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Biomedical subjects

L Lu

Publications and source records attributed to L Lu.

At least 487 records · Page 27Linked to original sources

In vivo effects of purified recombinant human macrophage colony-stimulating factor in combination with local hyperthermia on tumor progression in B16a melanoma bearing mice.

Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was evaluated, alone or in combination with local hyperthermia (LH), for their antitumor effects in mice inoculated with B16a melanoma cells. Several tumor related parameters and other hematopoietic and immunologic parameters were evaluated 5 weeks after subcutaneous (s.c.) inoculation of tumor cells into the right limbs of C57BL/6J male mice. RhuM-CSF was administered at 20 micrograms/injection, s.c., twice a day for 5 days/week for 2 weeks beginning 6 days after tumor cell inoculation and LH (43 +/- 0.2 degrees C) was given for 30 min twice/week for 2 weeks. Combined therapy prolonged survival of mice and caused significant inhibition of tumor growth, as measured by the volume or size of primary tumor, number and size of lung metastases, and chromatin fragment (CF) formation in tumor bearing mice, while treatment with M-CSF or LH alone had less or no effect. Combined therapy also resulted in increased numbers of splenic T-lymphocytes and the ratio of T-helper/suppressor cells, restoration of natural killer (NK) cell activity, increased numbers of peritoneal macrophages and their erythrophagocytosis capacity, and increased release or production of tumor necrosis factor (TNF)-alpha, but not interleukin (IL)-1 alpha or IL-6. These results add to previous evidence that M-CSF might be a relevant therapeutic agent in combination with other therapies in the treatment of certain malignant diseases.

Animals↗

Study on application of the silicone oil in the reattachment of complicated retinal detachment.

Sixty eyes with complicated retinal detachment were treated by vitrectomy combined with silicone oil tamponade (27 eyes of PVR grade D, 15 eyes of giant retinal tears with posterior flat folded-over, 13 eyes of posterior or macular hole, 5 eyes of traumatic PVR). After 3-24 months follow-up, the study showed retinal anatomic reattachment in 48 eyes in which the visual acuity of 32 eyes was 0.05 or better. The authors consider that vitrectomy and peeling make the silicone oil tamponade perfect the vitreous surgery and improve the successful rate. The theory of silicone oil tamponade, the indications, advantages and disadvantages of silicone oil tamponade are discussed in this paper.

Adolescent↗

Diamond-like carbon as biological compatible material for cell culture and medical application.

Ion beam assisted diamond-like carbon (DLC) films have been used for growing the human hematopoietic myeloblastic ML-1 cells and human embryo kidney 293 cells in the control environment. DLC films were directly deposited onto the P-35 plastic dishes by impacting the high kinetic energy (1000 eV) of methane ions at room temperature. The present results showed that both ML-1 and HEK 293 cells continuously grow with and without DLC films. It has demonstrated that human cells proliferated on DLC film with very high viability and DLC material had no toxicity to cultured human ML-1 and HEK 293 cells. We conclude that DLC film is a biological compatible material for potential cell culture matrix and bio-medical applications.

Biocompatible Materials↗

TV watching, soap opera and happiness.

One hundred and fourteen subjects reported the amount of time they spent watching television in general, and soap opera in particular. They also completed scales measuring happiness and other personality variables, such as extraversion and cooperativeness. In the multiple regression analysis, having controlled for the demographic variables, watching TV was related to unhappiness, whereas watching soap opera was related to happiness. Discriminant analysis showed that females, higher happiness and extraversion distinguished regular soap watchers (who nevertheless watched little TV in general) from irregular soap watchers (who nevertheless watched a lot of TV in general).

Adolescent↗

[The clinical use of steady-state flash visual evoked potentials].

