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Biomedical subjects

J Lin

Publications and source records attributed to J Lin.

At least 577 records · Page 32Linked to original sources
PubMed1995

Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa.

The Epstein-Barr virus (EBV) nuclear protein 3C (EBNA 3C) is essential for EBV-mediated transformation of primary B lymphocytes, is turned on by EBNA 2, and regulates transcription of some of the viral and cellular genes which are regulated by EBNA 2. EBNA 2 is targeted to response elements by binding to the DNA sequence-specific, transcriptional repressor protein J kappa. We now show that EBNA 3C also binds to J kappa. EBNA 3C causes J kappa to not bind DNA or EBNA 2. J kappa DNA binding activity in EBV-transformed lymphoblastoid cells is consequently reduced. More than 10% of the EBNA 3C coimmunoprecipitated with J kappa from extracts of non-EBV-infected B lymphoblasts that had been stably converted to EBNA 3C expression. EBNA 3C in nuclear extracts from these cells (or in vitro-translated EBNA 3C) prevented J kappa from interacting with a high-affinity DNA binding site. Under conditions of transient overexpression in B lymphoblasts, EBNA 2 and EBNA 3C associated with J kappa and less EBNA 2 associated with J kappa when EBNA 3C was coexpressed in the same cell. EBNA 3C had no effect on the activity of a -512/+40 LMP1 promoter-CAT reporter construct that has two upstream J kappa sites, but it did inhibit EBNA 2 transactivation of this promoter. These data are compatible with a role for EBNA 3C as a "feedback" down modulator of EBNA 2-mediated transactivation. EBNA 3C could, in theory, also activate transcription by inhibiting the interaction of the J kappa repressor with its cognate DNA. The interaction of two viral transcriptional regulators with the same cell protein may reflect an unusually high level of complexity or stringency in target gene regulation.

Antigens, Viral↗
PubMed1995

Nerve growth factor synthesis by intestinal epithelial cells.

Nerve growth factor (NGF) exists in the gut of adult rats. The cells responsible for NGF synthesis in the gut remain unknown. IEC-6 and Caco-2 cells, established cell culture models of intestinal epithelial cells, were studied to determine whether intestinal epithelial cells, were studied to determine whether they synthesize and release NGF. Conditioned media from both IEC-6 and Caco-2 cells stimulated neurite outgrowth in both rat pheochromocytoma (PC-12) cells and sensory neurons derived from embryonic chick dorsal root ganglia (DRG). The addition of anti-NGF antibody blocked neurite outgrowth in PC-12 cells and partially blocked outgrowth in DRG cells. An NGF-enzyme-linked immunosorbant assay readily detected immunoreactive NGF in conditioned media from both cell lines, whereas cellular extracts from IEC-6, Caco-2, and isolated rat intestinal epithelial cells had low levels of immunoreactivity. Caco-2 monolayers primarily secreted NGF from the basolateral compartment, and interleukin-1 enhanced its secretion. IEC-6, Caco-2, and isolated rat intestinal epithelial cells expressed NGF mRNA as determined by reverse transcription polymerase chain reaction. These observations suggest that intestinal epithelial cells are capable of NGF synthesis.

Animals↗
PubMed1995

Human recombinant interleukin-1 beta inhibits nicotinic transmission in neurons of guinea pig pelvic plexus ganglia.

