The dangers of one-dimensional RM.
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Humans↗
Biomedical subjects
L E Walker
Publications and source records attributed to L E Walker.
Advantages of risk-based project management.
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Humans↗
Dose-effect functions for cocaine self-administration: effects of schedule and dosing procedure.
Research related to determining how procedural variables can alter dose-effect functions for cocaine self-administration is limited. Toward clarifying the role of procedural variables, responding was maintained in rats under either variable-interval (VI) or fixed-ratio (FR) schedules of cocaine infusion. In addition to free-operant FR schedules, discrete-trial FR schedules were evaluated. The dose-effect functions were obtained by either substituting a dose for the usual daily dose, instituting a particular dose for several sessions, or making all doses available within a session. Dose-effect functions for response rate (or number of trials with infusions for the discrete-trial FR) were bitonic for the VI and discrete-trial FR schedules but tended to be strictly decreasing for the free-operant FR schedules. Responding was maintained under FR schedules by a low dose (0.083 mg/infusion) if the dose was substituted for a higher daily dose but not when made available daily. Rate of response was higher under ratio schedules at 0.17 mg/infusion when this dose occurred within the context of other higher doses within a session than when the dose was simply substituted for a higher daily dose. These data indicate that procedural variables can alter dose-response curves for cocaine self-administration.
Animals↗
Toxic shock syndrome after explantation of breast implants: a case report and review of the literature.
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Breast Implants↗
Within-session determination of dose-response curves for heroin self-administration in rats: Comparison with between-session determination and effects of naltrexone.
A procedure was employed in the present study to obtain dose-response curves for heroin self-administration within each experimental session. The data generated using this procedure were compared to dose-response data obtained using between-session dose manipulations. The dose of heroin (18, 30, 60 or 100 micrograms/kg/inf) was varied across 4-hourly segments separated by a 20-min time-out period during which heroin was not available. The within-session dose-response procedure yielded data similar to those obtained using between-session dose manipulations when the order of dose presentation was increasing or random. However, the dose-response curve for total drug-intake was flat when the doses were presented in decreasing order. Further analysis of the dose-response curves in the within-session procedure demonstrated that the rate of heroin intake increased in the third and fourth hourly components compared to the first component, suggesting acute tolerance to the reinforcing and/or rate-suppressive effects of heroin. Furthermore, using a random order of dose presentation, administration of 3.0 mg/kg of naltrexone prior to the session shifted the dose-response curve for heroin self-administration 5-fold to the right in the within-session procedure. The data indicate that the within-session dose-response procedure can be used to investigate the pharmacology of heroin self-administration in rodents.
Animals↗
Male-killing bacterium in a fifth ladybird beetle, Coleomegilla maculata (Coleoptera:Coccinellidae).
Inherited symbionts which selectively cause the death of male hosts are found widely across the Insecta. Previous studies have shown a single, but different micro-organism to be responsible for male-killing in each taxonomic group studied. We here produce evidence that within a group of insects, the Coccinellidae, there is more than one causal agent of male lethality. We report a novel observation of a male-killing trait in the species Coleomegilla maculata. Six of 26 crosses were found to produce a female-biased sex ratio associated with a low egg hatch-rate. The trait was matrilinearly inherited and was observed to be tetracycline-sensitive. However, tests which indicate the presence of a Rickettsia, previously found to cause male-killing in another member of the Coccinellidae, Adalia bipunctata, proved negative. We therefore conclude that the phenomenon of male-killing is multicausal, within, as well as between, taxonomic groups of the Insecta.
Animals↗
The French-line abdominoplasty.
This study presents 50 consecutive cases of abdominoplasty utilizing the authors' French-line method. This technique incorporates the basic principles of more traditional abdominoplasty procedures with significant modifications that allow for more aggressive plication of the fascia for accentuation of the waistline and relatively short oblique lateral incisions that are easily concealed within the French-cut one-piece bathing suit or reasonably modest bikini. The technique lends itself to adjunctive intra-abdominal procedures such as cholecystectomy or hysterectomy and is a safe method of abdominal reconstruction following transverse rectus abdominis musculocutaneous flap breast reconstruction. Complications are no more frequent than with "traditional" techniques. The only absolute contraindication is the presence of chronic obstructive pulmonary disease; relative contraindications are the same as for other abdominoplasty procedures.
Abdomen↗
Diagnostic value of clinical examination and various imaging techniques for breast implant rupture as determined in 81 patients having implant removal.
To determine sensitivity and specificity of magnetic resonance imaging (MRI) and ultrasonography (US) in the detection of breast implant rupture, and also to determine the relative merits of clinical examination and mammography, we studied 81 patients (160 implants). All patients had implants removed, thus allowing confirmation of the presence or absence of rupture. Clinical examination positively identified only one patient with implant rupture, and mammography detected only two implant ruptures (both extracapsular). The sensitivity for US was 70% and specificity was 90%, while for MRI it was 75.6% and 94%, respectively. These differences between MRI and US were not statistically significant. Combining the results of US and MRI did not seem to add to the diagnostic discrimination. The most cost-effective method of diagnosing implant rupture was US in our study.
