Biomedical subjects

C Yang

Publications and source records attributed to C Yang.

At least 379 records · Page 21Linked to original sources

PubMed1996

Effects of caffeine on intracellular calcium release and calcium influx in a clonal beta-cell line RINm5F.

We studied the effects of caffeine on intracellular calcium in a clonal insulin-secreting cell line RINm5F. Caffeine (1-30 mM) induced a dose-dependent intracellular Ca2+ release and Ca2+ influx. Pretreatment with combination of ryanodine (10 microM) and caffeine (10 mM), but not ryanodine alone, abolished subsequent caffeine-induced release of intracellular Ca2+. Pretreatment with another ryanodine receptor blocker procaine (0.1, 0.3, and 1mM) antagonized the caffeine-induced release of intracellular Ca2+. Pretreatment with thapsigargin (2 microM), the endoplasmic reticular Ca2+-ATPase inhibitor, abolished both the caffeine- and arginine vasopressin (AVP)-induced Ca2+ release. AVP induces Ca2+ release by increasing the formation of IP3. Pretreatment with AVP greatly reduced caffeine-induced Ca2+ release whereas pretreatment with caffeine also reduced AVP-induced Ca2+ release. The L-type Ca2+ channel blocker nimodipine (1 microM) inhibited caffeine-induced Ca2+ influx. In addition, depletion of intracellular Ca2+ stores with thapsigargin did not affect caffeine-induced Ca2+ influx. These results suggested that: 1) the ryanodine- and caffeine-sensitive Ca2+ store exists in RINm5F cells, 2) most of these Ca2+ release channels in RINm5F cells are closed in the resting state, since pretreatment with ryanodine alone failed to block the caffeine-induced Ca2+ release, 3) there is a "cross-talk" between the caffeine- and IP3-sensitive pools in RINm5F cells, 4) caffeine increases Ca2+ entry in RINm5F cells through L-type voltage-dependent Ca2+ channels, and 5) the caffeine-induced Ca2+ influx is independent of the Ca2+ release from the intracellular Ca2+ stores.

Animals↗

PubMed1996

Influence of adjuvants on murine immune responses against the C-terminal 19 kDa fragment of Plasmodium vivax merozoite surface protein-1 (MSP-1).

The immunogenicity of a yeast-expressed 19 kDa fragment of P vivax MSP-1 in the presence of different adjuvant formulations was evaluated. ICR mice were immunized with the 19 kDa antigen, using Freund's, alum, and block copolymer P1005 in water-in-oil (W/O) or oil-in-water (O/W) emulsions with or without detoxified lipopolysaccharide (RaLPS) as adjuvants. Five weeks following immunization with the antigen, mice were boosted with asexual blood-stage antigens. Three weeks after the last immunization with the 19 kDa antigen, mice from the Freund's group and most groups that received P1005 as adjuvant had higher total IgG titres than those that received alum as adjuvant or antigen alone. Antibody responses after the antigen immunization were predominantly of the IgG1 isotype, but mice in the Freund's and P1005 (W/O or O/W emulsion with or without RaLPS) groups also had high titres of IgG2a and IgG2b. Antibody titres against merozoites increased in all groups after the parasite antigen boost. IgG2a levels in the group that received antigen in P1005 plus RaLPS in the W/O emulsion were higher than those receiving Freund's, alum or the other copolymer adjuvants. The high IgG2a titres in this group were associated with reduced IL-10 production.

Adjuvants, Immunologic↗

PubMed1996

Lysophosphatidic acid-induced neurite retraction in PC12 cells: control by phosphoinositide-Ca2+ signaling and Rho.

