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Biomedical subjects

F Wang

Publications and source records attributed to F Wang.

At least 595 records · Page 33Linked to original sources

Immunosuppressive levels of glucocorticoid block extrauterine luteolysins in the rat.

Leukocytes, normal constituents of the corpus luteum, release prostaglandins (PGs), superoxide, and hydrogen peroxide (H2O2) upon activation. These products appear to mediate luteolysis, and it has been postulated that activated leukocytes serve a role in corpus luteum regression. Glucocorticoids prevent leukocyte infiltration and activation by inhibiting cytokine production, secretion, and action, and also inhibit eicosanoid synthesis. The objective of the present studies was therefore to assess whether glucocorticoid would influence luteal regression in the rat. Ovulation and pseudopregnancy were synchronized in prepubertal rats by gonadotropin treatment. In uterine-intact rats, functional luteal regression, assessed from serum progesterone levels, began on Day 10 and was complete by Day 14. Dexamethasone blocked luteal regression in uterine-intact animals when administered daily from early in pseudopregnancy for as long as treatment was continued (up to Day 17). Immunosuppressive effects of dexamethasone were evident in the inhibition of estrogen-induced infiltration of eosinophils, as shown by abrogation of estrogen-induced uterine peroxidase activity, and high continuous levels of dexamethasone were necessary to block luteolysis. Hysterectomy extended luteal function by several days, with maintenance of maximal serum progesterone levels up to Day 12; but serum progesterone levels were reduced about 50% by Day 16 and completely depressed by Day 19. Dexamethasone treatment of hysterectomized rats from Day 12 until Day 15 or 18 blocked the decline in serum progesterone levels. Dexamethasone treatment did not block the decrease in serum progesterone levels induced within 24 h by PGF2 alpha in uterine-intact animals on Day 9 or in hysterectomized animals on Day 19.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Plasma antioxidants and risk of cortical and nuclear cataract.

We evaluated nutritional risk factors for cataract in 660 subjects enrolled in the Baltimore Longitudinal Study on Aging. As a part of a regular cycle of visits, nuclear and cortical lens photographs were taken over a 2-year period. Measurements of plasma antioxidants (beta-carotene, ascorbic acid, and alpha-tocopherol) were obtained in this cohort as part of the study protocol up to 4 years before lens photographs were taken. We found that plasma beta-carotene and ascorbic acid levels were not associated with risk of nuclear or cortical lens opacities. Higher levels of plasma alpha-tocopherol, however, were associated with a reduced risk of nuclear opacity [odds ratio (OR) for highest quartile vs lowest quartile = 0.52, 95% confidence interval (CI) = 0.27-0.98; OR for middle two quartiles vs lowest quartile = 0.55, 95% CI = 0.30-0.98], after adjusting for age, sex, and history of diabetes. Middle levels of alpha-tocopherol were associated with a reduced risk of cortical opacity (OR = 0.57, 95% CI = 0.32-1.02), but no such association was observed for high levels of alpha-tocopherol. We constructed an index of overall antioxidant status, which indicated that higher levels of plasma antioxidants were not associated with risk of nuclear or cortical opacities.

Adult↗

Type I calmodulin-sensitive adenylyl cyclase is neural specific.

The distribution of type I calmodulin-sensitive adenylyl cyclase in bovine and rat tissues was examined by northern blot analysis and in situ hybridization. Northern blot analysis using poly(A)(+)-selected RNA from various bovine tissues indicated that mRNA for type I adenylyl cyclase was found only in brain, retina, and adrenal medulla, suggesting that this enzyme is neural specific. In situ hybridization studies using bovine, rabbit, and rat retina indicated that mRNA for type I adenylyl cyclase is found in all three nuclear layers of the neural retina and is particularly abundant in the inner segment of the photoreceptor cells. The neural-specific distribution of type I adenylyl cyclase mRNA and its restricted expression in areas of brain implicated in neuroplasticity are consistent with the proposal that this enzyme plays an important role in various neuronal functions including learning and memory.

Adenylyl Cyclases↗

Control of fibroblast growth factor receptor kinase signal transduction by heterodimerization of combinatorial splice variants.

