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Biomedical subjects

P Porter

Publications and source records attributed to P Porter.

At least 37 records · Page 2Linked to original sources
PubMed1997

Randomized trial of breast self-examination in Shanghai: methodology and preliminary results.

BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated. PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China. METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer. RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups. CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination. IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination.

Adult↗
PubMed1997

Effect of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model: implications for brain tumor therapy.

OBJECTIVE: This study sought to investigate the effects of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model. Two doses were investigated to determine a suitable therapeutic range. METHODS: We performed two experiments. Three treatment groups and one control group of male F-344 rats bearing 9L brain tumors 12 days after tumor inoculation were used in the first experiment. Day 12 tumors were an average of 4 to 6 mm in diameter. Animals treated with brachytherapy received a tumor dose of 80 Gy delivered to a 5.5-mm-radius volume. Total macroscopic tumor removal was achieved by microsurgical techniques. A subsequent experiment compared the survival of tumor-burdened rats treated with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume with a control group. RESULTS: Surgery alone produced an increased life span of 28.6% over control animals treated with sham surgery and dummy seed implants, a statistically significant increase in survival (P = 0.0023, log-rank test). Brachytherapy alone produced the most significant increase in survival over control animals (P = 0.0001, log-rank test; median survival not attained with an implant dose of 80 Gy delivered to a 5.5-mm-radius volume; and P = 0.0001, increased life span 121% with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume). This was not improved by the addition of surgical tumor removal. CONCLUSION: We have demonstrated a relationship between implant dose/volume and survival of tumor-burdened rats in this model that is not improved by the addition of tumor removal. Implications for brain tumor brachytherapy are discussed.

Animals↗
PubMed1997

Effects of age on perinatal substance abuse among whites and African Americans.

This descriptive study assessed age effects on perinatal use of alcohol, marijuana, and cocaine among African-American and white women. Data were derived from the California Perinatal Exposure Study, relying on a statistical probability sample n = 29,494) of women who underwent anonymous urine toxicology screening in birthing hospitals. The central hypothesis was that there would be no difference in age effects on drug use among white and African-American women. Marital status and payment source were used as risk factors in order to create detailed age-risk profiles for both racial-ethnic groups. Logistic regression analyses were used and findings indicated that cocaine use peaked in early adulthood for whites and in mid-adulthood for African-Americans who had higher prevalence levels with the same or fewer risk factors as whites. Over one third of African-American women in their mid-thirties who were not married and who had publicly assisted births tested positive for cocaine. In contrast, high risk whites had higher marijuana prevalence levels than African-American women, and prevalence increased with age. Alcohol prevalence increased with age for African-American and white women who were publicly assisted, but decreased with age for all others. Findings for alcohol and marijuana generally followed the same risk-adjusted patterns for African American and white women but with different prevalence levels; however, cocaine use had a unique pattern with higher prevalence among African-American women in mid-adulthood regardless of risk level.

Adolescent↗
PubMed1996

Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q21-23.

Dilated cardiomyopathy (DCM) is the most common form of primary myocardial disorder, accounting for 60% of all cardiomyopathies. In 20-30% of cases, familial inheritance can be demonstrated; an autosomal dominant transmission is the usual type of inheritance pattern identified. Previously, genetic heterogeneity was demonstrated in familial autosomal dominant dilated cardiomyopathy (FDCM). Gene localization to chromosome 1 (1p1-1q1 and 1q32), chromosome 3 (3p25-3p22), and chromosome 9 (9q13-9q22) has recently been identified. We report one family with 26 members (12 affected) with familial autosomal dominant dilated cardiomyopathy in which linkage to chromosome 10 at the 10q21-q23 locus is identified. Using short tandem repeat polymorphism (STR) markers with heterozygosity > 70%, 169 markers (50% of the genome) were used before linkage was found to markers D10S605 and D10S201 with a pairwise LOD score = 3.91, theta = 0, penetrance = 100% for both markers. Linkage to 1p1-1q1, 1q32, 3p25-3p22, and 9q13-9q22 was excluded. We conclude that a new locus for pure autosomal dominant FDCM exists, and that this gene is localized to a 9 cM region of 10q21-10q23. The search for the disease causing gene and the responsible mutation(s) is ongoing.

