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P Zhou

Publications and source records attributed to P Zhou.

At least 163 records · Page 9Linked to original sources
PubMed1995

Retrovirus-induced lymphoproliferative disease in mice: role of humoral immunity in perinatally exposed mice.

The mice born to female mice infected with LP-BM5 MuLV, the etiologic agent for lymphoproliferative disease and nursed for 4-6 weeks by them were less susceptible upon reinfection by i.v. transfusion of blood or plasma from infected donors with fully developed disease. Sera of 7 week or older perinatally exposed mice were capable of a complete in vitro neutralization of virus in plasma or blood from mice with fully developed disease. In contrast, sera from 3-week old perinatally exposed mice were ineffective. The neutralizing ability of the sera was drastically reduced or abrogated after their absorption with anti-mouse IgM. These observations are consistent with the notion that perinatally exposure results ina moderate form of the disease of the offspring. This perinatal infection is followed by a production of neutralizing antibodies of predominantly the IgM class that significantly alters the course of the lymphoproliferative disease and, in some instances, even prevents its development.

Animals↗
PubMed1995

Expression of basement membrane and endothelial cell adhesion molecules in vascular malformations of the brain: preliminary observations and working hypothesis.

Little is known about the pathogenesis and subsequent cellular biologic behaviour of human cerebral vascular malformations. Innovative therapeutic strategies will depend on more fundamental understanding of structural and functional lesion biology. We have freeze-processed four specimens of arteriovenous malformation (AVM), two cavernous malformations (CM), and resected cortex from one case of Sturge-Weber disease (SWD) for immunohistochemical studies. Probes of vascular maturity and cellular adhesion were examined, including Factor 8 related antigen (F8RAG), laminin, fibronectin, and adhesion molecules VCAM, ELAM and ICAM-1 (CD 54). Sections of the same lesions were permanently fixed and stained using Haematoxylin and Eosin, and MOVAT Pentachrome stain for identification of vascular wall structures. A double antibody staining battery was utilized with ultraviolet fluorescent microscopy, and was analysed by an observer blinded to the antibody and lesion type. All malformations showed strong expression on their luminal endothelial surface for F8RAG. There was no expression of ELAM in any lesion. Two AVMs expressed VCAM on the endothelial surface of some vessels. ICAM-1 was expressed faintly within two AVMs. The CMs expressed fibronectin within the endothelium and subendothelial matrix, and both lesions were devoid of laminin expression. The AVMs and the SWD vessels stained for laminin, while none of the AVMs expressed fibronectin. These preliminary observations are consistent with the hypothesis that AVMs and SWD represent more mature vessels, consistent with possible lesion genesis during early phases of embryonic vascular development (dysvasculogenesis). In contrast, CMs represent immature vessels devoid of laminin and other features of mature vessels, consistent with ongoing dysangiogenesis within a fibronectin rich matrix. Further studies should be aimed at better elucidation of these biologic probes, and correlation with specific lesion behaviour.

Basement Membrane↗
PubMed1995

Anti-alpha-galactosyl immunoglobulin A (IgA), IgG, and IgM in human secretions.

Anti-alpha-galactosyl (anti-Gal) is a natural human serum antibody that binds to the carbohydrate Gal alpha 1,3Gal beta 1,4GlcNAc-R (alpha-galactosyl epitope) and is synthesized by 1% of circulating B lymphocytes in response to immune stimulation by enteric bacteria. We were able to purify secretory anti-Gal from human colostrum and bile by affinity chromatography on silica-linked Gal alpha 1,3Gal beta 1,4GlcNAc. We found similar secretory anti-Gal antibodies in human milk, saliva, and vaginal washings. Secretory anti-Gal from milk and saliva was exclusively immunoglobulin A (IgA); that from colostrum and bile also contained IgG and IgM isotypes. Serum was also found to contain anti-Gal IgM and IgA in addition to the previously reported IgG. Anti-Gal IgA purified from colostrum and bile had both IgA1 and IgA2. Secretory anti-Gal from saliva, milk, colostrum, and bile agglutinated rabbit erythrocytes (RRBC) and bound to bovine thyroglobulin, both of which have abundant alpha-galactosyl epitopes. The RRBC-hemagglutinating capacity of human saliva, milk, bile, and serum was specifically adsorbed by immobilized Gal alpha 1,3Gal beta 1,4GlcNAc but not by Gal alpha 1,4Gal beta 1,4GlcNAc, Gal beta 1,3GalNAc, Gal beta 1,4GlcNAc, Gal beta 1,4GlcNAc alpha 1,2Man, or Fuc alpha 1,2Gal beta 1,4GlcNAc. No RRBC-hemagglutinating activity could be detected in rat milk, rat bile, cow milk, or rabbit bile, suggesting a restricted species distribution for secretory anti-Gal similar to that found for serum anti-Gal. Colostral anti-GaI IgA bound strongly to a sample of gram-negative bacteria isolated from the throats and stools of well children as well as to an Escherichia coli K-1 blood isolate. Colostral anti-GaI IgA inhibited the binding of a Neisseria meningitidis strain to human buccal epithelial cells, suggesting that this antibody may play a protective role at the mucosal surface.

