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Biomedical subjects

L Ding

Publications and source records attributed to L Ding.

At least 163 records · Page 9Linked to original sources

Dynamic filtration of blood: a new concept for enhancing plasma filtration.

We have shown previously that blood flow pulsations created by intermittent squeezing of the inlet blood line significantly increased the plasma filtration rate in membrane plasmapheresis. However, in order to avoid hemolysis, the filtration increase had to be limited to about 50%. We have now devised a more efficient pulsation generator. By properly matching the tubing compliance and the pulsation amplitude, it is possible to extract 50 ml/min of plasma from 90 ml/min of blood at 36% hematocrit with a 1000 cm2 polypropylene hollow fiber filter without hemolysis. Simultaneous recording of the time course of plasma filtration rate measured by an electromagnetic flow meter and transmembrane showed that the increase in mean plasma flow rate was due to a dynamic filtration process which prevents the establishment of concentration polarization. The transmembrane pressure (Ptm) increases over a 0.5-second interval when the tube is squeezed. The membrane responds with an increase in filtration since the concentration polarization layer takes a few seconds to build up. The Ptm then drops when the tube is released before the polarization layer has time to build up appreciably and a sudden acceleration of the blood flow (velocity spike) helps clean the membrane, reducing the polarization. Tests with bovine show that the system is very efficient in reducing membrane plugging with small area filters.

Animals↗

Albumin recovery enhancement in membrane plasma fractionation using pulsatile flow.

In therapeutic plasmapheresis using cascade filtration, it is important to maximize albumin recovery while rejecting as many gamma-globulins as possible. Several membrane fractionation techniques were investigated using fresh bovine and human plasma and cellulose acetate filters (PF 100, AKZO). In dead end mode the sieving coefficients were found to decrease as transmembrane pressure increased. This was due to membrane plugging during the course of filtration after about 20 minutes which lead to a rapid increase in transmembrane pressure. In single pass mode the albumin recovery factor generally remains around 40% since the permeate flux is much less than the inlet flow. When strong pulsations (4 to 6 Hz) were superposed on the inlet plasma flow in single pass mode, the albumin sieving coefficient remained at about 0.95 while the permeate flux was increased by 106%. As a result a recovery factor of more than 80% could be sustained for at least 90 minutes without membrane plugging. Therefore pulsatile flow plasma fractionation seems to be an interesting approach to combine continuous operation with high albumin recovery.

Animals↗

Oxidative cleavage of DNA mediated by hybrid metalloporphyrin-ellipticine molecules and functionalized metalloporphyrin precursors.

The nuclease activity of functionalized metalloporphyrins 1-8 and hybrid metalloporphyrin-ellipticine molecules 10-16 in the presence of potassium monopersulfate (KHSO5) or magnesium monoperoxyphthalate (MMPP), water-soluble oxygen atom donors at physiological pH, toward double-stranded phi X174 DNA is reported. The DNA cleavage efficiency as a function of the nature of functionalized metalloporphyrins, the length of the linkage between the two parts of the hybrid molecule, viz., metalloporphyrin and 9-methoxyellipticine, the nature of the central metal atom (Mn, Fe, or Zn) the ionic strength, and the nature of the oxygen donor has been studied. Single-strand breaks (SSBs) are observed on double-stranded DNA with a short incubation time of 2 min in the presence of manganese derivatives of both metalloporphyrins and hybrid molecules. Owing to their cytotoxic and nuclease activity, these new water-soluble hybrid molecules may be considered as efficient bleomycin models based on cationic metalloporphyrins.

Bacteriophage phi X 174↗

Application of target-specific drug immunoconjugates to experimental bone marrow replacement therapy in mice.

