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Biomedical subjects

L Yao

Publications and source records attributed to L Yao.

At least 91 records · Page 5Linked to original sources
PubMed1998

Contribution of the CXC chemokines IP-10 and Mig to the antitumor effects of IL-12.

The mechanisms by which interleukin-12 (IL-12) exerts antitumor effects have been difficult to dissect. In this study, we examined the potential contribution of the chemokines interferon-gamma-inducible protein-10 (IP-10) and Mig to the antitumor effects of IL-12. Using an athymic mouse model, local inoculations with IL-12 consistently produced tumor size reductions associated with characteristic tumor necrosis and vascular damage. These effects were indistinguishable from those produced by IP-10 or Mig injected locally in the same tumor model. Local and systemic treatment with IL-12 was associated with expression of the interferon-gamma (IFN-gamma), IP-10, and Mig genes and proteins in the tumor. Levels of IP-10 and Mig expression in the tumor, the liver, and the kidney were inversely correlated with tumor size. Administration in vivo of neutralizing antibodies to IP-10 and Mig reduced substantially the antitumor effects of IL-12 inoculated locally into the tumors. These results support the notion that IP-10 and Mig contribute to the antitumor effects of IL-12 through their inhibitory effects on tumor vasculature.

Animals↗
PubMed1998

A comparison of lycopene and canthaxanthin absorption: using the rat to study the absorption of non-provitamin A carotenoids.

The purpose of this study was to validate the use of the mesenteric lymph duct cannulated rat to study the absorption of carotenoids which do not have provitamin A activity. The absorption of two carotenoids, a hydrocarbon carotenoid (lycopene) and a xanthophyll carotenoid (canthaxanthin), were investigated. In the first experiment, lipid emulsions containing lycopene (LYC) or canthaxanthin (CTX) were continuously infused into the duodenum, and lymph was collected for analysis at 2-h intervals. The time course for absorption of carotenoids and triacylglycerol (TAG) was similar. Carotenoids and TAG reached steady-state concentrations in the lymph by 6 h. There was no evidence for a delayed release of either carotenoid from the intestine relative to TAG. During a second experiment, emulsions containing increasing concentrations of LYC or CTX (5, 10, 15, 20 mumol/L) were infused. The LYC and CTX in the lymph increased in a dose-dependent manner. The average efficiency of CTX absorption was 16% while the efficiency of LYC absorption averaged only 6%. Efficiency of carotenoid absorption was not related to concentration infused. Finally, to test whether LYC and CTX interact during absorption both were added to a lipid emulsion at equal concentrations (20 mumol/L) and infused. The carotenoids did not significantly affect each other's absorption. These results demonstrate the usefulness of the rat as an animal model to study the absorption of non-provitamin A carotenoids.

Animals↗
PubMed1998

Insulin-induced vasodilation is dependent on tetrahydrobiopterin synthesis.

Insulin has been shown to elicit vasodilation through increases in nitric oxide (NO) production. To examine whether insulin may modulate the availability of tetrahydrobiopterin (BH4) (an absolute cofactor requirement for NO synthase activation), we studied the effects of insulin (150 nmol/L) on femoral arterial reactivity (to norepinephrine [NE]) in the presence and absence of 2,4-diamino-6-hydroxypyrimidine (DAHP), a specific inhibitor of BH4 production. Our data indicate that inhibition of BH4 synthesis results in an attenuation in the vasodepressor effect of insulin. One possibility is that insulin may regulate NO production by increasing cofactor (BH4) availability for activation of NO synthase.

Animals↗
PubMed1998

Stress injuries of bone: analysis of MR imaging staging criteria.

RATIONALE AND OBJECTIVES: The authors examined the prognostic value of magnetic resonance (MR) imaging in stress injuries of bone. MATERIALS AND METHODS: Clinical follow-up data were collected in 35 patients who underwent MR imaging because of suspected stress fractures. MR findings were correlated with total duration of symptoms, the time to return to sports activity, and findings at follow-up radiography. RESULTS: The MR imaging finding of a "fracture" or "fatigue" line or a cortical signal intensity abnormality was predictive of a longer symptomatic period, whereas muscle edema was predictive of a shorter symptomatic period. A published grading system could be used in only 24 patients; the MR imaging grade of injury did not show correlation with clinical outcome. CONCLUSION: The MR imaging finding of either a medullary line or a cortical abnormality appears to indicate a more severe stress injury of bone. A previously published MR imaging grading system for stress injuries of the tibia was not prognostic in this more heterogeneous patient group.

