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Biomedical subjects

F Wang

Publications and source records attributed to F Wang.

At least 577 records · Page 32Linked to original sources
PubMed1993

Breast thermography is a noninvasive prognostic procedure that predicts tumor growth rate in breast cancer patients.

Our recent retrospective analysis of the clinical records of patients who had breast thermography demonstrated that an abnormal thermogram was associated with an increased risk of breast cancer and a poorer prognosis for the breast cancer patient. This study included 100 normal patients, 100 living cancer patients, and 126 deceased cancer patients. Abnormal thermograms included asymmetric focal hot spots, areolar and periareolar heat, diffuse global heat, vessel discrepancy, or thermographic edge sign. Incidence and prognosis were directly related to thermographic results: only 28% of the noncancer patients had an abnormal thermogram, compared to 65% of living cancer patients and 88% of deceased cancer patients. Further studies were undertaken to determine if thermography is an independent prognostic indicator. Comparison to the components of the TNM classification system showed that only clinical size was significantly larger (p = 0.006) in patients with abnormal thermograms. Age, menopausal status, and location of tumor (left or right breast) were not related to thermographic results. Progesterone and estrogen receptor status was determined by both the cytosol-DCC and immunocytochemical methods, and neither receptor status showed any clear relationship to the thermographic results. Prognostic indicators that are known to be related to tumor growth rate were then compared to thermographic results. The concentration of ferritin in the tumor was significantly higher (p = 0.021) in tumors from patients with abnormal thermograms (1512 +/- 2027, n = 50) compared to tumors from patients with normal thermograms (762 +/- 620, n = 21). Both the proportion of cells in DNA synthesis (S-phase) and proliferating (S-phase plus G2M-phase, proliferative index) were significantly higher in patients with abnormal thermograms. The expression of the proliferation-associated tumor antigen Ki-67 was also associated with an abnormal thermogram. The strong relationships of thermographic results with these three growth rate-related prognostic indicators suggest that breast cancer patients with abnormal thermograms have faster-growing tumors that are more likely to have metastasized and to recur with a shorter disease-free interval.

Age Factors↗
PubMed1993

Breast carcinoma and the role of iron metabolism. A cytochemical, tissue culture, and ultrastructural study.

Transferrin receptors on proliferating and malignant cells are well documented. Iron is an essential micronutrient for cell growth that plays an important role in energy metabolism and DNA synthesis. Malignant cells requiring more iron modulate a transferrin receptor. Iron-bound transferrin interacts with this receptor, facilitating the transport of iron across the cell membrane. Transferrin is a glycoprotein and is the chief iron transport protein in mammalian blood. The more aggressive the tumor, the higher the transferrin receptor levels and the greater the proliferative index. We have found by cytochemical and ultrastructural studies that ferritin, an iron storage protein, is increased in breast cancer tissue. Anaplastic tumors have higher tissue ferritin levels. Tissue ferritin concentration may be an indirect method of measuring transferrin receptors and thus might be an index of proliferation and a prognostic indicator. Transferrin may be used as a carrier to target toxic therapy selectively to tumor tissue. A platinum transferrin complex (MPTC-63) has been developed and shown to be cytostatic in tissue culture, animal, and human studies. It also sensitizes tissue to agents that produce free radicals, such as adriamycin, and thus is synergistic with other drugs and radiation. Other transferrin complexes and conjugates of gallium, indium, and daunorubicin have also shown growth inhibition in tissue culture and animals. Human studies are in progress. By studying iron metabolism in breast cancer, we may be able to selectively inhibit tumor growth without toxic effects, and with other tumor biologic data be better able to select the stage I patient for adjuvant therapy.

Adenocarcinoma↗
PubMed1993

Pyrularia thionin binding to and the role of tryptophan-8 in the enhancement of phosphatidylserine domains in erythrocyte membranes.