The actions of human recombinant interleukin-1 beta (hrIL-1 beta) were tested on guinea pig pelvic plexus ganglion neurons using intracellular electrophysiological methods in vitro. hrIL-1 beta caused membrane depolarization associated with a decreased input resistance or inward currents in 54% of neurons tested. hrIL-1 beta caused a hyperpolarization associated with an increase in input resistance or outward currents in 30% of neurons tested. hrIL-1 beta-evoked responses were not altered by hexamethonium (100 microM), atropine (0.5 microM), yohimbine (0.3 microM), or naloxone (1 microM), indicating that cholinergic, alpha 2-adrenergic, or opioid receptors were not involved. Drugs that inhibit Na+, Ca2+, or K+ channels did not change hrIL-1 beta-evoked responses. Stimulation of synaptic inputs to pelvic ganglion neurons evoked nicotinic cholinergic fast excitatory postsynaptic potentials (fEPSPs). hrIL-1 beta inhibited fEPSPs in 44% of neurons tested but had no effect on acetylcholine-induced depolarizations. An IL-1 beta receptor antagonist blocked all actions of hrIL-1 beta. In summary, hrIL-1 beta has excitatory and inhibitory actions on pelvic ganglion neurons. Inhibition of fEPSPs by hrIL-1 beta may be due to presynaptic inhibition of acetylcholine release.

Animals↗
PubMed1995

CD3 and CD2 ligation alters CD49d epitope expression.

The combination of anti-CD2 plus anti-CD3 monoclonal antibodies (mAbs) synergistically prolongs allograft survival and induces antigen-specific tolerance. Since altered expression of cell surface molecules might be important for tolerance induction, the effect of anti-CD2 and anti-CD3 mAbs on the expression of adhesion molecules was analyzed on splenic T cells with an in vitro model. The anti-CD2 mAb, 12-15, alone had no effect on the expression of integrin alpha 4-chain epitopes recognized by two anti-CD49d (VLA-4 alpha) mAbs, R1-2 and PS/2. The anti-CD3 mAb, 2C11, caused R1-2 epitope expression to decrease, while PS/2 epitope expression remained unchanged. The combination of anti-CD2 and anti-CD3 mAbs further decreased R1-2 epitope expression while preserving PS/2 epitope expression. The expression of integrin beta 1 and beta 7 chains, each of which form heterodimers with alpha 4 chains, also remained unchanged. Expression of other integrin, selectin, or immunoglobulin superfamily molecules (CD11a, CD18, CD44, CD45, CD48, CD54 and CD62L) were all significantly increased by anti-CD2 or anti-CD3 mAbs. Decreased R1-2 epitope expression was anti-CD3 dependent and specifically augmented by anti-CD2 mAb. CD2-regulated decreases in R1-2 epitope expression correlated with increased cAMP and could be prevented by addition of high doses of IL-2 but was not affected by the addition of other cytokines. R1-2 alpha 4 epitope expression could be specifically restored by the divalent cation Mn2+, which also increased functional binding to the VCAM-1 ligand. Significantly, the R1-2 but not the PS/2 mAb prolonged graft survival in a cardiac allograft model. These results show that anti-CD2 and anti-CD3 mAbs selectively decrease integrin alpha 4 chain epitope expression on T cells through conformational regulation. Decreased expression of a CD49d epitope is unique in comparison to the up-modulation of other T-cell adhesion receptors. These changes correlate with functional effects and provide an additional mechanistic explanation for the synergistic effect of anti-CD2 plus anti-CD3 in producing tolerance.

Animals↗
PubMed1995

Increased cAMP and cAMP-dependent protein kinase activity mediate anti-CD2 induced suppression of anti-CD3-driven interleukin-2 production and CD25 expression.

