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Biomedical subjects

L A Harris

Publications and source records attributed to L A Harris.

16 recordsLinked to original sources
PubMed2001

Preclinical studies to predict the disposition of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand in humans: characterization of in vivo efficacy, pharmacokinetics, and safety.

Apo2L/TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a member of the tumor necrosis factor gene family known to induce apoptosis in a number of cancer cell lines and may have broad-spectrum activity against human malignancies. These studies have evaluated the potency of recombinant soluble human Apo2L/TRAIL in a mouse xenograft model and the disposition and safety of Apo2L/TRAIL in rodents and nonhuman primates. Mice with established COLO205 tumors were given daily i.v. injections of Apo2L/TRAIL (30-120 mg/kg/day). Control tumors doubled in size every 2 to 3 days, while time to tumor doubling in the treatment groups was significantly longer and related to dose (14-21 days). For pharmacokinetic studies, Apo2L/TRAIL was given as an i.v. bolus to mice (10 mg/kg), rats (10 mg/kg), cynomolgus monkeys (1, 5, and 50 mg/kg), and chimpanzees (1 and 5 mg/kg). Apo2L/TRAIL was rapidly eliminated from the serum of all species studied. Half-lives were approximately 3 to 5 min in rodents and approximately 23 to 31 min in nonhuman primates. Allometric scaling provided estimates of Apo2L/TRAIL kinetics in humans, suggesting that on a milligram per kilogram basis, doses significantly lower than those used in xenograft studies could be effective in humans. Apo2L/TRAIL clearance was highly correlated with glomerular filtration rate across species, indicating that the kidneys play a critical role in the elimination of this molecule. Safety evaluations in cynomolgus monkeys and chimpanzees revealed no abnormalities associated with Apo2L/TRAIL exposure. In conclusion, these studies have characterized the disposition of Apo2L/TRAIL in rodents and primates and provide information that will be used to predict the pharmacokinetics of Apo2L/TRAIL in humans.

Algorithms↗
PubMed1994

Total quality improvement according to hospital nursing executives.

Total quality management (TQM) is certainly a hot topic in health care today. The Department of Veterans Affairs is not alone in launching the quality movement in their hospitals. The question is, can it succeed. The success of total quality lies in the commitment of the organizations' leaders. Nursing leadership has yet to be studied regarding TQM implementation. Nursing performs a vital role in hospitals, and if nursing leaders are opposed to total quality, then it is highly unlikely that the philosophy will succeed. This study is designed to measure the attitudes and perceptions of VA nursing chiefs regarding the total quality improvement (TQI) process.

Attitude of Health Personnel↗
PubMed1990

Purification, characterization, and localization of a protein antigen shared by thermophilic campylobacters.

A protein antigen with an apparent molecular weight (Mr) of 31,000 was isolated from 0.2 M glycine hydrochloride (pH 2.2) extracts of a typical human fecal isolate, Campylobacter jejuni VC74. The protein was purified to homogeneity on a preparative scale by immunoaffinity chromatography followed by molecular sieving with a Superose 12 column. Isoelectric focusing under nondenaturing conditions indicated a pI of 9.3, and amino acid composition analysis showed that the protein was unusually rich in lysine, containing 14.9 mol% of this basic amino acid. Cysteine and tryptophan were absent. The protein also contained approximately 35% hydrophobic amino acid residues, and N-terminal amino acid analysis showed that 17 of the first 38 residues were hydrophobic. This amino-terminal sequence to residue 22 was virtually identical to that of an antigenically cross-reactive 31,000-Mr protein isolated from another C. jejuni strain belonging to a different heat-labile serogroup. Western blotting (immunoblotting) of glycine extracts of other C. jejuni, Campylobacter coli, and Campylobacter laridis strains belonging to different thermolabile and thermostable serotypes, as well as Campylobacter fetus, with a rabbit polyclonal antiserum raised against the purified C. jejuni VC74 protein showed that all C. jejuni, C. coli, and C. laridis strains tested contained a 31,000-Mr protein with epitopes which were antigenically cross-reactive with the C. jejuni VC74 protein. The antigenically cross-reactive epitopes of this protein were also readily detected by immunodot blot assay of glycine extracts of C. jejuni, C. coli, and C. laridis with monospecific polyclonal antisera to the 31,000-Mr protein, suggesting that this serological test could be a useful addition to those currently employed in the rapid identification of these important pathogens. Slide agglutination reactions, immunofluorescence assay, and immunogold electron microscopy with antisera to purified 31,000-Mr protein and trypsin treatment of whole cells indicated that the cross-reactive epitopes of the 31,000-Mr protein were not exposed on the cell surface. Cell fractionation analysis and immunogold electron microscopy located the protein on the outer surface of the cytoplasmic membrane. This finding suggests that the 31,000-Mr protein is not a good candidate for inclusion in a monovalent subunit Campylobacter vaccine.

