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Biomedical subjects

P Porter

Publications and source records attributed to P Porter.

At least 19 recordsLinked to original sources

Expression of Her-2/neu oncogene protein product and epidermal growth factor receptors in surgical specimens of human breast cancers.

Her-2/neu protein product was immunocytochemically analyzed in 139 breast cancers. Epidermal growth factor receptors were similarly analyzed in 74 breast cancers from the same patient pool. These results were also separated on the basis of estrogen receptor proteins and of combined aneuploidy with elevated S-phase from flow cytometry. Invasive breast cancer yielded a positive label for Her-2/neu protein (26%) and for epidermal growth factor receptor (25%), with no significant difference. Correlations with estrogen receptor labeling yielded differences significant inversely for both Her-2/neu protein (p less than 0.02) and epidermal growth factor receptor (p less than 0.01). Positive Her-2/neu protein labels correlated with a positive combination of aneuploidy and elevated S-phase (37%) and a negative combination of aneuploidy and elevated S-phase (21%), with a statistically nonsignificant difference. Positive epidermal growth factor receptor cases with aneuploidy and an elevated S-phase (75%) and without aneuploidy and elevated S-phase (42%) did differ with significance at p less than 0.05. There were eight cases positive for both Her-2/neu protein and epidermal growth factor receptor, four of six cases with negative estrogen receptor, four of six cases with negative estrogen receptor, six of six cases aneuploid, and five of six cases with an elevated S-phase. All eight cases had threatening disease--either stage III or stage IV, with one case of extensive ductal carcinoma in situ (comedo). Correlation of negative Her-2/neu protein with negative epidermal growth factor receptor was significant (p less than 0.05) in 74 cases. However, positive Her-2/neu protein did not correlate with positive epidermal growth factor receptor; there was a trend toward inverse correlation. We conclude that epidermal growth factor receptor labeling results show similarities to Her-2/neu protein results, but epidermal growth factor receptor tended to correlate with unfavorable ploidy and S-phase. Epidermal growth factor receptor labeling might be useful in breast cancers with macrocysts reported to show high epidermal growth factor activity.

Adult

Controlled gastric emptying. II. In vitro erosion and gastric residence times of an erodible device in beagle dogs.

An erodible gastric retention device fabricated from various polymeric blends was examined in vitro for its dissolution properties and in vivo in fasting dogs for assessment of its gastric retention potential. Dissolution studies were conducted with extruded rods of polymer blends to assess their potential as candidates for the erodible component of a gastrically retained device. Based on results from dissolution studies, rods of poly(ortho ester)/polyethylene blends (POE/PE) (45% erosion at pH 1.5 and 24 hr) were used to fabricate arms for tetrahedron-shaped devices. Corners for the tetrahedral device were fabricated from Silastic 382 loaded with 15% barium sulfate for X-ray visualization. Beagle dogs were dosed with tetrahedron-shaped test devices administered in gelatin capsules and gastric retention monitored by X ray over a 24-hr period. A comparison of in vitro erosion rates and in vivo performance of various polymer blends indicated a definite trend for increased gastric retention of devices made from the more slowly eroding blends. The results indicate that the blending of erodible and nonerodible polymers is a valid approach for obtaining materials that will provide the necessary structural properties to achieve gastric retention yet lose integrity within a desired time.

Animals

Arrest of epidermal growth factor-dependent growth in fetal hepatocytes after ethanol exposure.

Exposure of the fetal rat hepatocyte to ethanol in vitro blocks epidermal growth factor (EGF)-dependent cell replication. To define possible mechanisms for this growth arrest, we determined the effects of ethanol on EGF binding and EGF receptor (EGF-R) levels. During a 24-h exposure to ethanol (1.7 mg/ml, 31 mM), cell replication was completely blocked while EGF binding per cell doubled. This effect was no specific for EGF, with variable degrees of increased binding noted for insulin, transferrin, and glucagon. Significantly increased EGF binding was seen after 6 h of ethanol exposure, and both growth arrest and enhanced EGF binding were reversed within 12 h of ethanol withdrawal. Increases in both "high" and "low" affinity sites were seen, with no changes in the apparent Kd's. Total RNA, beta-actin mRNA, and EGF-R mRNA were increased 50-70% in ethanol exposed cells. However, direct measurements of EGF-R synthesis rates by [35S]methionine incorporation revealed no differences between control and ethanol exposed cells. Internalization of EGF-R was significantly altered by ethanol exposure. A 2-h incubation resulted in the internalization of 57% of the ligand in control cells, while only 31% of bound EGF was internalized in the ethanol exposed cells. Thus, the enhanced EGF binding may be due to decreased efficiency of internalization.