Animals↗
PubMed1995

Anti-Gal binds to pili of Neisseria meningitidis: the immunoglobulin A isotype blocks complement-mediated killing.

alpha 1,3-Galactosyl antibodies (anti-Gal) are ubiquitous natural human serum and secretory polyclonal antibodies that bind to terminal galactose-alpha 1,3-galactose (alpha-galactosyl) residues. Serum immunoglobulin G (IgG) anti-Gal can block alternative complement pathway-mediated lysis of representative gram-negative enteric bacteria that bind it to lipopolysaccharide alpha-galactosyl structures, thereby promoting survival of such bacteria in the nonimmune host. We wanted to know whether anti-Gal also could bind to the lipooligosaccharides (LOS) of Neisseria meningitidis. To our surprise, we found that serum and secretory anti-Gal bound to pili but not to LOS of certain strains. This suggested the presence of an immunogenic pilus carbohydrate epitope. Mild periodate oxidation of sodium dodecyl sulfate-polyacrylamide gel electrophoresis-separated outer membrane preparations from strains that bound anti-Gal followed by labeling of the neoaldehyde groups resulted in the labeling of bands that corresponded to pilin and LOS, confirming that pilin contains carbohydrate structures. A Bandeiraea simplicifolia lectin that also binds terminal alpha 1,3-galactosyl residues also bound to pilin. Serum IgG, IgA, and IgM anti-Gal as well as colostral secretory IgA anti-Gal bound to pilin, as judged by immunoblotting, and to the pili of intact piliated organisms, as judged by immunoelectron microscopy. Total serum anti-Gal (IgG, IgA, and IgM) and purified serum IgA1 anti-Gal, but not its purified IgG isotype, blocked complement-mediated lysis of a piliated meningococcal strain that bound anti-Gal to its pili. Colostral anti-Gal secretory IgA blocked killing of the same strain. Thus, anti-Gal IgA may promote disease when it binds to the pili of N. meningitidis strains.

Animals↗
PubMed1995

Glucocorticoid receptor structure and function in an adrenocorticotropin-secreting small cell lung cancer.

ACTH secretion by tumors of nonpituitary origin is characteristically resistant to negative feedback regulation by glucocorticoids. One possible mechanism for the phenomenon could be a structural defect in the intracellular glucocorticoid receptor (GR). We studied the GR in DMS-79 cells derived from a human ACTH-secreting small cell lung cancer. Compared with control cells, DMS-79 cells were found to have greatly diminished GR ligand-binding activity and immunoreactive 94-kilodalton (kDa) GR content. Northern blot analysis revealed expression of GR transcripts that appeared to be slightly larger than those in control cells. A DMS-79 cell GR cDNA was cloned by reverse transcription/polymerase chain reaction amplification of mRNA using primers specific for full-length normal GR. The derived sequence of this full-length GR differed from the reported sequence by a single altered codon (G to A; Asn to Ser at codon 363) outside the steroid-binding domain. This N363S DMS-79 GR functioned normally to activate a target gene [mouse mammary tumor virus-chloramphenicol acetyl transferase (MMTV-CAT)] in transient transfection experiments in COS cells. Evidence for expression of a second type of GR mRNA was obtained by screening a DMS-79 cell cDNA library. This GR cDNA contained normal GR sequence up to nucleotide 2155, corresponding exactly to the end of exon 7 in the normal GR gene. The sequence appended to the GR sequences was not matched by any known sequence in DNA databases and included an in-frame termination codon after only 6 bases. The predicted truncated GR protein product (GR delta) has a mol wt of 73,740 and lacks most of the ligand-binding domain. Transient transfection of the GR delta form into COS cells did not reveal any dominant negative effect on the function of a cotransfected normal GR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Retrovirus-induced lymphoproliferative disease in mice undergoing graft-versus-host reaction.

