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Biomedical subjects

L Shen

Publications and source records attributed to L Shen.

At least 271 records · Page 15Linked to original sources
PubMed1991

Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.

Since the CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV), it has been suggested that a soluble truncated form of CD4 may compete with cell-surface CD4 for HIV binding and thus be of use in the therapy of AIDS. We have utilized the simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys to explore another possible therapeutic application of CD4 in AIDS--the use of recombinant soluble CD4 (rsCD4) as an immunogen. SIVmac-infected rhesus monkeys immunized with human rsCD4 developed not only an anti-human CD4 but also an anti-rhesus monkey CD4 antibody response. Coincident with the generation of this antibody response, SIVmac could not be isolated easily from peripheral blood lymphocytes and bone marrow macrophages of these animals. Furthermore, the decreased number of both granulocyte/macrophage and erythrocyte colonies grown from the bone marrow of these immunized monkeys rose to normal levels. These findings suggest that a modified human CD4 molecule serving as an immunogen might elicit an antibody response in man that could induce a beneficial therapeutic response in HIV-infected individuals.

Animals↗
PubMed1991

Recombinant virus vaccine-induced SIV-specific CD8+ cytotoxic T lymphocytes.

Evidence indicates that cytotoxic T lymphocytes (CTLs) may be important in containing the spread of the human immunodeficiency virus (HIV) in the infected host. Although the use of recombinant viruses has been proposed as an approach to elicit protective immunity against HIV, the ability of recombinant viral constructs to elicit CD8+ CTL responses in higher primates has never been demonstrated. A live recombinant virus, vaccinia-simian immunodeficiency virus of macaques (SIVmac), was used to determine whether such a genetically restricted, T lymphocyte-mediated antiviral response could be generated in a primate. Vaccinia-SIVmac vaccination elicited an SIVmac Gag-specific, CD8+ CTL response in rhesus monkeys. These CTLs recognized a peptide fragment that spans residues 171 to 195 of the Gag protein. The rhesus monkey major histocompatibility complex (MHC) class I gene product restricting this CTL response was defined. Both the vaccinated and SIVmac-infected monkeys that shared this MHC class I gene product developed CTLs with the same Gag epitope specificity. These findings support the use of recombinant virus vaccines for the prevention of HIV infections in humans.

Amino Acid Sequence↗
PubMed1991

Channel reconstitution in liposomes and planar bilayers with HPLC-purified MIP26 of bovine lens.

The major intrinsic protein (MIP26) of bovine lens membranes, purified by HPLC, was incorporated into liposomes and planar bilayers. Permeability of MIP26 channels was studied in liposomes by a spectrophotometric osmotic-swelling assay, and channel electrical properties were monitored in planar bilayers following liposome fusion. Particle formation in liposomes was determined by freeze fracture. MIP26 channels were permeable to KCl and sucrose. In planar bilayers, channel-conductance transitions were observed only after addition of liposomes to both chambers and with voltages greater than +/- 20 mV. Channel open probability decreased progressively as voltage increased, and an open probability of 50% was at 60-80 mV, indicating that the channels are voltage dependent. Histograms of single-channel current amplitudes at 80 mV showed a Gaussian distribution that peaked at 10 pA (approximately 120 pS), after subtraction of 1 pA baseline current. Frequency distributions of open and closed times at 80 mV were single exponential functions with time constants of 0.13 and 1.9 sec, respectively. Open time constants ranged from 0.1 to 0.3 sec, and closed time constants ranged from 1 to 7 sec. Cs+ did not decrease conductance, but reduced mean open time from 0.2 to 0.038 sec and mean closed time from 1.5 to 0.38 sec. The increase in channel flickering with Cs+ occurred in bursts. TEA affected neither conductance nor kinetics. Channel events were also observed in Na+ solutions (zero K+). These data indicate that MIP26 channels are not K(+)-selective channels. Channel characteristics such as: permeability to molecules larger than small ions, conductance greater than 100 pS, long open and closed time constants, etc., are similar to those of gap junction channels.

Animals↗
PubMed1991

[Identification of Yi nationality's secret recipe for treating snakebite].