Amino Acid Sequence↗
PubMed1989

Pre-employment screening: use or ornament?

Pre-employment screening (PES) in an occupational health department (OHD) in Inner London was evaluated by establishing its resource implications and devising methods to estimate its efficiency and effectiveness. The attitudes of those involved in PES were also examined. While coverage of student nurses applicants was in the region of 100 per cent, only 43 per cent of all other new employees were screened. Student nurse applicants were more likely to be referred to an occupational health nurse or doctor than other employees (45 per cent nurses, 18 per cent others), but only one person had been rejected on health grounds, as a result, during the previous 15 months. The majority of reasons for sickness absence or early retirement could not have been predicted by PES. Opinions as to the purpose of PES varied from employees who in general thought that PES was designed to protect their interests, to managers, who thought it was to protect theirs.

Attitude↗
PubMed1989

Abdominal actinomycosis: evaluation by computed tomography.

Actinomycosis causes disease in multiple organ systems and involves the abdomen approximately 20% of the time. We report a case of a 48-yr-old woman with a large abdominal mass secondary to actinomycosis. The patient demonstrates the clinical and pathologic features of this disease, as well as the role of evaluation by barium examination and computed tomography (CT). A discussion of abdominal actinomycosis is included.

Actinomycosis↗
PubMed1987

Antigenic variation of Campylobacter flagella.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of flagella dissociated from strains of Campylobacter coli and Campylobacter jejuni belonging to the heat-labile serogroup LIO 8 showed that some strains were capable of producing flagellin subunits of two different molecular weights (MrS), 59,500 and 61,500. Immunoelectron microscopy of cultures of the type strain of this serogroup, C. coli VC167, showed the presence of two flagellum filaments of different antigenic specificity. Epitopes on the surface of one of these flagella bound antibodies in LIO 8 typing antiserum, and Western blotting (immunoblotting) and immunoprecipitation showed that the flagellum was composed of flagellin of Mr 61,500. The other flagellum antigenic type did not bind LIO 8 antibodies but did possess serospecific epitopes which bound a second polyclonal antiserum, LAH2. This second antigenic flagellum type was composed of the Mr 59,500 flagellin. Cells producing either of the flagellum antigenic types serotyped as LIO 8, indicating that flagella composed of the Mr 61,500 flagellin do not carry the serological determinants for this serogroup. The ability of C. coli VC167 to produce these flagella of different subunit MrS was shown to represent a bidirectional antigenic variation. When measured in culture medium, the phase 1-to-phase 2 transition occurred at a rate of approximately 2.0 x 10(-5) per cell per generation, and the phase 2-to-phase 1 transition occurred at a rate of 1.2 x 10(-6) per cell per generation.

Antibodies↗
PubMed1987

Isolation and characterization of Campylobacter flagellins.

Sequential acid pH dissociation, differential ultracentrifugation, and neutral pH reassociation were used to partially purify serotypically distinct flagella from three strains of Campylobacter jejuni and the two antigenic phases of flagella of Campylobacter coli VC167. Each C. jejuni flagellin and C. coli VC167 antigenic phase 1 flagellin were purified to homogeneity by reverse-phase high-performance liquid chromatography with a C8 Spheri-10 column. C. coli VC167 antigenic phase 2 was purified to homogeneity by ion-exchange chromatography with a Mono-Q column. Amino acid compositional analysis put the C. jejuni flagellin molecular weight in the range 63,200 to 63,800 and the C. coli antigenic phase 1 and 2 flagellins at 61,500 and 59,500, respectively. The amino acid compositions of the C. jejuni were similar to each other and to the C. coli VC167 antigenic phase 1 and phase 2 flagellins. One-dimensional peptide mapping of the C. jejuni flagellins by partial digestion with trypsin or chymotrypsin confirmed the structural similarities of the C. jejuni flagellins and the C. coli VC167 antigenic phase 1 flagellin and showed that C. coli VC167 antigenic phase 2 flagellin was structurally distinct from the phase 1 flagellin. The antigenic phase 2 flagellin was especially sensitive to digestion by chymotrypsin. Amino-terminal sequence analysis showed that the 20 N-terminal amino acids of the Campylobacter flagellins were highly conserved. The Campylobacter flagellins also shared limited sequence homology with the N-terminal sequences reported for Salmonella and Bacillus flagellins.

