Biomedical subjects

P Ji

Publications and source records attributed to P Ji.

At least 37 records · Page 2Linked to original sources

PubMed1999

Integrin alpha IIb beta 3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PI 3-kinase.

Activation of the focal adhesion kinase pp125FAK correlates with its phosphorylation on tyrosine residues and is mediated by multiple receptor-ligand pairs. In platelets, pp125FAK phosphorylation is triggered by alpha IIb beta 3 integrin or Fc gamma RII receptor interaction with immobilized fibrinogen and IgG, respectively. In this study we used platelets as a model system to explore the role of PI 3-kinase relative to pp125FAK phosphorylation. Treatment of the platelets with two PI 3-kinase inhibitors, wortmannin and LY294002, inhibited in a dose-dependent manner alpha IIb beta 3-mediated platelet spreading on fibrinogen having no effect on platelet spreading on IgG. Both inhibitors also completely abolished alpha IIb beta 3-mediated pp125FAK phosphorylation but not pp72syk phosphorylation. Furthermore, Fc gamma RII- and thrombin-induced pp125FAK phosphorylation were not affected by wortmannin and LY294002. Finally, the PI 3-kinase inhibitors' effect on alpha IIb beta 3-mediated spreading and pp125FAK phosphorylation was reversed by phorbol ester treatment. These results establish that the role of PI 3-kinase relative to pp125FAK phosphorylation in platelets is receptor type-specific yet essential for alpha IIb beta 3-mediated cell spreading and pp125FAK phosphorylation.

Androstadienes↗

PubMed1999

Phospholipase A2 enzymes regulate alpha IIb beta3-mediated, but not Fc gammaRII receptor-mediated, pp125FAK phosphorylation in platelets.

The alphaII(b)beta3 integrin and FcgammaRII receptors mediate, respectively, platelet adhesion and spreading on fibrinogen and immunoglobulin (IgG) coated surfaces. Platelet adhesion to fibrinogen resulted in a partial conversion of the faster to the slower migrating (phosphorylated) form of Ca(+2)-sensitive cytosolic phospholipase A2(cPLA2) but failed to trigger arachidonic acid (AA) release. Full mobility shift of cPLA2 and a massive release of AA release were stimulated by platelet adhesion to IgG or addition of thrombin to the fibrinogen adherent platelets. IgG and thrombin induced AA production were blocked by methyl arachidonyl fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and the Ca(+2)-independent phospholipase A2 (iPLA2). In contrast, bromoenol lactone (BEL), a specific inhibitor of iPLA2 had no effect on the release of AA. MAFP and BEL prevented pp125FAK phosphorylation and platelet spreading on fibrinogen having no effect on pp125FAK phosphorylation or platelet spreading on immobilized IgG. We conclude that alpha(IIb)beta3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PLA2 enzymes.

Arachidonic Acid↗

PubMed1998

Blockade of induced xenoantigen expression prevents rejection after retransplantation of accommodated hamster-to-rat heart xenografts.

BACKGROUND: We have shown previously that a 2-week course of leflunomide (LF) together with a maintenance therapy of cyclosporine (CsA) rendered hamster-to-rat heart xenografts (Xg) resistant against anti-hamster IgM xenoantibody (XAb)-mediated rejection, a state compatible with the notion of accommodation. Our aim in this study was to investigate the mechanism underlying this Xg accommodation. METHODS: "Accommodated" Xgs were retransplanted to CsA-treated naive rats in the presence or absence of additional LF treatment or anti-hamster IgM serum injection. Immunohistopathology and fluorescence-activated cell sorting was performed to detect IgM and complement (C) deposition in Xgs, and endothelial cell (EC) expression of P- and E-selectin, ICAM-1, and VCAM-1 in vivo and in vitro. RESULTS: Retransplanted accommodated Xgs were rejected in CsA-treated naive rats and elicited IgM XAbs. Passive transfer of IgM XAbs provoked hyperacute rejection of both control and retransplanted Xgs. Addition of a 5-day course of LF prevented the rejection of only accommodated Xgs. Adoptively transferred IgM XAbs were deposited in rejected control and accommodated Xgs, but not in accommodated Xgs accepted by LF-treated rats. LF blocked the EC induction of P- and E-selectins in both control fresh and accommodated Xgs. Hence, after retransplantation accommodated Xgs express mainly induced xenoantigens (XAgs), such as P- and E-selectins, that can entirely be suppressed by LF. In contrast, control hamster Xgs express additional XAgs and remain susceptible to XAb-mediated rejection. These findings are in agreement with in vitro studies showing that LF totally suppressed induced EC antigens (e.g., P-selectin and E-selectin), but not constitutively expressed antigens (e.g., ICAM-1). CONCLUSION: Accommodated Xgs show a down-regulation of constitutive XAgs, but may be rejected after retransplantation by a mechanism involving EC expression of inducible XAgs. LF is able to block this latter XAg induction.

