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Biomedical subjects

D Lu

Publications and source records attributed to D Lu.

At least 235 records · Page 13Linked to original sources
PubMed1996

Parvoviral vectors for the gene therapy of cancer.

Gene transfer vectors based on the replication-defective (adeno-associated virus, AAV) and autonomous parvoviruses are emerging as promising vehicles for gene therapeutic approaches for the treatment of cancer. AAV-based vectors are nonpathogenic, possess an extremely wide host and tissue range, stably integrate into cellular DNA, and transduce both proliferating and nonproliferating cells. Unlike AAV, autonomous parvoviruses such as the minute virus of mice (MVM) do not integrate. However, their tropism for transformed tissues and innate oncolytic properties may permit rapid in situ therapies. In this article, we briefly review basic parvovirus biology as it relates to vector development. In addition, parvoviral vectors are discussed within the context of applications for gene transfer approaches to cancer treatment including genetic marking studies, hematopoietic progenitor chemoprotection, interruption of oncogene expression, and modulation of antitumor immunity.

Animals↗
PubMed1996

The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.

Molecular cloning experiments have led to the identification and characterization of a family of five receptors for the melanocortin (melanotropic and adrenocorticotropic) peptides. The first two members of the family cloned were the well-characterized melanocyte-stimulating hormone receptor (MSH-R) and adrenocorticotropin receptor (ACTH-R). The three new melanocortin receptors have been termed the MC3-R, MC4-R, and MC5-R, according to the order of their discovery, and little is known at this point concerning their function. Agouti and extension are two genetic loci known to control the amounts of eumelanin (brown-black) and phaeomelanin (yellow-red) pigments. Chromosomal mapping demonstrated that the MSH-R, now termed MCI-R, mapped to extension. Extension was shown to encode the MCI-R, and mutations in the MCI-R are responsible for the different pigmentation phenotypes caused by this locus. Functional variants of the MCI-R, originally characterized in the mouse, have now also been identified in the guinea pig and cow. Dominant constitutive mutants of the MCI-R are responsible for causing dark black coat colors while recessive alleles result in yellow or red coat colors. Agouti, a secreted 108 amino acid peptide produced within the hair follicle, acts on follicular melanocytes to inhibit alpha-MSH-induced eumelanin production. Experiments demonstrate that agouti is a high-affinity antagonist, acting at the MCI-R to block alpha-MSH stimulation of adenylyl cyclase, the effector through which alpha-MSH induces eumelanin synthesis. The MCI-R is thus a unique bifunctionally controlled receptor, activated by alpha-MSH and antagonized by agouti, both contributing to the variability seen in mammalian coat colors. The variable tan and black coat color patterns seen in the German Shepherd, for example, can now be understood on the molecular level as the interaction of a number of extension and agouti alleles encoding variably functioning receptors and a differentially expressed antagonist of the receptor, respectively.

Agouti Signaling Protein↗
PubMed1996

Research into analgesia by inhaling analgesic.

This article deals with analgesia by inhaling analgesic. According to Chinese medical theories, TCM analgesics were chosen from the literature and folk prescriptions screened and proved by analgesic tests on animals. A reasonable prescription was made up and the drug inhaled. Its analgesic effect was superior to that of dolantin injection (3 mg/kg body weight, intraperitoneal injection). Clinical trials showed its analgesic effect in 3-10 minutes and it lasted for more than 2 hours in over 70% of the cases for a total effective rate of 94.6%. The drug is absorbed quickly and acts directly on the nerve center. Its use is not addictive.

Administration, Inhalation↗
PubMed1996

[Histopathological and immunohistochemical studies on gliosarcoma].

Immunohistochemical staining of 5 gliosarcomas was performed. Neoplastic glial component stained positive by GFAP. Endothelial cells lining the lumina of glomeruloid vascular structures stained positively with both UEA-1 and FVIII/RAg antibodies. Mesenchymal cells of sarcomatous areas stained positively with SMSA antibody and presence of PDGFR. The staining results demonstrate that the sarcomatous component of gliosarcoma is of smooth muscle origin and suggest that the vascular smooth muscle hyperplasia is related to PDGF.

