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Biomedical subjects

P Lin

Publications and source records attributed to P Lin.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Chemoprevention of esophageal cancer].

OBJECTIVE: Our goal was to test and pursue the achievement achieved in Heshun township of Linxian county, Henan province. Since 1992, we have been conducting block therapy for precancerous lesions of the esophagus in 9 townships of Ci county, Hebei province, a high risk area of esophageal cancer. METHODS: By means of a cytological survey, 3,990 and 5,346 cases of severe and mild dysplasia of esophageal epithelium were selected. These cases are divided randomly into the treated group and the control group. In the treated group, the Chinese herbal medicine Zeng Sheng Ping were given to the patients with severe dysplasia, and tablets of riboflavin Calcium were given to the patients with mild dysplasia. Placebo were given to the control group. After administration of drugs for 3 years, the esophageal cytological reexamination was repeated in July 1996. RESULTS: In the severe dysplasia treated group, RR = 0.50, 95% CI = 0.33-0.75, inhibitory rate of canceration 49.9%; using the method of cytological five grade-six kinds as the mark of standard to calculate the general grade effects, and using the control group as the standard group, the treated group Ridit = 0.58, 95% CI = 0.56-0.60; in the mild dysplasia treated group, RR = 0.80, 95% CI = 0.52-1.22, inhibitory rate 20.4%; Ridit = 0.59, 95% CI = 0.57-0.61. CONCLUSIONS: These herbal blocking results indicated that the effects of the Chinese herbal medicine Zeng Sheng Ping on esophageal precancerous lesions were worthy of being highly considered.

Adult↗
PubMed1998

Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor.

Vascular endothelial growth factor (VEGF) is a leading candidate for an endogenous mediator of tumor angiogenesis. Recently, two endothelial cell surface receptors, flk-1 and flt-1, have been shown to mediate the angiogenic activities of VEGF. In this study, we have evaluated whether a soluble VEGF receptor could suppress tumor angiogenesis and thereby inhibit tumor growth. A soluble VEGF receptor was constructed by fusing the entire extracellular domain of murine flk-1 to a six-histidine tag at the COOH terminus (ExFlk.6His). In vitro, recombinant ExFlk.6His protein bound VEGF with high affinity (Kd, 16 nM) and blocked receptor activation in a dose-dependent manner and inhibited VEGF-induced endothelial cell proliferation and migration. ExFlk.6His bound to endothelial cells only in the presence of VEGF, and cell surface cross-linking yielded a high molecular weight complex consistent with the VEGF-mediated formation of a heterodimer between ExFlk.6His and the endogenous VEGF receptor. In vivo, ExFlk.6His potently inhibited corneal neovascularization induced by conditioned media from a rat mammary carcinoma cell line (R3230AC). Moreover, when ExFlk.6His protein was administered into a cutaneous tumor window chamber concomitantly with R3230AC carcinoma transplants, tumor growth was inhibited by 75% (P < 0.005) and vascular density was reduced by 50% (P < 0.002) compared with control-treated tumors. These results demonstrate the potential of ExFlk.6His to inhibit VEGF action by a potent "dominant-negative" mechanism and suggest that targeting VEGF action using a soluble receptor may be an effective antiangiogenic therapy for cancer and other "angiogenic" diseases.

Animals↗
PubMed1998

Concentrations of carotenoids, tocopherols, and retinol in paired plasma and cervical tissue of patients with cervical cancer, precancer, and noncancerous diseases.