Adolescent↗
PubMed1998

Surface lesions of bone.

A surface lesion of bone may arise within the cortex, between the cortex and the periosteum, within the periosteum, or in the tissues immediately adjacent to the periosteum including tendinous and ligamentous attachments. While these lesions generally reflect the spectrum of more common intramedullary lesions and have an appearance similar to that of their intramedullary counterparts, their unusual surface origin often renders diagnosis difficult. Surface sarcomas are usually of a lower grade than that of the intramedullary tumor, and often they have a more favorable prognosis. Traumatic lesions of the bone surface are common and should be considered in the differential diagnosis of a surface lesion, especially in the young or athletic individual. An elevated peripheral white blood cell count and erythrocyte sedimentation rate may herald an infection of the bone surface.

Bone Diseases↗
PubMed1998

Anterolateral impingement of the ankle: effectiveness of MR imaging.

PURPOSE: To determine the effectiveness of magnetic resonance (MR) imaging in the diagnosis of anterolateral impingement of the ankle. MATERIALS AND METHODS: MR images were reviewed in 12 patients (12 ankles) with arthroscopically proved anterolateral impingement and in 19 control subjects (20 ankles) with diagnoses other than impingement. MR images were scored by means of consensus of two musculoskeletal radiologists and independently by a third radiologist. Patients underwent imaging at 1.5 T, with use of standard imaging sequences and a dedicated extremity coil. RESULTS: For the consensus reading, the sensitivity, specificity, and accuracy of MR imaging for the diagnosis of impingement were 42%, 85%, and 69%, respectively. The frequency of lateral gutter fullness and anterior talofibular ligament thickening on MR images was higher in the 12 ankles with impingement (seven [58%] and seven [58%] ankles, respectively) than in the 20 control ankles (seven [35%] and five [25%] ankles, respectively), but these trends did not reach statistical significance. Interobserver agreement for anterior talofibular ligament thickening was high, whereas that for lateral gutter fullness was fair. CONCLUSION: Conventional MR imaging of the ankle is insensitive for anterolateral impingement. Anterior talofibular ligament thickening and soft-tissue fullness in the lateral gutter may be suggestive of the diagnosis, but the reliability of the latter finding is questionable.

Adult↗
PubMed1998

Direct vasodepressor effects of pioglitazone in spontaneously hypertensive rats.

Effects of pioglitazone on plasma insulin levels, systolic blood pressure and arterial reactivity were studied in spontaneously hypertensive (SH) rats. Chronic treatment of SH rats with pioglitazone decreased plasma insulin levels and blood pressure. Direct effects of pioglitazone on vascular reactivity were also studied in aortae and superior mesenteric arteries from SH rats. Pioglitazone markedly inhibited arginine vasopressin (AVP) and norepinephrine (NE) responses without affecting responses to potassium chloride (KCl). These data suggest that (a) antihypertensive effects of pioglitazone in SH rats may be mediated via a direct vasodepressor effect, and (b) vasodilation may be coupled to insulin sensitivity in SH rats.

Animals↗
PubMed1998

Osteochondromalike parosteal osteosarcoma: a report of six cases of a new entity.