Aged↗
PubMed1996

Morphological classification of facial features in adult Caucasian males based on an assessment of photographs of 50 subjects.

Fifty sets of photographs showing facial features of Caucasian males aged 18 to 60 years were examined to establish a morphological classification of the face. It is suggested that such a classification could assist facial identification by photocomparison. The selection criteria stress the importance of interassessor agreement and discrimination among feature subset units in formulating the proposed classification.

Adolescent↗
PubMed1996

Suppression of haematopoiesis by sera from patients with aplastic anemia.

To describe the suppressive effect of sera from patients with aplastic anemia (AA) on heamatopoietic progenitor cells and explore further the features of serum inhibitor, we first examined the inhibiting activity of the serum on the colony formation of burst-forming units of erythrocyte (BFU-E) and colony-forming units of granulocyte/macrophage (CFU-GM). The potent inhibiting activity was demonstrated in six of 20 patients. Five of the six patients were severe AA (SAA). The suppressive effect did not change after elimination of monocyles and lymphocytes from target MNC. The haematopoietic inhibitory activity of sera from three of the six patients was almost totally neutralized by the MoAb against gamma-IFN. All these three patients were SAA. These data suggest that inhibitor of haematopoietic progenitor cells is present in most of SAA patients. In some patients, the inhibitor was gamma-IFN, which play an important role in the pathogenesis of SAA.

Adolescent↗
PubMed1996

Acute bacterial meningitis in children in Hefei, China 1990-1992.

OBJECTIVE: To obtain etiologic and epidemiologic information about bacterial meningitis, especially the H influenza type B (Hib), from a medium-sized city, Hefei, China. METHODS: Data were collected prospectively over 3 years, from 1990 to 1992 by a well-organized group including 13 hospitals. All children with a clinical diagnosis of acute bacterial meningitis were enrolled and the specimens were taken for the etiologic studies. CSF and blood were tested by standard bacteriologic technique. CSF, blood and concentrated urine were tested directly for detection of antigen by countercurrent immuno-electrophoresis (CIE). Data were analyzed by epidemiologic methods. RESULTS: Bacterial culture and CSF Gram's staining were positive only in 13.3% and 11.7%, respectively. Bacterial antigen detection was positive in up to 90% by CIE which was more sensitive than bacterial culture (chi 2 = 67.7, P < 0.005). The annual incidence of acute bacterial meningitis in the city is calculated as 9.3 cases/100,000 children from 1 month to 15 years of age and 19.2 cases/100,000 children from 1 month to 5 years of age. Hib meningitis accounted for 51.7%, N. meningitis (Nm) for 38.3%, and S. pneumoniae (Sp) for 8.3%. There was no significant seasonal variation. Of the patients, 76.7% were children under 5 years of age, and 51.7% under 1 year of age. The case fatality rate was 11.7% for all bacterial meningitis, 9.7% for Hib, 17.4% for Nm and 20% for Sp. A total of 22.6% of survivors suffered from neurological or psychological problems. CONCLUSIONS: Using antigen detection combined with bacterial culture, we could make an etiologic diagnosis in up to 90% of the patients in this group. Hib, Nm and Sp were the predominant pathogens, which was similar to the findings in other countries. Hib was the most common cause of bacterial meningitis, but the incidence was much lower than in most parts of the world.

Child↗
PubMed1996

Recombinant human granulocyte colony-stimulating factor after allogeneic bone marrow transplantation.

