Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 289 records · Page 16Linked to original sources

PubMed1994

Using ofloxacin as a time marker in hair analysis for monitoring the dosage history of haloperidol.

Hair samples were obtained 1-5 months after ingestion of the antimicrobial ofloxacin, which had been given for 1 or 3 days at the commencement of haloperidol administration, or when its dosage was reduced. The axial distribution of ofloxacin, haloperidol and its active metabolite, reduced haloperidol, was analysed in segments from single strands of hair. Ofloxacin was detected where the content of haloperidol and reduced haloperidol along the hair shaft showed a sharp change, corresponding to the change in dose. When we matched the time scale of the dosage history to the growth rate, which was estimated using ofloxacin as the time marker, the distribution of the haloperidol and reduced haloperidol precisely coincided with the rise and fall in the dose of haloperidol. These findings demonstrate that ofloxacin can serve as a time marker when drug distribution along the hair shaft is used to obtain the drug exposure history of an individual.

Adult↗

PubMed1994

Analysis of a new fluoroquinolone derivative (Q-35) in human scalp hair as an index of drug exposure and as a time marker in hair.

Scalp hair samples were obtained every month for three months after administration from healthy male volunteers who participated in the phase I study of a new antimicrobial fluoroquinolone derivative (Q-35). Hairs were cut into 1 cm long pieces successively from the scalp end. Corresponding pieces of 5 hair strands were dissolved in 1 M NaOH and assessed for Q-35 by HPLC. The drug was detectable in the hairs of all subjects taking either a single (400 mg, n = 6) or repeated oral doses of Q-35 (400 mg/day for 6.5 days, total 2600 mg, n = 6). The hair portions containing the drug were shown in most subjects to move outwards along the hair shafts month by month in proportion to the hair growth rate of about 1 cm/month. Q-35 (600 mg/day) was also given to 6 healthy male volunteers for 6.5 days (total 3900 mg) and hair samples were obtained 1 and 3 months after administration. When Q-35 was analyzed along a single hair shaft, the drug was detectable only in 1-2 consecutive 1 cm long pieces, which were also shown to move outwards along the hair shaft with time. A detailed analysis revealed that the drug was contained only in 2-4 consecutive 2.5 mm long pieces of a single hair collected after 3 months, showing that there was no significant axial diffusion of the drug along the hair shaft with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Oncogene-targeted antisense oligodeoxynucleotides combined with chemotherapy or immunotherapy: a new approach for tumor treatment?

Synthetic oligodeoxynucleotides (antisenses) complementary to bcr/abl breakpoint junction transcript on Philadelphia chromosome, or c-myb protooncogene inhibit partially the proliferation of Philadelphia positive leukemic cells (antisenses against bcr/abl and c-myb) and other tumor cells (antisenses against c-myb). This phenomenon is accompanied by specific downregulation of mRNA level of the particular gene. To develop a more effective procedure of tumor treatment the combination of low dose of cytostatic and bcr/abl or c-myb antisenses against Philadelphia chromosome positive cell line BV173, and the combination of anti-tumor cytotoxic T lymphocytes (CTL) and c-myb antisenses against melanoma cell line MM-28, were tested in vitro. Our results indicate that the combinations of conventional chemotherapeutic agent and antisense against bcr/abl or c-myb or tumor specific CTL and antisense against c-myb, are highly effective in killing of tumor cells and sparing normal cells. This creates the possibility to develop a more selective and effective treatment of neoplasia.

Bone Marrow Cells↗

PubMed1994

Expression of adhesion molecule ICAM-1 (CD54) in thyroid papillary adenocarcinoma.

The expression of adhesion molecules in thyroid specimens from 10 cases of papillary adenocarcinoma, 5 cases of follicular adenoma and 3 normal thyroid specimens was examined by an immunohistochemical method. Thyroid epithelial cells from all cases of papillary adenocarcinoma expressed the intercellular adhesion molecule 1 (ICAM-1, CD54). The ICAM-1-positive staining in these was detected predominantly on the apical site of malignant thyroid epithelial cells. However, no ICAM-1 expression was detected on thyrocytes of adenoma, and normal thyroid tissues. Furthermore, thyroid epithelial cells in patients with thyroid tumor and normal thyroid tissue did not react with anti-LFA-1, anti-VLA-4, anti-VCAM-1 and anti-ELAM-1 monoclonal antibodies. It is speculated that ICAM-1 expression in thyroid papillary adenocarcinoma may have a functional significance.

Adenocarcinoma, Follicular↗

PubMed1994

Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix.

