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Biomedical subjects

P S Lin

Publications and source records attributed to P S Lin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Expression of oestrogen receptor and transforming growth factor-alpha in MCF-7 cells after exposure to fractionated irradiation.

The expression of critical growth controlling genes was studied in MCF-7 cells after exposure to cumulative radiation doses of 20 and 60 Gy yielding cell lines called MCF-IR-1 and MCF-IR-3, respectively. The irradiated cell lines exhibited increased plating efficiencies but no differences in growth rates. MCF-IR-1/-IR-3 cells showed a reduced oestrogen responsiveness as indicated by their diminished response to tamoxifen-induced growth arrest and 17 beta-oestradiol (E2)-induced growth stimulation. The reduced expression of oestrogen receptor (ER) was determined by quantitative immune peroxidase staining of single cells and by total cellular E2 binding. There was also a radiation dose-dependent increase in the radiosensitivity of MCF-IR-3 cells as determined by the radiobiological parameters alpha, beta, and D (mean inactivation dose). Using RNA protection assays the irradiated cell lines produced steady-state ER mRNA at reduced levels while the levels of TGF-alpha were unchanged in MCF-IR-1 cells but increased 2.8-fold in MCF-IR-3 cells. A similar pattern was seen for TGF-alpha protein. While the current analyses cannot differentiate between radiation-induced altered gene expression or cell selection the results demonstrate that reduced ER expression and increased TGF-alpha expression are associated with the survival of MCF-7 cells after fractionated irradiation in vitro. In contrast, the MCF-IR cells were found to be more radiosensitive in acute survival experiments.

Breast Neoplasms↗
PubMed1992

Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization.

Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.

Animals↗
PubMed1991

Effects of tamoxifen and protein kinase C inhibitors on hyperthermic cell killing.

The effects of the anti-estrogen, tamoxifen, and the protein kinase C inhibitor, 1-(5-isoquinolinylsulfonyl)2-methylpiperazine (H7), on hyperthermic cytotoxicity were studied. Three cell lines were used, a human colon cancer cell line (HT-29), a human mammary carcinoma cell line (MCF-7), and Chinese hamster V79 lung fibroblasts. With all three cell lines, tamoxifen at concentrations greater than 7.5 microM during heating or with a 3-hr exposure prior to heating significantly sensitized cells to heat. When cells were preincubated with 10-20 microM tamoxifen for 1-2 hr at 37 degrees C prior to heat treatment, washed free of extracellular tamoxifen, heated to generate thermoresistance, and examined 18 hr later for thermoresistance, tamoxifen treated HT-29 and MCF-7 cells were significantly more heat sensitive than thermotolerant controls not previously exposed to tamoxifen. In contrast, the degree of induced thermoresistance of V79 cells was unchanged after tamoxifen treatment. H7, but not its structural analogue and low affinity protein kinase C inhibitor, HA1004, also sensitized cells to heat. Neither H7 nor HA1004 had any apparent effect on the degree of heat-induced thermoresistance in the three cell lines tested.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Hyperthermia enhances the cytotoxic effects of reactive oxygen species to Chinese hamster cells and bovine endothelial cells in vitro.

Hyperthermia is under intensive investigation as a treatment for tumors both alone and in combination with other therapeutic agents. Hyperthermia has a profound effect on the function and structural integrity of tumor microvasculature; this has often been cited as a reason for its effectiveness in treatment of tumors. To test the role of hyperthermia in cytotoxic effects of active oxygen species, Chinese hamster, V79, and bovine endothelial cells were treated by the active oxygens, O not equal to 2 and H2O2, generated from the hypoxanthine/purine and xanthine oxidase reactions. It was found that cytotoxicity to V79 cells depends on the concentrations of purine and xanthine oxidase. A high level of cytotoxicity may be initiated in hyperthermia-treated tumors because high xanthine oxidase activity is known to be associated with tumors and endothelial cells, and degradation processes produce high concentrations of xanthine oxidase substrates in tumors. Since the cytotoxic effect can be reduced by the xanthine oxidase inhibitor, allopurinol, and the H2O2 removal enzyme, catalase, the cytotoxic effect in this experimental system is dependent on xanthine oxidase and H2O2. Adding erythrocytes at the same time as purine and xanthine oxidase could also prevent the cytotoxicity. Elevated temperatures stimulated the reaction of purine and xanthine oxidase and resulted in an increased cytotoxic effect. A similar effect is observed in growth inhibition and colony formation in endothelial cells without adding xanthine oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Response of erythrocytes to heat in the presence of D2O, glycerol, and anisotonic saline.