Animals↗

PubMed1998

Induction of specific transplantation tolerance across xenogeneic barriers in the T-independent immune compartment.

After transplantation of primarily vascularized xenografts (Xgs), T-independent mechanisms may lead to Xg rejection before T-cell activation even takes place. The possibility of achieving T-independent xenotolerance was evaluated in nude rats that normally reject hamster cardiac Xgs within 4 days by non-T cell-mediated mechanisms. After donor antigen infusion, temporary NK-cell depletion and a 4-week administration of Leflunomide, hamster heart grafts survived even after withdrawal of immunosuppression. Tolerant rats accepted second hamster hearts, but promptly rejected mouse heart Xgs. In vivo immunization and in vitro cytotoxicity assays indicated that this species-specific tolerance was based on B-lymphocyte and NK-cell tolerance respectively.

Animals↗

PubMed1998

[Clinical observation of seventeen cases of carcinoma of the external auditory canal and middle ear].

The clinical observation of 17 cases with carcinoma of the external auditory canal and middle ear revealed that no other factors can affect the prognosis greatly except the death caused by recurrence of primary focus. Because operations would destroy the local anatomic structure and in most cases it is difficult to excise widely aggressive tumors perfectly, the author suggests that the auditory canals should be excised or extended mastoidotympanectomy with radiotherapy after operation be performed for the tumors limited to external canal or middle ear. Radiotherapy before operation can be conducted before extended mastoidotympanectomy or subtotal temporal bone resection for the cases with tumors beyond the middle ear. For the cases with tumors largely beyond the middle ear mastoidotomy can be performed before thorough radiotherapy.

Adenocarcinoma↗

PubMed1998

[Multiple dose pharmacokinetic and bioavailability studies of oral sustained release and conventional formulations of isosorbide-5-mononitrate in healthy volunteers].

The pharmacokinetics of a new sustained release tablets (40 mg, qd) of isosorbide-5-mononitrate (IS-5-MN) was investigated together with a conventional preparation (20 mg, bid) after multiple oral administration in ten healthy human subjects using an open, randomized two-way crossover experimental design. Based on three statistical analyses of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be bioequivalent (P > 0.1), with a relative bioavailability of 108.95% for the IS-5-MN sustained release formulation. Pharmacokinetic data showed that the sustained release formulation reached mean peak plasma levels significantly later and lower minimum plasma concentration (Cmin), compared with the conventional preparation. But no statistically significant difference was found for other pharmacokinetic parameters including peak plasma levels (Cmax), AUC, elimination constant (Ke), elimination half-life (T1/2) and fluctuation index (FI) between the two preparations (P > 0.05).

Adult↗

PubMed1998

Single and multiple dose pharmacokinetic studies of oral sustained release and non-sustained release formulations of isosorbide-5-mononitrate in healthy volunteers.