The authors applied 30Hz flash stimuli to record steady-state flash visual evoked potentials (FVEP) and extracted the amplitudes and phases of the first and second harmonics as the characteristic value by discrete Fourier transform (DFT). 46 normal controls (89 eyes) and 78 patients (109 eyes) were detected and analysed by this method. The result showed that the characteristic values of the normal controls are significantly different in three age groups and showed the positive in 35 eyes with the optic never diseases (82.9%), 25 eyes with age-related macular degeneration (92%), and 9 eyes with retinal detachment involved macular (100%). It indicates the method is a sensitive index to evaluate the macular visual function. After preliminary observation, the visual acuities of postoperation were found above 0.4 in cataracts (28 eyes) or opacities (12 eyes) if preoperative FVEP were normal and non-complicated, or less than 0.4 if preoperative FVEP were abnormal. This suggests the method is one of the effective index to detect the postoperative vision of the media opacities. The advantages, disadvantages and the clinical applications were discussed.

Adolescent↗

Influence of recombinant human interleukin (IL)-7 on disease progression in mice infected with Friend virus complex.

Recombinant human (rhu) IL-7 was evaluated for its influence on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC). DBA/2 mice were injected i.v. with FVC, and then treated s.c. with rhuIL-7. IL-7 significantly prolonged survival time and decreased spleen focus-forming virus (SFFV) levels, expression of SFFV mRNA and SFFV protein production in FVC-infected mice. IL-7 did not appear to directly inactivate SFFV. Although both splenic weight and cellularity in FVC-infected mice treated with IL-7 were higher than those of normal mice, they were respectively 58% and 66% lower than those of the untreated FVC-infected mice. NK-cell activity was substantially lower in FVC-infected mice than in normal mice, while IL-7 restored NK-cell activity to normal levels. IL-6 and IFN-gamma levels were markedly reduced in FVC-infected mice compared to normal mice, but treatment of FVC-infected mice with IL-7 restored these cytokine levels. While the actual mechanisms of these effects are not yet known, the results suggest the potential therapeutic efficacy of IL-7 for certain hematopoietic and viral disorders, possibly mediated through an action on accessory cells and cytokine production.

Animals↗

Differentiation-induced changes in protein-tyrosine phosphatase activity and commensurate expression of CD45 in human leukemia cell lines.

Pharmacologic differentiation of the promyelocytic leukemia HL60 is associated with an increase in cellular tyrosine phosphatase activity. We asked (a) if this increase might, at least in part, be due to changes in a transmembranous protein-tyrosine phosphatase, CD45; and (b) if CD45 changes similarly in other differentiating leukemias. Differentiation of HL60, several chronic myelogenous leukemias, a monocytic leukemia (THP-1), and a monoblastoid leukemia (U-937) could be induced by phorbol ester, 1,25-dihydroxy vitamin D3, dimethyl sulfoxide, or cyclic AMP analogues. This differentiation was associated with a marked increase in (a) total cellular tyrosine phosphatase activity (2-4-fold as measured by the ability to dephosphorylate a tyrosine-phosphorylated peptide); (b) CD45-specific tyrosine phosphatase activity (2-4-fold); (c) CD45 cell surface expression by flow cytometry (2-5-fold); (d) synthesis of both exon B-dependent M(r) 205,000 and exon ABC- M(r) 185,000 CD45 proteins, as revealed by immunoprecipitation with antisera specific for CD45 isoforms. Both isoforms have enhanced electrophoretic mobility when isolated from the differentiated cells. This enhanced mobility did not appear to be due to decreased stoichiometry of CD45 phosphorylation on serine/threonine residues. Interestingly, 12-O-tetradecanoylphorbol-13-acetate transiently reduced CD45 protein-tyrosine phosphatase activity in the chronic myelogenous leukemia cell RWLeu4 without altering the CD45 amount (as measured by cell surface immunofluorescence). Modulation of CD45 tyrosine phosphatase activity (and protein levels) may play a role in differentiation or in maintaining cells in a nonproliferative state or may represent a phenotypic marker of differentiation.

Antigens, CD↗

Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites.