Mammalian erythrocytes that lack cytoplasmic organelles and a nucleus are a useful model for studying the effect of heat on the cell membrane and cytoskeleton. The effect of heat on the membrane bilayer and cytoskeleton of erythrocytes is remarkably similar to that observed in nucleated cells. Some concentrations of D2O and glycerol can effectively protect erythrocytes from heat-induced damage to the membrane and cytoskeleton. These results are similar to observations in nucleated cells. Heating erythrocytes in some concentrations of anisotonic NaCl solutions reduced damage, an observation that does not apply to enhanced killing of nucleated cells. This difference implies that some components of the cytoplasm or nucleus, or both, may contribute to the enhancement of cytotoxicity of nucleated cells when they are heated in the anisotonic NaCl solution. Incremental heating, dividing a heat treatment into two fractions, and preheating of erythrocytes all modify the effect of heat on erythrocytes slightly, but the results suggest little, if any, development of thermotolerance. The response of chicken erythrocytes is similar to that of mammalian erythrocytes, although higher temperatures are required to produce a heat effect in chicken erythrocytes. These observations suggest that the characteristic differences in heat sensitivity in nucleated and enucleated cells involve components other than the cell membrane.

Acclimatization↗
PubMed1990

Recessive oncogenes in lung cancer.

The observation that carcinogen exposure is strongly associated with the probability of developing pulmonary neoplasms has suggested for many years that acquired somatic mutations play a key role in the genesis of these environmentally induced cancers. With the advent of new techniques in cytogenetics and in the molecular analysis of DNA extracted from lung tumors, it has now become possible to test this hypothesis and to search for candidate genes that may be targeted by the chronic exposure of these environmental insults. Early work in this field, studying lung tumors of different histologic types, appears to implicate several distinct chromosomal loci (at chromosomes 3p, 13q, 17p, and others), suggesting that sequential genetic events occur during the initiation and progression pathways to pulmonary tumorigenesis. Identifying the candidate gene products and understanding the chronology and stringency of mutational events at these loci will be an essential goal to understanding the cellular basis of lung tumors and for developing strategies for the next generation of diagnostic and therapeutic studies.

Carcinoma, Small Cell↗
PubMed1989

Modulation in the radiosensitivity of MCF-7 human breast carcinoma cells by 17B-estradiol and tamoxifen.

Colony-forming ability after exposure to ionizing irradiation was compared for proliferating hormone response MCF-7 breast carcinoma cells and cells whose growth was inhibited by tamoxifen or 17B-estradiol. As compared with controls (Do = 1.20 Gy, n = 3.1), cells in 1 microM or 5 microM tamoxifen were less radiosensitive (Do = 1.20 Gy, n = 7.0; Do = 1.22 Gy, n = 7.0, respectively) with the predominant effect being a widened shoulder on the survival curve. This protective effect could be abolished by co-incubation of 5 microM tamoxifen with 100 nM 17B-estradiol (Do = 1.30 Gy, n = 2.6; Do = 1.20 Gy, n = 2.6, respectively). The decrease in radiosensitivity induced by tamoxifen was similar to that seen when replating of irradiated plateau-phase cultures was delayed for 24 h (Do = 1.30 Gy, n = 6.0). In contrast, when proliferation of MCF-7 cultures was inhibited by 10 microM 17B-estradiol, radiosensitivity was increased with a markedly diminished survival curve shoulder (Do = 1.40 Gy, n = 1.0). Different hormonal manipulations of cycling human breast carcinoma cells may have profound but disparate effects on radiosensitivity such that tamoxifen and estrogens may serve as useful agents with which to study the biochemical mechanisms of repair.

Breast Neoplasms↗
PubMed1988

The role of lipids in Plasmodium falciparum invasion of erythrocytes: a coordinated biochemical and microscopic analysis.

The role of lipids in Plasmodium falciparum invasion of erythrocytes was investigated by biochemical and fluorescent microscopic analysis. Metabolic incorporation of radioactive oleate or palmitate and fractionation of radiolabeled phospholipids by thin-layer chromatography revealed no difference in the major phospholipid classes of schizonts and early ring forms after merozoite invasion. Fluorescent anthroyloxy derivatives of oleate and palmitate were also metabolically incorporated into parasite phospholipids. By microscopic analysis, the fluorescent phospholipids were seen localized in the plasma membrane and, within the merozoite, concentrated near the apical end. During invasion fluorescent phospholipid appeared to be injected from the apical end of the merozoite into the host membrane, both within and outside the parasite-host membrane junctions. After invasion fluorescent lipid was only found in the parasite plasma membrane and/or parasitophorous vacuole membrane. Parallel experiments with a fluorescent cholesterol derivative, incorporated into parasite membranes by exchange, revealed neither heterogeneous distribution of label within the parasite nor evidence for cholesterol transfer from merozoite to host cell membrane. Results suggest that during invasion no major covalent alteration of parasite lipids, such as lysophospholipid formation, occurs. However, invasion and formation of the parasitophorous vacuolar membrane apparently involves insertion of parasite phospholipids into the host membrane.

Animals↗
PubMed1987

Stability of heating temperature on cytotoxicity.