Immunoconjugates whose cytotoxic component consists of a phytopeptide are often used as purging agents in bone marrow replacement therapy. Less popular are drug immunoconjugates containing a small molecular weight cytotoxic drug attached to the target-specific conjugand via an appropriate spacer molecule. High target specificity, resistance of the drug to intralysosomal proteases and, once cleaved from the spacer, ready exist of the drug from the lysosome are among the advantages drug immunoconjugates hold over phytotoxin immunoconjugates. The cytotoxic drug daunomycin attached via an acid-sensitive spacer to monoclonal antibody of appropriate specificity was shown to purge murine bone marrow of contaminating tumor cells without affecting its hematopoietic potential. Lethally irradiated mice reconstituted with syngeneic bone marrow from which contaminating lymphoma cells had been removed survived indefinitely. Furthermore, lymphoma-bearing mice, provided they were sufficiently irradiated to eliminate tumor cells in situ, were successfully reconstituted with fully allogeneic bone marrow from which potentially graft-versus-host-reactive T-cells had been purged.

Animals↗

Effective drug-antibody targeting using a novel monoclonal antibody against the proliferative compartment of mammalian squamous carcinomas.

mAb 174H.64, which selectively recognizes an epitope expressed on the proliferating cells of mammalian squamous carcinomas, was covalently coupled to daunomycin (DM) by an acid-sensitive linker and tested for its selective cytotoxicity for squamous carcinomas. A murine lung squamous carcinoma model for chemoimmunotherapy using mAb 174H.64-DM conjugates was developed. This model utilizes the KLN-205 cell line, which metastasizes to the lungs following i.v. injection and shows a pattern of growth similar to those of spontaneous squamous carcinomas, characterized by highly proliferative cells at the periphery of the tumor (reactive with 174H.64) with the keratinized differentiated cells toward the center (not reactive with 174H.64). 174H.64-DM conjugates showed marked and specific cytotoxicity against KLN-205 cells both in vitro and following i.v. injection of the immunoconjugate in mice with established lung metastases. The conjugate was nearly as effective as daunomycin alone when incubated in vitro with KLN-205 cells and much more effective than daunomycin alone in vivo or other control immunoconjugates, which were ineffective. Finally, while the free 174H.64 mAb produced a significantly increased time of survival of mice bearing KLN-205 metastases, a much greater survival was found with mice treated with the 174H.64-DM immunoconjugate, some mice apparently demonstrating long-term survival (greater than 100 days). We conclude that mAb 174H.64 may have potential therapeutic benefit against squamous carcinoma.

Animals↗

Cytotoxic T lymphocyte recognition of the H-2-erbB hybrid gene product lacking the complete H-2 domain structure.

The chimeric mouse MHC class I gene derived from a recombinant H-2Kb gene, in which the coding region for a large part of alpha 1 and alpha 2 extracellular domains was replaced with a partial avian erythroblastosis virus erbB gene segment encoding the kinase domain, was successfully introduced into a mouse mastocytoma line P1.HTR (H-2d) and transcribed to mRNA. The transfectant cells expressed the chimeric gene product, which was reactive to a phosphotyrosine-specific antibody. When the chimeric gene transfectant was inoculated into CDF1(H-2d) or BDF1(H-2d/b) mice, it grew at an early time but regressed thereafter. Transfectant-specific as well as parental P1.HTR-specific antibody activities were demonstrated in the sera of these mice. Transfectant-specific cytotoxic T lymphocytes (CTL) were generated in the antigen-sensitized culture of spleen cells from the transfectant-immune mice. The CTL-mediated lysis of target chimeric gene transfectant cells was poorly inhibited by anti-H-2d antiserum, which blocked the lysis of parental P1.HTR cells by anti-tumor CTL developed in parallel. The former was, however, inhibited by either anti-transfectant antiserum or anti-phosphotyrosine antibody, which was ineffective for blocking the latter. Target cell lysis by either anti-transfectant or anti-tumor CTL was blocked by anti-CD8 monoclonal antibody but not by anti-CD4 antibody. It was suggested from these results that the H-2K-erbB hybrid gene product, which lacks complete three-domain class I structure, was recognized by CTL in a manner that was endogenous H-2 class I-independent but CD8-dependent.