The effect of graft-versus-host reaction on the course of concommitant retrovirus-induced lymphoproliferative disease was investigated. The graft-versus-host reaction was elicited by a single i.v. injection of 1.2 x 10(8) parental spleen cells into adult F1 mice. Lymphoproliferative disease was induced by a single transfusion of 0.2 ml of whole blood from donors with fully developed disease, induced by infection with retrovirus LP-BM5 MuLV. Graft-versus-host reaction and the lymphoproliferative disease each separately produced similar syndrome consisting of splenomegaly, lymphadenopathy, leukopenia, neutrophilia, reduced in vitro proliferation of spleen cells and suppression of in vivo immune responsiveness. The above symptoms were usually less pronounced during graft-versus-host reaction. Ongoing graft-versus-host reaction neither aggravated nor accelerated the course of the virus-induced lymphoproliferative disease in genetically susceptible F1 hybrids. Likewise, an ongoing graft-versus-host reaction in genetically resistant F1 hybrids did not alter their susceptibility to the retrovirus infection. The apparent lack of the effect of graft-versus-host reaction -dependent immunosuppression on the severity and the course of the concommitant retrovirus-induced lymphoproliferative disease suggests pathogenic differences between the murine syndrome and human AIDS for which the murine disease is considered by some to be an animal model.

Animals↗
PubMed1994

Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells.

Mcl-1, a protein increased early in the differentiation of human myeloblastic ML-1 cells, has sequence similarity to Bcl-2. In the present study, we determined whether Mcl-1 has functional similarity to Bcl-2 by testing its ability to inhibit apoptosis induced by c-Myc overexpression. This was carried out using Chinese hamster ovary 5AHSmyc cells which contain the human c-myc proto-oncogene under the control of a heat shock promoter. Heat treatment induces c-Myc overexpression and thus apoptosis as determined by internucleosomal DNA fragmentation. We transfected 5AHSmyc cells with mcl-1 and found that clones expressing the introduced Mcl-1 protein exhibited reduced DNA fragmentation. Mcl-1 was also capable of delaying the onset of cell death as judged by loss of membrane integrity, although it could not provide complete protection from c-Myc overexpression. Thus, Mcl-1 has functional homology to Bcl-2 in that Mcl-1 can enhance cell viability under conditions that otherwise cause apoptosis.

Animals↗
PubMed1994

Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease.

The MCL1 gene, recently identified in a myeloid leukemia cell line, has sequence similarity to BCL2, the gene at the t(14;18) translocation in follicular lymphoma. The chromosomal location of MCL1 has now been determined. The human locus (MCL1) was mapped to the long arm of human chromosome 1q21, using the methods of in situ hybridization and somatic cell hybrid analysis. In the mouse, MCL1-related sequences were mapped to positions on two mouse chromosomes (chromosomes 3 and 5), using haplotype analysis of an interspecific cross. The location of the locus on mouse chromosome 3 (Mcl1) was homologous to that of MCL1 on human chromosome 1; the second locus (Mcl-rs on mouse chromosome 5) may represent a pseudogene. The proximal long arm of human chromosome 1, where MCL1 is located, is duplicated and/or rearranged in a variety of preneoplastic and neoplastic diseases, including hematologic diseases and solid tumors. MCL1 is thus a candidate gene for involvement in cancer.

Animals↗
PubMed1994

A system for gene cloning and manipulation in the yeast Candida glabrata.

The opportunistic pathogenic yeast, Candida (Torulopsis) glabrata, is an asexual imperfect fungus that exists largely as a haploid. Besides being a clinically important pathogen, this yeast also provides a model system for understanding basic biological mechanisms such as metal-activated metallothionein-encoding gene transcription. To facilitate molecular genetic studies in C. glabrata, we isolated a strain auxotrophic for uracil biosynthesis. The ura- mutation could be functionally complemented by the URA3 gene of Saccharomyces cerevisiae, consistent with a defect in the C. glabrata URA3 gene in this strain. We also found that the centromere-based S. cerevisiae plasmid pRS316 could stably transform and replicate in multiple copies in C. glabrata. In contrast, high-copy-number S. cerevisiae plasmids containing the 2 mu circle autonomous replication sequence were not able to replicate productively in C. glabrata. We cloned the C. glabrata URA3 gene, encoding orotidine-5'-phosphate decarboxylase, by complementation of a ura3- strain of S. cerevisiae. The deduced amino-acid sequence is highly similar to that of the URA3 protein from S. cerevisiae. C. glabrata URA3 provides a genetic locus for targeted gene integration in C. glabrata. Integrative plasmids were constructed based on the cloned C. glabrata URA3 and are applicable for directed insertions of genes of interest at the ura3 locus through homologous recombination.