Animals

Immunochemical criteria for successful matching of monoclonal antibodies to immunoassays of peptide hormones for assessment of pregnancy and ovulation.

The development of simple, robust enzyme immunoassay (EIA) systems for measurement of levels of hCG and LH, suitable for use both in the home and in the clinic, imposes a number of constraints on the selection of antibody for the assay. Important criteria must be met with regard to specificity, sensitivity, and stability of the materials involved in the chemistries of solid-phase and enzyme coupling. Furthermore, pairing of antibodies that react with distinct epitopes, thereby allowing maximum sensitivity with minimum non-specific interaction with related analytes, places stringent demands on the selection of antibody-producing clones. These requirements are exemplified by the characteristics of a number of clones which provide antibodies with specificities for epitopes on alpha subunits, beta subunits, and intact hormone, and which were selected from several hundred potential clones. An optimized, two-site, sandwich assay was developed from a matrix study of solid-phase and enzyme-conjugate reagents. The assay was then converted to a simpler reaction format in which the chosen solid phase and the enzyme conjugate were organized to react simultaneously with analyte. A procedure for overcoming any "hook effect" due to high levels of hormone was also developed.

Animals

Bovine monoclonal antibodies to the F5 (K99) pilus antigen of E. coli, produced by murine/bovine hybridomas.

Lymph node cells from calves immunized with purified pilus antigen of K99+ enterotoxigenic E. coli (ETEC) were fused with mouse myeloma (NSO) cells, and with non-Ig producing mouse/calf hybridomas or with a bovine Ig-producing mouse/calf/calf secondary hybridoma. Lines secreting bovine monoclonal IgG1 specific for K99 pilus antigen in an ELISA were obtained in each case. The two lines derived from xenohybridoma fusion partners have been secreting anti-K99 bovine monoclonal antibody for over one year in continual passage. None of the antibodies cross-reacted with other pilus types including K88, CFAI, CFAII, 987P or CP; they all inhibited agglutination of horse RBC (which have a K99 receptor) in the presence of K99 antigen; they showed positive fluorescence in an indirect binding assay on K99+ ETEC and inhibited K99+ ETEC adhesion to piglet enterocytes. These antibodies have potential prophylactic and therapeutic use in control and treatment of diarrhoea.

Animals

Epitope masking and immunodominance--complications in the selection of monoclonal antibodies against HCG.

Spleen cells from Balb/c mice immunized with HCG were subjected to the normal hybridoma procedures. The resulting MCA's (from 78 clones) were evaluated in radioimmunoassay, haemagglutination and enzyme immunoassay with whole HCG. The RIA analysis was extended to include HCG subunits and intact LH. The alpha-chain of HCG was found to be strongly immunodominant, as shown by the very high frequency (46 of 78) of MCA's directed at the alpha-chain epitopes. These antibodies would bind luteinizing hormone as well as HCG. Only 1 of the 78 clones was specific for the B subunit of HCG, in RIA. This clone was later found to be positive for LH in EIA, thus making the derivation of antibodies specific for this B-epitope extremely difficult. Most MCA's were found to be applicable in the three types of assay systems (48 of 78), but some were compatible in just one or two of the systems. These differences are believed to be due to epitope masking resulting from the way in which the antigen was handled and presented in the different systems.

Animals

Inter-relationship between mucosal and systemic immunity determining the balance between damage and defense in the bovine gut in response to environmental antigens.

At weaning, the complex interactions of macromolecular components embracing maternally derived antibodies and antigens of microbial and dietary origin, grossly influence the immune response, directing it towards protective or damaging reactions in the intestinal mucosa. In young calves, passively acquired maternal antibody surprisingly enhances the systemic IgG1 mediated type III hypersensitivity reactions to dietary antigen. Furthermore, unresponsiveness to orally administered protein antigen in the young calf fails to develop. Additionally, antigens from gram negative bacteria can influence the development of IgE mediated hypersensitivity reactions. In the normal deleterious gut reactions to protein antigens from the lumen, IgE responses infrequently occur, and are transient. However, these can be reinforced by simultaneous challenge with protein and microbial antigen. These observations bring some new perspectives on health and nutrition of young farm animals at weaning.