Recombinant human bone morphogenetic protein (BMP)-2, BMP-4 and transforming growth factor (TGF)-beta 1 combined with collagen matrix as a carrier were examined for their effects on pulp regeneration and dentine formation. Seventy days after implantation of 2 micrograms of BMP-2, mineralized osteodentine-like tissue containing embedded osteodentinocytes was seen in the cavity. Unmineralized fibrous tissue and pulp-like loose connective tissue were also found in the same cavity. In teeth implanted with 660 ng of BMP-2 only unmineralized fibrous and pulp tissues were seen. In teeth with 220 ng of BMP-2 or collagen alone, pulp tissue was seen. It is therefore likely that the cavity fills with pulp tissue and that spindle-shaped cells elaborate extracellular matrix that mineralizes to be osteodentine in a dose-dependent manner. Similar osteodentine was seen in teeth implanted with 4 micrograms of BMP-4 and collagen. No distinct tubular dentine was formed, unlike an earlier experiment in which BMP-2 or -4 was implanted with enriched, inactivated dentine matrix. These findings suggest that both BMP-2 and -4 induce osteodentine formation if combined with collagen matrix; some other matrix component present in inactivated dentine matrix might be essential for further differentiation into odontoblasts. In teeth implanted with TGF-beta 1, the carrier collagen remained in the cavity and little pulp tissue proliferation was seen, suggesting a possible inhibitory effect of TGF-beta 1 in pulp regeneration. It is likely that the response to growth and differentiation factors is dependent on the state of differentiation of pulp cells.

Animals↗

PubMed1994

Experimental intimal thickening studies using the photochemically induced thrombosis model in the guinea-pig femoral artery.

We have used the photochemically induced thrombosis model to study intimal thickening in the guinea-pig femoral artery. The femoral artery was occluded by a combination of rose bengal and green light which caused endothelial cell damage followed by formation of platelet rich thrombus at the site of endothelial damage. Thrombolysis was then achieved by administration of tissue-type plasminogen activator. Intimal thickening in the femoral arteries was histologically measured at 0, 1, 3, 6 and 9 weeks after the treatment. The neointimal areas gradually increased until 3 weeks and then remained unchanged up to 9 weeks. Cells in the neointima were identified as smooth muscle cells by immunohistochemical staining with an actin-specific antibody, HHF35. Cell proliferation in the media begun within 48 h after the thrombolysis and bromodeoxyuridine labeled cells appeared to migrate to the intima within 1 week after the thrombolysis. Administration of an angiotensin converting enzyme inhibitor, cilazapril (30 mg/kg/day, p.o.) for 3 weeks, suppressed intimal thickening and decreased the medial area in the femoral artery. These observations suggest that in this model cell proliferation and migration characteristics of pathological intimal thickening occur and this model is useful for investigating the effect of pharmacological preparations on intimal thickening.

Animals↗

PubMed1994

Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.

Antibodies, Monoclonal↗

PubMed1994

Enhancement of thrombotic arterial occlusion following cholesterol feeding in the guinea-pig: a role for thromboxane A2.

We have developed a photochemical model to induce thrombotic occlusion of the guinea-pig femoral artery. Using this model, we investigated the effect of cholesterol feeding on arterial occlusion time in the guinea-pig. Animals were divided into two groups, one on standard diet and the other on standard diet containing 0.5% cholesterol for 3 weeks. The time for femoral artery occlusion was significantly shorter (p < 0.05) in cholesterol fed animals as compared to the control group. In vitro collagen-, U-46619- (a thromboxane A2 adenosine diphosphate analogue) and (ADP)-induced platelet aggregation responses in whole blood in cholesterol-fed animals were increased 13-, 10- and 4-fold, respectively. U-46619- and collagen-induced washed platelet aggregation responses were also significantly enhanced by cholesterol feeding (p < 0.01). Further, TXA2 generation by collagen-stimulated washed platelets in cholesterol-fed animals increased similar to the platelet aggregation responses. However, platelet-activating factor (PAF)-induced platelet aggregation in whole blood was relatively unaffected by cholesterol feeding. 11-dehydro TXB2 levels in plasma were increased significantly by cholesterol feeding. Our observations suggest that increased plasma TXA2 level and platelet aggregation response to TXA2 and stimulated TXA2 synthesis in platelets play a role in enhanced arterial occlusion in cholesterol fed guinea-pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1994

Effects of volatile anesthetics, enflurane, isoflurane, and halothane on ventricular delayed activation in a canine myocardial infarction model.