Paired blood (collected after an overnight fast) and cervical tissue (cancerous, precancerous, and noncancerous) samples were obtained from 87 patients (age, 21-86 years) who had a hysterectomy or biopsy due to cervical cancer, precancer (cervical intraepithelial neoplasia I, II, and III), or noncancerous diseases. The samples were analyzed using high-performance liquid chromatography for 10 micronutrients (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, alpha-tocopherol, gamma-tocopherol, and retinol). The results indicated that: (a) among the three patient groups, the mean plasma concentrations of all micronutrients except gamma-tocopherol were lowest in the cancer patients; however, the mean tissue concentrations of the two tocopherols and certain carotenoids were highest in the cancerous tissue; and (b) among the 10 micronutrients, only the concentrations of beta-carotene and cis-beta-carotene were lower in both the plasma and tissue of cancer and precancer patients than in those of noncancer controls. These results suggest that: (a) not all of the micronutrient concentrations in plasma reflect the micronutrient concentrations in cervical tissue; thus, in some cases, it may be necessary to measure the tissue micronutrient concentrations to define the role of the micronutrients in cervical carcinogenesis; and (b) maintaining an adequate plasma and tissue concentration of beta-carotene may be necessary for the prevention of cervical cancer and precancer.

Adult↗
PubMed1998

Status of deleted in colorectal cancer gene expression correlates with neuroblastoma metastasis.

Neuroblastoma is an embryonal tumor of neural crest origin noted for its heterogeneity at the clinical, histologic, and molecular levels. The deleted in colorectal cancer (DCC) protein is an adhesion family molecule of unequivocal importance in neural development that has also been implicated in several malignancies, including neuroblastoma, through its apparent loss of function. Immunohistochemical assessment of the DCC protein was performed on a group of 49 neuroblastoma specimens and examined in relation to important clinical, histologic, and molecular parameters. DCC expression was significantly associated with neuroblastoma dissemination as primary tumors from Stage 1 to 3 patients (15/20, 75%) more frequently exhibited the DCC protein than those from Stage 4 patients (5/13, 38%; p = 0.0415). Primary tumors were more frequently DCC-positive (20/33, 61%) as compared with metastatic deposits (3/16, 19%; p = 0.0063), and a single case of a paired primary and metastatic deposit demonstrated the apparent loss of DCC gene expression with tumor progression. The remaining five paired specimens were DCC-negative in both the primary tumor and metastatic deposit. No significant association was appreciated between DCC expression and patient age, the Shimada histologic classification, or N-Myc amplification. These results provide evidence that DCC expression may be lost in the course of metastatic spread in a subset of neuroblastomas. Moreover, DCC function is implicated in neuroblastoma dissemination in a manner independent of N-Myc.

Cell Adhesion Molecules↗
PubMed1997

Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.

Tie2 is a novel receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Disruption of Tie2 function in transgenic mice resulted in embryonic lethality secondary to characteristic vascular defects; similar defects occurred after disruption of the Tie2 ligand. These findings indicate that the Tie2/Tie2 ligand pathway plays important roles during development of the embryonic vasculature. To determine whether the Tie2 pathway was involved in pathologic angiogenesis in adult tissues, a soluble form of the extracellular domain of murine Tie2 (ExTek.6His) was developed and used as a Tie2 inhibitor. After a single application of the ExTek.6His protein into a rat cutaneous window chamber, growth of a mammary tumor inside the chamber was reduced by > 75% (P < 0.005), and tumor vascular length density was reduced by 40% when compared with control-treated tumors (P < 0.01). In the rat cornea, ExTek.6His blocked angiogenesis stimulated by tumor cell conditioned media. ExTek.6His protein did not affect the viability of cultured tumor cells, indicating that the antitumor effect of ExTek.6His was due to the inhibition of tumor angiogenesis. These data demonstrate a role for the Tie2 pathway in pathologic angiogenesis, suggesting that targeting this pathway may yield effective antiangiogenic agents for treatment of cancer and other angiogenic diseases.

Animals↗
PubMed1997

Chromosome 19 single-locus and multilocus haplotype associations with multiple sclerosis. Evidence of a new susceptibility locus in Caucasian and Chinese patients.