OBJECTIVE: To examine the effect of rhG-CSF on allogeneic bone marrow transplantation. PATIENTS AND METHODS: One hundred and twenty patients with acute or chronic leukemia received HLA-A.B.DR identical and MLC negative sibling donor allo-BMT. Among them, 58 cases of were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF), while the other 62 cases of the 120 patients were treated as control. RESULTS: Clinical results showed that the time taken to reach an absolute neutrophil count > 0.5 x 10(9)/L was significantly faster in patients who received rhG-CSF compared with control patients (16.24 +/- 0.25 vs 25.20 +/- 0.16 days. P < 0.001), with significantly less early fever days in patients received rhG-CSF (1.17 +/- 1.10 vs 4.01 +/- 0.37 P < 0.001). We did not observe any increase in acute GVHD and relapse in myeloid leukemia patients. But 7 of 16 patients with ALL relapsed after allo-BMT in rhG-CSF group, while only 3 of 11 patients with ALL relapsed after allo-BMT in control grant (P > 0.05). This phenomenon has not been reported up to now. CONCLUSIONS: rhG-CSF can promote engraftment and reduce early fever days after BMT. rhG-CSF has not any effect on a GVHD. The effect of rhG-CSF on leukemia relapse needs to be further studied.

Adolescent↗
PubMed1996

Implantation of autologous skin fibroblast genetically modified to secrete clotting factor IX partially corrects the hemorrhagic tendencies in two hemophilia B patients.

OBJECTIVE: To examine the safety and effects of gene therapy for hemophilia B by implantation of autologous fibroblasts genetically modified to secrete clotting factor IX (hFIX). PATIENTS AND METHODS: Two hemophilia B patients LD and LW were selected from one family to accept gene transfer study. The hFIX protein of both patients were about 100 ng/ml plasma and hFIX activity was about 2%. The autologous skin fibroblasts of the two patients were genetically modified by retrovirus-mediated gene transfer with XL-IX and N2CMVIX vector (HBSF-IX). Human hFIX protein was measured by ELISA, hFIX activity was measured by one-stage clotting assay and barium citrate sorbent method. hFIX inhibitor was assayed by Bethesda methods. Human hFIX cDNA was detected by PCR. HBSF-IX cells were mixed with collagen for injection after safety assessments. RESULTS: The HBSF-IX cells from the two patients secreted hFIX at high levels in vitro. After implantation of autologous HBSF-IX cells, no treatment-related side effects were observed. Plasma hFIX protein in both patients increased over 2 folds after several injections of HBSF-IX cells and persisted for more than 420 days. Blood clotting activity increased significantly in both patients, hemorrhagic tendencies have been partially corrected after treatment. Further elevation of hFIX can be achieved by repeating the same treatment 420 days later in Patient LD. CONCLUSIONS: Implantation of autologous fibroblast genetically modified to secrete human hFIX offers a simple, safe and effective approach to gene therapy of hemophilia B.

Adolescent↗
PubMed1996

[Experimental study on human glioma SHG44 treated by HSV-tk gene therapy].

The paper reports the construction of retroviral vector pLNTK carrying HSV-tk gene driven by PGK promoter and the successful transfer into human glioma cell SHG44. The in vitro study confirmed that ayclovir (ACV) sensitive level of the gene-transferred glioma cell (SHGLNTK) was 1,000 times that of SHG44. 3H-TdR incorporation confirmed that the DNA replication in SHGLNTK was considerably suppressed when treated with ACV. The in vivo study confirmed that ACV could suppress tumor formation of the SHGLNTK cells. In situ gene transfer treatment of nude mice carrying SHG44 tumor showed good therapeutic results. Such treatment may be used as an innovative method for brain tumor therapy.

Acyclovir↗
PubMed1996

[Applied anatomical study of the lingual nerve].

The lingual nerve and its adjacent structures were observed and measured on 32 adult cadavours. Its length was 69.7 mm and it was divided, bounded by the internal pterygoid muscle, into three segments and the length and diameter of them were respectively measured. According to its relationship with the lingual nerve, the submandibular ganglion can be classified into fusion type (being 46.9%) and free type (being 53.1%), and its superoinferior and transeversal diameters were separately measured to be 2.7 and 2.9 mm. The lingual nerve and its lingual branches were closely related to submandibular duct and there were two intersects. The relation and clinical significance of the third segment of lingual nerve and its neighbor structures were studied.