OBJECTIVE: Our purpose was to describe a rare juxtacortical bone sarcoma with deceptively benign, osteochondromalike histologic characteristics. We present criteria by which this low-grade malignant neoplasm can be distinguished from other benign and malignant surface lesions of bone with particular emphasis on the imaging features. MATERIALS AND METHODS: Six cases of a low-grade, chondroossifying parosteal sarcoma of bone were reviewed. Patients included four males and two females 11 months to 66 years old. Histologic findings from initial tumors and from recurrent tumors were reviewed. Two musculoskeletal radiologists analyzed the imaging studies, which included plain films, CT scans, MR images, and a bone scan. RESULTS: Histologically, the lesions were characterized by a thin layer of proliferating, periosteally derived spindle cells overlying a thin, low-grade malignant cartilage cap that underwent calcification, neovascularization, and conversion into benign bone and marrow fat. These lesions were unique in that the malignant elements were only at their periphery. All six cases were initially misdiagnosed as benign lesions on pathologic evaluation. In each patient, imaging revealed a "pasted-on" ossified surface lesion with an intact underlying cortex and no medullary involvement. In three cases, recurrent tumors had histologic appearances consistent with conventional parosteal osteosarcoma. Dedifferentiation, metastases, and death occurred in one of these three cases. CONCLUSION: To our knowledge, this surface lesion of bone has not been specifically described. Whether this tumor constitutes a distinct entity or is a specialized variant of parosteal osteosarcoma is unclear. Precise radiologic-pathologic correlation is essential for appropriate diagnosis and management.

Adolescent↗
PubMed1998

[Expression of human granulocyte-macrophage colony stimulating factor(hGM-CSF) by recombinant vaccinia virus and its effect on immunogenicity].

hGM-CSF was inserted into the down stream of P11K promoter of pJSB1175, which consists of HSV-1gD under the promoter P7.5K. The constructed plasmid pJSB1175D/GM-CSF was cotransfected with vaccinia virus Tiantan Strain into TK-143. After selection and screening, recombinant virus RVJSB11D/GM-CSF was harvested. It was proved that the recombinant virus could express GM-CSF and HSV-1gD at the same time by MTT assay and IFA in vitro. In vivo study showed that the expression of GM-CSF by RVJSB1175D/GM-CSF did not interfere with the HSV-1gD antibody production.

Animals↗
PubMed1998

Varying effects of ethanol on transfected cell lines.

The use of transfected cell lines has provided a powerful approach to study the functions of transfected proteins. This approach has also proven useful to determine the effects of acute and chronic ethanol exposure on particular proteins. We show here, however, that the effects of ethanol on transfected proteins vary between transiently transfected cells and stably transfected cell lines. Moreover, we found that the effect of ethanol on a particular protein depends on the plasmid vectors used for the transfection.

Animals↗
PubMed1997

Interactions between protein kinase C and pleckstrin homology domains. Inhibition by phosphatidylinositol 4,5-bisphosphate and phorbol 12-myristate 13-acetate.

Pleckstrin homology (PH) domains comprised of loosely conserved sequences of approximately 100 amino acid residues are a functional protein motif found in many signal-transducing and cytoskeletal proteins. We recently demonstrated that the PH domains of Tec family protein-tyrosine kinases Btk and Emt (equal to Itk and Tsk) interact with protein kinase C (PKC) and that PKC down-regulates Btk by phosphorylation. In this study we have characterized the PKC-BtkPH domain interaction in detail. Using pure PKC preparations, it was shown that the Btk PH domain interacts with PKC with high affinity (KD = 39 nM). Unlike other tested phospholipids, phosphatidylinositol 4,5-bisphosphate, which binds to several PH domains, competed with PKC for binding to the PH domain apparently because their binding sites on the amino-terminal portion of the PH domains overlap. The minimal PKC-binding sequence within the Btk PH domain was found to correspond roughly to the second and third beta-sheets of the PH domains of known tertiary structures. On the other hand, the C1 regulatory region of PKCepsilon containing the pseudosubstrate and zinc finger-like sequences was found to be sufficient for strong binding to the Btk PH domain. Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC that interacts with the C1 region of PKC, inhibited the PKC-PH domain interaction, whereas the bioinactive PMA (4-alpha-PMA) was ineffective. The zeta isoform of PKC, which has a single zinc finger-like motif instead of the two tandem zinc finger-like sequences present in conventional and novel PKC isoforms, does not bind PMA. Thus, as expected, PH domain binding with PKCzeta was not interfered with by PMA. Further, inhibitors that are known to attack the catalytic domains of serine/threonine kinases did not affect this PKC-PH domain interaction. In contrast, the presence of physiological concentrations of Ca2+ induced less than a 2-fold increase in PKC-PH domain binding. These results indicate that PKC binding to PH domains involve the beta2-beta3 region of the Btk PH domain and the C1 region of PKC, and agents that interact with either of these regions (i.e. phosphatidylinositol 4,5-bisphosphate binding to the PH domain and PMA binding to the C1 region of PKC) might act to regulate PKC-PH domain binding.

