Search PubMed⌕ Search

Biomedical subjects

J Sun

Publications and source records attributed to J Sun.

At least 559 records · Page 31Linked to original sources
PubMed1996

[Intramedullary spinal teratoma].

We treated 5 cases of intradullary spinal teratomas from 1974 to 1995, accounting 0.636% of all intraspinal tumors and 45.45% of all teratomas of spinal cord admitted in the same time. The origin of this tumor is controversial. It is not easy to differentiate this tumors from other intramedullary spinal tumors on clinical grounds. CT and MR scans of this tumor enabled us to make the preoperative diagnosis of teratoma. Resection is the only treatment of choice.

Adolescent↗
PubMed1996

[Detection of immunoglobulin heavy chain (IgH) gene rearrangement in ANLL by polymerase chain reaction amplification and Southern blot].

Immunoglobulin heavy chain (IgH) gene rearrangement serves as a marker of clonality in B lymphoproliferative malignancies. In order to study the IgH rearranged gene in acute nonlymphoblastic leukemia (ANLL) patients we combine polymerase chain reaction (PCR) with Southern blot to detect 41 ANLL patients and 7 of them (17.1%) were found to have IgH rearrangement by PCR amplification. All these 7 positive cases were confirmed by Southern blot. The sensitivity of this method was 10(-4)-10(-5) level. In 12 patients with complete remission, 3 (25.0%) were found to have IgH rearranged gene. All these 3 cases had clinical relapse within 6 months. Our results show that IgH rearrangement not only may occur in lymphoblastic leukemia of B lineage, but also can be found in ANLL. The mechanism may be that in some ANLL patients, the leukemic transforming event might involve stem cells capable of both B cell and myeloid differentiation or ANLL might differentiate along different lineage with predominant appearance of one or the other subclone in the course of the disease.

Blotting, Southern↗
PubMed1996

[DNA replication and cellular proliferation in the noise damaged basilar papillar of chicks].

An acoustic trauma model for study of the repair of the auditory epithelia was established in postnatal 8-14 days chicks. The animals were continuously exposed to the wide band noise at 115 dB (A) for 72 hours. The tracer of DNA replication-[3H] thymidine (3H-dR) was given in vivo or in vitro during or after exposure. The basilar papilla were cultured and processed with autoradiographic technique. The results demonstrated that at 48 hours following initial labelling of tracer, the incorporation of 3H-TdR was found over the nucli of supporting cells (or precursor cells) in the injured region of basilar papilla. The labelled hair cells appeared at 96 hours near the labelled supporting cells. Until the fifth to sixth days of culturing, the regenerated hair cells were still immature morphologically. No sign of labelled hair cells were detected in the control animals. Our findings indicated the potential capability of cellular proliferation and DNA replication in damaged auditory epithelia in vitro. Some kind of supporting cells in damaged region could be the precursors for regenerating hair cells. The positive cells labelled with 3H-TdR migrated to the surface of basilar papilar and differentiated into hair cells eventually. Therefore, it could be speculated that a homogeneous relationship may exist between labelled supporting cells and labelled hair cells.

Animals↗
PubMed1996

[Effects of growth factors on the survival status and the neurite regeneration of auditory neurons in vitro].

To confirm the biological effects of peptide growth factors on auditory neuron (AN) in vitro, the influence of NFG and bFGF on the survival status and the neurite regrowth of dissociated primary AN in postnatal chicks was studied with serum-free culture technique and cytologic quantitative method. The results demonstrated that the growth of non-neuron elements such as Schwann's cell was predominant in the earlier stage of culture. The neurite regrowth (bipolarity or unipolarity) of AN was observed at 24 hours after seeding. The growth rate increase during 48-72 hours in the surviving AN. These findings indicated that both growth factors exerted direct neuronotrophic effect on dissociated AN in vitro. NGF and bFGF acted in cooperation to promote the axon regeneration of AN. The concentration-dependent effect of NGF on neurite regrowth and neurone survival was found in the present study. The biological mechanism of NGF and bFGF on AN in vitro has been discussed.