The endogenous phospholipid mediator lysophosphatidic acid (LPA) caused growth cone collapse, neurite retraction, and cell flattening in differentiated PC12 cells. Neurite retraction was blocked by cytochalasin B and ADP-ribosylation of the small-molecular-weight G protein Rho by the Clostridium botulinum C-3 toxin. LPA induced a transient rise in the level of inositol 1,4,5-trisphosphate, and retraction was blocked by inhibitors of phospholipase beta. Repeated application of LPA elicited homologous desensitization of the Ca2+ mobilization response. The activation of the phosphoinositide (PIP)-Ca2+ second messenger system played a permissive role in the morphoregulatory response. Blockers of protein kinase C--chelerythrine, a myristoylated pseudosubstrate peptide, staurosporine, and depletion of protein kinase C from the cells by long-term phorbol ester treatment--all diminished neurite retraction by interfering with LPA-induced Ca2+ mobilization, which was required for the withdrawal of neurites. A brief 15-min treatment with 4 beta-phorbol 12-myristate 13-acetate also blocked retraction and Ca2+ mobilization, by inactivating the LPA receptor. Inhibition of protein tyrosine phosphorylation by herbimycin diminished retraction. Although activation of the PIP-Ca2+ second messenger system appears necessary for the Rho-mediated rearrangements of the actin cytoskeleton, bradykinin, which activates similar signaling events, failed to cause retraction, indicating that a yet unidentified novel mechanism is also involved in the LPA-induced morphoregulatory response.

Actins↗

PubMed1996

The epidemiology of Chlamydia trachomatis within a sexually transmitted diseases core group.

Female sex workers in Nairobi were prospectively evaluated for risk factors of incident Chlamydia trachomatis infection. Independent risk factors included cervical ectopy (P=.007), gonococcal infection (P=.002), human immunodeficiency virus (HIV) seropositivity (P=.003), HIV seroconversion (P=.001), and duration of prostitution (P=.002). Eighteen different C. trachomatis outer membrane protein (omp1) genotypes were identified, with the allelic composition of the C. trachomatis population changing significantly over time (P=.005). Seventeen of 19 reinfections > or = 6 months apart were with different C. trachomatis omp1 genotypes. Women with HIV infection had an increased proportion of visits with C. trachomatis infection (P=.001) and an increased risk of reinfection (P=.008). Overall, the data demonstrate significant fluctuations in the genotype composition of the C. trachomatis population and a reduced rate of same-genotype reinfection consistent with the occurrence of strain-specific immunity.

Amino Acid Sequence↗

PubMed1996

Protecting fibrinogen with rutin during UVC irradiation for viral inactivation.

Fibrinogen solutions were irradiated with UVC (254 nm) to inactivate contaminating viruses. In order to protect fibrinogen during UVC irradiation, 0.5 mM rutin was added prior to UVC exposure and subsequently removed during processing. Viral kill by 0.1 J/cm2 UVC resulted in the following inactivation values (log 10): non-lipid-enveloped viruses: Parvo > or = 5.5; encephalomyocarditis virus > or = 6.5; hepatitis A virus > or = 6.5: lipid-enveloped viruses: human immunodeficiency virus > or = 5.7; vesicular stomatitis virus > or = 5.7. Fibrinogen irradiated with 0.5 mM rutin did not significantly differ from unirradiated material in terms of clot time and breaking strength. In the absence of rutin, UVC irradiation of fibrinogen at similar fluence led to loss of solubility, increased clot time and the cleavage of fibrino-peptides that reacted with dinitrophenyl hydrazine as a test for ketonic carbonyl groups. High-performance liquid chromatography and mass spectrometry data showed that rutin exposed to UVC formed numerous breakdown, oxidation and combinational products. Experiments with 3H-rutin showed that after UVC irradiation, subsequent processing by a C18 resin and alcohol precipitation removed > 99% rutin, representing < 10 ppm rutin in the final fibrinogen preparations. Residual 3H-rutin was not covalently bonded to the fibrinogen. Immunochemical studies with rabbit antisera to UVC irradiated (with rutin) fibrinogen showed the absence of neoimmungens. By all measures, rutin prevents fibrinogen degradation during virucidal UVC irradiation.

Animals↗

PubMed1996

Sulfated polyanions inhibit invasion of erythrocytes by plasmodial merozoites and cytoadherence of endothelial cells to parasitized erythrocytes.