Amino Acid Sequence↗
PubMed1997

Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity.

Mast cells derived from Bruton's tyrosine kinase (Btk)-defective xid or btk null mice showed greater expansion in culture containing interleukin-3 (IL-3) than those from wild-type (wt) mice. Although the proliferative response to IL-3 was not significantly different between the wt and xid mast cells, xid and btk null mast cells died by apoptosis more slowly than their wt counterparts upon IL-3 deprivation. Consistent with these findings, the apoptosis-linked c-Jun N-terminal kinase/stress-activated protein kinase (JNK) activity was compromised in these btk-mutated cells upon Fc(epsilon)RI crosslinking or upon stimulation with IL-3 or with stem cell factor. p38 activity was less severely, but significantly, affected by btk mutation, whereas extracellular signal-regulated kinases were not affected by the same mutation. Btk-mediated regulation of apoptosis and JNK activity was confirmed by reconstitution of btk null mutant mast cells with the wt btk cDNA. Furthermore, growth factor withdrawal induced the activation and sustained activity of JNK in wt mast cells, while JNK activity was consistently lower in btk-mutated mast cells. These results support the notion that Btk regulates apoptosis through the JNK activation.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1997

Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo.

Mig, the monokine induced by interferon-gamma, is a CXC chemokine active as a chemoattractant for activated T cells. Mig is related functionally to interferon-inducible protein 10 (IP-10), with which it shares a receptor, CXCR3. Previously, IP-10 was found to have antitumor activity in vivo. In the present study, murine Mig RNA was found to be expressed at higher levels in regressing Burkitt's lymphoma tumors established in nude mice compared with progressively growing tumors. Daily inoculations of purified recombinant human Mig into Burkitt's tumors growing subcutaneously in nude mice consistently caused tumor necrosis associated with extensive vascular damage. These effects were indistinguishable from those produced by intratumor inoculations of Burkitt's tumors with IP-10. These results support the notion that Mig, like IP-10, has antitumor activity in vivo.

Animals↗
PubMed1997

Vascular insulin resistance in fructose-hypertensive rats.

Evidence suggests that insulin has direct, potent and physiologically relevant vasodilatory effects. This has led to the hypothesis that in states of insulin resistance, insulin's vasodilatory effects may be blunted leading to an increase in vascular tone and blood pressure. To examine this proposition we studied the direct effects of insulin on the reactivity of aortae from control and insulin-resistant fructose-hypertensive rats to angiotensin II. Insulin incubation caused marked vasodepressor effects in control aortae. Strikingly, this effect was absent in aortae from fructose-hypertensive rats. These data suggest the presence of vascular insulin resistance in fructose-hypertensive rats and provide a hemodynamic basis for hypertension in states of insulin resistance.

Animals↗
PubMed1997

Increased secretion of TNF-alpha by costimulation of mast cells via CD28 and Fc epsilon RI.

The present study unequivocally demonstrated the expression of CD28 on murine bone marrow-derived cultured mast cells and a mast cell line, MCP-5. Stimulation of surface CD28 molecules on mast cells with anti-CD28 mAbs induced tyrosine phosphorylation of cellular proteins, including several protein tyrosine kinases and their substrates, such as Itk/Emt (Emt), Btk, Syk, c-Cbl, Shc, and Vav. CD28-stimulated tyrosine phosphorylation was followed by a rebound hypophosphorylation. Interestingly, CD28 stimulation alone elicited a low level secretion of TNF-alpha. On the other hand, cross-linking of the high affinity IgE receptor (Fc epsilon RI) on mast cells induces a set of activation events, i.e., degranulation, secretion of eicosanoids, secretion of cytokines, and DNA synthesis. Concurrent stimulation of mast cells through CD28 enhanced Fc epsilon RI-induced TNF-alpha secretion in a dose-dependent manner. Together, the present data suggest a role for CD28-mediated costimulation of mast cells in the initiation and progression of allergic responses and other diseases.

Agammaglobulinaemia Tyrosine Kinase↗