The authors examined the effects of volatile anesthetics (enflurane, isoflurane, and halothane) on ventricular activation in a canine myocardial infarction model. Enflurane at 1 minimum aveolar concentration further delayed or blocked delayed activation in the infarcted zones with only slight effects on activation of the normal zones. Halothane showed similar and comparable effects on ventricular activation to those of enflurane. Although isoflurane also showed similar effects, they were of a lesser extent. Enflurane and halothane, but not isoflurane, inhibited ventricular stimulation-induced arrhythmias. Thus, enflurane and halothane produced marked depression of delayed activation in myocardial infarction, which may affect, that is, inhibit or provoke, ventricular arrhythmias in myocardial infarction.

Animals↗

PubMed1994

Application of in vivo microdialysis to transdermal absorption of methotrexate in rats.

Microdialysis was applied to determine the in vivo transdermal absorption of methotrexate (MTX) in rats with or without a new penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101). A solution composed of 2.5 mM MTX and 3% (w/v) HPE-101 was applied to the shaved abdomen, in which a semipermeable membrane cannula of 10-mm length was inserted intracutaneously with the use of an L-shaped needle. Intradermal microdialysis was performed at a flow rate of 1.0 microL/min for 12 hr. The concentration of MTX in the dialysate was measured by fluorescence polarization immunoassay (FPIA). HPE-101 (3%, w/v) significantly increased the dermal MTX concentration from 0.06 +/- 0.04 microM in the control to 56 +/- 26 microM in the dialysate from 8 to 12 hr. HPE-101 at concentrations of 0.75, 1.5, 2.25, and 3% (w/v) enhanced the total recovery of MTX in dermal dialysate from 0 to 10 hr by approximately 5, 18, 42, and 500 times compared with the control, respectively. The microdialysis system is useful for assessing in vivo transdermal drug absorption.

Administration, Cutaneous↗

PubMed1994

Proliferation, phenotype, and cytotoxicity of human lymphocytes isolated from lymph nodes invaded by melanoma cells.

The effects of human recombinant interleukin-4 (rIL-4) on metastatic melanoma (lymph node)-derived T lymphocytes cultured with human recombinant interleukin-2 (rIL-2) were studied. Lymphocytes isolated from melanoma-invaded lymph nodes were cultured in media with rIL-2 in the presence (MB-2,4) or absence (MB-2) or rIL-4 for up to 48 days. A majority of lymphocytes grown in both cultures were CD3+ T lymphocytes. Addition of rIL-4 to the rIL-2 culture abrogated the growth of the CD3-, CD56+ cell population [natural killer (NK) cell], which were present in culture with rIL-2 alone. Lymph-node-derived T lymphocytes that had expanded under MB-2,4 conditions lysed only autologous melanoma cells and they maintained the autologous-specific cytolytic activity during the entire culture period. They did not lyse K562, Daudi, or allogeneic target cells. Monoclonal antibodies (MAbs) against CD3 molecules and MHC class I molecules but not MHC class II molecules inhibited the specific lytic functions of T lymphocytes under MB-2,4 culture conditions. Collectively, these data indicate that in lymphocyte culture derived from melanoma-invaded lymph nodes, rIL-4 inhibits the rIL-2-dependent proliferation of NK cells and antigen nonspecific killer T lymphocytes and also effectively abrogates the rIL-2-induced NK and lymphokine-activated killer (LAK) activities.

Cytotoxicity Tests, Immunologic↗

PubMed1994

The expression of adhesion molecules in thyroid glands from patients with Graves' disease.

We studied the potential role of adhesion molecules in the pathogenesis of Graves' disease. Thyroid specimens of Graves' thyroid glands and control thyroid glands were stained with monoclonal antibodies against adhesion molecules by an immunohistologic method. Thyroid tissues obtained from patients with Graves' disease had an enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on capillary endothelial cells around the thyroid follicles and on postcapillary endothelial cells in lesions with aggregates of mononuclear cells. Positive staining for ICAM-1, lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4) was found on the infiltrating mononuclear cells. The postcapillary vascular endothelial cells expressed increased endothelial-leukocyte adhesion molecule-1 (ELAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 and ELAM-1 were detected on the dendritic-like cells in the germinal centers of lymphoid follicle-like areas. No significant expression of these adhesion molecules was detected on normal thyroid glands. These results suggest that the LFA-1/ICAM-1 and ELAM-1 pathways may be responsible for the migration of mononuclear cells into the thyroid glands of patients with Graves' disease, and that the VLA-4/VCAM-1 pathway plays a critical role in the cellular interactions that lead to the formation of B-memory cells and the excess production of antibodies.