Sulfated proteoglycans have been shown to be involved in the binding of sporozoites of malaria parasites to hepatocytes. In this study, we have evaluated the effect of sulfated glycosaminoglycans on the invasion of erythrocytes by Plasmodium falciparum merozoites and cytoadherence of parasitized erythrocytes (PRBC) to endothelial cells. Invasion of erythrocytes by HB3EC-6 (an HB3 line selected for high binding to endothelial cells) was inhibited by dextran sulfate 500K, dextran sulfate 5K, sulfatides, fucoidan, and heparin but not by chondroitin sulfate A. With the exception of sulfatides, the invasion-inhibitory effect was not mediated by killing of parasites. Cytoadherence of HB3EC-6 to human microvascular endothelial cells (HMEC-1) and inhibited by these sulfated glycoconjugates. The highly sulfated dextran sulfate 500K had the highest inhibitory effect on both invasion and cytoadherence, whereas the positively charged protamine sulfate promoted cytoadherence. Because preincubation of PRBC with sulfated glycosaminoglycans and treatment of target cells with heparinase had no significant inhibition on cytoadherence, it is unlikely that sulfated glycoconjugates are used directly by endothelial cells as cytoadhesion receptors. In an vivo experiment, we found that the administration of dextran sulfate 500K to CBA/Ca mice infected with Plasmodium berghei ANKA reduced parasitemia and delayed the death associated with anemia. These observations suggest that sulfated polyanions inhibit the invasion of erythrocytes by merozoites and cytoadherence of PRBC to endothelial cells by increasing negative repulsive charge and sterically interfering with the ligand-receptor interaction after binding to target cells.

Animals↗

PubMed1996

Molecular cloning and characterization of the Coccidioides immitis complement fixation/chitinase antigen.

Detection of anti-Coccidioides complement-fixing (CF) antibody is a valuable diagnostic and prognostic aid in coccidioidomycosis. The CF antibody response is directed against a heat-labile antigen that has chitinase activity, hereafter referred to as the CF/chitinase protein. To identify and clone this immunoreactive enzyme, we constructed a Coccidioides immitis cDNA lambda ZAP expression library from spherule RNA and detected fusion peptides expressing CF epitopes by immunoscreening. A cDNA clone consisting of 1,623 bp was identified, sequenced, and found to contain a single open reading frame that encodes a protein of 47 kDa with 427 amino acids. Deduced amino acid sequence analyses showed that the cloned CF/chitinase cDNA contains a 35-amino-acid region, beginning at Ser-18 and ending at and ending at Arg-52 which has 92% homology with the reported N-terminal amino acid sequence of authentic CF/chitinase protein. The first 17 amino acids in the deduced sequence of the cloned cDNA are not present on the mature CF/chitinase protein, suggesting that it may be a signal peptide. Expression of the CF/chitinase cDNA insert by using the pGEX-4T-3 vector yields a fusion peptide that bears CF-specific epitopes and shows chitinase activity. The CF/chitinase clone will enable large-scale production of the recombinant CF antigen for use in immunoassays and facilitate studies on the role of chitinase in the morphogenesis of C. immitis.

Amino Acid Sequence↗

PubMed1996

Molecular cloning and characterization of Coccidioides immitis antigen 2 cDNA.

Previous experiments have provided evidence that Coccidioides immitis antigen 2 (Ag2) is a major T-cell-reactive component of mycelia and spherule cell walls. Here we report the identification and cloning of the cDNA that encodes Ag2 from a lambda ZAP cDNA expression library constructed from spherule-derived RNA. DNA sequence analysis established that the 1,255-bp clone contains a 174-bp 5' untranslated region, a 582-bp open reading frame which encodes for a protein consisting of 194 amino acids, and a 375-bp 3' untranslated region, including a poly(A) tail. The recombinant Ag2 protein has a predicted molecular mass of 19.5 kDa and contains an 18-amino-acid N terminus which has been tentatively identified as a signal peptide. The Ag2 cDNA was ligated into the pGEX-4T-3 vector and expressed in Escherichia coli TG-1 cells as a glutathione S-transferase fusion protein. The recombinant fusion protein showed reactivity with sera from patients with coccidioidomycosis and elicited delayed-type footpad hypersensitivity responses in Coccidioides-immune mice. These results suggest that the Ag2 cDNA can be used for the large-scale production of this immunologically important protein.

Amino Acid Sequence↗

PubMed1996

Analysis of the cell fusion activities of chimeric simian immunodeficiency virus-murine leukemia virus envelope proteins: inhibitory effects of the R peptide.