Adult↗
Utility of magnetic resonance imaging and ultrasonography in diagnosing breast implant rupture.
We prospectively evaluated 81 patients (with 160 implants) who subsequently had implants removed to determine sensitivity and specificity of both magnetic resonance imaging and ultrasonography. Positive and negative predictive values were also calculated to determine whether a statistically beneficial interaction existed when ultrasonography and magnetic resonance imaging were used in combination to examine an implant. Finally, the misdiagnoses were retrospectively evaluated to identify the pitfalls of the investigations. Positive diagnostic criteria were described. The sensitivity and specificity of ultrasonography were 47% and 83%, respectively, and of MRI, 46% and 88%, respectively. On retrospective review by the radiologist, the sensitivity and specificity of ultrasonography were 70% and 90%, respectively, and of magnetic resonance imaging, 75.6% and 94%, respectively. Although definite conclusions could not be obtained, there did not seem to be an additive benefit from using both ultrasonography and magnetic resonance imaging.
Breast↗
Clinical relevance of positive breast periprosthetic cultures without overt infection.
The true incidence of positive breast periprosthetic cultures in the absence of overt infection is not clearly established. We retrospectively reviewed data from 389 implants that were removed for reasons other than clinical infection. Many of these patients presented with a variety of musculoskeletal ailments. Others had symptomatic capsular contracture as the presenting complaint. In a few a known implant rupture was the reason for explantation. We identified a positive culture rate of 23.5 percent from capsule tissue. Most of these organisms were coagulase-negative staphylococci and anaerobic diphtheroids, but fungi and other organisms (generally felt to be more pathogenic than the less virulent coagulase-negative staphylococci) also were cultured. In an attempt to identify the clinical relevance of these positive cultures, we statistically evaluated the culture results for associations with capsular contracture, implant rupture, type of implant, and location of implant. Of these, the only statistically significant correlation was between positive culture result and symptomatic capsular contracture (Baker class IV).
Adult↗
A review of 198 patients (389 implants) who had breast implants removed.
Because of the large number of women now returning to their plastic surgeons with concerns about their breast implants many years after surgery, we are afforded an ideal opportunity to evaluate these patients over the long-term. This study reviewed 198 patients (389 implants) who underwent explantation by two surgeons over a 2-year period, correlating prosthesis type, location, and length of time since implantation with two adverse endpoints, implant rupture and symptomatic capsular contracture. Significant findings included a relatively high rate of implant rupture in patients whose implants had been in place over 20 years, an increased incidence of both symptomatic capsular contracture and implant rupture in single lumen gel implants and a positive correlation between severity of capsular contracture and implant rupture.
Adult↗
Structure--activity relationships of sialyl Lewis x-containing oligosaccharides. 1. Effect of modifications of the fucose moiety.
Leukocyte adhesion to the vasculature is mediated by E-, P-, and L-selectins. The natural ligands for E- and P-selectins have not been fully characterized but have been shown to contain the tetrasaccharide sialyl Lewis x structure (SLe(x)). To determine the importance of the fucose moiety of SLe(x), various analogs of SLe(x) containing modifications thereof were prepared and tested as inhibitors of E-selectin-mediated cell adhesion. Cellular experiments indicate that replacement of the hydroxyl groups of fucose by hydrogen abrogated E-selectin binding. However, the arabinose analog of fucose (CH3 delta H) inhibited cell adhesion but was 5-fold less potent than native SLe(x). This data suggests that modifications of fucose on SLe(x) are generally deleterious toward E-selectin binding.
Cell Adhesion↗
Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma.
The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.
Aged↗
cDNA cloning and immunological characterization of the rye grass allergen Lol p I.
The complete amino acid sequence of two "isoallergenic" forms of Lol p I, the major rye grass (Lolium perenne) pollen allergen, was deduced from cDNA sequence analysis. cDNA clones isolated from a Lolium perenne pollen library contained an open reading frame coding for a 240-amino acid protein. Comparison of the nucleotide and deduced amino acid sequence of two of these clones revealed four changes at the amino acid level and numerous nucleotide differences. Both clones contained one possible asparagine-linked glycosylation site. Northern blot analysis shows one RNA species of 1.2 kilobases. Based on the complete amino acid sequence of Lol p I, overlapping peptides covering the entire molecule were synthesized. Utilizing these peptides we have identified a determinant within the Lol p I molecule that is recognized by human leukocyte antigen class II-restricted T cells obtained from persons allergic to rye grass pollen.