Amino Acid Sequence↗
PubMed1994

Molecular cloning of TPAR1, a gene whose expression is repressed by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA).

We previously isolated a partial cDNA sequence, termed TPAR1 (TPA repressed gene 1), from a cDNA library constructed from C3H10T1/2 mouse embryo fibroblasts treated with TPA, using a differential screening procedure. (M.D. Johnson et al. Mol. Cell. Biol. 7, 2821-2829, 1987). In the present study, we have cloned two corresponding full-length 1.9- and 3.4-kb cDNAs of TPAR1 from murine cDNA libraries. Sequence analysis of these TPAR1 cDNAs revealed that they encode 89 and 93 amino acid polypeptides, respectively, with a putative leader sequence and show significant homology with the human cytokine interleukin-8 (IL-8) and its superfamily. Genomic DNA isolation and structural characterization provide evidence that the TPAR1 mRNAs are transcribed from a single gene with alternative splicing. TPAR1 mRNAs are expressed ubiquitously among adult mouse tissues as three major transcripts, 1.9, 3.4, and 6.5 kb, whose expression depends on the tissue type. The levels of TPAR1 mRNAs were markedly decreased in fibroblasts following TPA treatment and also in serum-deprived quiescent fibroblasts stimulated by serum. The levels of TPAR1 mRNAs were dramatically down-regulated in regenerating rat liver when compared to normal adult liver. In addition, there was no detectable expression of TPAR1 in three rat hepatoma cell lines and several transformed fibroblast cell lines. Thus, the TPAR1 gene is a new member of the cytokine IL-8 superfamily, whose expression is down-regulated in rapidly dividing cells. Further studies are required to determine whether it plays a negative role in controlling cell proliferation and tumorigenesis.

Amino Acid Sequence↗
PubMed1994

Combination therapy with a synthetic peptide of C-reactive protein and interleukin 2: augmented survival and eradication of pulmonary metastases.

A synthetic peptide (RS-83277) derived from the structure of human C-reactive protein (CRP) was previously shown to have antitumor activity in three different murine tumor models when administered in multilamellar vesicles (MLV). The therapeutic effects were comparable to those seen with MLV-encapsulated native CRP. The present study evaluated the therapeutic and immunomodulatory effects of administering CRP peptide RS-83277 MLV simultaneously with low-dose recombinant interleukin-2 (IL-2) to C57Bl/6 mice bearing established pulmonary metastases of fibrosarcoma T241. Results demonstrated that the capacity of RS-83277 MLV to inhibit tumor metastases and prolong survival was significantly augmented by combination with 10,000 U/day IL-2 i.p. Treated animals showed no evidence of toxicity. By immunohistochemistry, increased Thy 1.2+ cells were detectable in lungs of RS-83277 MLV/IL-2-treated animals compared to those receiving RS-83277 MLV alone. Circulating tumor necrosis factor alpha (TNF) and interferon (IFN) were not detectable in animals receiving RS-83277 MLV alone, but TNF was significantly elevated in animals receiving IL-2. In the presence of combination therapy, however, circulating TNF was not detectable. Results suggest that the combination of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a therapeutic advantage over either agent alone.

Animals↗
PubMed1994

Murine AIDS: a model for the human disease or a distinct entity?

The LP-BM5 mixture of murine retroviruses elicits a disease in mice referred to as murine immunodeficiency syndrome (MAIDS) that is considered by some to be an animal homologue of human AIDS. In this article, we present and discuss some recent findings on the pathogenesis of the murine disease and their implications for the proposed homology between murine and human syndromes. The murine disease seems to display as many similarities to as it does differences from human AIDS. Among the latter are: definitive and exclusive viral etiology, a strong genetic effect on susceptibility to infection, expansion of the CD4+ cell population in spleen and peripheral blood, consistent transmissibility by a single transfusion of the minute amounts of blood or plasma from infected donors, and striking similarity between virus-induced alteration of the in vitro spleen cell proliferation and those caused by treatment with a protein kinase inhibitor K252a. With this in mind, the use of the noncommittal term retrovirus-induced murine lymphoproliferative disease instead of MAIDS appears to be more appropriate at this time.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Regulation of monocyte chemoattractant protein-1 expression in adult human non-neoplastic astrocytes is sensitive to tumor necrosis factor (TNF) or antibody to the 55-kDa TNF receptor.