Pyrularia thionin is a small, strongly basic peptide which interacts readily with cellular and synthetic membranes. With cells it induces hemolysis, depolarizes the cellular membrane with an accompanying influx of Ca2+, and activates an endogenous phospholipase A2. Evidence points toward a binding site involving phosphatidylserine (PS). This study shows that addition of the peptide to erythrocyte membranes as well as to vesicles formed from phospholipids isolated from erythrocyte membranes causes an enhancement of phospholipid domains which are made visible by the use of fluorescence digital imaging microscopy with fluorescent derivatives of PS (NBD-PS) and phosphatidylcholine (NBD-PC). Addition of thionin caused a large increase in NBD-PS domains, with an accompanying enrichment of NBD-PC in another separate domain. Double-labeling experiments performed with a Texas Red derivative of thionin show that the peptide binds to the domain enriched in NBD-PS. P thionin inactivated by modification of Trp-8 with N-bromosuccinimide lost the ability to enhance PS domains, although it bound to the membrane with the same affinity as native P thionin. This shows that binding to the membrane is not in itself sufficient to cause the NBD-PS and NBD-PC redistribution into domains.

Animals↗
PubMed1993

Comparative analysis of NFAT (nuclear factor of activated T cells) complex in human T and B lymphocytes.

Nuclear factor of activated T cells (NFAT) is a transcriptional activator that binds to sequences in the interleukin-2 (IL-2) promoter and is thought to be largely responsible for the T cell-specific inducibility of IL-2 expression. Electrophoretic mobility shift assays (EMSA) showed that specific NFAT binding activity could also be induced in human B cells. The B cell NFAT complex, however, was not functional, since it failed to activate transcription from an NFAT-driven chloramphenicol acetyltransferase (CAT) construct. Competition with an AP-1 motif or with anti-Jun and anti-Fos antibodies abolished binding to the NFAT motif in both T and B cells, indicating that Jun and Fos are critical for NFAT complex formation in both cell types. Purified recombinant Jun and Fos proteins failed to bind directly to the NFAT motif. However, when combined with unstimulated B or T cell extracts, full-length, but not truncated, Jun/Fos heterodimers were able to form an NFAT complex, indicating the presence of a constitutively expressed nuclear factor(s) in B and T cells necessary for the formation of the NFAT complex in both cell types. An NFAT oligonucleotide carrying mutations in the 5' purine-rich part of the NFAT sequence failed to form a complex and to compete with the wild type motif for NFAT complex formation in both T and B cells. We therefore propose a model whereby a core NFAT complex consisting of Jun, Fos, and a constitutive nuclear factor is formed in both T and B cells, but an additional factor and/or post-translational modification of a factor, missing in B cells, might be required for transactivation by NFAT.

B-Lymphocytes↗
PubMed1993

A widely expressed transmembrane serine/threonine kinase that does not bind activin, inhibin, transforming growth factor beta, or bone morphogenic factor.

Molecular cloning of complementary DNAs (cDNA) whose expression products bind activin and transforming growth factor beta (TGF-beta 1 and -beta 2) suggests that transmembrane serine/threonine kinases constitute a new class of signaling molecules. A human liver cell cDNA which codes for a new serine/threonine kinase receptor (SKR1) was identified using degenerate oligonucleotide primers complementary to coding sequence for mouse activin and Caenorhabditis elegans daf-1 serine/threonine receptor kinase subdomains VI and VIII in the polymerase chain reaction. The deduced 509-amino acid product consisted of a cysteine-rich extracellular domain and a cytoplasmic serine/threonine kinase domain which are 10-20 and 40% homologous to the respective domains in the activin and transforming growth factor beta receptor kinases. Cells overexpressing SKR1 exhibited no increase in binding of activin, inhibin, TGF-beta 1, TGF-beta 2, or bone morphogenic factor type 2B. Except for its absence in bone and spleen, SKR1 exhibits a tissue expression pattern similar to the TGF-beta receptor II gene. Similarly, SKR1 is expressed in normal parenchymal cells, endothelial cells, fibroblasts, and tumor-derived epithelial cells. The expression pattern and lack of binding to prototypic members of the TGF-beta 1-5 branch of the TGF-beta superfamily suggests that SKR1 is potentially a receptor for a new member of the TGF-beta branch of the ligand superfamily.