The authors have investigated and found an effective secret recipe for the treatment of snakebite in Mabian, an autonomous county of the Yi nationality in Sichuan Province. Morphologic identification has shown that the recipe is composed of the herb of Pedicularis muscicola and the rhizome of Polygonum viviparum in the ratio of one to one. To facilitate further application, popularization and improvement of the recipe, its histological characteristics have also been studied microscopically.

Drugs, Chinese Herbal↗
PubMed1991

[Biological characteristics of Cryptoporus volvatus (peck) Hubb., a medicinal fungus].

Through ecological investigations and experimental studies, it has been shown that C. volvatus is a fungus growing on decaying matter; the carbon source of culture medium comes from glucose, honey, fructose, mannitol, etc; and its nitrogen source from peptone, yeast powder, etc. The best ratio of carbon to nitrogen (C/N) is 20-25: 1, optimum pH 5.5-6.5 and optimal temperature 25-30 degrees C.

Culture Media↗
PubMed1991

[Pharmacognostical study on the Chinese drug nanshashen].

The Chinese drug nanshashen is taken from a variety of plants. In this paper, 11 kinds of nanshashen derived from 11 plants of Adenophora have been studied in their pharmacognostical characters and microproperties. A key has been compiled based on the experimental results.

Medicine, Chinese Traditional↗
PubMed1990

Expression cloning of a human Fc receptor for IgA.

IgA, the predominant isotype in secretions, mediates the neutralization and removal of environmental antigens from mucosal sites. Although cell surface receptors for the Fc region of IgA (Fc alpha R) have been implicated in a variety of immune effector mechanisms, the molecular features of Fc alpha R remain only marginally characterized. In this report, we describe the isolation of a clone from a myeloid cell line cDNA library that directs the expression of a cell surface molecule with IgA binding specificity. The cDNA encodes a peptide of Mr 30,000 including a putative transmembrane region with features atypical of conventional membrane-anchored proteins. Databank searches indicate that the human myeloid cell Fc alpha R sequence is unique, is a member of the immunoglobulin gene superfamily, and is related to Fc receptors for IgG (Fc gamma RI, II, and III) and IgE (Fc epsilon RI).

Amino Acid Sequence↗
PubMed1990

Evaluation of the antibody-dependent cytotoxic capabilities of individual human monocytes. Role of Fc gamma RI and Fc gamma RII and the effects of cytokines at the single cell level.

In this report we present evidence that not all human peripheral blood monocytes mediate antibody-dependent cellular cytotoxicity (ADCC), and that this function may be determined on an individual cell by both the type and level of expression of FcR, and by the state of cellular activation and/or differentiation. Although the diverse range of effector and regulatory functions performed by human monocytes suggests the possibility of distinct subsets, it is not clear whether observed functional heterogeneity reflects the presence of true monocyte subpopulations, or whether this diversity represents a continuum of maturational states present in the peripheral circulation. In an attempt to address this question, we investigated the ability of human monocytes to carry out ADCC at the single cell level, with emphasis on the role of the three FcR for IgG (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) in mediating cytotoxicity. Using a modified plaque assay, 58.3% +/- 4.9 of freshly isolated monocytes mediated ADCC, as evidenced by the formation of lytic plaques in monolayers of ox erythrocyte (oxE) target cells. Significant increases in the number of plaque-forming cells were observed after positive selection by flow microfluorimetry for those monocytes expressing high levels of Fc gamma RI and Rc gamma RII, but not Fc gamma RIII. Bispecific antibodies composed of Fab fragments of anti-oxE antibody covalently coupled to Fab fragments of anti-Fc gamma R antibodies were used to independently evaluate the ability of Fc gamma RI, Fc gamma RII, and Fc gamma RIII to mediate single cell cytotoxicity. Significant increases in the number of plaque-forming cells were observed in the presence of anti-Fc gamma RI x anti-oxE and anti-Fc gamma RII x anti-oxE bispecific antibodies, confirming the efficiency of Fc gamma RI and Fc gamma RII as cytotoxic trigger molecules on human monocytes. Incubation of monocytes with purified rIFN-gamma and granulocyte macrophage-CSF, but not IL-2, IL-3, IL-4, IL-6, or TNF-alpha, also resulted in significant increases in the number of monocytes mediating cytotoxicity, suggesting that cytotoxic ability at the single cell level may be influenced by factors which effect monocyte activation and differentiation, respectively. Overall, these studies demonstrate that freshly isolated human monocytes are heterogeneous in their ability to mediate ADCC, and suggest that this functional diversity arises not from discrete subpopulations of cells, but from a continuum of maturational/activational states present within the peripheral circulation.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Human alveolar macrophage FcR-mediated cytotoxicity. Heteroantibody- versus conventional antibody-mediated target cell lysis.