Adult↗

PubMed1994

Pharmacokinetics and safety of BO-2727, a new injectable 1-beta-methyl carbapenem antibiotic, and its effect on the faecal microflora in healthy male volunteers.

The safety and pharmacokinetics of BO-2727, a new injectable 1-beta-methyl carbapenem antibiotic, and its effect on the faecal microflora were evaluated in single- and multiple-dose studies involving twenty-four healthy male adult volunteers following a preliminary safety evaluation of 25, 50 and 125 mg iv doses in six volunteers. BO-2727 was administered by iv infusion over 30 min. There was a good correlation between BO-2727 concentrations assayed by HPLC and a microbiological method; the HPLC results were used in the pharmacokinetic analysis. The single-dose study indicated that plasma concentration versus time curves at doses of 250, 500 and 1000 mg were well described by a two-compartment open model. The mean (+/- S.D.) elimination half-life ranged from 1.41 +/- 0.21 h to 1.54 +/- 0.10 h, and the peak plasma concentrations (Cmax) and the area under the plasma concentration versus time curves increased linearly with the dose. The mean urinary recoveries within the first 24 h were 70.63 +/- 5.24% to 77.38 +/- 4.55% of the dose. The highest concentration of BO-2727 in saliva was 0.72 mg/L which was reached 1 h after the start of the 1000 mg infusion and accounted for approximately 1% of the Cmax. No BO-2727 was found in faecal samples collected 24 and 48 h after a single 1000 mg dose. In the multiple-dose study, BO-2727 500 mg bd was administered for 4.5 days. There were no obvious differences in plasma concentrations and urinary recoveries between the single- and multiple-dose regimens. BO-2727 did not accumulate as determined by plasma concentrations and urinary recoveries. No marked changes in the aerobic and anaerobic faecal microflora were observed during multiple-dose administration. There were no significant adverse reactions, and likewise no abnormalities in physical and laboratory examinations that were definitely related to the drug.

Adolescent↗

PubMed1994

Effects of MS-551, a new class III antiarrhythmic drug, on programmed stimulation-induced ventricular arrhythmias, electrophysiology, and hemodynamics in a canine myocardial infarction model.

We examined the effects of MS-551 (1,3-dimethyl-6-[(2-[N-(2-hydroxyethyl)-3-(4- nitrophenyl)propylamino]ethylamino] 2,4(1H,3H)-pyrimidinedione hydrochloride), a new class III antiarrhythmic drug, on programmed electrical stimulation (PES)-induced ventricular arrhythmias, the effective refractory period (ERP), intraventricular conduction, and hemodynamics in a canine myocardial infarction (MI) model. MS-551 was administered intravenously (i.v.) in two consecutive doses; the first dose (low dose) was 0.5 mg/kg/min after a bolus injection of 0.3 mg/kg, and a second dose (high dose) was 0.1 mg/kg/min after a bolus injection of 0.3 mg/kg. PES induced ventricular tachycardia (VT) or ventricular fibrillation (VF) in 10 of 12 animals. MS-551 abolished or lessened the ventricular arrhythmias in 7 of 10 animals at both doses. ERP was significantly prolonged by MS-551 in both the normal and infarcted zones in a dose-dependent fashion. Ventricular conduction of a premature excitation induced by a premature stimulation with various coupling intervals was decreased only at a coupling interval approximating that of ERP. MS-551 at either low or high dose did not significantly change the heart rate (HR), mean blood pressure (MBP), cardiac output (CO), or maximum rate of increase in left ventricular pressure (LVP) significantly. MS-551 produced a suppression of the PES-induced ventricular arrhythmias through prolongation of ERP without having any significant effect on hemodynamics in a canine MI model.

Animals↗

PubMed1994

Effects of the Ca2+ antagonist RO 40-5967 on endothelium-dependent responses of isolated arteries.

Experiments were designed to determine whether the Ca2+ channel inhibitor RO 40-5967 [(1S,2S)-2-[2-[[3-(2-benzimidazolyl)propyl]methylamine]ethyl]-6- fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl methoxyacetate dihydrochloride] causes endothelium-dependent relaxations or inhibits endothelium-dependent contractions of isolated blood vessels. Rings of dog femoral, carotid, and basilar arteries and of rat aorta, with and without endothelium, were suspended in conventional organ chambers for measurement of isometric force. During contractions evoked by phenylephrine (full alpha 1-adrenergic agonist), St 587 (partial alpha 1-adrenergic agonist) and endothelin-1 (ET), RO 40-5967 caused concentration-dependent relaxations of rings of dog femoral arteries; the relaxations to RO 40-5967 were greater in rings with endothelium than in those without endothelium. Nitro-L-arginine (NLA) and methylene blue (MB) inhibited the endothelium-dependent component of the response to RO 40-5967 during contractions to phenylephrine (PE) St 587 and ET. The endothelium-dependent relaxations evoked by RO 40-5967 during contractions to PE were not affected by diltiazem in the femoral artery, suggesting that this effect of the compound may not be related to its calcium channel inhibitor properties. Under bioassay conditions, RO 40-5967 stimulated release of relaxing factors from the endothelium of canine carotid arteries; the response of the detector tissues was inhibited by MB. In strips of canine femoral artery with endothelium, in which membrane potential of vascular smooth muscle cells (VSMC) was recorded with glass microelectrodes, RQ 40-5967 did not cause endothelium-dependent hyperpolarizations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1994

