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Biomedical subjects

M Phillips

Publications and source records attributed to M Phillips.

At least 235 records · Page 13Linked to original sources
PubMed1988

Polymerization of G-actin by myosin subfragment 1.

The polymerization of actin from rabbit skeletal muscle by myosin subfragment 1 (S-1) from the same source was studied in the depolymerizing G-actin buffer. The polymerization reactions were monitored in light-scattering experiments over a wide range of actin/S-1 molar rations. In contrast to the well resolved nucleation-elongation steps of actin assembly by KC1 and Mg2+, the association of actin in the presence of S-1 did not reveal any lag in the polymerization reaction. Light scattering titrations of actin with S-1 and vice versa showed saturation of the polymerization reaction at stoichiometric 1:1 ratios of actin to S-1. Ultracentrifugation experiments confirmed that only stoichiometric amounts of actin were incorporated into a 1:1 acto-S-1 polymer even at high actin/S-1 ratios. These polymers were indistinguishable from standard complexes of S-1 with F-actin as judged by electron microscopy, light scattering measurements, and fluorescence changes observed while using actin covalently labeled with N-(1-pyrenyl)iodoacetamide. F-actin obtained by polymerization of G-actin by S-1 could initiate rapid assembly of G-actin in the presence of 10 mM KC1 and 0.5 mM MgCl2 and showed normal activation of MgATPase hydrolysis by myosin.

Actins↗
PubMed1988

The Drosophila wing test: a comparison of the sensitivity of different strains.

A range of 5 chemical mutagens were tested in the Drosophila wing test using 2 different strains and carrying out the experiments in parallel under standardised conditions. The mutagens chosen for the study were the 2 alkylating agents MMS and ENU and the anti-cancer drugs methotrexate, cytosine-arabinoside and adriamycin. As a result of the different genetic backgrounds there was a marked variation in the response of the 2 strains to the mutagens.

Alkylating Agents↗
PubMed1988

Economic assessment of crop damages due to air pollution: the role of quality effects.

Biological research has established that air pollution can affect the yield and quality of agricultural crops. Economic assessments of crop exposure to air pollution have focused on the yield effect. This study illustrates the implications of considering crop quality effects in addition to crop yield changes for the case of O3 impacts on soybeans. An economic model of US soybean, soybean oil, and soybean meal markets is used to simulate the impacts of increased soybean yields due to reduced O3 concentrations with and without changes in soybean quality. The simulations with quality effects are richer in their distributional implications and show larger increases in economic surplus than the simulations with yield effects only.

Journal Article↗
PubMed1988

The ultrastructural morphology of endotoxins and lipopolysaccharides.

Endotoxins and LPS are constituents unique to the outer surface of gram-negative bacteria. Cell-associated endotoxins are now readily observable on the cell outer membrane with labelled monoclonal antibodies. These probes are not only more specific than those used in the past, but also easier to see. Interest in free endotoxin as a method to generate outer membrane proteins without contamination with other cell constituents is also increasing (Gamazo and Moriyon, 1987). The morphologic identification and characterization of LPS by electron microscopy has been facilitated recently by advances in chemical extraction and purification techniques. LPS, originally thought to be heterogenous, exists in forms that are dependent upon (1) the method of its extraction, (2) its chemical composition, and (3) the physical or chemical conditions of its environment. New models were proposed on the arrangement of LPS molecules in molecular aggregates (i.e. discs, vesicles or ribbons) and a schematic was presented on the dissociation from one morphologic type to another. Morphologic studies on endotoxins and LPS will continue in the future. Using molecular biological techniques, carbohydrate epitopes of LPS from one bacterial species will be expressed with increasing frequency in other bacterial species (Manning et al., 1986; Stein et al., 1988). Electron microscopy will help visualize the distribution of the 'new' LPS on the recipient cell surface. Labelled monoclonal antibodies will also differentiate host cell LPS from the recombinant LPS. As molecular model programming becomes more complex, new schematics will help visualize the arrangement of LPS in membranes to explain recombinant LPS structure as well as other characteristics (i.e. membrane permeability to various antibiotics).

Antibodies, Bacterial↗
PubMed1988

Suppression of SV40-promoted gene expression by differentiation of preadipose cells.

When a plasmid bearing the chloramphenicol acetyltransferase (CAT) gene under the control of an SV40 early promoter is introduced into preadipose or adipose cells of line 3T3-F442A, the promoter directs high levels of transient expression of CAT. However, when the plasmid is introduced into preadipose cells and the cells are then allowed to differentiate into adipose cells, the expression of the CAT gene is suppressed. In this process, the plasmid is not changed detectably in amount, topology, or state of methylation. Stably transformed preadipose cells bearing an integrated plasmid express the transferase, but if the cells are allowed to differentiate, the expression of the gene is similarly suppressed. The decline in CAT activity is associated with a decrease in the transcription rate of the gene. Transcription of a gene coding for neomycin phosphotransferase driven by the SV40 promoter is also greatly diminished by differentiation. Because suppression of CAT does not occur when the gene is under control of a retroviral long terminal repeat (LTR), a specific mechanism exists for the recognition and inactivation of the SV40 early promoter during differentiation.