Animals

Novel mucosal anti-microbial functions interfering with the plasmid-mediated virulence determinants of adherence and drug resistance.

Mucosal antibodies in vivo and in vitro interfere with the stability of plasmids coding for important virulence determinants in porcine enteropathogenic E. coli (EEC), such as the adhesion determinants K88ab and K88ac. The effector antibody is not directed against K88 antigens and is not serotype specific, but an antigen common to K88+ strains is implicated. Further lack of pathogen specificity is exemplified by antibody elimination of the more recently discovered K88ad plasmid. Antibodies that interfere with K88 plasmids do not affect K99, which now appears as an alternative adhesion factor in porcine enteropathogenic E. coli. This plasmid can be eliminated, however, by antibodies having K99 specificity. In extending the studies to drug-resistance plasmids, further evidence has emerged that mucosal antibodies may assist in host control of the reservoir of R factors in the intestinal microflora. A major effector mechanism is that secretory IgA and IgM antibodies from orally immunized pigs can block the transfer of R factors between donor and recipient strains of E. coli.

Adhesiveness

School intervention for the neuromuscularly handicapped child.

School problems are common in children with neuromuscular disease irrespective of their degree of handicap. They are related to difficulties in transportation and access, difficulties with adaptation of school tasks to the motorically handicapped, and difficulties that arise because of misunderstanding of the disease processes by teachers and parents. Most of these can be easily rectified by efforts by the clinic staff to educate school personnel and to enlist them as members of the treatment team. In view of the importance of the school experience to this group of patients, it is urged that these problems be identified and aggressively managed by those involved in the care of neuromuscularly handicapped children.

Adolescent

Evaluation of "in feed" vaccination of piglets and sows against enteropathogenic "E. coli" using environmental production parameters.

Current approaches to the immunological control of enteric E. coli infections in pig herds concentrate on the provision of passive immunity for the neonate by multiple parenteral vaccination of the sow to stimulate colostral antibody production. Little account is taken of the kinetics of the animals' natural immune response. In particular the potential of the gut as a target organ for immunization has largely been ignored in practical disease control. A new approach to the problem, which combines oral with parenteral vaccination, stimulates a colostral antibody response closely mimicking a sow's natural response to infections and comparison between this and classical parenteral vaccination, using an acute E. coli infection model, demonstrated the greater protective efficacy conferred by the new protocol. The widespread use of this method of vaccination has been continuously monitored, using production parameters most relevant to the farming industry. From this evaluation of user experience and results of trials conducted in various locations, a new perspective is emerging which indicates the vaccine has a wider spectrum of biological activity than was expected. Production, health and environmental benefits are arising which could not have been predicted from a model merely concerned with the control of alimentary E. coli infection.

Age Factors

Immunogenic and antigenic epitopes of immunoglobulins I. Cross-reactivity of murine monoclonal antibodies to human IgG with the immunoglobulins of certain animal species.

Antibody-producing hybridoma clones have been isolated following immunization of mice with human IgG. Twenty-five monoclonal antibodies (nine anti-C gamma 3, fourteen anti-C gamma 2, one anit-kappa and one anti-lambda) were selected for study of their cross-reactivity with the IgG of fifteen mammalian species and chicken immunoglobulin. Each antibody exhibited a unique reaction profile suggesting that human IgG expresses a very large repertoire of immunogenic epitopes. Whilst some antibodies showed a very restricted cross-reactivity profile for others a very wide reactivity profile was observed-including two clones producing autoantibodies. Antibodies demonstrating cross-reactivity between human Fc gamma and 7S chicken immunoglobulin allow its definitive assignment as a homologue of human IgG. Four clones demonstrated specificity for bovine IgG subclass gamma 1 and gamma 2 and the degree of reactivity allows their application to qualitative and quantitative assay systems. These studies suggest new perspectives for the characterization of immunoglobulins and the standardization of anti-immunoglobulin reagents.

Animals

Sow vaccination by combined oral and intramuscular antigen: a field study of maternal protection against neonatal Escherichia coli enteritis.

A field trial was conducted to test the efficacy of a vaccination programme which combines oral and parenteral antigen administration to produce IgM antibody in the colostrum of the sow. The trial involved 11 herds, each selected because of their history of neonatal Escherichia coli enteritis. Following more than 2300 farrowings, the progeny from vaccinated sows required 75 per cent less medication to maintain a good standard of health. The average neonatal mortality decreased from 13.8 to 7.0 per cent and the number of pigs weaned increased by 0.6 per litter.

Animals