Activins↗
PubMed1993

An essential heparin-binding domain in the fibroblast growth factor receptor kinase.

Heparin or heparin-like heparan sulfate proteoglycans are obligatory for activity of the heparin-binding fibroblast growth factor (FGF) family. Heparin interacts independently of FGF ligand with a specific sequence (K18K) in one of the immunoglobulin-like loops in the extracellular domain of the FGF receptor tyrosine kinase transmembrane glycoprotein. A synthetic peptide corresponding to K18K inhibited heparin and heparin-dependent FGF binding to the receptor. K18K and an antibody to K18K were antagonists of FGF-stimulated cell growth. Point mutations of lysine residues in the K18K sequence abrogated both heparin- and ligand-binding activities of the receptor kinase. The results indicate that the FGF receptor is a ternary complex of heparan sulfate proteoglycan, tyrosine kinase transmembrane glycoprotein, and ligand.

Amino Acid Sequence↗
PubMed1993

A new protein kinase C, nPKC eta', and nPKC theta are expressed in human platelets: involvement of nPKC eta' and nPKC theta in signal transduction stimulated by PAF.

We have detected in human platelets two protein kinase C isozymes that have not been reported previously. Using an anti-nPKC theta antibody and Western blotting, we calculated the molecular weight of platelet nPKC theta as 79K. This molecular weight is identical to that described for nPKC theta in skeletal muscle and in COS cells transfected with the nPKC theta-cDNA. Using an anti-nPKC eta antibody, we determined the molecular weight of an immunoreactive protein, which we called nPKC eta', to be 95K. This molecular weight is higher than that of nPKC eta found in lung and skin tissue of 82K and 78K, and it is higher than nPKC eta of COS cells transfected with the nPKC eta-cDNA expression plasmid. Together with previous reports, these findings make the total number of PKC isozymes in human platelets equal to six. These are the PKC isozymes: alpha, beta, delta and zeta, which have been previously described, and eta' and theta which we describe here. To assess the functionality of these new PKC isoforms, we stimulated platelets with PAF. We found a 200% and 175% increase in the levels of membrane-bound nPKC eta' and nPKC theta, respectively, in human platelets stimulated by PAF. A concomitant decrease in the level of these isoforms in the cytoplasm was observed. This PAF-induced translocation was time-dependent, and it reached its peak after a 1 minute incubation of human platelets with PAF for nPKC theta and 30 seconds for nPKC eta'.

Amino Acid Sequence↗
PubMed1993

Regulation of actomyosin interactions in Limulus muscle proteins.

Contraction of striated muscle from Limulus polyphemus, the horseshoe crab, is regulated by both calcium binding to a troponin-tropomyosin-dependent thin filament array and a myosin light chain kinase-dependent phosphorylation of myosin. We have isolated myosin from Limulus striated muscle and examined how these two regulatory systems affect the sliding velocity of actin filaments over myosin, using an in vitro motility assay. Our results show that in the presence of ATP, Limulus myosin must be phosphorylated in order to move actin filaments. No movement was observed for actin filaments interacting with dephosphorylated Limulus myosin. Calcium was not required for actin movement. In contrast, when both troponin and tropomyosin are bound to actin filaments, calcium is required for the movement of actin filaments over phosphorylated myosin. These results demonstrate that the "off" state of either the thin filament or thick filament regulatory system is dominant and that for the movement to occur, both phosphorylated Limulus myosin and an activated troponin-tropomyosin system are required. Tropomyosin by itself increases the sliding velocity of actin filaments over phosphorylated Limulus myosin about 10-fold in a calcium-independent manner. Tropomyosins from turkey gizzard smooth muscle, bovine cardiac muscle, and Limulus muscle all have a profound effect in increasing the velocity. Troponin alone does not change the velocity. Partial sequences of the tryptic phosphopeptides of Limulus myosin regulatory light chains generated following the phosphorylation by gizzard myosin light chain kinase yield ATS(PO4)NVFAMFEQNQIA for 21 kDa and SGS(PO4)NVFSMFT for 31-kDa light chain.