CONTEXT: Susceptibility to multiple sclerosis (MS) involves a genetically complex autoimmune component. However, except for genes in the HLA system, specific susceptibility loci are unknown or unconfirmed. OBJECTIVE: To investigate several loci spanning 3 candidate regions for a role in multiple sclerosis (MS) susceptibility in 2 ethnic groups using both single-locus and haplotype analyses. The 3 regions include HLA on chromosome 6p21.3, APOE on chromosome 19ql 3.2, and MBP(myelin basic protein) on chromosome 18q23. DESIGN: Case-control association testing. SUBJECTS: A total of 120 Caucasian patients with MS and 107 unrelated control individuals from California, and 32 patients and 32 unrelated control individuals from Beijing, China. All patients with MS were diagnosed as having clinically definite disease according to published criteria. MAIN OUTCOME MEASURES: Chi2 Testing of loci and individual alleles and haplotypes. Haplotype frequencies were estimated with standard maximum likelihood methods. RESULTS: The HLA effect is due to the class II DR2 haplotype, DRB1*1501-DQA1*0102-DRB1*0602; contributions to MS susceptibility from additional DRB1-DQB1 alleles or other HLA region loci were not observed. Variation within the MBP locus on chromosome 18q23 showed no effect in MS. The distribution of haplotypes from 5 loci within the chromosome 19q13.2 region, including D19S178, D19S574, APOE, APOC2, and D19S219, differed between patient and control samples. D19S574 showed a significant effect (P=.015) in Caucasian patients with MS due to the increased frequency of a single allele (P=.002). The APOE variation, prominent in other neurological diseases, showed no influence on MS susceptibility, despite its location within the chromosome 19q13.2 region. Interaction effects between DR2 and chromosome 19q13.2 or MBP in MS susceptibility were not apparent. CONCLUSIONS: The significant chromosome 19q13.2 single-locus and multilocus haplotype associations with MS in Caucasian and Chinese patient samples indicate an effect from a nearby disease susceptibility locus. These initial observations are an encouraging step toward the description of non-HLA genetic susceptibility to MS.

Alleles↗
PubMed1997

The unique hetero-oligomeric nature of the subunits in the catalytic cooperativity of the yeast Cct chaperonin complex.

The structural and functional organization of the Cct complex was addressed by genetic analyses of subunit interactions and catalytic cooperativity among five of the eight different essential subunits, Cct1p-Cct8p, in the yeast Saccharomyces cerevisiae. The cct1-1, cct2-3, and cct3-1 alleles, containing mutations at the conserved putative ATP-binding motif, GDGTT, are cold-sensitive, whereas single and multiple replacements of the corresponding motif in Cct6p are well tolerated by the cell. We demonstrated herein that cct6-3 (L19S), but not the parolog cct1-5 (R26I), specifically suppresses the cct1-1, cct2-3, and cct3-1 alleles, and that this suppression can be modulated by mutations in a putative phosphorylation motif, RXS, and the putative ATP-binding pocket of Cct6p. Our results suggest that the Cct ring is comprised of a single hetero-oligomer containing eight subunits of differential functional hierarchy, in which catalytic cooperativity of ATP-binding/hydrolysis takes place in a sequential manner different from the concerted cooperativity proposed for GroEL.

Amino Acid Sequence↗
PubMed1997

Bispecific humanized anti-IL-2 receptor alpha beta antibodies inhibitory for both IL-2- and IL-15-mediated proliferation.