It was previously reported that truncation or proteolytic removal of the C-terminal 16 amino acids (the R peptide) from the cytoplasmic tail of the murine leukemia virus (MuLV) envelope protein greatly increases its fusion activity. In this study, to investigate the specificity of the effect of the R peptide on the fusion activity of viral envelope proteins, we expressed simian immunodeficiency virus (SIV)-MuLV chimeric proteins in which the entire cytoplasmic tail of the SIV envelope protein was replaced by either the full-length MuLV cytoplasmic tail or a truncated MuLV cytoplasmic tail with the R peptide deleted. Extensive fusion of CD4-positive cells with the chimeric protein containing a truncated MuLV cytoplasmic tail was observed. In contrast, no cell fusion activity was found for the chimeric protein with a full-length MuLV cytoplasmic tail. We constructed another SIV-MuLV chimeric protein in which the MuLV R peptide was added to an SIV envelope protein cytoplasmic tail 17 amino acids from its membrane-spanning domain. No fusion activity was observed within this construct, while the corresponding truncated SIV envelope protein lacking the R peptide showed extensive fusion activity. No significant difference in the transport or surface expression was observed among the various SIV-MuLV chimeric proteins and the truncated SIV envelope protein. Our results thus demonstrate that the MuLV R peptide has profound inhibitory effects on virus-induced cell fusion, not only with MuLV but also in a distantly related retroviral envelope protein which utilizes a different receptor and fuses different cell types.

Amino Acid Sequence↗

PubMed1996

Experimental Campylobacter jejuni infection in the chicken: an animal model of axonal Guillain-Barré syndrome.

OBJECTIVE: To develop and characterise an animal model of paralytic neuropathy after Campylobacter jejuni infection. Campylobacter infection precedes development of many cases of Guillain-Barré syndrome and is particularly associated with cases having prominent axonal degeneration. Understanding the pathogenesis of Guillain-Barré syndrome after C jejuni infection has been slowed by the lack of animal models. METHODS: A spontaneous paralytic neuropathy is described that developed in chickens from the farms of four patients with Guillain-Barré syndrome. The production of paralytic neuropathy in chickens experimentally fed Campylobacter jejuni isolated from one of these patients is reported. The sciatic nerves of the spontaneously paralysed chickens were examined pathologically in teased fibres, in plastic embedded sections, and by electron microscopy. Two large groups of chickens were then fed cultures of a C jejuni (Penner type O:19) isolated from one of these patients. RESULTS: The chickens with spontaneous paralysis had pathologically noninflammatory neuropathy. Pathology in the sciatic nerves ranged from no detectable changes to severe Wallerian-like degeneration. In the experimentally inoculated groups, an average of 33% of the chickens became paralysed. The median time after inoculation to paralysis was 12 days. The lesions found in the first few days of paralysis included nodal lengthening and paranodal demyelination. In those animals that survived for several days after onset of weakness, the pathology was dominated by extensive Wallerian-like degeneration. Animals that survived for weeks with no clinically apparent neuropathy had paranodal remyelination in some teased nerve fibres, reflecting earlier paranodal demyelination. CONCLUSION: Experimental inoculation with C jejuni may provide a new model for understanding some forms of Guillain-Barré syndrome.

Animals↗

PubMed1996

A 60-kilodalton protein in rat hepatoma cells overexpressing insulin receptor was tyrosine phosphorylated and associated with Syp, phophatidylinositol 3-kinase, and Grb2 in an insulin-dependent manner.

Tyrosine phosphorylation of cellular proteins is an early and key step after activation of the insulin receptor kinase (IRK). The study of the properties of these proteins should contribute to our understanding of insulin action. In rat hepatoma cells overexpressing human insulin receptors (HTC-IR), insulin treatment resulted in rapid tyrosine phosphorylation of proteins of 180, 94, 68, and 60 kDa. When lysates from insulin-treated cells were immunoprecipitated with anti-Syp antibody, subsequent immunoblotting identified p65 and p68, which reacted with anti-Syp, and p6O and p68, which reacted with antiphosphotyrosine antibody. Thus, insulin treatment yielded tyrosine phosphorylation of both Syp and a Syp-associated p6O molecule. When lysates from insulin-treated cells were adsorbed with a glutathione S-transferase (GST)-Syp-Src homology-2 (SH2) fusion protein, tyrosine- phosphorylated p6O was sequestered. After subjecting lysates to SDS-PAGE, the GST-SypSH2 fusion protein was found to bind to p18O, p94, and p6O. Thus, Syp associates directly with a 60-kDa IRK substrate via its SH2 domains. Syp-associated p6O differed from the 60- to 62-kDa proteins, associating with ras guanosine triphosphatase-activating protein, which also underwent modest tyrosine phosphorylation in response to insulin. Preadsorption of cell lystates with antibody against the 85-kDa subunit (p85) of phosphatidylinositol 3-kinase substantially reduced the amount of p60 subsequently immunoprecipitated by anti-Syp. Thus, p60 associates with both Syp and p85. The amount of tyrosine-phosphorylated p60 exceeded that of p180 in anti-Syp immunoprecipitates, whereas their proportion was comparable in anti-p85 immunoprecipitates. Grb2 was also observed in the anti-Syp immunoprecipitates. When lysates from insulin-treated cells were adsorbed with GST-p85SH2 domains or GST-Grb2, the subsequent eluates contained tyrosine-phosphorylated p60, as determined by immunoblotting with antiphosphotyrosine. Membrane binding assays using GST fusion proteins showed that these associations were direct. Studies in rat liver, muscle, and adipose tissue identified insulin-dependent association of Syp, Grb2, and p85 with tyrosine-phosphorylated p60 in adipose tissue only. We conclude that insulin treatment of HTC-IR cells and rat adipose tissue results in the tyrosine phosphorylation of p60, which might participate in the recruitment of downstream effectors involved in insulin signal transduction.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Comparative study of antigen retrieval heating methods: microwave, microwave and pressure cooker, autoclave, and steamer.