Amino Acid Sequence↗
PubMed1987

Presumptive antibiotics for penetrating abdominal wounds.

The optimal antibiotic agent or agents for penetrating abdominal injuries remains undetermined. During the two year period ending April 1985, 150 consecutive patients undergoing celiotomy for penetrating abdominal trauma were prospectively randomized to receive either mezlocillin (4 grams every six hours) or clindamycin (600 milligrams every six hours) and gentamicin (loading dose of 2.0 milligrams per kilogram, then 1.5 milligrams per kilogram every eight hours). Antibiotics were begun in the emergency department with duration of coverage based upon the injury pattern--colon, five days; other hollow visceral injury, two days, and all others, one day. Ten patients were excluded due to breach in protocol and other patients died within 48 hours of presentation. The two study groups, comprised of the remaining 130 patients, were comparable with respect to age, sex, injury mechanism, incidence of colonic injuries, intraoperative blood replacement and abdominal trauma index. Overall incidence of septic morbidity was similar among the groups; ten of the 61 patients receiving mezlocillin and nine of those receiving clindamycin and gentamicin had infection develop. There was no significant difference with respect to extensive abdominal infection (10 versus 3 per cent). The pattern of postoperative infection and offending pathogens were similar in the study groups. Enterobacteriaceae, enterococcus and Bacteroides species were most frequently isolated. Infection was due to an organism resistant to the initial study regimen in one of the ten failures with mezlocillin and in two of the nine failures with clindamycin and gentamicin. Mezlocillin, a single agent broad spectrum penicillin, achieved comparable results with more expensive potentially toxic combination therapy for penetrating wounds.

Abdominal Injuries↗
PubMed1985

Are consumers provided with adequate information on the actions and uses of ipecacuanha syrup?

The results of a study to assess the level of consumer information about the action and uses of Ipecacuanha Syrup (Emetic) Australian Pharmaceutical Formulary (APF) are reported. Of 40 community pharmacies selected at random from the 321 pharmacies in the Perth metropolitan area, four were unable to supply the syrup. Dosage information provided on the labels of branded products was, for the most part, comprehensive and in line with APF recommendations. Syrup samples dispensed under pharmacy labels provided much less detailed dose information and no information on contraindications on the labels. Counselling by pharmacists was mostly adequate, but information provided by pharmacy assistants was much less detailed. The active alkaloid content of about 77% of the samples of ipecacuanha syrup was within +/- 12% of the target concentration; the remainder had only 56%-58% of the required alkaloid concentration, which indicates a need for more stringent quality control.

Adult↗
PubMed1983

Ecological validity of laboratory-type discrimination-learning tasks.

Brooks and Baumeister (1977a, 1977b) have questioned the ecological validity of laboratory-type research on discrimination learning, memory, and other cognitive processes. Their criticisms were rebutted by House (1977). The present report established the relationship among learning and retention of two-choice discrimination tasks, "real-life" adaptive behavior in an institution, and IQ. These measures were substantially interrelated, and we concluded that laboratory-type discrimination-learning tasks have ecological validity.

Discrimination Learning↗
PubMed1982

Learning, memory, and transfer in profoundly, severely, and moderately mentally retarded persons.

Discrimination learning, memory, and transfer capacity were assessed in representative samples of institutionalized retarded persons in order to provide information on trainability. The 56 subjects were selected from moderately, severely, and two levels of profoundly retarded adults. They learned and relearned three successive two-choice discrimination problems. Generally, the higher functioning subjects, defined by IQ and adaptive behavior learned more rapidly than did the lower functioning subjects. Forgetting was related to IQ/adaptive behavior level. Interproblem transfer was negligible at all levels of retardation, but ceiling effects may have obscured positive transfer in the higher functioning groups. Backward learning curves revealed large differences between lower and higher functioning persons in the presolution trials, but once learning began even profoundly retarded subjects solved these problems as rapidly as did the moderately retarded subjects. Ten of the 56 subjects failed to learn all three problems.

Adult↗
PubMed1969

Schwarz'S lemma in normed linear spaces.

In this paper we show that any Fréchet holomorphic function mapping the open unit ball of one normed linear space into the closed unit ball of another must be a linear mapping if the Fréchet derivative of the function at zero is a surjective isometry. From this fact we deduce a Banach-Stone theorem for operator algebras which generalizes that of R. V. Kadison.

Journal Article↗