Humanized anti-Tac (HAT) and Mik beta1 (HuMik beta 1) Abs directed at IL-2R alpha and IL-2R beta, respectively, inhibit IL-2 binding and biological activity and together act synergistically in vitro. The Abs have been used successfully in primate models of allograft rejection, graft-vs-host disease, and autoimmunity. We produced bifunctional humanized anti-IL-2R alpha beta Abs (BF-IgG) to combine the specificity of the two Abs into one entity by fusing HAT-producing NSO cells and HuMik beta 1-producing Sp2/0 cells. BF-IgG was purified using protein G-Sepharose affinity chromatography, followed by IL-2R alpha and IL-2R beta affinity chromatography and hydrophobic interaction chromatography. BF-IgG exhibited both anti-IL-2R alpha and anti-IL-2R beta specificities in binding assays. While the Ab binds the IL-2R with intermediate affinity (Kd = 2.82 nM), it does not inhibit IL-15 binding to its high affinity IL-15R. In Kit225/K6 (IL-2R alpha beta gamma+) cells, BF-IgG was 10-fold more potent than a HAT/HuMik beta 1 equimolar mixture in blocking IL-2-induced proliferation and, unexpectedly, was at least 65-fold more active than the mixture in blocking IL-15-induced proliferation. This dual inhibitory activity may be due to cross-linking of the IL-2R alpha and IL-2R beta, thus blocking IL-2 binding and possibly impeding the association of IL-2R beta with IL-15R. BF-IgG has potent immunosuppressant activities against both IL-2- and IL-15-mediated responses, and this antagonist could be more efficacious than HAT and/or HuMik beta 1 for the treatment of autoimmunity and the prevention of allograft rejection.

Antibodies, Bispecific↗
PubMed1997

In vivo modification of the C-terminal lysine of human lens alphaB-crystallin.

Both the structural and chaperone-like properties of lens alpha-crystallins have been implicated in maintaining lens transparency. Modifications of lens alpha-crystallins may lead to formation of cataract by affecting the close-packing of the crystallins or by reducing the chaperone-like activity of the alpha-crystallins. A previously unreported modified alphaB-crystallin, whose molecular weight is 72 u greater than unmodified alphaB-crystallin, has been isolated from human lenses by size exclusion chromatography, reversed phase HPLC and ion exchange HPLC. Approximately one nanomole of this modified alphaB-crystallin was obtained from each of five human eye lenses. Molecular weight determinations of peptides produced by digestion with trypsin or endoproteinase Asp-N showed that the modification is in the C-terminal region of alphaB-crystallin. The fragmentation pattern of peptides from the C-terminal region, analysed by tandem mass spectrometry, located the modification of the epsilon-amino group of the C-terminal lysine. The elemental composition of this modification, determined from its exact mass, is C3H4O2. Because this modification decreases the net charge of alphaB-crystallin by one unit, and because the C-terminus has been implicated in the chaperone activity attributed to alphaB-crystallin, this modification at Lys 175 may have a significant role in cataractogenesis.

Adult↗
PubMed1997

Neutralizing IGF-1 monoclonal antibody with cross-species reactivity.

We report the generation of a murine IGF-1 monoclonal antibody designated 35I17, which exhibits unique cross-species reactivity. The antibody recognizes recombinant human and rat IGF-1 in ELISA, Western blots, and in an 125I-recombinant human IGF-1 Scintillation Proximity Assay. In addition, 35I17 blocks cell proliferation induced by recombinant human and rat IGF-1, and inhibits cell proliferation induced by sera from human, rat, calf, dog, goat, or mouse. The antibody inhibits rat IGF-1 binding to IGF-1 receptors, and prevents IGF-1-stimulated receptor and IRS-1 phosphorylation in LISN C4 cells, an IGF-1 receptor-transfected cell line. The cross-species and neutralizing properties of 35I17 may be useful in in vitro and in vivo animal studies for elucidating the role of IGF-1 in cancer, rheumatoid arthritis, and other diseases.

3T3 Cells↗
PubMed1997

Analysis of mutationally altered forms of the Cct6 subunit of the chaperonin from Saccharomyces cerevisiae.