The pharmacokinetics of a new sustained release tablet (40 mg, "test") of isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) was investigated together with a reference preparation (20 mg, "reference") after single and multiple oral administration in ten healthy human subjects using an open, randomised two-way crossover experimental design. Based on the statistical evaluation of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be the same with regard to the amount absorbed. Pharmacokinetic data showed that with the test tablet significantly lower and delayed mean peak plasma levels (Cmax) were reached compared with the reference preparation in both single and multiple dose studies. The test formulation also produced lower minimum plasma concentration (Cmin). However, there was no statistically significant difference for other pharmacokinetic parameters, including the elimination rate constant (Kel), the elimination half-life (t1/2) and the peak-trough fluctuation constant (PTF) between the two treatments. It was demonstrated that the new sustained release formulation of isosorbide-5-mononitrate could be useful in clinical practice for the treatment of angina pectoris and congestive heart failure.

Adult↗

PubMed1997

Nitric oxide synthase distribution in the enteric nervous system of children with cardiac achalasia.

OBJECTIVE: To study the distribution of nitric oxide synthase (NOS) in the enteric nervous system of children with cardiac achalasia. METHODS: Biopsy specimens of the lower esophagus, cardia, gastric fundus and pylorus from 13 patients with cardiac achalasia and 6 controls were obtained and studied histochemically with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and immunohistochemically with a specific polyclonal antiserum. RESULTS: NOS was abundant in the myenteric plexus and the nerve fibers of musculatures in the esophagus, cardia and gastric fundus in control group, while it was nearly absent in the patient group. The distribution of NOS in the pylorus was similar in the two groups. CONCLUSION: These findings suggest that a lack of NOS in the lower esophagus, cardia and gastric fundus is involved in the pathophysiology of cardiac achalasia in children.

Adolescent↗

PubMed1996

The FcgammaRII receptor triggers pp125FAK phosphorylation in platelets.

Platelets express a single low affinity receptor for immunoglobulin, FcgammaRII, that triggers multiple cellular responses upon interaction with multivalent immune complexes. In this study we show that immobilized IgG is also a potent stimulant of platelet activation triggering adhesion, aggregation, massive dense granule secretion, and thromboxane production. Platelet adhesion to IgG was blocked by the FcgammaRII receptor-specific monoclonal antibody, IV. 3. Pretreatment of the platelets with cytochalasin D to inhibit actin polymerization similarly prevented cell binding to IgG having no effect on platelet binding to fibrinogen. Platelet adhesion to IgG also led to the induction of tyrosine phosphorylation of multiple proteins including pp125(FAK) and p72(SYK). These proteins were also tyrosine-phosphorylated in alphaIIbbeta3-deficient IgG-adherent platelets from patients with Glanzmann's thrombasthenia. These data demonstrate that FcgammaRII mediates pp125(FAK) phosphorylation and platelet adhesion to IgG independent of the integrin alphaIIbbeta3. Treatment of the platelets with bisindolylmaleimide to inhibit protein kinase C prevented phosphorylation of pp125(FAK) as well as several other proteins, but not p72(SYK) phosphorylation. This study establishes that the FcgammaRII receptor mediates pp125(FAK) phosphorylation via protein kinase C.

Antibodies, Monoclonal↗

PubMed1996

Protein kinase C regulates tyrosine phosphorylation of pp125FAK in platelets adherent to fibrinogen.

Platelet adhesion to immobilized fibrinogen stimulates the induction of tyrosine phosphorylation of multiple proteins. However, platelet spreading and tyrosine phosphorylation of three proteins, the focal adhesion kinase pp125FAK and proteins of 101 and 105 kD (pp101 and pp105), require a second adenosine diphosphate (ADP)-dependent costimulatory event. In this study we show that protein kinase C (PKC) inhibitors prevented the induction of tyrosine phosphorylation of pp125FAK, pp101 and pp105, and abolished spreading. These inhibitory effects were not observed after treatment of the platelets with the intracellular Ca2+ chelator BAPTA-AM. This suggested that in platelets, PKC regulates spreading and related protein tyrosine phosphorylation. In addition, the inhibitory effects of apyrase, an ADP scavenger, on spreading and tyrosine phosphorylation of pp125FAK, pp101, and pp105, were not observed in the presence of phorbol 12-myristate 13-acetate (PMA). These data implied that in fibrinogen-adherent platelets integrin ligation and an agonist receptor occupancy are required for the functional association of PKC and the alpha IIb beta 3-mediated signaling pathways. Taken together these results show that PKC plays a central role in the transduction of intracellular signals downstream from alpha IIb beta 3 that regulate spreading and pp125FAK phosphorylation.