Actins↗
PubMed1993

Electroblotting proteolytic products from native gel for direct N-terminal sequence analysis: an approach for studying protein-protein interaction.

Proteins which are electroblotted from native gels onto polyvinylidene difluoride (PVDF) membranes are suitable for detailed structural analysis. This method, in conjunction with limited proteolysis and N-terminal sequencing, has been used to study the molecular interactions between native protein molecules. The interaction between recombinant interleukin-2 (rIL-2) and its receptor (rIL-2R alpha) was examined as a model system. The working strategy consists of (i) proteolysis of rIL-2R alpha and rIL-2R alpha/rIL-2 complex, (ii) separation of the major proteolytic products by native polyacrylamide gel electrophoresis followed by electroblotting onto PVDF membrane, and (iii) sequence analysis of the blotted protein bands for the identification of peptide regions sensitive to proteolysis. Results have indicated that the exon 3 encoded region in rIL-2R alpha is sensitive to proteolysis regardless whether it is complexed with rIL-2 or not. This suggests that no major conformational changes occur in rIL-2R alpha during interaction with rIL-2. This electroblotting approach is, therefore, useful for studying protein-protein interaction in solution.

Animals↗
PubMed1993

Purification and properties of a diisopropyl-fluorophosphatase from squid Todarodes pacificus steenstrup.

A diisopropyl-fluorophosphatase (DFPase) was purified from brain and ganglia of squid Todarodes pacificus steenstrup. The DFPase had a preference in hydrolysis toward diisopropylphosphorofluoridate (DFP). It also was able to hydrolyze O-1,2,2-trimethylpropyl methylphosphofluoridate (soman) and O-isopropyl methylphosphonofluoridate (sarin) at nearly equal hydrolytic rates but only 1/10 that of DFP. The hydrolytic activity toward diethyl-p-nitrophenylphosphate (paraoxon) was very low compared with DFP, soman, and sarin. The DFPase was purified 330-fold to a specific activity of 18,300 n mol/min/mg protein. Its molecular weight was 34,000 dalton determined by gel-filtration chromatography. Mn2+ stimulation of the DFPase was not observed when DFP and soman were the substrates, but with sarin, the rate increased onefold in the presence of 1.0 mM of Mn2+. Ethylenediamine tetraacetic acid disodium (EDTA-Na2) at 0.05 M inhibited the DFPase activity about 30%. It could be concluded that this DFPase belongs to the squid-type DFPase.

Animals↗
PubMed1993

Factors affecting filament velocity in in vitro motility assays and their relation to unloaded shortening velocity in muscle fibers.

The measurement of fluorescently labeled actin filament movement driven by mechanoenzymes (e.g. myosin) is an important methodology for the study of molecular motors. It is assumed that the filament velocity, Vf, is analogous to the unloaded shortening velocity, Vu, seen in muscle fibers. To evaluate this assumption we compared Vf to literature values for Vu with regard to the effects of [ATP], [ADP], [Pi], pH, ionic strength (10-150 mM) and temperature (15-30 degrees C). Vf and Vu are quantitatively similar with respect to the effects of substrate and product concentrations and temperatures > 20 degrees C. However, Vf is more sensitive to decreases in pH and temperatures < 20 degrees C than is Vu. At ionic strengths of 50-150 mM, Vf and Vu exhibit similar ionic strength dependencies (decreasing with ionic strength). At ionic strengths < 50 mM, Vf is markedly reduced. Thus while Vf is a good analogue for Vu under certain conditions (elevated ionic strength and temperatures > 20 degrees C), under others it is not. The results of motility assays must be cautiously interpreted.

Actin Cytoskeleton↗
PubMed1993

Heparin-binding fibroblast growth factors and prostate cancer.