Animals↗

Cloning, expression, and characterization of the Escherichia coli K-12 rfaD gene.

The rfaD gene encodes ADP-L-glycero-D-mannoheptose-6-epimerase, an enzyme required for the biosynthesis of the lipopolysaccharide precursor ADP-L-glycerol-D-mannoheptose. The precise localization of the rfaD gene on a 1.3-kilobase SspI-HpaI fragment is reported. The rfaD gene and the flanking regions were completely sequenced. The location of the rfaD gene on the physical map of the Escherichia coli chromosome was determined. Primer extension studies were used to define the regulatory region of the rfaD gene. The cloned rfaD gene directed the synthesis of a 37,000-dalton polypeptide in several in vivo and in vitro expression systems. N-terminal analysis of purified ADP-L-glycero-D-mannoheptose-6-epimerase confirmed the first 34-amino-acid sequence deduced from the nucleotide sequence of the rfaD gene coding region. The primary structure of the rfaD protein contains the sequence fingerprint for the ADP-binding beta alpha beta fold at the N terminus.

Adenosine Diphosphate↗

Modulation by glycyrrhizin of the cell-surface expression of H-2 class I antigens on murine tumour cell lines and normal cell populations.

Glycyrrhizin (GL), a saponin fraction of licorice with defined chemical structure, was shown to display a definite action in vitro augmenting the cell-surface expression of H-2 class I antigens as well as class I gene transcription on various tumour cell lines. The magnitude of augmentation was varied among eight different cell lines tested, but reached more than three times. It was also found that GL enhanced the expression of H-2Dd antigens in some normal cell populations in vivo. The augmentation of H-2 class I antigens on tumour cell lines in vitro was probably not mediated by the interferon, which might have been produced by the cultured cells. These findings may suggest a new immunopharmacological action of GL.

Animals↗

[Low birth weight infant and its risk factors].

A case-control study on low birth weight was conducted in Qiaokou District, Wuhan City in 1987. 162 low birth weight infants were included with 324 controls. The controls were matched by stratified birth weights (2500-2999g, 3000-3999g). The results showed that beside incomplete pregnancy, severe edema-proteinuria-hypertension syndrome (OR 5.26, 8.18), insufficient prenatal care (OR 5.90, 10.04), heavy physical work during third pregnancy trimester (OR 2.84, 6.43), undernutrition (OR 3.40, 18.50) and cigarette smoking (OR 1.41, 5.50) are risk factors to low birth weight. These relationships became more evident when the low birth weight infants were compared with the higher birth weight infants of Control Group 2. This suggests that treating pregnant complications and strengthening prenatal care must be done to reduce the birth rate of low birth weight infants.

Female↗

[Study of dental maturity in children aged 3-16 years in Chengdu].

Dental maturity was studied in a group of 903 healthy children (boys: 465, girls: 438) born in Chengudu from 1972 through 1988. Dental maturity was estimated by the method of Demirjian and Goldstein, which is based on the development of seven left mandibular permanent teeth; teeth formation was studied. The standard and curves of dental maturity for Chengdu children (boys and girls) were constructed. At 3-5 years old, boys had their dental maturity slightly earlier than girls; there was no significant difference between boys and girls (P greater than 0.05). At the age of 7-14, girls were more advanced than boys (P less than 0.05). Developmental curves of seven left mandibular permanent teeth were plotted. The sexual difference was smaller at the crown developmental stage, and it increased during the root development. In all, girls were more advanced by 0.45 year than boys. The maximum average difference was 0.85 year for the canine. The time that each developmental stage has taken was shorter in 50% of girls as compared with that in boys, and it was longer in 28% of girls. There was no difference between boys and girls in the remaining 22% of cases.