Animals↗
PubMed1996

[Influence of temperature on the chemical constituents and pharmacological effects of semen Cassiae].

The influence of temperature on the chemical constituents and pharmacological effects of seeds of Cassia tora was examined. As the baking temperature was raised, the contents of free chrysophanol increased. The contents of antihepatotoxic constituents in the samples baked at different temperatures were compared. They decreased as the temperature rose. The pharmacological results basically accorded with the contents of the constituents.

Alanine Transaminase↗
PubMed1995

The effects of out-of-plane rotations on two dimensional portal image registration in conformal radiotherapy of the prostate.

PURPOSE: Rotations of the patient out of the image plane can significantly degrade the accuracy of two-dimensional (2D) image registration. This study determines the magnitude of the geometric errors introduced by 2D image registration as a result of out-of-plane rotations, and analyzes the dosimetric effects of these errors. METHODS AND MATERIALS: The magnitude of the errors introduced by 2D registration were determined by comparing orthogonal view portal images of a rotated phantom to simulator reference images of the same phantom without rotation. Dosimetric effects were calculated for three-dimensional (3D) conformal prostate treatments by applying the registration errors to patient treatment plans. The calculations were performed using a modified version of the dose calculation software used in our Cancer Center for 3D treatment planning based on computed tomography (CT). A method to detect out-of-plane rotations, specific to pelvic treatments, is introduced that uses the relative displacement of the centers of gravity of the acetabula in lateral images. RESULTS: The inherent uncertainty in the registration algorithm was 0.6 +/- 0.5 mm in translation and 0.7 +/- 0.8 degree in rotation within the image plane. For a 2 degrees out-of-plane rotation, the errors increase to 2.3 +/- 1.0 mm and 1.2 +/- 1.1 degrees. In some clinically realizable treatment scenarios it was observed that the errors introduced by the registration procedure could result in an overdosing of the rectal wall. The method to detect out-of-plane rotations was found to have an accuracy of better than 1 degree for rotations of less than 10 degrees. CONCLUSIONS: The errors introduced to the patient position by 2D image registration have dosimetrically significant consequences for out-of-plane rotations of 2 degrees or more. However, when used in conjunction with the method to detect out-of-plane rotations, 2D registration software was found to cause insignificant dose errors and, thus, become a more reliable and accurate clinical tool.

Humans↗
PubMed1995

Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes.

Ras-induced malignant transformation requires Ras farnesylation, a lipid posttranslational modification catalyzed by farnesyltransferase (FTase). Inhibitors of this enzyme have been shown to block Ras-dependent transformation, but the mechanism by which this occurs remains largely unknown. We have designed FTI-276, a peptide mimetic of the COOH-terminal Cys-Val-Ile-Met of K-Ras4B that inhibited potently FTase in vitro (IC50 = 500 pM) and was highly selective for FTase over geranylgeranyltransferase I (GGTase I) (IC50 = 50 nM). FTI-277, the methyl ester derivative of FTI-276, was extremely potent (IC50 = 100 nM) at inhibiting H-Ras, but not the geranylgeranylated Rap1A processing in whole cells. Treatment of H-Ras oncogene-transformed NIH 3T3 cells with FTI-277 blocked recruitment to the plasma membrane and subsequent activation of the serine/threonine kinase c-Raf-1 in cells transformed by farnesylated Ras (H-RasF), but not geranylgeranylated, Ras (H-RasGG). FTI-277 induced accumulation of cytoplasmic non-farnesylated H-Ras that was able to bind Raf and form cytoplasmic Ras/Raf complexes in which Raf kinase was not activated. Furthermore, FTI-277 blocked constitutive activation of mitogen-activated protein kinase (MAPK) in H-RasF, but not H-RasGG, or Raf-transformed cells. FTI-277 also inhibited oncogenic K-Ras4B processing and constitutive activation of MAPK, but the concentrations required were 100-fold higher than those needed for H-Ras inhibition. The results demonstrate that FTI-277 blocks Ras oncogenic signaling by accumulating inactive Ras/Raf complexes in the cytoplasm, hence preventing constitutive activation of the MAPK cascade.