Mouse ornithine decarboxylase (ODC) was expressed in Escherichia coli and the purified recombinant enzyme used for determination of the binding site for pyridoxal 5'-phosphate and of the residues modified in the inactivation of the enzyme by the enzyme-activated irreversible inhibitor, alpha-difluoromethylornithine (DFMO). The pyridoxal 5'-phosphate binding lysine in mouse ODC was identified as lysine 69 of the mouse sequence by reduction of the purified holoenzyme form with NaB[3H]4 followed by digestion of the carboxymethylated protein with endoproteinase Lys-C, radioactive peptide mapping using reversed-phase high pressure liquid chromatography and gas-phase peptide sequencing. This lysine is contained in the sequence PFYAVKC, which is found in all known ODCs from eukaryotes. The preceding amino acids do not conform to the consensus sequence of SXHK, which contains the pyridoxal 5'-phosphate binding lysine in a number of other decarboxylases including ODCs from E. coli. Using a similar procedure to analyze ODC labeled by reaction with [5-14C]DFMO, it was found that lysine 69 and cysteine 360 formed covalent adducts with the inhibitor. Cysteine 360, which was the major adduct accounting for about 90% of the total labeling, is contained within the sequence -WGPTCDGL(I)D-, which is present in all known eukaryote ODCs. These results provide strong evidence that these two peptides form essential parts of the catalytic site of ODC. Analysis by fast atom bombardment-mass spectrometry of tryptic peptides containing the DFMO-cysteine adduct indicated that the adduct formed in the enzyme was probably the cyclic imine S-(2-(1-pyrroline)methyl)cysteine. This is readily oxidized to S-((2-pyrrole)methyl)cysteine or converted to S-((2-pyrrolidine)methyl)cysteine by NaBH4 reduction. This adduct is consistent with spectral evidence showing that inactivation of the enzyme with DFMO does not entail the formation of a stable adduct between the pyridoxal 5'-phosphate, the enzyme, and the inhibitor.

Amino Acid Sequence↗

CFTR protein expression in primary and cultured epithelia.

The gene responsible for the lethal disorder cystic fibrosis encodes a 1480-amino acid glycoprotein, CFTR. Using polyclonal antibodies directed against separate phosphorylation sites in the pre-nucleotide-binding fold (exon 9) and the R domain (exon 13), we have identified a 165-kDa protein in Xenopus laevis oocytes injected with recombinant CFTR cRNA transcribed from the full-length CFTR plasmid pBQ4.7. A protein of the same mobility was also detected with Western blotting techniques in whole cell extracts of cells that express CFTR mRNA (T84, FHTE, HT-29), including biopsied human nasal and bronchial tissue. Immunodetectable 165-kDa protein was concentrated in the apical membrane fraction of ileal villus tissue. We also report that the 165-kDa protein levels can be modulated pharmacologically, and these levels are appropriately correlated with second-messenger-regulated Cl- efflux. Thus, native or recombinant CFTR can be recognized by these anti-CFTR peptide polyclonal antibodies.

Animals↗

Absence of cortical white matter changes in three patients undergoing long-term vigabatrin therapy.

Chronic administration of the experimental antiepileptic drug vigabatrin (gamma-vinyl GABA) to animals has been shown to cause dose-dependent neuropathological changes characterized by a microvacuolation in specific white matter tracts. This finding has led to some concern as to whether similar pathologic changes might occur in patients taking this medication. Here we report on analysis of tissue specimens taken during neurosurgery from three patients undergoing chronic vigabatrin therapy (4 g/day). The first patient, a 34-year-old woman, had taken vigabatrin for 2 years prior to surgery, the second, a 50-year-old man, had taken the drug for 1 year, and a 34-year-old man had taken the drug for 5.3 years. For comparison, similar specimens were taken from three other patients not taking vigabatrin who were undergoing surgery for intractable epilepsy. Specimens from each subject were prepared in an identical manner and examined with light and electron microscopy. All specimens were examined in a blinded fashion. There was some minor nonspecific myelinic splitting seen in both controls and vigabatrin-treated patients but there was no evidence for any drug-induced lesions similar to that seen in experimental animals.