Allergens↗
Biosynthesis and glycosylation of the carcinoma-associated antigen recognized by monoclonal antibody KS1/4.
Monoclonal antibody KS1/4 recognizes an epitope expressed on the cell surface of human adenocarcinoma cells and certain epithelia. Western blotting analyses of tumor cell extracts utilizing KS1/4 reveal staining of a major Mr 40,000 band and a minor Mr 42,000 band. Both components are also detectable in KS1/4 immunoprecipitates of L-[35S]methionine- and D-[3H]glucosamine-labeled human lung tumor cell extracts. When synthesis occurs in the presence of tunicamycin or when the immunoprecipitates are treated with peptide:N-glycosidase F, a single polypeptide component (Mr 37,000) is precipitated. Immediately following translation, digestion of Mr 40,000 and Mr 42,000 glycoproteins with endo-beta-N- acetylglucosaminidase H also yields a single polypeptide component at Mr 37,000. However, over a 3-h period beginning at 10 min posttranslation, a Mr 39,000 major component and a Mr 41,000 minor component gradually appear in the endo-beta-N-acetylglucosaminidase H digests as the Mr 37,000 component gradually disappears. Analysis of tryptic glycopeptides derived from the Mr 40,000 and 42,000 components suggests that the two components differ by the addition of one extra oligosaccharide to the Mr 42,000 component. Nonequilibrium pH gradient electrophoresis/sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of KS1/4 immunoprecipitates resolves each of the two components into multiple spots. Digestion of the KS1/4 immunoprecipitates with neuraminidase prior to two-dimensional analysis or immunoprecipitation of short pulse-labeled extracts reduces the number of spots to three each at the Mr 40,000 and Mr 42,000 positions. Digestion of the KS1/4 immunoprecipitates with peptide:N-glycosidase F, immunoprecipitation of extracts labeled in the presence of tunicamycin, or endo-beta-N-acetylglucosaminidase H digestion of immunoprecipitates of short pulse-labeled extracts prior to two-dimensional analysis results in a single series of Mr 37,000 spots, suggesting that the polypeptide portions of the Mr 40,000 and Mr 42,000 components may be identical. Endo-beta-N-acetylglucosaminidase H digestion of KS1/4 immunoprecipitates of short pulse-labeled extracts, followed by nonequilibrium pH gradient electrophoresis, V8 protease digestion, and polyacrylamide gel electrophoresis revealed an apparently identical set of polypeptides derived from each of the three Mr 37,000 spots, suggesting that the three spots derive from highly similar polypeptides.
Adenocarcinoma↗
Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.
A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.
Adult↗
Isolation and characterization of a cDNA encoding the KS1/4 epithelial carcinoma marker.
The mAb KS1/4 recognizes a novel cell surface glycoprotein on a variety of epithelial carcinomas which may be a useful target Ag for antibody-directed diagnostic and therapeutic approaches. Here we report the isolation and characterization of a full length cDNA clone coding for the KS1/4 Ag, as well as, physical and biochemical studies on the antigen derived from an adenocarcinoma of the lung cell line. Affinity purification of the KS1/4 Ag reveals three glycosylated species by NaDodSO4 PAGE with molecular weights of 42, 40, and 35 kDa. The 42- and 40-kDa species are similar at the protein level, differing by their degree of glycosylation, and the 35-kDa protein results from a dibasic proteolytic cleavage of the larger m.w. species. Although both the 42- and 40-kDa forms are found on the cell surface, the 40-kDa protein appears to be the predominant species. A cDNA clone containing the complete KS1/4 coding sequence and the 5'- and 3'-non-translated regions was isolated from a library constructed from the human adenocarcinoma of the lung derived cell line, UCLA-P3. The cDNA clone contains an open reading frame of 314 amino acids which includes a putative signal sequence of 23 amino acids. Northern blot analysis shows a single RNA species of 1.5-kb. Sequence analysis of the 5' and 3' noncoding regions of the KS1/4 cDNA revealed homologies to known proto-oncogenes and inflammatory mediators.
Adenocarcinoma↗
Compartmental biodistribution of a monoclonal antibody against human lung adenocarcinoma grown in athymic mice.
The biodistribution of the radioiodinated monoclonal antibody KS1/4 and of its F(ab) and F(ab')2 fragments were studied in tumor-bearing nude mice. Intravenous administration of the intact antibody resulted in the highest tumor retention and tumor/blood ratios. No metabolites or antigen-antibody conjugates were detectable, in serum, by HPLC analyses. Reasonable correlations were obtained between the estimated time-course of KS1/4 and experimental biodistribution data using an eight-compartment linear radiopharmacokinetic model, suggesting that such models may be useful in predicting the biodistribution and effective targeting of this monoclonal antibody.
Adenocarcinoma↗