A differentiated liver cell (HepG2), which exhibits a dose-dependent growth-stimulatory and growth-inhibitory response to heparin-binding fibroblast growth factor type 1 (FGF-1), displays high- and low-affinity receptor phenotypes and expresses specific combinatorial splice variants alpha 1, beta 1, and alpha 2 of the FGF receptor (FGF-R) gene (flg). The extracellular domains of the alpha and beta variants consist of three and two immunoglobulin loops, respectively, while the intracellular variants consist of a tyrosine kinase (type 1) isoform and a kinase-defective (type 2) isoform. The type 2 isoform is also devoid of the two major intracellular tyrosine autophosphorylation sites (Tyr-653 and Tyr-766) in the type 1 kinase. An analysis of ligand affinity, dimerization, autophosphorylation, and interaction with src homology region 2 (SH2) substrates of the recombinant alpha 1, beta 1, and alpha 2 isoforms was carried out to determine whether dimerization of the combinatorial splice variants might explain the dose-dependent opposite mitogenic effects of FGF. Scatchard analysis indicated that the alpha and beta isoforms exhibit low and high affinity for ligand, respectively. The three combinatorial splice variants dimerized in all combinations. FGF enhanced dimerization and kinase activity, as assessed by receptor autophosphorylation. Phosphopeptide analysis revealed that phosphorylation of Tyr-653 was reduced relative to phosphorylation of Tyr-766 in the type 1 kinase component of heterodimers of the type 1 and type 2 isoforms. The SH2 domain substrate, phospholipase C gamma 1 (PLC gamma 1), associated with the phosphorylated type 1-type 2 heterodimers but was phosphorylated only in preparations containing the type 1 kinase homodimer. The results suggest that phosphorylation of Tyr-653 within the kinase catalytic domain, but not Tyr-766 in the COOH-terminal domain, may be stringently dependent on a trans intermolecular mechanism within FGF-R kinase homodimers. Although phosphotyrosine 766 is sufficient for interaction of PLC gamma 1 and other SH2 substrates with the FGF-R kinase, phosphorylation and presumably activation of substrates require the kinase homodimer and phosphorylation of Tyr-653. We propose that complexes of phosphotyrosine 766 kinase monomers and SH2 domain signal transducers may constitute unactivated presignal complexes whose active or inactive fate depends on homodimerization with a kinase or heterodimerization with a kinase-defective monomer, respectively. The results suggest a mechanism for control of signal transduction by different concentrations of ligand through heterodimerization of combinatorial splice variants from the same receptor gene.

Amino Acid Sequence↗

A new stable human dicentric chromosome, tdic(4;21)(p16;q22), in a woman with first trimester abortion.

A woman with first trimester abortion and a dicentric chromosome formed from a 4 and a 21 is described. The dicentric chromosome was stable and in the majority of cells the 21 centromere was active, while in a minority the chromosome 4 centromere was active. This shows that both centromeres were functional, but that only one functioned in any given cell. Suppression of the activity of one centromere might be the mechanism by which this dicentric chromosome achieved its stability. A dicentric formed from a chromosome 4 and a 21 has not apparently been previously reported.

Abortion, Spontaneous↗

Coordinate induction and activation of metalloproteinase and ascorbate depletion in structural luteolysis.

Structural luteolysis was found decades ago to be induced by PRL in the hypophysectomized rat, but the mechanisms of this process are unknown. To gain information on mechanisms of luteal involution, we developed an animal model that circumvented complex surgery and provided ample tissue for analyses. Gonadotropin-synchronized ovulation and luteinization were induced in immature rats, followed by treatment with ergot alkaloid and PRL. PRL-induced structural luteolysis, as shown by loss of luteal weight, protein, and DNA after pretreatment with ergot alkaloid, was evident after 36 h. Ascorbic acid depletion was rapid, severe, and lasting in luteal tissue during structural luteolysis, but lipid peroxidation or depletion of vitamin E was not evident. PRL treatment of animals with functional corpora lutea did not induce luteal involution. Significantly, after natural functional luteolysis occurred, PRL was highly effective in inducing structural luteolysis. Thus, either natural or ergot-induced functional luteolysis permitted the luteolytic expression of PRL. A greater depletion of protein than DNA was seen during PRL-induced structural luteolysis and was associated with a significant increase in neutral caseinase activity in luteal extracts. Caseinase activity was markedly reduced by calcium chelators and profoundly inhibited by the chelator orthophenanthroline; only slightly reduced activity was seen with serine, aspartate, or cysteine proteinase inhibitors. These findings implicate metalloproteinase (MMP) as the relevant caseinase that was increased during structural luteolysis. The major proteinase identified by zymography had apparent sizes of 72 and 66 kilodaltons (kDa), and slight but detectable activity was also seen at 92 and 84 kDa. Organomercurial treatment caused a major shift of the 72-kDa band to 66 kDa and the 92-kDa band to 84 kDa, confirming MMP-2 and MMP-9 by activation of latent activity of each MMP, respectively. Structural luteolysis caused a significant increase in the activated 66-kDa form and the latent 72-kDa form of MMP-2, which occurred before a loss of luteal weight or protein. As MMP-2 degrades collagen (type IV) in basement membranes, we conclude that an early event in PRL-induced structural luteolysis is the degradation of extracellular matrix. This conclusion is further emphasized by the marked and lasting depletion of ascorbic acid, a vitamin long known to serve an essential role in collagen synthesis.