Alkyl and Aryl Transferases↗
PubMed1995

Interaction between CD8 and major histocompatibility complex (MHC) class I mediated by multiple contact surfaces that include the alpha 2 and alpha 3 domains of MHC class I.

The cell surface glycoprotein CD8 functions as a coreceptor with the TCR on cytotoxic T lymphocytes. Mutational analysis of the binding site of CD8 for MHC class I predicted that distinct surfaces of CD8 would interact with both the alpha 2 and alpha 3 domains of class I. Using a cell-cell adhesion assay, we identified three residues Q115, D122, and E128 in the alpha 2 domain of class I critical for interaction with CD8. The side chains of these residues point towards a cavity formed by the alpha 1/alpha 2 platform, the alpha 3 domain and beta 2-microglobulin (beta 2m) of class I. These residues were predicted to contact CD8 based on a bivalent model of interaction between one CD8 alpha/alpha homodimer and two MHC class I molecules. These results therefore provide support for the model.

Animals↗
PubMed1995

Alternative splicing of a specific cytoplasmic exon alters the binding characteristics of murine platelet/endothelial cell adhesion molecule-1 (PECAM-1).

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a membrane glycoprotein expressed on endothelial cells, platelets, and leukocytes. Analysis of PECAM-1 expression in the developing mouse embryo has revealed the presence of multiple isoforms of murine PECAM-1 (muPECAM-1) that appeared to result from the alternative splicing of exons encoding cytoplasmic domain sequences (exons 10-16) (Baldwin, H. S., Shen, H. M., Yan, H., DeLisser, H. M., Chung, A., Mickanin, C., Trask, T., Kirschbaum, N. E. Newman, P. J., Albelda, S., and Buck, C. A. (1994) Development 120, 2539-2553). To investigate the functional consequences of alternatively spliced muPECAM-1 cytoplasmic domains, L-cells were transfected with cDNA for each variant and their ability to promote cell aggregation was compared. In this assay, full-length muPECAM-1 and all three isoforms containing exon 14 behaved like human PECAM-1 in that they mediated calcium- and heparin-dependent heterophilic aggregation. In contrast, three muPECAM-1 variants, all missing exon 14, mediated calcium- and heparin-independent homophilic aggregation. Exon 14 thus appears to modulate the ligand and adhesive interactions of the extracellular domain of PECAM-1. These findings suggest that alternative splicing may represent a mode of regulating the adhesive function of PECAM-1 in vivo and provides direct evidence that alternative splicing involving the cytoplasmic domain affects the ligand specificity and binding properties of a cell adhesion receptor.

Alternative Splicing↗
PubMed1995

Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion.

Farnesylation of the oncoprotein Ras is required for its cancer-causing activity. We have designed farnesyltransferase inhibitor (FTI)-276, a tetrapeptide mimetic of the carboxyl terminus of K-Ras4B, as a highly potent and selective inhibitor of Ras farnesylation in vitro and in vivo. FTI-276 blocked the growth in nude mice of a human lung carcinoma that expresses the two most prevalent genetic alterations in human cancers (K-Ras oncogenic mutation and deletion in the tumor suppressor gene p53). In contrast, FTI-276 did not inhibit tumor growth of a human lung carcinoma that harbors no Ras mutations. Furthermore, FTI-276 inhibited oncogenic signaling and tumor growth of NIH 3T3 cells transformed with the ras but not the raf oncogene. Inhibition of tumor growth in vivo was dose dependent and correlated with inhibition of Ras processing in tumors in vivo. The work described here identifies FTI-276 as a highly selective suppressor of Ras-dependent oncogenicity and suggests that a broad spectrum of human cancers with aberrant Ras function could benefit from farnesyltransferase inhibitor treatment.

3T3 Cells↗
PubMed1995

Production and characterization of recombinant human proteinase inhibitor 6 expressed in Pichia pastoris.