Studies of model rat prostate tissue and derived cells indicate the insulin-like (IGF), epidermal growth factor (EGF), transforming growth factor beta (TGF-beta) and heparin-binding fibroblast growth factor (HBGF) families and their receptors may play important roles in regulation of normal prostate cell growth. Tumor cells at different levels in the progression from slow-growing, hormone-dependence to fast-growing, hormone-independence exhibit distinct alterations in expression of specific growth factors and their receptor phenotype. Distinct IGF-I and HBGF mRNAs are constitutively expressed in the mesenchymal cells of slow-tumors, but alteration in HBGF receptor phenotype occurs in the epithelial cells. Fast-tumors exhibit even higher constitutive expression of multiple HBGFs. Splice variants in cDNA for the HBGF receptor in fast-tumors suggest constitutive expression of an intracellular receptor, that together with intracellular HBGFs, may constitute an intracellular autocrine system that is independent of exogenous hormones and growth factors.

Amino Acid Sequence↗
PubMed1993

Limited tryptic digestion of recombinant human interleukin-2: structure-binding relationships with the alpha chain of the interleukin-2 receptor.

The surface topography and structural features of interleukin-2 (IL-2) in relation to its interaction with the alpha subunit of its receptor (IL-2R alpha) have been probed by limited tryptic digestion followed by detailed structural analyses. Four sensitive cleavage sites in IL-2 (Lys8, Lys9, Lys35, and Arg38) were identified as surface amino acids, suggesting that they are potential binding sites for IL-2R alpha. To examine the involvement of these residues in IL-2R alpha binding, a truncated IL-2 molecule lacking the amino-terminal residues through Arg38 was generated and it was found to be incapable of binding IL-2R alpha in a solid-phase receptor binding sequencing assay. These studies have led to the conclusion that the IL-2R alpha contact region of IL-2 includes residues Lys35 and Arg38. This finding is supported by the refined three-dimensional structure of IL-2 in which these residues are located outside of the compact bundle of four helices and thus are readily available for interaction with IL-2R alpha.

Amino Acid Sequence↗
PubMed1993

A new hypothesis about the relationship between free radical reactions and hemorheological properties in vivo.

This paper is concerned with a hypothesis that disturbance of free radical reactions may lead to abnormality of hemorheological properties in vivo, and so the free radicals generated in vivo may damage certain tissue cells indirectly by reducing the supply of oxygen and nutrients to these cells through slowing the circulation of blood. This hypothesis is based on the following evidence: A. We have found that the whole blood viscosity at low shear rate correlates to the lipid peroxidation in the patients suffering from certain cardio- or cerebrovascular diseases, and in dogs during liver ischemia reperfusion or hemorrhagic pancreatitis. B. Reports have shown that several alterations of hemorheological properties may take place as a result of free radical reactions, such as lipid peroxidation. For instance, lipid peroxidation may lead to decrease of deformability of red cells, increase of aggregation of red cells, formation of liquid thrombin, etc. C. We have demonstrated that some alterations of hemorheological properties involve the role of free radicals in rats suffering from intestinal ischemia/reperfusion. As evidence for this conclusion, superoxide dismutase (SOD) used as a specific scavenger of superoxide anion radical (O2-) can significantly prevent the intestinal ischemia/reperfusion induced changes of lipid peroxidation, red cell aggregation, Cassion's viscosity and whole blood viscosity at low shear rate in rats.

Animals↗
PubMed1993

The epidemiology of iodine-deficiency diseases in China.

Iodine-deficiency diseases (IDDs) are wide-spread in China, distributed mainly in the inland and mountainous regions. About one-third of the total Chinese population lives in IDD-endemic areas. The severity of IDD is related to the severity of iodine deficiency. All the selenium-deficient areas of China are also IDD-endemic areas; however, IDD can be very severe in areas where selenium status is thought to be adequate. The distribution of myxedematous cretinism in China is not related to selenium deficiency. In the Tarim Basin, the selenium status of the population is normal and myxedematous cretinism is prevalent. In the northeastern regions of China, selenium deficiency is common and neurological cretinism is very rare.

Cardiomyopathies↗
PubMed1993

Antiribosomal P protein antibodies in different populations of patients with systemic lupus erythematosus.

We report a significantly increased prevalence of antiribosomal P protein antibodies in Malaysian Chinese patients (38%) with SLE compared to white Caucasian (13%) and Afro-Caribbean (20%) patients. The increased prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients.

Antibodies, Anti-Idiotypic↗