Anti-CD2 monoclonal antibody (mAb) can act synergistically with anti-CD3 to produce tolerance and diminish the anti-CD3-induced cytokine syndrome. Since interleukin(IL)-2 production and IL-2 receptor (IL-2R; CD25) expression are important determinants of CD3-driven T cell activation, the effects of anti-CD2 on anti-CD3-induced CD25 expression and IL-2 production were analyzed and related mechanistically to CD2-stimulated cAMP signaling with an in vitro model of T cell activation. The anti-CD2 mAb, 12-15, alone had no effect on splenic T cell CD25 expression and IL-2 production, while the anti-CD3 mAb, 145-2C11, caused significant increases in both CD25 expression and IL-2 production. The addition of anti-CD2 inhibited anti-CD3-induced increases in CD25 and IL-2. The inhibitory signal delivered by anti-CD2 was effective in many forms of T cell activation, since other stimuli which increased CD25, such as concanavalin A, phytohemagglutinin, and Staphylococcal enterotoxin B (SEB), could also be inhibited by anti-CD2. The inhibitory effect of anti-CD2 on CD25 could not be reversed by high doses of supplemental IL-2 added to the culture. Anti-CD2 increased cytoplasmic cAMP in a dose- and time-dependent manner. Reagents that increased cytoplasmic cAMP such as forskolin, cholera toxin, and 3'-isobutyl-1-methylxanthine could mimic the inhibitory effect of anti-CD2 on anti-CD3-driven CD25 expression. Anti-CD2 also increased the activity of cAMP-dependent protein kinase (PKA). H8, a PKA antagonist, blocked the inhibitory effect of anti-CD2 on CD25 expression, further confirming the role of PKA in CD2-induced negative signaling. The use of paired agonists to PKA demonstrated that a type I PKA was the preferential enzyme isoform stimulated by CD2 ligation. These findings show that increased cAMP and PKA activity mediate anti-CD2-induced suppression of anti-CD3-driven IL-2 production and CD25 expression, and provide mechanisms for anti-CD2-induced immunosuppression and inhibition of the cytokine syndrome associated with anti-CD3 treatment.

Animals↗
PubMed1995

Nicotine attenuates the ventilatory response to hypoxia in the developing lamb.

Decreased ability to generate a hyperventilatory response to hypoxemia is believed to be an important mechanism in the pathophysiology of sudden infant death syndrome, and maternal smoking is a leading risk factor. To investigate whether there may be a link between these two observations, we studied five lambs at mean ages of 7, 17, and 27 d to determine the effects of an i.v. infusion of nicotine (0.5 microgram/kg/min) on ventilation when peripheral chemoreceptor activity was stimulated by hypoxia (0.1 FiO2) or briefly inhibited by hyperoxia. Ventilatory measurements were performed using a computer-aided occlusion valve device which permitted breath-by-breath determinations of inspiratory occlusion pressures (P0.1) and minute ventilation. Nicotine attenuated the early ventilatory response to hypoxia (min 1, 2, and 3 of the test) by 8, 26, and 37%, respectively, at the age of 7 d (analysis of variance overall, p < 0.05), by 23%, 23 and 37% at 17 d (p = NS) and by 40, 45, and 37% at 27 d (p < 0.05). The decrease in ventilation in response to hyperoxia during the control study without nicotine was 18, 35, and 34% at 7, 17, and 27 d, respectively. Nicotine caused a greater decrease in the response: 31, 45, and 46%, respectively, (p < 0.05 at 27 d). The paradoxical effects of nicotine, attenuation of the ventilatory response to hypoxia and augmentation of the response to hyperoxia, suggest that nicotine altered peripheral chemoreceptor oxygen sensitivity and most likely also affected central processing of the chemoreceptor input.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Effect of an interleukin-1 receptor antagonist on the hemodynamic manifestations of group B streptococcal sepsis.

IL-1 is purported to be a proximal mediator in the cascade leading to septic shock. To characterize its hemodynamic effects and to ascertain whether its blockade would ameliorate the deleterious consequences of sepsis, an IL-1 receptor antagonist (IL-1ra) was administered to 16 anesthetized, mechanically ventilated piglets that received a continuous infusion of group B streptococci (GBS) (7.5 x 10(7) colony-forming units/kg/min). Systemic (Psa), pulmonary artery (Ppa), and wedge (Pwp) pressures and cardiac output were measured pre-GBS and every 30 min during GBS infusion. After 15 min of bacterial infusion the control group received normal saline, whereas the treatment group received a bolus of IL-1ra (40 mg/kg) followed by a continuous infusion of IL-1ra (60 micrograms/kg/min). In comparing IL-1ra-treated animals with controls from the 15-min GBS baseline to the succeeding septic study period (45-120 min), the following treatment effects were noted (120-min values shown): mean Psa remained elevated in treatment compared with control animals (12.7 +/- 2.5 versus 9 +/- 3.5 kPa; p < 0.001) as did CO (0.21 +/- 0.07 versus 0.13 +/- 0.08 L/min/kg; p < 0.001). Pwp decreased in the treatment compared to the control group over the study period (1 +/- 0.3 versus 1.6 +/- 0.7 kPa; p < 0.02). Mean Ppa and mean Pra were not different between groups over time. Median length of survival was significantly longer (p = 0.04) in treated (226 min) compared with control animals (150 min). These data suggest that IL-1 plays an important role in GBS sepsis and septic shock, and that IL-1ra may in part ameliorate the cardiovascular alterations associated with GBS sepsis in the neonate.