The human intracellular serine proteinase inhibitor, proteinase inhibitor 6 (PI-6), was expressed in the methylotropic yeast Pichia pastoris. The PI-6 cDNA was modified to encode six histidine residues immediately after the initiation codon, and was placed under the control of the P. pastoris alcohol oxidase promoter in the vector pHIL-D2. On the methanol induction, active recombinant PI-6 was produced within the yeast cells, and following cell lysis, was separated from yeast proteins by affinity chromatography using nickel nitrilo-tri-acetic acid (NTA) resin. The interaction of recombinant PI-6 with a range of serine proteinases was studied. Second order association rate constants (ka) were derived for the interaction with trypsin (1.8 x 10(6) M-1 s-1), thrombin (1.2 x 10(5) M-1 s-1), urokinase plasminogen activator (4.0 x 10(4) M-1 s-1), plasmin (1.3 x 10(6) M-1 s-1), and activated protein C (7.5 x 10(3) M-1 s-1). By monitoring complex formation, recombinant PI-6 was also shown to interact with factor Xa. No complex formation was observed with chymotrypsin, human leukocyte elastase, cathepsin G and tissue plasminogen activator, although PI-6 is apparently a substrate for chymotrypsin, leukocyte elastase and cathepsin G.

Amino Acid Sequence↗
PubMed1995

Resonance Raman studies of Escherichia coli cytochrome bd oxidase. Selective enhancement of the three heme chromophores of the "as-isolated" enzyme and characterization of the cyanide adduct.

Cytochrome bd oxidase is a terminal bacterial oxidase containing three cofactors: a low-spin heme (b558), a high-spin heme (b595), and a chlorin d. The center of dioxygen reduction has been proposed to be at a dinuclear b595/d site, whereas b558 is mainly involved in transferring electrons from ubiquinone. One of the unique functional features of this enzyme is its resistance to high concentrations of cyanide (Ki in the millimolar range). With the appropriate selection of laser lines, the ligation and spin states of the b558, b595, and d hemes can be probed selectively by resonance Raman (rR) spectroscopy. Wavelengths between 400 and 500 nm predominantly excite the rR spectra of the b558 and b595 chromophores. Spectra obtained within this interval show a mixed population of spin and ligation states arising from b558 and b595, with the former more strongly enhanced at higher energy. Red excitation wavelengths (590-650 nm) generate rR spectra characteristic of chlorins, indicating the selective enhancement of the d heme. These rR results reveal that cytochrome bd oxidase "as isolated" contains the b558 heme in a six-coordinate low-spin ferric state, the b595 heme in a five-coordinate high-spin (5cHS) ferric state, and the d heme in a mixture of oxygenated (FeIIO2 <--> FeIIIO2-; d650) and ferryl-oxo (FeIV = O; d680) states. However, the rR spectra of these two chlorin species indicate that they are both in the 5cHS state, suggesting that the d heme is lacking a strongly coordinated sixth ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyanides↗
PubMed1995

Burkitt lymphoma Daudi cells contain two distinct farnesyltransferases with different divalent cation requirements.

Farnesylation is a lipid posttranslational modification required for the biological function of several signaling proteins including the Ras oncoprotein where this modification is required for malignant transformation. Here we report the identification of two distinct farnesyltransferases (FTases) in Burkitt lymphoma Daudi cells. Separation of Daudi cell cytosolic fractions by ion exchange chromatography resulted in two peaks (FTases I and II) that, on gel filtration, show molecular masses of 90 000 and 250 000 Da, respectively. Immunoblotting experiments showed that FTase I is composed of an alpha/beta-heterodimer of about 50 000 Da each. FTase II contained a beta-subunit that is immunologically indistinguishable from the beta-subunit of FTase I and the previously reported human and rat brain FTase but contained an alpha-subunit that reacted poorly with a rat brain anti-alpha-antibody. As in rat brain FTase, Daudi FTases I and II both required magnesium for enzymatic activity. However, their zinc requirements differed. In the absence of Zn2+, FTase I had little activity (10%) whereas FTase II had 30% of its maximum activity (maximum activity obtained in the presence of Zn2+). Furthermore, whereas both FTases I and II were potently inhibited by KB-Ras C-terminal Cys-Val-Ile-Met tetrapeptide mimics, only FTase I but not FTase II required zinc for peptide binding and inhibition.