Adolescent↗
PubMed1996

A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice.

SUMMARY: Targeted disruption of the murine p27(Kip1) gene caused a gene dose-dependent increase in animal size without other gross morphologic abnormalities. All tissues were enlarged and contained more cells, although endocrine abnormalities were not evident. Thymic hyperplasia was associated with increased T lymphocyte proliferation, and T cells showed enhanced IL-2 responsiveness in vitro. Thus, p27 deficiency may cause a cell-autonomous defect resulting in enhanced proliferation in response to mitogens. In the spleen, the absence of p27 selectively enhanced proliferation of hematopoietic progenitor cells. p27 deletion, like deletion of the Rb gene, uniquely caused neoplastic growth of the pituitary pars intermedia, suggesting that p27 and Rb function in the same regulatory pathway. The absence of p27 also caused an ovulatory defect and female sterility. Maturation of secondary ovarian follicles into corpora lutea, which express high levels of p27, was markedly impaired.

Adenoma↗
PubMed1996

Thrombospondin-1, an inhibitor of angiogenesis, is regulated by progesterone in the human endometrium.

Thrombospondin-1 (TSP1), a multifunctional extracellular matrix glycoprotein, has been shown to suppress the angiogenic response in vivo and in vitro. We hypothesized that TSP1 might play a role in the inhibition of capillary morphogenesis during the endometrial cycle and examined its expression in 46 human endometrial specimens. Our results show that the expression of TSP1 in the endometrium is (a) cycle-dependent, (b) associated with periods of low capillary growth, and (c) regulated by progesterone. TSP1 protein was identified in the basement membrane of capillaries of the functional endometrium during the secretory phase. Abundant expression of TSP1 mRNA in the secretory phase was also detected by in situ hybridization, in contrast to the low levels seen in the proliferative phase. These findings were confirmed by Northern analysis of proliferative and secretory endometrium. Transcripts for TSP1 were observed predominantly in stromal cells, but signal was also detected in some endothelial and smooth muscle cells. Since the proliferation of endometrial tissue is regulated by steroid hormones, we tested the effects of estrogen and progesterone on TSP1 expression by stromal cells isolated from human endometrium. We found that levels of TSP1 mRNA and protein were increased after incubation with progesterone. Maximal stimulation of mRNA was observed after 8 h of treatment with 10-50 microM progesterone, and the effect was suppressed by the progesterone antagonist RU-486. Induction by progesterone was cell-specific and equivalent to the stimulation mediated by PDGF. Finally, the levels of TSP1 present in progesterone-stimulated cultures were sufficient to inhibit the migration of endothelial cells in vitro; this effect was nullified by anti-TSP antibodies. We therefore propose that the production of TSP1 at later stages of the endometrial cycle is linked to the inhibition of vessel formation and that TSP1 expression is progesterone-dependent in this tissue.

Adult↗
PubMed1994

Assay and purification of Fv fragments in fermenter cultures: design and evaluation of generic binding reagents.

Fv fragments whose genes have been cloned using common PCR primers carry identical peptide motifs at their termini. We have raised antibodies against the C-terminal motif of the VH chain GQGTTVTVSS and evaluated their utility as reagents for the assay and purification of Fvs in the fermenter culture. Three different Fvs were included in the investigation. We found that the motif was exposed and available for capture when Fv fragments were blotted onto nitrocellulose paper or adsorbed directly onto microtiter plates. In contrast, the motif was either partially or totally obscured when the Fv was complexed with immobilised antigen or when free in solution. This reactivity profile enabled us to develop a general-purpose assay for Fv protein, but not a general-purpose assay for monitoring active Fv. The apparent inaccessibility of the C-terminus of VH conflicts with currently held views on the three-dimensional structure of these molecules.

Amino Acid Sequence↗
PubMed1991

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