Human alveolar macrophage have three distinct receptors for IgG: FcRI, FcRII, and FcRIII. In order to compare the ability of these receptors to mediate target cell lysis, three different assay systems were examined. First, we studied lysis of chicken E (CE) opsonized with heteroantibodies, which are synthetic antibodies composed of Fab fragments with anti-FcR activity covalently linked to Fab fragments with anti-CE activity. We found alveolar macrophage readily lysed heteroantibody-opsonized CE via each of the three FcR classes (FcRI, 20 +/- 5%; FcRII, 27 +/- 7%; and FcRIII, 13 +/- 13%, p less than 0.05). Non-FcR-dependent lysis of anti-beta 2-microglobulin x anti-CE heteroantibody-opsonized CE was not detected. Second, lysis of hybridoma cell lines bearing anti-FcR antibodies on their cell surface was examined to assess killing of "tumor-like" target cells. Whereas peripheral blood monocytes and lymphocytes were able to lyse hybridoma cell lines bearing surface anti-FcR mAb, alveolar macrophages were not. Third, activity of alveolar macrophage FcR was examined in a conventional antibody-dependent cellular cytotoxicity assay by using O+ (R1,R2) human RBC opsonized with human anti-D and anti-CD serum as target cells. We found lysis of anti-D and anti-CD opsonized human RBC was mediated exclusively via FcRI. No activity of FcRII or FcRIII was detected in these latter assays even if performed under conditions that impair FcRI activity. Thus, all three FcR present on alveolar macrophage mediate lysis of heteroantibody-opsonized CE; in contrast, with the use of a conventional antibody-dependent cellular cytotoxicity assay, only FcRI activity was detected. We were unable to demonstrate lysis of anti-FcR-bearing hybridoma cell lines by alveolar macrophages.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Phagocytosis mediated by three distinct Fc gamma receptor classes on human leukocytes.

We have evaluated the capacity of the three major classes of human Fc gamma R to mediate phagocytosis by measuring the ability of adherent phagocytes to internalize erythrocytes coated with anti-Fc gamma R mAb. Five different cell types were studied, freshly purified monocytes, cultured monocytes, alveolar macrophages, freshly purified polymorphonuclear neutrophilic leukocytes, and PMNs cultured in IFN-gamma. Fc gamma RI and Fc gamma RII on whichever cells they were expressed were capable of phagocytosing anti-Fc gamma R mAb-coated erythrocytes. Furthermore, Fc gamma RIII on mononuclear phagocytes, which appears to be a conventional integral membrane protein that spans the lipid bilayer, was capable of phagocytosing anti-Fc gamma RIII-coated erythrocytes. However, Fc gamma RIII on neutrophils, a molecule linked to the membrane by a phosphatidylinositol-glycan moiety, although binding anti-Fc gamma RIII-coated erythrocytes vigorously was incapable of mounting a phagocytic response. This deficiency correlates with the limited capacity of Fc gamma RIII on neutrophils to mediate superoxide generation and antibody-dependent cell-mediated cytotoxicity and it may be related to the unique structural features of Fc gamma RIII.

Antibodies↗
PubMed1990

A deletion panel of the long arm of the X chromosome: subregional localization of 22 DNA probes.

Two males and two females with different but overlapping deletions on the proximal long arm of the X chromosomes have been investigated. Their karyotypes, which have been well characterized by high resolution banding techniques, are 46,Y,del(X)(pter----q21.1::q21.33----qter); 46,Y,del(X)(pter----q21.2::q21.31----qter); 46,X,del(X)(pter----q21.31::q24.3----qter) and 46,X,del(X)(pter----q21.1:). A deletion panel, which makes it possible to subdivide the long arm of the X chromosome into seven subregions, has been established using the genomic DNA from the four families, and applied to the fine subregional localization of the loci for 22 DNA probes. Based on the results obtained, the possible location of the loci in question has been narrowed down considerably, in some cases to an area of only 5% of the previously assigned region; hybridization to Southern blots of a panel with well-characterized chromosome deletions is thus a powerful means of localizing DNA probes, especially with respect to the X probes.