The Cct double-ring chaperonin complex of Saccharomyces cerevisiae is comprised of eight essential subunits, Cct1p-Cct8p, and assists the folding of substrates such as actins and tubulins. Single and multiple amino acid replacements of Cct6p were constructed by oligonucleotide-directed mutagenesis, including changes of charged to alanine residues and uncharged to charged residues. The replacements were targeted, in part, to residues corresponding to functionally critical regions identified in the published crystal structure of the Escherichia coli chaperonin, GroEL. Here, we report the critical hydrophobic residues and clusters of hydrophilic residues in regions corresponding to those from the apical domain of GroEL implicated in peptide binding and peptide release, and certain residues in the putative equatorial domain implicated in subunit-to-subunit interaction. In contrast to their homologous counterparts in Cct2p and Cct1p, the highly conserved putative ATP binding motifs of Cct6p were relatively amenable to mutations. Our data suggest that the entire Cct6p molecule might be essential for assembly of Cct complex and might participate in binding substrates. However, there appeared to exist a functional hierarchy in ATP binding/hydrolysis among Cct subunits, as suggested by the high tolerance of Cct6p to mutations within the putative ATP binding pocket.

Amino Acid Sequence↗
PubMed1997

[Reconstruction of the hypopharyngeal and cervical esophagus using flap of epiglottis].

Reconstruction of the hypopharyngeal and cervical esophagus was performed for eight patients after the resection of hypopharyngeal carcinoma. The flap of the epiglottis and the facial flap of the sternohyoid muscle or the uninvolved mucous membrane of the hypopharynx were used for the reconstruction of the hypopharyngeal and cervical esophagus. A good swallowing function was obtained. No pharyngeal-cervical fistula occurred. Although stomach transposition or colon interpolation and pectoralis major myocutaneous flap could be used to reconstruct the hypopharynx and the cervical esophagus, however, the operative time became longer, more complex and the patient suffered more. The procedure of the flap of epiglottis had the following advantages: (1) a rich vascularized flap; (2) simple operative technique; (3) higher success rate; and (4) few complications.

Adult↗
PubMed1997

Does vaginal cuff closure decrease the infectious morbidity associated with abdominal hysterectomy?

BACKGROUND: Infectious morbidity after total abdominal hysterectomy includes fever (31%) and antibiotic administration (45%). Whether vaginal cuff closure reduces postoperative infectious morbidity remains unresolved. STUDY DESIGN: We reviewed the records of 172 consecutive abdominal hysterectomies for nonmalignant disease performed at an inner-city hospital. We identified potential risk factors for infectious morbidity by univariate analysis and determined adjusted odds ratios by multiple logistic regression analysis. RESULTS: The open vaginal cuff technique was associated with an increased risk of wound infection. Use of prophylactic antibiotics was associated with a decreased risk of febrile morbidity and a decreased risk of prolonged hospitalization. Body weight in the heaviest quartile was associated with increased risk of wound infection, increased risk of prolonged hospitalization, and decreased risk of postoperative vaginal cuff granulation tissue. Older age was associated with an increased risk of prolonged hospitalization. CONCLUSIONS: Closure of the vaginal cuff and use of prophylactic antibiotics at total abdominal hysterectomy were associated with decreased infectious morbidity in a high-risk population.

Antibiotic Prophylaxis↗
PubMed1997

[The shrinkage of ovarian and uterine size and the decline of serum estradiol level in post-menopausal women].

OBJECTIVE: To investigate the shrinkage of ovarian and uterine size, and the decline of serum estradiol (E2) level in normal women. METHODS: Ovarian and uterine area of 92 perimenopausal and 292 postmenopausal women, measured by transvaginal ultrasonography, were analysed retrospectively and were compared with those of the controls consisting of 41 normal women in midfollicular phase, so did the serum E2 levels. RESULTS: As compared with the control group, ovarian area and endometrium thickness shrunk on an average of 30%, 2% and 56%, 48% in early perimenopausal and postmenopausal groups respectively. Serum E2 level and uterine area increased by 11% and 38% in early perimenopausal group, but decreased by 67% and 21% in postmenopausal groups respectively. No obviously further decline of serum E2 level was found 1 year after menopause, and of ovarian, uterine area 3-5 years after menopause. CONCLUSION: These data represent a normal profile of ovarian and uterine shrinkage and decline of serum E2 levels related to the time of menopause.