Adenosine Diphosphate↗

PubMed1995

Elastin morphology in normal and obstructed guinea-pig bladders. Localization of elastin to the trigone.

Elastin is the major component of elastic fibers in aortic tissue and has been suggested to be important for the stretch and recoil of the bladder. We have mapped the histologic distribution of elastin throughout the entire guinea-pig bladder as well as changes in the distribution of elastin during bladder-outlet obstruction. We used an animal model in which a jeweler's ring is placed around the urethra of the young guinea pig. As the animal grows, outlet obstruction is gradually induced, and the bladder gradually increases in total weight to as much as 8-fold that of controls. We localized the elastin histologically in normal and obstructed bladders by serially sectioning entire bladders and staining the sections with an elastin-specific stain, Verhoff-van Gieson stain (VVG). Surprisingly, we found that the elastin was predominantly localized only to the trigone of the bladder and that the elastin in this area was increased during obstruction. These results are consistent with the predominantly mesodermal embryologic origin of the trigone, since mesodermal tissues are more often associated with elastin expression.

Animals↗

PubMed1995

[Significance of immunohistochemical study in the diagnosis and differential diagnosis of chordoma].

Seven cases of chordoma were studied immunohisto-chemically with antibodies directed to epithelium, nerve, mesenchyme, muscle and histiocyte. Six cases of chondrosarcoma and three cases of mucinous carcinoma of colon were studied as control. The results showed that the chordomas were positive for cyto-K 6/7, EMA 7/7, CEA 6/7, Vim 7/7, S-100 7/7, alpha-AT 7/7, Lyso 4/7, while negative for GFAP and Des in all 7 cases indicating that chordoma, just like notochord, had the potentiality of multidirectional differentiation. In contrast, none of the chondrosarcomas was positive for cyto-K, EMA or CEA, but positive for Vim and S-100 in 6 cases. Three cases of colon mucinous carcinoma were positive for epithelial antibodies, but none reacted with other antibodies. Thus, immunohistochemical studies are of help in the diagnosis and differential diagnosis of chordoma.

Adenocarcinoma, Mucinous↗

PubMed1994

Transfer of shuttle vectors containing Bacillus thuringiensis toxin gene into wild-type B. cereus, B. brevis and B. subtilis by electroporation.

Gram positive and negative bacterial shuttle vectors carrying Bacillus thuringiensis (B.t.) toxin gene were introduced by electroporation into wild-type Bacillus cereus, B. brevis and B. subtilis. The transformation efficiencies for these bacteria were around 10(1)-10(4) transformants per micrograms DNA based on the numbers of neomycin- and ampicillin-resistant colonies produced. The structure of the transferred plasmids proved identical with the original ones both in size and restriction pattern. Toxicity assays showed that the transformants gave a mortality of 90-100% against caterpillar of Heliothis assulta, indicating that the gene function was not changed by electroporation.

Bacillus↗

PubMed1992

[Effect of anoxia on the growth of cultured neurons from embryonic chick forebrain].

Pure neurons from embryonic day 8 chick forebrain were cultured under anoxic condition (95% N2 and 5% CO2). After 24, 48 and 72 h in culture, MTT colorimetric microassay showed a reduced production of formazan, indicating that the neurons were seriously damaged. In addition, the glucose of the cultured media was significantly depleted. Even when glucose concentration was increased to 800-1,200 mg/100 ml, anoxia still caused neurons to die. The results indicate that brain neurons in embryo are sensitive to anoxia, and any protective influence of glia on anoxic neurons could not be mediated by supplying the latter with glycogen.

Animals↗

PubMed1986