Adult↗
PubMed1996

[Prevention of peridural fibrosis and adhesion after laminectomy: an experimental study in rats].

An experimental study on the effectiveness of various materials including poly carboxymethylcellulose (PCMC), gelatin foam (GF), ligment (L), free fat (FF) in prevention of peridural fibrosis and adhension (PDA) was done in 144 SD rats using a total laminectomy model (L1-2). PDA was measured with a double-blind protocol at 2, 4, 8, 12 weeks postoperatively by gross anatomical appearance (blunt-dissection), microscopical evaluation, computed imaging analysis and MRI enhanced with gadolinium. The results demonstrated that the peak of PDA is within 8 weeks after operation. PCMC, as a three dimensional protective material, could effectively inhibit PDFA after laminectomy, but GF and L could not. SHA had some effect in the early stage, but not in the late period. For FF though it could effectively prevent PDA, the incision infection rate was higher, the atrophy and necrosis of FF were serious. What is more, almost all transplanted fat remained in situ extended into the spinal cord in some measure after 8 weeks postoperatively.

Animals↗
PubMed1995

Loss of nm23 and Alu DNA in human lung cancer propagated in nude mice.

Freshly resected human non-small cell lung cancer (NSCLC) has been successfully transplanted and propagated subcutaneously in nude mice (Cancer Letters 61 (1991) 53-60). We used this model to study the changes of the human metastasis suppressor genes, nm23-H1 and nm23-H2, through the process of propagation and metastasis of human NSCLC. Using a non-radioisotopic Southern analysis, the nm23-H1 and nm23-H2 genes were detected without evidence of deletion in the early generations of the tumor grafts. These genes, however, were absent from the tumor grafts sampled past 4 generations of propagation and from all the propagated metastases originated from the subcutaneous grafts. Further restriction analysis revealed that only mouse DNA, but no human Alu DNA, was present in the tumor specimens which lacked the human nm23 genes. Thus, there is a loss of human DNA but a gain of mouse DNA in the propagated tumors originated from the transplanted human NSCLC. The mechanisms of loss of human DNA in these propagated tumors in nude mice have yet to be delineated.

Animals↗
PubMed1995

Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors.

The cloning of the melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) receptors (MC1-R and MC2-R, respectively) recently has led to the identification of three additional melanocortin receptors, MC3-R, MC4-R, and MC5-R. The MC2 receptor primarily recognizes only ACTH peptides, but the other four receptors all recognize alpha-melanocyte-stimulating hormone (alpha-MSH) and potent alpha-MSH agonists such as [Nle4,D-Phe7]alpha-MSH-NH2 and Ac-Nle4-c[Asp5,D-Phe7,Lys10]alpha-MSH-(4-10)-NH2 as well as ACTH. The absence of any known physiological role for these new receptors, expressed both in the brain (MC3-R and MC4-R) and throughout a number of peripheral tissues (MC5-R), has necessitated as search for potent and receptor selective agonists and antagonists. We report here that analogues of the superpotent cyclic agonist analogue Ac-Nle4-c[Asp5,D-Phe7, Lys10]alpha-MSH-(4-10)-NH2, in which a bulky aromatic amino acid is substituted in the 7-position, can produce potent and selective antagonists for melanocortin receptors. Thus, the D-p-iodophenylalanine7-containing analogue Ac-Nle4-c[Asp5,D-Phe(pI)7,Lys10]alpha-MSH-(4-10)-NH2 is a potent antagonist (pA2 = 10.3) in the classical frog skin (Rana pipiens) assay (MC1-R), as is the D-2'-naphthylalanine7 (D-Nal(2)7)-containing analogue Ac-Nle4-c[Asp5,D-Nal(2)7,Lys10]alpha-MSH-(4-10)-NH2 (pA2 > 10.3). Interestingly, the D-p-chloro- and D-p-fluorophenylalanine7-containing analogues lacked antagonist activities at all melanotropin receptors, and both exhibited full agonist potency in the frog skin assay. The activity of these analogues also was examined at four mammalian melanocortin receptors. Interestingly, Ac-Nle4-c[Asp5,(D-Nal(2)7,Lys10] alpha-MSH-(4-10)-NH2 was found to be a potent antagonist of the MC4-R (pA2 = 9.3) with minimal agonist activity, a less potent antagonist of the MC3-R (pA2 = 8.3) with minimal agonist activity, and a full agonist of the MC1 and MC5 receptors. Surprisingly, Nle4-c[Asp5,D-Phe(pI)7,Lys10]alpha-MSH was found to be a potent agonist at the cloned human MC1-R (EC50 = 0.055 nM) and mouse MC1-R (EC50 = 0.19 nM) but had potent antagonist activities at the human MC4-R (pA2 = 9.7) and human MC3-R (pA2 = 8.3) with significant partial agonist activities (EC50 = 0.57 and 0.68 nM, respectively) as well. Thus, highly potent and receptor selective antagonist analogues can arise from substitution of the D-Phe7 residue with a bulky aromatic amino acid. These analogues can be used to help determine the functional roles of these receptors.