Adult↗

CCK, bombesin, and carbachol stimulate c-fos, c-jun, and c-myc oncogene expression in rat pancreatic acini.

To identify possible nuclear signals mediating long-term regulation of the pancreas by gastrointestinal hormones, the expression of c-fos, c-jun, and c-myc was investigated in rat pancreatic acini. Stimulation of the acini with cholecystokinin octapeptide (CCK-8, 100 pM), bombesin (10 nM), or carbachol (10 microM), but not gastrin (100 nM), secretin (100 nM), or vasoactive intestinal peptide (10 nM) induced an increase in oncogene mRNA expression. The percent increases of c-fos, c-jun, and c-myc mRNA were 207 +/- 40, 171 +/- 26, and 46 +/- 19 (n = 5) for CCK-8; 223 +/- 71, 159 +/- 31, and 43 +/- 21 (n = 5) for bombesin; and 125 +/- 51, 123 +/- 58, and 67 +/- 19 (n = 5) for carbachol, respectively. CCK-induced increases in oncogene mRNA were rapid and transient. c-fos and c-jun mRNA levels were increased after 30 min stimulation, peaked at 1 h, and returned to basal level in 2 h. Activation of c-myc was more prolonged with levels remaining elevated for at least 3 h. The effects of CCK-8 were concentration dependent. Detectable stimulation was seen at 10 pM; maximal stimulation occurred at 10 nM and was not affected by further increase in the concentration of CCK-8. JMV-180, a high-affinity site CCK receptor agonist and low-affinity site antagonist, alone did not stimulate c-fos mRNA expression but inhibited c-fos mRNA expression induced by CCK-8. These results suggest that the interaction between CCK and the low-affinity state of the CCK receptor is responsible for oncogene activation.

Animals↗

Immunohistochemical differentiation of atypical hyperplasia vs. carcinoma in situ of the breast.

The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ.

Actins↗

[Micro-vitreoretinal surgery for failed common retinal detachment repair].

In this paper we analyzed 49 cases (49 eyes) of micro-vitreoretinal surgery for failed common retinal detachment repair. Reattachment was achieved in 37 cases (75.51%) and final visual acuity of 10/200 or better was attained in 32 cases (65.31%). It was suggested that common operation failure in these patients was due to PVR. Cryopexy, diathermy and repeat operation can render the formation of the PVR. Micro-vitreoretinal surgery should be performed on these patients. There was a linear relationship between the effectiveness and the degree of PVR. It is best to perform the surgery 3 months after common operation. Finally, the authors discuss the reasons for failure of vitreoretinal surgery and conclude that the anterior PVR and the invalid fixing are the main reasons for failure of vitreoretinal surgery.

Adolescent↗

Influence of combinations of cytokines on proliferation of isolated single cell-sorted human bone marrow hematopoietic progenitor cells in the absence and presence of serum.

Human mast cell growth factor (MGF, a c-kit ligand) and colony stimulating factors (Epo, GM-CSF, G-CSF, IL-3) were assessed in the absence or presence of serum for stimulation in semi-solid medium of single CD34 , CD34 HLA-DR+, or CD34 HLA-DR+CD33- cells sorted per microtiter well. The % of wells containing CFU-GM and erythroid containing (BFU-E and CFU-GEMM) colonies increased in proportion to the number of cytokines added. In the presence of serum, 1, to 4 cytokine combinations resulted in respective increases in cloning efficiencies of 10 to 21.0, 19.5 to 31.5, 35.8 to 42.9, and 46.3 to 60.0%. MGF had little effect by itself, but did act in combination with CSFs to enhance numbers and size of the colonies from isolated single cells. High cloning efficiencies were also obtained in the absence of serum when multiple cytokines were used. The results demonstrate that MGF and CSFs can act directly on the proliferation of single hematopoietic progenitor cells in the absence of accessory cells and serum.