Adolescent↗

The immunohistochemistry and in situ cDNA-mRNA hybridization of carbamyl phosphate synthetase I in enzyme-altered liver cells during carcinogenesis.

The changes of carbamyl phosphate synthetase I (CPS 1) in diethylnitrosamine-(DEN)-induced enzyme-altered liver cells were studied by means of immunohistochemical (PAP) and in situ cDNA-mRNA hybridization methods. The experimental rats were treated with DEN, 2-acetylaminofluorene (2-AAF) and 2/3 hepatectomy according to Solt-Farber's protocol and were further promoted by oral daily administration of 0.05% phenobarbital in drinking water. The results showed that the average number of lesions showing abnormal expression of CPS 1 was relatively constant over the course of the experiment (8 months), while the number of normally expressing lesions gradually decreased. The former lesions were also larger in volume than the latter ones. We conclude that in DEN-initiated lesions the abnormally expressed CPS 1 lesions may grow continuously, thus leading to the formation of larger nodules. We also suspect that some of these lesions have increased tendencies to develop into tumors.

Animals↗

The Gibbs report.

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Hospital Administration↗

Mental health services.

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Community Mental Health Services↗

Further evidence for H-2-unrestricted induction of minor histocompatibility antigens-specific T cell immunity in vivo.

Antigenic requirements for inducing minor histocompatibility antigens (MIHA)-specific T cell immunity for second set rejection (SSR) of a MIHA-allogeneic tumor were studied. An intravenous injection of surprisingly small numbers (10(4)-10(5] of live allogenetic spleen cells (SC) effectively primed mice for SSR of the allogeneic tumor, and this immunity was developed as early as 2-3 days after injection of the SC. In contrast, sonication-disrupted allogeneic SC, which should be readily processed by host antigen presenting cells (APC), were not active as immunogens, even at a dose 1000 times higher than the minimum effective dose of live SC. The possibility that host APC preferentially receive MIHA antigens shed by live allogeneic SC for T cell activation was ruled out. These results demonstrated that antigen processing via conventional pathways is very little involved in the mechanism of T cell activation. Under such restricted experimental conditions, the induction phase but not the effector phase of the MIHA-specific T cell immunity was shown to be H-2-unrestricted.

Animals↗

Methylation at specific altered aspartyl and asparaginyl residues in glucagon by the erythrocyte protein carboxyl methyltransferase.

Protein carboxyl methyltransferases from erythrocytes and brain appear to catalyze the esterification of L-isoaspartyl and/or D-aspartyl residues but not of normal L-aspartyl residues. In order to identify the origin of these unusual residues which occur in subpopulations of a variety of cellular proteins, we studied the in vitro methylation by the erythrocyte enzyme of glucagon, a peptide hormone of 29 amino acids containing 3 aspartyl residues and a single asparagine residue. Methylated glucagon was digested with either trypsin, chymotrypsin, pepsin, or endoproteinase Arg C, and the labeled fragments were separated by high-performance liquid chromatography and identified. In separate experiments, methyl acceptor sites were determined by digesting glucagon first with proteases and then assaying purified glucagon fragments for methyl acceptor activity. Using both approaches, we found that the major site of methylation, accounting for about 62% of the total, was at the position of Asp-9. Chemical analysis of fragments containing this residue indicated that this site represents an L-isoaspartyl residue. A second site of methylation, representing about 23% of the total, was detected at the position of Asn-28 and was also shown to represent an L-isoaspartyl residue. Methyl acceptor sites were not detected at the positions of Asp-15 or Asp-21. Preincubation of glucagon under basic conditions (0.1 M NH4OH, 3 h, 37 degrees C) increased methylation at the Asn-28 site by 4-8-fold while methylation at the Asp-9 site remained unchanged. These results suggest that methylation sites can originate from both aspartyl and asparaginyl residues and that these sites may be distinguished by the effect of base treatment.

Amino Acid Sequence↗