Animals↗

Measuring progression of lens opacities for longitudinal studies.

A number of classifications schemes for the grading of lens opacities have been developed but none of them have been examined for reliability and validity in prospective or longitudinal studies. The purpose of this study was to develop and test a method for determining progression which was sufficiently sensitive to true change and insensitive to measurement error. The method consists of assessing various sources of measurement error, determining the likely magnitude of the error, and setting boundaries for changes in opacification which incorporate this error. Measurement error was assessed in 203 nuclear lens photographs graded using a decimal system and 136 cortical lens photographs graded in 1/16th area. 95% confidence intervals were calculated of the distribution of differences between photographs and graders and the width of this intervals defined as measurement error. The magnitude of the measurement error was +/- 0.7 units for nuclear opacities and +/- 2/16 for cortical opacities. The utility of this approach was tested in a series of 84 clinic patients followed at irregular intervals for up to 3 years. Only one eye showed "improvement" and progression rates ranged from 1.8 to 5.5% for nuclear opacities and 0 to 7.4% for cortical opacities in this clinic-based series. This approach appears to be useful for discarding noise and enabling the assessment of progression for use in longitudinal studies.

Cataract↗

Hydrophobicity of oligopeptides having un-ionizable side chains.

The hydrophobicity of any peptide is a physicochemical property not only of the amino acid sequence, but also of the secondary and tertiary structure. It is also an essential factor to consider in peptide drug delivery, which has become increasingly important in recent years with the discovery of many peptides with potential pharmaceutical uses. The hydrophobicities (log P) of dito pentapeptides reported by Akamatsu and Fujita have been correlated with 12 parameters including 7 indicator variables. We have tried to simply this equation by using more common and simple parameters. Good correlations have been obtained for log P with a five-parameter equation using the sum of the hydrophobicity of component amino acids (log Paa), molecular weight (log MW), the frequency of beta-turn formation (F beta) of peptides, which is an important tertiary structural parameter, the dipole moment (mu) calculated with a computer-assisted program, and the number of amino acids in a peptide (N). This equation should be useful in drug delivery in predicting the relative hydrophobicity of new peptides with no ionizable side chains.

Amino Acid Sequence↗

Characterization of recombinant human acidic fibroblast growth factor: comparative studies with bovine acidic fibroblast growth factor.

Recombinant human acidic fibroblast growth factor (haFGF) was purified from E. coli lysate by heparin-sepharose affinity chromatography. The purified haFGF exhibited potent mitogenic activity in stimulating DNA synthesis in 3T3 cells and this activity could be significantly increased by heparin. By analysis of mitogenic activity and immunological properties, a marked difference was found between haFGF and bovine aFGF (baFGF). The main difference was that the heparin-dependence of haFGF was stronger than that of baFGF.

3T3 Cells↗

Benign persistent pneumoperitoneum in systemic sclerosis.

We describe a 50-year-old Chinese woman who had severe gastrointestinal manifestations from systemic sclerosis complicated by spontaneous pneumoperitoneum in the absence of either visceral perforation or pneumatosis cystoides intestinalis. This is a rare complication of systemic sclerosis; only four other cases have been reported. Recognition of this condition is important so as to avoid unnecessary surgery.

Female↗

Antiphospholipid antibodies and stroke in the young--a study of three cases.

Cerebral infarction in the young is likely to be non-atheromatous. While in previous studies no cause has been found in 40% to 50% of patients, an increasing role for haemorheological factors is becoming apparent. Among these, an association between antiphospholipid antibodies (aPLs) and ischaemic cerebrovascular disease is now well-recognised. This entity has not been previously reported in Malaysian patients. In a study of 80 patients with stroke below the age of 50 years who were seen at the University Hospital, Kuala Lumpur, between January 1982 and May 1992, 3 patients with ischaemic cerebral infarction were found to have aPLs. aPLs was detected using ELISA method for anticardiolipin antibodies (aCLs), and presence of lupus anticoagulant (LA) was established by kaolin clotting time, thromboplastin inhibition test and platelet neutralisation procedure. Only 1 patient had active systemic lupus erythematous. Cerebrovascular events were recurrent in one of the 2 non-lupus patients. aPL-related stroke should be considered in young patients who have cerebral ischaemia occurring without obvious cause. More cases are likely to emerge in Malaysia with active screening.

Adolescent↗

Radioimmunodetection of Hodgkin's disease and non-Hodgkin's lymphomas with monoclonal antibody to eosinophil peroxidase.