Blotting, Southern↗
PubMed1990

The effect of cytokines on the expression and function of Fc receptors for IgG on human myeloid cells.

We examined expression and cytotoxic triggering capability of the three Fc receptors for IgG (Fc gamma R) on human monocytes, PMNs and myeloid cell lines after in vitro culture with various cytokines. Fc gamma R expression was evaluated using specific anti-Fc gamma R monoclonal antibodies (mAb). The cytotoxic capability of each Fc gamma R was examined after the effector cells were treated with the recombinant cytokines IFN-gamma. TNF alpha, GM-CSF, G-CSF, M-CSF, IL-1, IL-2, IL-3, IL-4, or IL-6. Hybridoma cell lines (HC) bearing antibody directed to Fc gamma RI (HC 32), Fc gamma RII (HC IV.3) or Fc gamma RIII (HC 3G8) were used as targets, as were chicken erythrocytes (CE) sensitized with heteroantibodies composed of anti-Fc gamma R mAbs (32, IV.3, 3G8) linked to anti-CE antibody. Only IFN-gamma treatment significantly increased Fc gamma R expression and then only Fc gamma RI. IFN-gamma dramatically up-regulated Fc gamma RI expression on all cells tested. However, ADCC was enhanced by treatment with a number of cytokines other than IFN-gamma. GM-CSF, TNF, and IFN-gamma treatment enhanced killing of HC 32 and HC IV.3 by in vitro cultured monocytes. G-CSF treatment enabled PMNs to kill HC through Fc gamma RII, whereas PMN killing of HC through Fc gamma RIII could not be induced by any of the cytokines studied. Although only IFN-gamma treatment increased ADCC of CE by monocytes, GM-CSF treatment as well as IFN-gamma treatment augmented ADCC of CE by PMNs. In addition to IFN-gamma treatment, IL-6 treatment enabled U937 cells to lyse CE. Whereas IFN-gamma-treated U937 cells killed CE through both Fc gamma RI and Fc gamma RII, IL-6-treated U937 cells killed CE only through Fc gamma RI. In addition to IFN-gamma treatment, G-CSF treatment enabled HL-60 cells to lyse CE through both Fc gamma RI and Fc gamma RII. These results demonstrate that although IFN-gamma appears unique in regulating Fc gamma R expression on myeloid cells, cytokines other than IFN-gamma affect ADCC by these cells in a receptor-specific manner.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Exclusion mapping of 12 X-linked disease loci and 10 DNA probes from the long arm of the X-chromosome.

Specific chromosome rearrangements associated with disease entities are invaluable resources for physical mapping. A deletion on the X chromosome of a male leads to the nullisomy for X-linked genes, resulting in the onset of genetic diseases and/or the absence of the DNA probe detectable sequences. This permits the localization of these loci within the deleted area. On the other hand, the region for some other X-linked loci can be excluded from the deleted area according to the absence of the characteristic symptoms of the disease and/or the presence of the hybridization signals. An interstitial deletion on the long arm of the X chromosome of a male has been characterized by high resolution banding. The karyotype of the proband is 46,Y,del(X)(pter----q21.1::q21.33----qter). The regions for 12 X-linked disease loci as well as 10 DNA probes are excluded from the deleted area, and localized either proximally or distally to the deletion. The results also reveal a controversy in the present linkage data concerning the assignment of these loci.

Abnormalities, Multiple↗
PubMed1990

[Relation of tongue color changes and red-cell immune adherence activity in patients with malignant bone tumor].