Alkyl and Aryl Transferases↗
PubMed1995

CAAX peptidomimetic FTI-244 decreases platelet-derived growth factor receptor tyrosine phosphorylation levels and inhibits stimulation of phosphatidylinositol 3-kinase but not mitogen-activated protein kinase.

Cysteine farnesylation of the Ras carboxyl terminal tetrapeptide CAAX motif (where C = cysteine, A = leucine, isoleucine, or valine, and X = methionine or serine) is required for Ras biological activity. In this report, we describe the effects of inhibitors of farnesyltransferase (FTase), the enzyme responsible for this lipid modification, on platelet-derived growth factor (PDGF) signaling in NIH-3T3 cells. In vitro, the CAAX peptidomimetic FTI-232 exhibits potent inhibition of FTase activity (IC50 = 150 nM) and its carboxyl-methylated counterpart, FTI-244, inhibits Ras processing in vivo. Treatment of NIH-3T3 cells with FTI-244 inhibits PDGF-induced DNA synthesis but not stimulation of mitogen-activated protein kinase (MAPK). However, FTI-244 significantly reduces PDGF-induced tyrosine phosphorylation levels of PDGF receptor (PDGFR) as well as its association with, and activation of, phosphatidylinositol-3-kinase (PI-3-K), a key enzyme in PDGF-induced mitogenesis.

3T3 Cells↗
PubMed1995

Deletion of spontaneous rat liver allograft acceptance by donor irradiation.

Liver transplants in rodents or pigs are often spontaneously accepted across a complete MHC mismatch. They induce tolerance to grafts of other organs or skin of liver donor strain and can even suppress ongoing rejection of heart grafts. It has not been established whether liver-induced tolerance is due to components of the liver or to passenger leukocytes within the liver. We depleted populations of passenger leukocytes from the transplanted liver by irradiation of the donor with 10 Gy, followed after 7 days by transplantation of the liver. Recipients of livers from irradiated donors had a median survival of 16 days compared with > 100 days for recipients of livers from normal donors. Examination of recipients of irradiated donor livers showed that allograft rejection was the cause of death. Syngeneic transplants of irradiated PVG donor to PVG recipient or of irradiated DA donor to DA recipient survived indefinitely. Parking of livers from irradiated PVG donors in normal PVG animals for 36 hr reconstituted tolerance when the livers were retransplanted to DA recipients. Livers from irradiated donors had greatly reduced passenger leukocyte numbers compared with normal or parked livers, with virtually complete loss of lymphocytes. These results show that spontaneous liver allograft acceptance is associated with populations of passenger leukocytes that are depleted by donor irradiation.

Animals↗
PubMed1995

Study of dosimetric penumbra due to multileaf collimation on a medical linear accelerator.

PURPOSE: Investigations of dosimetric penumbra produced by multileaf collimation on a medical linear accelerator are presented. METHODS AND MATERIALS: Multileaf collimators (MLCs) can be designed with at least three different shaped leaf-end profiles: straight, divergent, and curved. Assessment of the dosimetric effects of the collimator edge profiles was implemented using a fast Fourier transform (FFT) convolution algorithm. Accelerator source intensity was considered to have a Gaussian distribution. The calculated dose profile, for a source-to-surface distance of 100 cm and at depth of 10 cm in a water phantom, was fitted to a penumbral-forming function from which the penumbral width between 80% and 20% of the central axis dose was obtained. RESULTS: Calculation performed at various field sizes showed that curved collimator leaf-end produces a wider penumbra than the diverging collimator leaf-side. Film measurements agreed with the calculations within an uncertainty of less than 2 mm. The effect of backup jaws for the MLC and of the lower pair of diverging diaphragms on dosimetric penumbra was also investigated. CONCLUSIONS: This study is useful for characterizing collimator edge effects and for optimizing new collimator designs.

Algorithms↗