The purpose of this study was to determine if a radiolabeled murine monoclonal antibody (EOS) directed against eosinophil peroxidase would localize specifically to tumor sites in patients with lymphomas infiltrated by eosinophils. Ten patients with Hodgkin's disease and eosinophilia, three patients with non-Hodgkin's lymphomas and eosinophilia and five control patients received an intravenous injection of 3-10 mg of EOS antibody radiolabeled with 74-155 MBq (2.0-4.2 mCi) of 111In. At intervals of 24, 48 and 72 hr after injection, gamma camera images were obtained along with blood and urine specimens and the imaging results were correlated with the results of other staging modalities. As early as 24 hr after antibody injection, there was clear visualization of identifiable sites of lymphoma with eosinophilia greater than 1 cm in size, including the spleen, bone marrow and lymph nodes. Although EOS also localized nonspecifically to the liver and, in some patients, to the nasopharynx, there was no appreciable uptake in normal bone marrow, spleen, uninvolved lymph nodes, lymphomas without eosinophilia or various other pathologic conditions without eosinophilia. Except for transient pain at tumor sites in three patients, no adverse reactions were noted. We conclude that a radiolabeled monoclonal antibody directed against eosinophil peroxidase localizes to lymphoma sites infiltrated by eosinophils.

Adult↗

[Augmentation of cytotoxicity of nonparenchymal cell of the liver after continuous IL-2 administration via the portal vein].

In this study, we discussed the influence of recombinant interleukin-2 (rIL-2) on nonparenchymal cell of the liver. Donryu rats (8-10 weeks, male) were continuously administered rIL-2 (IL-2 group) or saline (control group) for 6 days via the portal vein. On day 0 or 7 after administration, rats were sacrificed to obtain the blood and liver. Blood mononuclear cell (BMC) and nonparenchymal cell (NPC) of the liver were collected, and their cytotoxicity (NK activity and LAK activity) was measured by 51Cr release-assay. NK activity and LAK activity of BMC in IL-2 group were increased on day 0 and day 7 compared to those in the control group. NK activity and LAK activity of NPC in IL-2 group were augmented on day 0, and NK activity in IL-2 group was still high on day 7. These results suggest that preoperative IL-2 administration may be effective for prevention of formation and/or proliferation of liver metastasis, that are provoked by surgical intervention in cancer of the digestive organs.

Animals↗

Vitamin E requirement of rats fed on a diet containing grains from the endemic region of Keshan disease.

Keshan disease (KD) is an endemic cardiomyopathy occurring in China. Combined selenium and vitamin E (VE) deficiency might be involved in the development of KD. It was shown in this paper that addition of 20 and 100 mg/kg DL-alpha-tocopherol tended to decrease malondialdehyde (MDA) content of myocardium in the rats receiving the low selenium (0.013 ppm) grains from the endemic region of KD, but not to a statistically significant extent. And addition of 200 mg/kg DL-alpha-tocopherol significantly decreased the myocardial MDA content, which suggested that VE requirement of the rats receiving KD endemic grains was 200 mg/kg DL-alpha-tocopherol. However, the MDA content in the myocardium of rats receiving KD grains added with 100 mg/kg DL-alpha-tocopherol was significantly decreased when selenium (0.1 ppm) was supplemented, which suggested that VE requirement of these rats was decreased to 100 mg/kg DL-alpha-tocopherol in the presence of selenium. The ability of VE in counteracting free radicals in myocardium of rats appeared greater than that of selenium.

Animals↗

Tophaceous gout in young patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) and gout have been associated infrequently. We describe 3 young adults with SLE who developed tophaceous gout relatively early in the course of their disease. All were underexcretors of uric acid but were studied after the development of renal disease; 2 were treated with diuretics. In 2 cases, gout became obvious while lupus was quiescent.

Adult↗

The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B.

A20 is an inducible zinc finger protein that confers resistance to tumor necrosis factor alpha cytotoxicity. A survey of various cell lines revealed that A20 was constitutively expressed in Epstein-Barr virus (EBV)-immortalized B-cells. Transfection experiments demonstrated that the EBV latent membrane protein LMP1 induced A20 expression. LMP1 is a transforming protein of EBV that has dramatic effects on cell growth, activation, and survival. An integral membrane phosphoprotein, LMP1 bears no homology to other recognized membrane signaling molecules, and its signal transduction pathway is not known. However, studies using the A20 promoter demonstrated that LMP1 transcriptionally activates the A20 gene through cis-acting kappa B sites. In addition, electrophoretic mobility shift assays confirmed LMP1-inducible binding of an NF-kappa B-like factor to kappa B sequences within the A20 promoter. This is the first report implicating NF-kappa B in signaling by LMP1, a fundamentally important viral transforming protein.

Antigens, Viral↗