Animals↗
PubMed1995

[Simplified enzyme-linked immunoadsorbent assays for myelin basic protein and antibodies to myelin basic protein].

Synchronous quantitative determination using simplified enzyme-linked immuno adsorbent assay has been developed for myelin basic protein (MBP) and antibodies to myelin basic protein (Anti-MBP). Antisera were prepared by immunizing rabbits with purified MBP from human white matter. Antibodies to MBP was conjugated with horseradish peroxidase (HRP) by using modified periodate oxidation method. Minimum detection amounts of MBP and Anti-MBP are 0.25 ng/ml and 0.20 ng/ml respectively. The activities of Anti-MBP-HRP conjugates are stable (stored at -30 degrees C) for at least 2 years. The detection procedure can be accomplished within 24 hours.

Animals↗
PubMed1995

Evidence showing a different repertoire of antibodies against unfolded cobrotoxin in anticobrotoxin and anti-reduced and S-carboxymethylated cobrotoxin antisera.

Antibodies which specifically reacted with reduced and S-carboxy-methylated(RCM) cobrotoxin were purified from anticobrotoxin antisera and anti-RCM-cobrotoxin antisera, respectively. Results using a competitive immunoassay revealed that the antibodies from anti-RCM-cobrotoxin antisera had a greater affinity for RCM-cobrotoxin than for cobrotoxin. Whereas the reactivity of the antibodies from the anticobrotoxin antisera toward cobrotoxin and RCM-cobrotoxin had a reversed order of binding. In contrast to observations made with S. aureus V8 protease-digest hydrolysates, the antigenic structures of RCM-cobrotoxin recognized by antibodies from anti-RCM-cobrotoxin antisera were notably affected following hydrolysis of RCM-cobrotoxin with chymotrypsin. Moreover, the chymotryptic hydrolysates showed a comparable reactivity as RCM-cobrotoxin toward the antibodies purified from anticobrotoxin antibodies, but a decrease in antigenicity with the V8 protease hydrolysates. These results reveal that the repertoire of antibodies against the unfolded cobrotoxin are not the same in anticobrotoxin and anti-RCM-cobrotoxin antisera. Moreover, it suggests that the repertoire of antibodies from the different sources against the same antigen can be differentiated by measurement of their reactivities with the proteolytic hydrolysates of the antigen.

Animals↗
PubMed1995

[The changing of orofacial structure by bite opening with Begg technique].

Cephalometric study of 30 deep-bite cases treated with extraction of four first premolars and Begg stage I appliance shows that the bite opening consists of not only intrusion of the upper and lower incisors but also extrusion of the upper and lower molars, furthermore, the lower incisors depressed more than the upper ones and the lower molars are elevated more than the upper ones. The moving type of teeth, the changing of base bone and soft tissue profile are also discussed in this article.

Adolescent↗
PubMed1995

Regulation of transcription functions of the p53 tumor suppressor by the mdm-2 oncogene.