Adult↗
PubMed1996

Failure to activate interleukin 1beta-converting enzyme-like proteases and to cleave retinoblastoma protein in drug-resistant cells.

We previously found that retinoblastoma (RB) is cleaved at the initiation of apoptotic execution. Here we report that when an HL-60 cell line resistant to cytosine arabinoside (Ara-C) was exposed to this anticancer drug, neither RB cleavage nor apoptosis was detected. Consistent with that, processing of interleukin 1beta-converting enzyme (ICE) and CPP32 (an ICE-like protease) was also prevented in these cells. In contrast, treatment of the HL-60-Ara-C-resistant cells with etoposide induced all of these apoptotic events. Furthermore, the etoposide-induced RB cleavage was inhibited by a specific tetrapeptide ICE-like inhibitor. Our results demonstrate that activation of the RB cleavage enzyme, an ICE-like protease, is required for overcoming drug resistance.

Caspase 1↗
PubMed1996

Formation of interstrand DNA cross-links by bis-(2-chloroethyl)sulfide (BCES): a possible cytotoxic mechanism in rat keratinocytes.

Interstrand cross-links in the DNA of epidermal basal keratinocytes may be responsible for cell death and consequent vesication in skin exposed to BCES. The formation of cross-links and cytotoxicity were compared when cells in primary monolayer cultures of rat epidermal keratinocytes, synchronized at the G1/S boundary or in the G1 phase of the cell cycle, were exposed to BCES. The dose-responsive formation of cross-links, measured with an ethidium bromide-fluorescence assay, was determined immediately after exposure of cells at either position of the cycle. At 24 hr post-exposure, the level of cross-links in cells exposed at the G1 phase showed had not decreased significantly and was still dose-dependent. However, cells exposed in the G1 phase showed a major decrease in cross-links. Formation of interstrand DNA cross-links appears to be related to the mustard's cytotoxicity.

Animals↗
PubMed1996

Somatic histone H1 microinjected into fertilized mouse eggs is transported into the pronuclei but does not disrupt subsequent preimplantation development.

We injected somatic subtypes of histone H1 into newly fertilized mouse eggs, which do not naturally contain this chromosomal protein, and examined the fate of the injected protein and its effect on preimplantation development of recipient eggs. Rhodamine-labelled H1 injected into the cytoplasm of 53 eggs was transported into the pronuclei in 51 cases, and this nuclear accumulation could be detected within 15 min of injection. Unlabelled histone H1, which was detected using immunofluorescence, was also transported following microinjection to the pronuclei, where it colocalized with the chromatin and remained associated with the nuclei following cleavage to the two-cell stage. Nuclear accumulation of injected H1 was inhibited when injected eggs were incubated in the presence of drugs that prevent mitochondrial electron transport or glycolysis, which indicates that nuclear transport occurs through an energy-dependent process, as previously observed in tissue culture cells. To determine whether the presence of somatic H1 in early embryonic nuclei would influence subsequent development, fertilized eggs were injected with an approximately physiological quantity (1-5 pg) of somatic H1 or, as controls, with another small basic protein, cytochrome c. Fifty-three eggs were injected with cytochrome c, of which 51 divided to the two-cell stage, and 32 (60%) reached the blastocyst stage, after 5 days in culture. One hundred and eleven eggs were injected with somatic H1, of which 95 divided to the two-cell stage, and 53 (48%) reached the blastocyst stage, after 5 days in culture. The two groups did not differ statistically (chi 2, P > 0.1) with respect to the fraction of injected embryos that developed to the blastocyst stage. These results show that, although mouse embryos lack the somatic subtypes of histone H1 until the four-cell stage of development, they are able to progress through preimplantation development when these subtypes are present beginning at the one-cell stage. This may imply that the distinctive chromatin composition that characterizes early embryos of a variety of species is not essential for early development in mammals.

Animals↗