We present a study comparing the most popular heating methods currently used for antigen retrieval (AR) immunostaining: the microwave oven, microwave with pressure cooker, autoclave, and steamer heating. A panel of 21 antibodies was tested on formalin fixed, paraffin embedded sections using these heating methods and Tris-HC1 buffer, pH 9.5, plus 5% urea as the AR solution. Three observers independently evaluated the intensity of AR immunostaining. All heating methods yielded good results for AR immunostaining. There were only minor differences among the heating methods for AR when the optimal concentration of primary antibody for normal immunostaining was used; however, background staining may occasionally be troublesome if antibodies are not retitrated and diluted further for use on tissues after AR. Significant differences were observed only after further dilution of the primary antibodies: the microwave pressure cooker, extended microwave heating (5 min x 4) and autoclave heating then showed a similar intensity of staining that was stronger than results obtained with the steamer (20 min) or regular microwave heating (5 min x 2). Extension of the steamer heating time, however, yielded equivalent results. This study indicates that different heating methods can yield similar intensities of AR immunostaining if the heating times are adjusted appropriately. It is noteworthy that, in general, the adjusted conditions for maximal retrieval differ from those most widely cited in the literature, or recommended by manufacturers. That several heating devices may provide similar results permits the use of different AR heating methods according to the equipment available. This study also is an early step in standardizing the AR immunostaining protocol by providing uniform conditions for "maximal retrieval" as a common end point for all laboratories.

Antigens↗

PubMed1996

Enhancement of v-src transforming activity by simian virus 40 small t antigen.

The simian virus 40 (SV40) small t (t) antigen is known to be able to induce cell proliferation and to enhance the transforming activity of SV40 large T antigen. Here we report that t could also enhance the transforming activity of v-src oncogene. When t was transfected into the v-src-transformed NIH3T3 cells, the t-expressing stable clones grew faster and grew to higher density than did the parental or vector-transfected cells. Furthermore, these t-expressing cells also showed better plating efficiency and grew more efficiently in soft agar than did the parental or vector-transfected cells. More importantly, the t-expressing cells displayed high tendency to aggregate and detached easily from the dishes, while the parental or vector-transfected cells never exhibited such phenotype. This last observation suggests that t may affect the expression of adhesion molecules in the v-src-transformed NIH3T3 cells. Taken together, we concluded that t could enhance the transforming activity of v-src and alter the transformed morphology of v-src-transformed NIH3T3 cells.

3T3 Cells↗

PubMed1996

[The effects of fertility compression on birth sequence and age composition in Taiwan: a simulation].