BACKGROUND: Mdm-2, a zinc finger protein, negatively regulates the p53 tumor suppressor gene product by binding to it and preventing transcriptional activation (16). MATERIALS AND METHODS: Assays for p53 mediated transcription, repression and activation by mutant and wild-type p53 proteins were used to measure the ability of mdm-2 to block each activity. RESULTS: Mdm-2 was able to inhibit all three functions of the wild-type and mutant p53 activities; transcriptional activation by the wild-type protein, transcriptional activation by the mutant p53 protein, and repression by the wild-type protein. CONCLUSIONS: The mdm protein binds to the amino terminal portion of the p53 protein and, in so doing, blocks the ability of p53 to interact with the transcriptional machinery of the cell (23). The mdm-2 protein binds to both leucine-tryptophan residues at amino acids 22 and 23, from the amino terminal end of the protein, and in so doing, prevents all p53 functions. The ability of a mutant p53 protein to transactivate a multidrug resistance-1 gene promoter is blocked by mdm-2 and the ability of the wild-type p53 protein to repress transcription of some genes is also blocked by the mdm-2 protein. Thus, all three functions of the p53 protein-transcriptional activation, repression and mutant protein activation-require the p53 amino terminal domain functions and are regulated by the mdm-2 protein in a cell. When mdm-2 is overproduced, resulting in a tumor or transformation of a cell, all of the p53 activities are inactivated.

Base Sequence↗
PubMed1995

Limb salvage surgery with microsurgical reconstruction for the treatment of musculoskeletal tumours involving the upper extremity.

Microsurgical reconstructive techniques have been applied in the management of 14 patients with malignant bone and soft tissue tumours as well as for 30 patients with benign but aggressive bone lesions affecting the upper extremity. Vascularised bone grafts were used in 6 patients with malignant bone tumours and 30 patients with aggressive bone lesions. Reconstruction with soft tissue free flap transfer was required in 6 patients with soft tissue defects, primarily following excision of soft tissue tumours in 2 and after excision of recurrent tumours in 4 patients. Microneural dissection and vascular reconstruction were performed in 2 patients with tumours around the major neurovascular bundles. The patients were followed up for varying periods, ranging from 1 to 12 years and assessment of the limb function was performed using Enneking's system of evaluation. There were no local recurrences. In the malignant tumour group, 3 patients died of systemic disease, 7 were alive but with disease and 4 were disease free. Extremity function was excellent in 3 patients, good in 6 patients, fair in 4 patients and poor in 1 patient. In the benign bone tumour group, extremity function was graded as excellent in 12 patients, good in 14 patients, fair in 3 patients and poor in 1 patient. The vascular bone grafts united in all but 3 patients at 4 months following surgery. Minimal donor site complications had been recorded and there had been no failures. Useful limb salvage may thus be achieved with the application of microsurgical techniques for a variety of indications in limb salvage surgery after tumour excision.

Adolescent↗
PubMed1995

Regulation of anti-SRBC antibody production by opioids and their mechanisms.

This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro. It was found that morphine, a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cells to generate antibody and leukotriene C4 and conversely, dynorphin was able to stimulate the capacity of murine spleen cells to generate antibody and leukotriene C4. Morphine, a-CAO, MENK, DADLE, dynorphin decreased intracellular cAMP level, increased [Ca2+]i and calmodulin activity. The effects were completely blocked by naloxone, the specific opioid antagonist. Our results showed that opioids regulate the production of antibody in murine spleen cells, and alter intracellular cAMP, [Ca2+]i calmodulin activity, and leukotriene C4 production by way of binding to different receptor types.

Animals↗
PubMed1995

In patients with hypertensive left ventricular hypertrophy and coronary heart disease, coronary flow reserve is similarly impaired.