This article presents that preliminary study on the changes of the tongue colour and the red-cell immune adherence (RCIA) activity in 40 patients with malignant bone tumor, as compared with 40 healthy persons. The results showed that the rate of erythrocyte C3b receptor yeast rosette were no statistically significant different between the pink and the crimson tongues in the bone tumor group and control group (P greater than 0.05). It appeared RCIA activity was no depression in the patients with malignant bone tumor during pink and crimson tongue. In the bone tumor group with the pale and the cyanotic tongues, the rate of erythrocyte C3b receptor yeast rosette and erythrocyte immune complex rosette was significantly lower than that of the control group (P less than 0.05, P less than 0.01). It appeared that RCIA activity in these patients was markedly impaired. The authors suggested that the tongue colour changes in the patients with malignant bone tumors could roughly reflect the level of RCIA activity. This phenomenon is beneficially to predict the body capacity against the malignant tumor.

Adolescent↗
PubMed1989

My 43, a monoclonal antibody that reacts with human myeloid cells inhibits monocyte IgA binding and triggers function.

A mAb My 43 of the IgM isotype was obtained from a fusion of spleen cells immunized against human monocytes. This mAb inhibited monocyte binding of both soluble FITC-labeled IgA and IgA-coated E, whereas it did not inhibit IgG binding. The Ag recognized by My 43 was induced on HL-60 cells in parallel with IgA binding ability by 1-25 dihydroxy-vitamin D3 treatment. Phagocytosis of IgA-coated E by monocytes and 1-25 dihydroxyvitamin D3-treated HL-60 cells was inhibited by My 43. Furthermore, a heteroantibody of My 43 x F(ab)'2 anti-E promoted phagocytic uptake of E by monocytes. Production of superoxide anion by IFN-gamma treated U-937 cells was stimulated by My 43 but not by other IgM mAb recognizing myeloid cells. By these criteria My 43 recognized a molecule capable of triggering function. Moreover, its binding reactivity, ability to block binding of IgA and IgA-complexes, and its ability to induce activation of IgA receptor bearing myeloid cells, are consistent with the possibility that My 43 reacts with the IgA receptor on these cells.

Animals↗
PubMed1989

Fc gamma R-mediated killing by eosinophils.

In this report we present data on the ability of the different Fc gamma R present on eosinophils to mediate killing of erythroid and tumor targets, and on a comparison of eosinophil and neutrophil Fc gamma R-mediated killing. Erythroid target killing was assessed using chicken erythrocytes (CE) and heteroantibodies composed of Fab fragments of anti-CE antibodies covalently coupled to Fab fragments of anti-Fc gamma R antibodies. Such anti-CE x anti-Fc gamma R reagents permit linkage of CE target cells with the FcR molecules on the eosinophil or neutrophil effector cells. Tumor target killing was assessed using hybridoma cell lines (HC) bearing anti-Fc gamma R antibodies on their cell surface. Freshly isolated eosinophils and neutrophils constitutively express similar amounts of the low affinity Fc gamma R, Fc gamma RII on their cell surface, but neither cell type expresses the high affinity Fc gamma R, Fc gamma RI. In contrast, eosinophils have only about 5% as much of the low affinity Fc gamma R found on human granulocytes and large granular lymphocytes (Fc gamma RIII) as neutrophils. Untreated, freshly prepared eosinophils or neutrophils did not lyse any of the anti-Fc gamma R bearing HC nor did they lyse CE in the presence of anti-Fc gamma R containing heteroantibodies. Upon treatment with granulocyte monocyte-CSF (GM-CSF), both cell types lysed HC-bearing antibody to Fc gamma RII (HC IV.3A) and CE in the presence of anti-CE x anti-Fc gamma RII heteroantibodies. However, neither cell type lysed HC-bearing antibody to Fc gamma RI or Fc gamma RIII, or CE in the presence of anti-CE x anti-Fc gamma RI HA. Treatment with GM-CSF did not significantly alter the number of Fc gamma R on either cell type. Treatment of neutrophils with IFN-gamma for 18 h induced the expression of Fc gamma RI on these cells and their ability to lyse anti-Fc gamma RI- or Fc gamma RII-bearing HC and CE through Fc gamma RI, Fc gamma RII, and Fc gamma RIII. In contrast, 6-h treatment of eosinophils or neutrophils with IFN-gamma induced neither Fc gamma RI expression on either cell type nor killing of HC or CE through Fc gamma R. In summary, incubation with GM-CSF, induced eosinophils and neutrophils to kill anti-Fc gamma RII-bearing HC and to lyse CE through Fc gamma RII. This augmented killing was not associated with enhanced expression of Fc gamma RII.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