"Based on the cohort component projection, this paper simulates the effects of fertility compression on birth sequence and age composition in Taiwan, and explores the implications for social welfare. As a first step, we fix the fertility schedule on the age pattern of 1956 while leaving the TFR to shift as it was, [and] simulate the single year of age population groups from 1956 to 1992.... We subsequently assumed a fixed age pattern of fertility, a compressed pattern and an expanded pattern in a projection of five year...age groups from 1997 to 2097." (SUMMARY IN ENG)

Age Distribution↗

PubMed1996

[Diagnostic arthroscopy of the Maraca mulatto's TMJ]

To gain further knowledge about features of Maraca mulatto's TMJ,occlusion,and teeth,we underwent examining 4 rhesus monkeys with 8 joints.The same and different features were concluded between Maraca mulatto's anatomical structures and human begins.Afterwards,10 aged rhesus monkeys with 20 joints were examined by TMJ arthroscopy.The results showed that the appearances in 70%(14/20) of the aged were the same as those in human pathologic TMJs. In conclusion,the Maraca mulatto can suffer from the same arthropathy as human being,and it is possible to choose the aged as a natural pathologic model.

Journal Article↗

PubMed1996

[A prospective study evaluating effectiveness of TMJ arthroscopy for particular stages of internal derangement]

The purpose of this prospective study is to evaluate effect on particular stages of internal derangement by TMJ arthroscopy.According to Wilkes-Bronstein classification,the distributions between 81 joints and particular stages of ID were:25 joints in II stage,18 in III,24 in IV,and 14 in V.The total 81 joints were undergone by arthroscopic surgery,the total success rates of different stages of ID were:24/25 joints in II stage,16/18 in III,13/24 in IV,and 7/14 in V particularly.The success rates were no statically significance (P>0.05) between II stage and III stage or between IV and V or V stages.The conclusion is that these cases in II or III stages of ID choose arthroscopic surgery than those cases in IV or V stages.

Journal Article↗

PubMed1996

[A retrospective study evaluating effectiveness of different TMJ arthroscopic techniques for discal displacement with or without reducing]

The three arthroscopic techniques were particularly method I(lysis and lavage),method II(disc repositioning and sclerotherapy plus method I),method III(traction,fixation plus method II) in order to make comparative study.The distributions between the 76 joints and three techniques were:14 joints in method I,31 in II,and,31 in III.The total follow-up was 30m(6-84m),and the total success rate was 73.7%(53/76).The mean follow-ups were particularly:28.6m in method I,38.4m in II.and,74.2%(23/31) in III,particularly.There were no statically significance between I and II.In disc displacement with reducing,there were no statically significance between method II(18/20) or III(14/15) and I(1/40),and no statically significance between II and III.In disc displacement without reducing,there were no statically significance between method I(6/10)and II(8/11) or III(9/16),or between II and III.Conclusions were that II or method III was effective on disc displacement with reducing,and that it don't make clear for any one of three methods to be more effective on disc displacement without reducing.

Journal Article↗

PubMed1996

Protein tyrosine phosphatase regulation of endothelial cell apoptosis and differentiation.

Apoptosis, or programmed cell death, occurs during development and may also be an important factor in many diseases. However, little is known about the signal transduction pathways regulating apoptosis. In these studies, loss of endothelial cell-substrate attachment and apoptosis after removal of growth factors was associated with dephosphorylation of tyrosine residues at the cell periphery. Dephosphorylation of total cellular proteins accompanied apoptosis and was reduced by orthovanadate, an inhibitor of protein tyrosine phosphatases. Orthovanadate blocked the fragmentation of nuclear DNA, inhibited DNA laddering, and suppressed the expression of TRPM-2, an apoptosis-associated gene. The tyrosine phosphorylation levels of FAK125, erk1 (mitogen-activated kinase kinase), and cdc-2 were reduced during apoptosis. FAK125 dephosphorylation was inhibited by orthovanadate, but premature activation (tyrosine dephosphorylation) of cdc-2 was not. Orthovanadate was as effective as basic fibroblast growth factor in activating erk1 without increasing cell proliferation and in preventing the apoptosis of endothelial cells after treatment with tumor necrosis factor alpha. Endothelial cell differentiation on extracellular matrix (Matrigel) was also stimulated by orthovanadate in the absence of basic fibroblast growth factor without affecting growth arrest and inhibition of DNA synthesis. Expression of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1) was down-regulated during the early stages of differentiation, remained low for at least 6 hours as differentiation proceeded, and increased upon completion of differentiation. Cells that failed to down-regulate p21 mRNA on Matrigel in the absence of angiogenic factors underwent apoptosis. These results suggest that protein tyrosine phosphatases are actively involved in signal transduction during apoptosis and may regulate p21 expression to inhibit endothelial cell differentiation.

Apoptosis↗