater than denudatin B greater than WEB 2086 greater than BN 52021 greater than WEB 2170. In high potassium (60 mM)-induced contraction of rat aorta, kadsurenone and denudatin B caused marked relaxation, while WEB 2086, WEB 2170 and BN 52021 had only a slight effect. It is concluded that WEB 2086, WEB 2170 and BN 52021 are specific PAF antagonists in rabbit platelets, and weak relaxants in rat aorta. Two other PAF antagonists, kadsurenone and denudatin B, may inhibit some aspects of signal transduction, e.g., thromboxane formation or intracellular Ca2+ mobilization in rabbit platelets, and cause vasorelaxation in rat aorta by inhibiting calcium influx.

Animals↗

Cyclosporine therapy for advanced Langerhans cell histiocytosis.

Prompted by evidence that Langerhans cell histiocytosis (LCH) is a nonmalignant disorder of immune regulation, we used cyclosporine (12 mg/kg/d orally) to treat three young children with advanced multisystem LCH. All three patients had partial responses to cyclosporine within 2 months of therapy, as evidenced by complete resolution of organ dysfunction and regression of the majority of lesions. Complete responses were attained by adding relatively nontoxic chemotherapy (ie, prednisone and vinblastine). Toxicity from cyclosporine comprised mild and reversible elevations of the serum creatinine and blood urea nitrogen. These results indicate that further evaluation of cyclosporine for the treatment of patients with advanced LCH is warranted.

Cyclosporins↗