Infiltration of the central nervous system (CNS) by monocytes is a characteristic of many non-malignant disease processes, although the signals regulating such traffic are unclear. Tumor necrosis factor (TNF) and other inflammatory cytokines have been shown to elicit production of monocyte chemoattractant activity in glioma cells, but the regulation of such activity in non-neoplastic adult astrocytes has not been examined. We previously observed that TNF constituted a proliferative signal for non-neoplastic adult human astrocytes in vitro involving the 55-kDa TNF receptor. In the present study, we demonstrate that TNF exposure enhances the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and functional monocyte chemoattractant activity in non-neoplastic astrocytes. Results indicated that MCP-1 mRNA expression was maximal within 3 h, and was further augmented by the protein synthesis inhibitor cycloheximide (CY). Antibody (htr-9) directed against the 55-kDa TNF receptor also elicited MCP-1 mRNA expression while antibody to the 75-kDa TNF receptor (utr-1) was ineffective. Secretion of monocyte chemoattractant activity was significantly greater in TNF- or htr-9-treated astrocytes than in utr-1-treated or untreated controls; activity was abolished by treatment with antibody to MCP-1. These findings suggest that non-neoplastic adult human astrocytes may contribute to CNS inflammatory responses by mediating recruitment of peripheral blood monocytes.

Antibodies, Monoclonal↗
PubMed1994

Acquired immunodeficiency in murine lymphoproliferative disease: considerations on pathogenesis.

C57BL/6Kh mice were infected with a single i.p. injection of 1 x 10(5) FFU of LP-BM5 MuLV. The development and progress of the virus-induced lymphoproliferative disease was followed for 12 weeks after infection. As anticipated, progressive splenomegaly and lymphadenopathy, as well as almost total abrogation of immune responsiveness ensued. In contrast to previous reports, there was a dramatic increase in the frequency of CD4+ cells in spleens among which over 20% expressed V beta 5 TCR, as compared with fewer than 3% in spleens of normal mice. Spleen cells from infected mice retained their in vitro ability to proliferate upon stimulation with IL-2 and anti-CD3, but were unable to respond when stimulated with phorbol ester and either a low dose of IL-2 or calcium ionophore (ionomycin). A similar pattern of in vitro proliferative responses was obtained when normal spleen cells were treated with K252a compound, a known inhibitor of protein kinase C activity. Together with the observations that viral infection impaired down-regulation of the phorbol-induced kinase activity and that the kinase inhibitor only marginally enhanced suppression of virus-infected cells proliferation, this finding suggests that disturbances of protein kinase C activity may underly the pathological effects seen after viral infection. However, since no apparent quantitative and qualitative changes in protein kinase C itself and its translocation were observed, it is more likely that the virus may interfere with either the substrate or product of kinase activity.

Animals↗
PubMed1994

Relationship between ftsZ gene expression and chromosome replication in Escherichia coli.

Transcriptional levels within the ftsQAZ region of the Escherichia coli chromosome were correlated with chromosome replication and the division cycle. The transcripts were measured either in synchronous cultures generated by the baby machine technique or in dnaC2(Ts) mutants that had been aligned for initiation of chromosome replication by temperature shifts. Transcription within the ftsZ reading frame was found to fluctuate during the cell cycle, with maximal levels about midcycle and a minimum level at division, in cells growing with a doubling time of 24 min at 37 degrees C. Examination of transcription in dnaC(Ts) mutants aligned for chromosome replication indicated that the periodicity was due to a reduction in transcripts coincident with replication of the ftsQAZ region. Transcription originating upstream of the ftsA gene exhibited the periodicity and accounted for a significant proportion of the transcripts entering ftsZ. The most obvious interpretation of the data is that replication of the region transiently inhibits transcription, but alternative explanations have not been ruled out. However, no other relationship between transcription and either replication or division was detected.

Bacterial Proteins↗
PubMed1994

Blood transfusion as a means for transmission of retrovirus-induced lymphoproliferative disease in mice.

Lymphoproliferative disease was elicited in C57BL/6KH and (BALB/c x C57BL/6)F1 hybrids by a single intraperitoneal injection of 10(5) FFU of LP-BM5 virus preparation. The disease could reproducibly be transferred by a single intravenous transfusion of 0.2 ml of whole blood as well as 0.1 ml of blood cells, plasma or serum from the infected animals. F1 hybrids displayed a delayed development of the disease when an acellular virus preparation was administered, but they were fully susceptible to the disease when syngeneic blood from infected F1 donors was transfused. Blood from donors in the prodromal stage was as effective in transmission of the disease as blood from donors with fully developed disease. This indicated that in murine lymphoproliferative disease viremia develops very early in the course of the disease. It seems that using the blood transfusion one could develop a reliable semiquantitative assay for the infectiveness of the animals suffering from LP-MB5-induced lymphoproliferative disease.

Animals↗