Comparative pharmacokinetic and pharmacodynamic properties of oral and intravenous (+)-sotalol in healthy volunteers.

The pharmacokinetic and pharmacodynamic properties of (+)-sotalol (BMY-5763) were studied to analyse the relationship between plasma concentration and QTc prolongation in healthy male volunteers given single oral doses of 50, 100, 200 and 300 mg, repeated oral doses of 200 mg twice daily for 6.5 days, and single intravenous doses of 1.0 and 1.5 mg kg-1. The plasma concentration of (+)-sotalol peaked about 3 h after oral administration and declined with a half-life of 7.9-9.7 h. The Cmax and AUC showed dose-related increases, while the urinary recovery as the unchanged form remained constant (66-68% of the dose). During repeated oral administration the plasma concentration of (+)-sotalol reached almost a steady state on the 3rd day and there was no change in renal clearance of (+)-sotalol measured on the 1st, 4th and 7th days. After intravenous administration, (+)-sotalol in plasma decreased bi-exponentially with a terminal half-life of 7.6-8.3 h and the urinary recovery as unchanged drug amounted to 84-88% of the dose. The increase in QT interval was significant after a single oral administration except for the lowest dose, and regression analysis revealed a significant correlation between QTc interval and concentration of (+)-sotalol in plasma. The same correlation was evident with repeated oral doses on the 1st, 4th and 7th days. In the case of single intravenous administrations of (+)-sotalol, a combined pharmacokinetic-pharmacodynamic model was attempted by assuming an effect compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Expression of basic fibroblast growth factor in synovial tissues from patients with rheumatoid arthritis: detection by immunohistological staining and in situ hybridisation.

OBJECTIVE: The distribution and production of basic fibroblast growth factor (bFGF) was examined on the synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The localisation of bFGF was determined by an immunohistochemical staining procedure using anti-bFGF monoclonal antibody. The expression of bFGF mRNA was detected by nonradioactive in situ hybridisation using bFGF antisense oligo DNA. RESULTS: The bFGF was found in the synovial lining cell, sublining stromal fibroblast-like cells, and vascular endothelial cells from patients with RA and OA. Little or no bFGF was found in non-inflamed synovium. Immunostaining of bFGF in the synovial cells was more extensive and intense in synovium of patients with RA than that of patients with OA. The nuclei of the synovial lining cell layer were also immunostained. These nuclear staining were more intense in the lining cell layer from RA patients with moderate or severe proliferation of synovial cells than in RA patients with mild proliferation. The bFGF mRNA was also detected in the synovial lining cell layer of the inflamed synovium. CONCLUSION: The synovial lining cells produced bFGF. The proliferation of synovial cells in the inflamed joints may be the results of stimulation by the bFGF in autocrine manner.

Aged↗

PubMed1994

Interleukin 4 increases human synovial cell expression of VCAM-1 and T cell binding.

OBJECTIVE: The effects were studied of interleukin 4 (IL-4) on T cell-synovial cell adhesion and on the expression of adhesion molecules on the surface of synovial fibroblast-like cells. METHODS: The adhesion of T cells toward the synovial cells were measured by 51chromium-labelled adhesion assay. The expression of adhesion molecules on synovial cells were analysed by flowcytometry. RESULTS: Stimulation of synovial cells with IL-4 increased T cell-synovial cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VCAM-1 on the surface of synovial cells, but not the expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on the expression of ICAM-1 or VCAM-1 on the surface of synovial cells. The increased adhesion of T cells to IL-4 stimulated synovial cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti-VCAM-1 antibodies blocked completely T-cell binding to IL-4 stimulated synovial cells. CONCLUSIONS: These results suggest that the increased adhesion of T cells to IL-4-stimulated synovial cells is mediated by VLA-4/VCAM-1 pathway.

Adult↗