Antigens, CD↗

Human interleukin (IL)-9 specifically stimulates proliferation of CD34+++DR+CD33- erythroid progenitors in normal human bone marrow in the absence of serum.

The cDNA encoding human interleukin (IL)-9 has recently been cloned and the recombinant molecule found to enhance erythroid colony formation in vitro by bone marrow, peripheral blood, and cord blood cells. In our present report, recombinant human (rhu) IL-9 was evaluated, alone and in combination with other cytokines, for its effect on colony formation by erythroid progenitor (erythroid burst-forming units, BFU-E) and precursor (erythroid colony-forming units, CFU-E) cells in low density (LD), nonadherent LD density T-lymphocyte-depleted (NALT-), and immunofluorescence-sorted CD34+++DR+ and CD34+++DR+CD33- cells from normal human bone marrow. When highly enriched CD34+++DR+ and CD34+++DR+CD33- cells were plated at 200 and 100 cells/ml in the presence of 5% (vol/vol) 5637-cell-conditioned medium and erythropoietin (Epo) under serum-containing conditions, 46 and 51 day-14 BFU-E were observed, respectively. The enhancing effect of rhuIL-9 was similar to that of 5637 CM on colony formation by Epo-dependent BFU-E and CFU-E in these enriched sorted CD34+++DR+ and CD34+++DR+CD33- cells under serum-containing and serum-depleted culture conditions. No significant synergistic or additive effect of rhuIL-9 was noted when used in conjunction with rhu interleukin 3 (rhuIL-3), rhu interleukin 6 (rhuIL-6), and/or rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) under the same culture conditions. The cloning enhancing effect elicited by human IL-9 is Epo dependent, although IL-9 alone sustains the survival of erythroid progenitor cells in vitro, as assessed by delayed additions of Epo to the cultures. The ability of human IL-9 to stimulate BFU-E and CFU-E colony formation using low numbers of highly enriched progenitor cells in serum-depleted conditions demonstrates the direct effect of IL-9 on erythroid progenitors and implicates its potential role in the enhancement of erythropoiesis.

Antigens, CD↗

BCR/ABL confers growth factor independence upon a murine myeloid cell line.

The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes, BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines. To investigate the ability of BCR/ABL to generate growth factor independence in myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54 and A74 were capable of IL-3 independent growth and tumor formation in syngeneic mice. Relief of growth factor dependence was not mediated by autocrine release of IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant constitutive expression of c-myc, c-jun, and c-fos was observed in the p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL transformation and relief of IL-3 dependence involve not only pathways that can substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also pathways that recruit constitutive c-jun and c-fos expression.

Animals↗

Lipoma of cervical spinal cord and posterior fossa. Case report.

A case is reported of cervical spinal cord lipoma with extension into the posterior fossa and a leading symptom of apnea. A C1-C7 laminectomy and debulking of the medullary portion of the lipoma were performed with good results. The apneic spells were completely resolved. Intraspinal lipoma with posterior fossa extension is a rare condition and requires surgical intervention to relieve symptoms.

Cerebral Ventricle Neoplasms↗

The structural basis of the poor fibrin specificity of urokinase(I)--knowledge-based prediction of kringle structures of urokinase and its related proteins.

The Kringle-1 structure of plasminogen (PGK-1), the Kringle-2 structure of tissue plasminogen activator (PAK-2) and the Kringle structure of prourokinase (UKK) has been modeled on the basis of the three-dimensional structure of Kringle-1 of prothrombin (PTK-1) at 2.8 A resolution. The predicted three-dimensional structure of these Kringles shows that the binding site of PGK-1 is characterized by an apparent dipolar site, the polar parts of which are separated by a hydrophobic region. PAK-2 possesses the anionic center but has not a cationic binding center which might be provided by a guanidinium group from Arg-69 located adjacent to the Arg-71 position. UKK possesses neither the anionic binding center nor the cationic center which are probably the main reason for the poor fibrin specificity of urokinase.

Amino Acid Sequence↗