Amino Acid Sequence↗
PubMed1995

Characterization of a messenger RNA polynucleotide vaccine vector.

We have constructed mRNA transcripts encoding luciferase and human carcinoembryonic antigen (CEA) which are capped, polyadenylated, and stabilized by human beta-globin 5' and 3' untranslated regions. The mRNA construct encoding human CEA directed CEA expression in mouse fibroblasts in vitro following liposome-mediated transfection. The luciferase encoding mRNA transcripts mediated luciferase expression in vivo following i.m. injection. Based on the demonstration of protein expression in vitro and in vivo, the feasibility of using such a vector as a tumor vaccine was examined. In this pilot study, seven mice received 50 micrograms mRNA transcripts encoding CEA twice weekly for 5 weeks by i.m. injection followed by challenge with syngeneic, CEA-expressing tumor cells. This dose and schedule "primed" an immune response to CEA. Five of seven mRNA-immunized mice demonstrated anti-CEA antibody 3 weeks after tumor challenge whereas control mice had no evidence of antibody response. This strategy might be particularly useful to induce an immune response to a proto-oncogene product or growth factor which poses a risk of inducing malignant transformation consequent to prolonged protein expression.

Animals↗
PubMed1995

Delivery of angiotensin II type 1 receptor antisense inhibits angiotensin action in neurons from hypertensive rat brain.

Increased brain angiotensin II (AII) type 1 receptor (AT1R) expression has been implicated in the hyperactive brain angiotensin system and the development and maintenance of hypertension in the genetically spontaneously hypertensive (SH) rat. Neuronal cells in primary culture from the cardioregulatory-relevant brain areas (hypothalamus/brainstem) mimic increased brain AT1R gene expression and AT1R function of the adult SH rat. They have been utilized in the present study to determine whether cellular actions of AII could be regulated by the transfer of AT1R antisense (AT1R-AS) with the use of a retroviral-mediated gene delivery system developed for the central nervous system cultures. AII stimulates norepinephrine (NE) uptake in neuronal cultures of both normotensive (Wistar Kyoto) and SH rat brains. This neuromodulatory action is mediated by the AT1R subtype, is significantly higher in SH neurons, and is associated with a parallel stimulation of mRNAs for c-fos and NE transporter. Infection of neuronal cultures with a retrovirus vector that contains AT1R-AS (LNSV-AT1R-AS) results in an inhibition of AT1R-mediated stimulation of both c-fos and NE transporter mRNA, as well as NE uptake in both strains of rats; however, the inhibition is more pronounced in SH neurons compared with Wistar Kyoto rat brain neurons. The higher sensitivity of the SH rat brain neurons is further supported by our observation that a certain dose of LNSV-AT1R-AS that fails to induce inhibition of cellular actions of AII in WKY neurons causes a significant inhibition of AII actions in SH neurons. These observations show that retrovirally mediated delivery of AT1R-AS could be used to selectively control the actions of AII in primary neuronal cultures from SH rat brain.

Angiotensin II↗