Chinese hamster V79 cells were used to test the cytotoxic effect of heat which alternates between high and low temperatures during the treatment period. This type of temperature fluctuation is often encountered in clinical hyperthermia. Two sets of heating protocols were used in the experiments: Temperature alternates (a) between 42 and 43 degrees and (b) between 42 and 44 degrees in cycle with equal total "thermal dose," that is heating temperature X heating time. The effectiveness of these heating protocols expressed in average percentage of cell survival depend on the initial temperature attained and the length of the time of this temperature alternation. If the period of temperature change is short such as every 5 or 10 minutes, the cytotoxicity shows very little difference whether the initial treatment temperature is low or high. However, when the period is longer than 20 minutes, the difference in cell survival between the initial temperature at 42 degrees and at higher temperatures is substantial. Cells obtained from logarithmic or plateau phases of growth yield the same result. The difference is likely resulted from a combination of thermotolerance and step-down heating mechanisms. In addition, the effects of heating temperature fluctuation on cytotoxicity is not altered by a 500 cGy of gamma-ray radiation applied either immediately before or after the heat treatment.

Animals↗
PubMed1987

Adult B-cell repertoire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells.

Fetal pre-B cells rearrange a very restricted set of immunoglobulin variable genes for the heavy chain (VH). To determine whether the adult B-cell repertoire is similarly skewed, we first identified the genes that rearrange in pre-B cells from BALB/c mice and then determined their frequency of rearrangement in adult B cells. In fetal pre-B cell lines, two genes, VH81X from the 7183 subfamily and VHOx2 from the Q52 subfamily, comprise 75% of the rearranged alleles of an estimated 1000 genes (P less than 0.001). Sequencing analyses revealed that rearrangements involving the two genes were both productive and nonproductive. The biased rearrangement of these two VH genes persists in B-cell hybridomas from adult mice at a frequency of 22%, as determined by Southern gel analysis and RNA sequencing. The sequence of one VHOx2 rearrangement from a hybridoma shows that the rearrangement is productive, suggesting that the gene encodes an antibody that could participate in the immune response. The data indicate that the adult B-cell repertoire is not random concerning usage of individual VH genes, and it may be shaped by the unknown mechanisms that cause preferential rearrangement of certain genes early in ontogeny.

Amino Acid Sequence↗
PubMed1987

Acute bowel entrapment and perforation following operative reduction of pelvic fracture.

The potential for multiple organ system injury with pelvic fracture is well known. This report illustrates a case whereby medially displaced acetabular fragments had become adherent to small bowel. Delayed posterior pelvic open reduction caused entrapment of this bowel within the fracture site followed by acute obstruction and perforation.

Accidents, Traffic↗
PubMed1987

Iliofemoral fusion for proximal femoral focal deficiency.

Iliofemoral fusion, as performed for proximal femoral focal deficiency, is designed so that the knee, acting at the level of the triradiate cartilage, will act as the hip. This procedure was indicated in four of our patients to promote fitting of a prosthesis. The results after follow-up of more than five years are reported. Two of the patients also had a Van Nes rotationplasty and two had a Syme amputation. The Syme amputation produced better results. Distal epiphyseodesis of the ipsilateral femur also was performed in three of the four patients to minimize the anterior prominence of the knee. Two patients required a closing wedge osteotomy of the distal part of the femur to improve the alignment. All four patients walked well as functional above-the-knee amputees.

Amputation, Surgical↗
PubMed1986

Uptake of irradiated human low density lipoprotein by cultured Chinese hamster V79 cells.

Specific binding and degradation of native and gamma-rays irradiated (100-2000 rad; 100 rad/min; 137Cs) human low density lipoprotein by Chinese hamster V79 cells and mouse peritoneal macrophage line, J774G were studied. Low density lipoproteins were labeled with 125I for studying the specific binding and subsequent degradation. The specific binding and degradation of irradiated 125I-low density lipoproteins (mixed with irradiated native lipoprotein) by Chinese hamster V79 cells are considerably reduced. The uptake depends on the concentration of thiobarbutaric acid-reactive products generated in the irradiated lipoproteins which in turn depends on the concentration of carotenoids. In contrast the rate of uptake of oxidized low density lipoproteins is enhanced by Chinese hamster macrophages. The alteration in the surface amino groups of apo-B of low density lipoprotein either due to direct damage of peptide bonds by gamma-rays or via interaction with lipid peroxides (generated in the core upon irradiation) are invoked as possible mechanisms for the reduction in specific binding and subsequent degradation by V79 cells.

Animals↗
PubMed1986

Human-human hybridomas secreting monoclonal antibodies to the Mr 195,000 Plasmodium falciparum blood stage antigen.

Using the human lymphoblastoid cell line, GM 4672, and PBL of Gambian adults immune to Plasmodium falciparum (Pf) malaria, we have produced human-human hybridomas and selected those that produce mAb against Pf antigens. The fusion frequency, using PWM-stimulated donor lymphocytes was between 6.8 X 10(-5) and 1.5 X 10(-6). Using immune fluorescence, immune precipitation, and Pf in vitro growth inhibition, we cloned four hybridomas that reacted with the Pf Mr 195,000 schizont/merozoite protein. The differences in proteins immune precipitated and in growth inhibition indicate that, during development of protective immunity against Pf malaria, a spectrum of antibodies is produced reacting with different epitopes on the same antigen. Only a portion of these antibodies exhibits biological activity, suggesting that the recognition of certain epitopes is required for the development of a protective immune response.

Animals↗