Coronary blood flow reserve (CFR) was assessed by transesophageal Doppler echocardiography in normal subjects (group A, n = 20), hypertensive non-left ventricular hypertrophy (non-LVH) patients (group B, n = 22), hypertensive patients with LVH (group C, n = 32) and coronary heart disease patients (group D, n = 33) with the volume sample placed at the bifurcation of the left main and left descending coronary artery. Coronary blood flow velocity (CBFV) was evaluated at rest, 2 minutes after dipyridamole (0.56 mg/kg, i.v.), and 2 minutes after aminophylline i.v. The ratio of dipyridamole to rest maximal diastolic velocity (D/R PDV) was considered the index of coronary blood flow reserve. It was found that D/R PDV was significantly less in groups C and D compared with that in groups A and B(D/R PDV, 1.84 +/- 0.57, 1.57 +/- 0.41 versus 2.59 +/- 0.70 and 2.22 +/- 0.58, respectively), with no difference in D/R PDV between groups C and D. Twenty-four out of 32 patients in group C with D/R PDV were less than 2.0 compared to 29 out of 33 patients in group D (P > 0.05). Significant negative correlation was found between D/R PDV, D/R PSV and interseptal thickness, left ventricular mass index in hypertensive patients. These data show that impaired CFR in hypertensive patients with LVH is comparable to that in patients with coronary heart disease.

Adult↗
PubMed1995

[Effects of thymectomy and glucocorticoid therapy on peripheral lymphocytes in myasthenia gravis].

Clinical manifestations and peripheral blood lymphocyte subset changes were studied in patients with myasthenia gravis (MG) to elucidate the mechanism of clinical improvement following treatment, with thymectomy (Tx) or glucocorticoid (GC) therapy. The changes found were: 1. There was a significant increase in percentages of CD3+, CD29+ CD4+ cells and CD4/CD8 ratio and a significant decrease in percentages of CD8+ and CD16,56+ cells in patients who had never been treated with any immune therapy. 2. After Tx or GC therapy, CD3+ and CD4+, CD29+ cells were decreased, but the number CD19+ and CD16, CD56 cells did not change. 3. Tx had a special effect on CD8+ cells. In most of the patients who showed clinical improvement after Tx, CD8+ cells were increased and CD4/CD8 ratio wad decreased. 4. Anti-acetylcholine receptor (AChRAb) titers were markedly decreased after GC therapy. These results indicate that there were obvious abnormalities in cell-mediated immunity in addition to those in humoral immunity in myasthenia gravis. These abnormalities tended to be normalized after Tx or GC therapy.

Adolescent↗
PubMed1995

[Experimental study on targeting therapy of human hepatocellular carcinoma in nude mice using adriamycin-anti-transferrin receptor conjugate].

Conjugate between adriamycin and anti-transferrin receptor monoclonal antobody WuT9 was prepared with Dextran T10 as a bridge, and it was proved to retain both the drug cytotoxity and antibody activity. The conjugate or its individual components were administered to athymic mice bearing SMMC-7721 human hepato-cellular carcinoma (HCC) cells. These agents were given 2, 5, 8 days after inoculation of tumor cells (1 x 10(7) per mouse). Tumor size was measured daily (geometric mean diameter, GMD) and latent period recorded. All the animals were killed on day 35 to measure tumor weight and natural killer (NK) activity of splenic lymphocytes. The results showed that the latent period in the conjugate treated group was much longer than that in Adr treated group (33.0 days vs 25.0 days), and that GMD on day 35 in the conjugate treated group was much smaller than that in Adr treated group (3.80 +/- 1.9 mm vs 6.69 +/- 2.3 mm, P < 0.05). In addition, NK activity in the conjugate treated group was higher than that in Adr treated group (28.2 +/- 8.2% vs 15.1 +/- 3.6%, P < 0.05). The results suggest that adriamycin-anti-transferrin receptor conjugate might be useful in the treatment of human HCC.

Animals↗
PubMed1995

[Status and strategy of parasitosis control in preventive health care in China].

According to the result of nationwide human parasitic disease distribution survey, the public significance of parasitosis control was set forth in terms of preventive health care and economic impact as well as parasitosis control and primary health care. A suggestion was made on the control strategy aiming at the parasitosis of priorities listed in the above survey.

China↗