Adipose Tissue↗
PubMed1988

Prevention of nitroimidazole resistance in Campylobacter pylori by coadministration of colloidal bismuth subcitrate: clinical and in vitro studies.

One hundred patients with duodenal ulceration and Campylobacter pylori in their stomach were entered into a double blind placebo controlled prospective study. Treatment schedules were cimetidine and placebo, or cimetidine and tinidazole, or colloidal bismuth subcitrate (CBS) and placebo, or CBS and tinidazole. Seventeen per cent of isolates of C pylori obtained at the first endoscopy were resistant to tinidazole and 70% of the second isolates from patients given cimetidine and tinidazole became tinidazole resistant. Suspensions of nitroimidazole sensitive cultures of C pylori showed that three of 22 isolates had a nitroimidazole resistant subpopulation. In patients who healed and remained free of C pylori after treatment ulcers recurred less often than in patients who healed but retained C pylori (23% v 73% over 12 months, p less than 0.001).

Anti-Ulcer Agents↗
PubMed1988

Validity and reliability of the Chinese Hamilton Depression Rating Scale.

The reliability and validity of the Chinese version of the 17-item Hamilton Depression Rating Scale (CHDS) was assessed. Interrater reliability was excellent, the item total-score correlations were good, and the internal reliability was satisfactory. The concurrent validity was tested by correlating the CHDS score with the Global Assessment Scale score; the strong negative correlation found indicated that the CHDS reflects the overall level of disability. Five distinct factors were generated by principle-component analysis; these factors account for 52.4% of the total variance. Rigorous evaluation of the numerous translated scales being used in clinical and research settings of non-Western countries is important.

Adult↗
PubMed1987

Phase I trial of spiromustine (NSC 172112) and evaluation of toxicity and schedule in a murine model.

Phase I evaluation of spiromustine was performed using an every-3-week schedule and a weekly X 3 schedule. Neurotoxicity was the dose-limiting toxicity presenting as alterations in cortical integrative functions (orientation, language, coordination), leading to a decrease in the level of consciousness. Traditional criteria for grading neurotoxicity poorly characterized these toxicities. The maximum tolerated dose was 6 mg/m2 every 3 weeks and 3 mg/m2 weekly X 3. Concurrent murine studies confirmed spiromustine as a schedule independent drug with toxicity correlating with peak plasma levels. Physostigmine had little effect on decreasing neurotoxicity in the murine model. The solvating agent used was not responsible for the neurotoxicity. Injection of spiromustine on a split-dose schedule decreased the acute neurological toxicity in mice and allowed a larger total dosage to be delivered (compared to single bolus dosage). Based on these results a split-dose schedule is suggested for future clinical trials.

Animals↗
PubMed1987

Detection of endogenous ethanol and other compounds in the breath by gas chromatography with on-column concentration of sample.

A new method is described for collecting and concentrating volatile compounds in the breath, in order to facilitate their assay by gas chromatography. Breath was collected into sealed Mylar bags containing an internal standard (isopropyl alcohol). The sample was pumped through a cooled gas chromatograph column, where the volatile compounds were concentrated by adsorption onto the resin packing (Porapak Q) at 35 degrees C. The column was then heated, and the volatilized sample was separated for assay by flame ionization detection. The assay was highly sensitive for ethanol (detecting at least 4.0 nmol) and linear up to 20 nmol (r2 = 0.98). Accuracy and precision were determined by assaying nine replicates of a sample containing 12.0 nmol ethanol; a mean value of 12.18 nmol ethanol was obtained with a coefficient of variation of 10.26%. In a group of normal volunteers, endogenous breath ethanol concentrations ranged from 2.23 to 6.51 nmol/liter. This assay provided a number of advantages over previously described methods: The use of breath collection bags enabled the collection of samples outside the laboratory. The use of an internal standard in the collection bag reduced errors that might have resulted from leakage of the specimen. An on-column concentration of the sample in the gas chromatograph eliminated the need for an additional preconcentration device, such as a cryogenic or adsorptive trapping apparatus.

Breath Tests↗
PubMed1987

Abnormal findings in "normal" research volunteers.

We report three cases in which medical students who participated in clinical studies as normal volunteers were discovered, during the course of the research, to have potentially serious abnormalities. Their previously unsuspected conditions included chronic persistent hepatitis, a lesion in the cerebral cortex, and seropositivity for hepatitis B and HIV antibodies. These findings were surprising and distressing to both subject and investigator, and raised questions of the need for institutional guidelines, and the potential legal liability of the investigator. We discuss how improvements in Informed Consent Forms might aid in reducing these problems, by alerting the researcher and the subject to the possibility that unsuspected disease might be discovered during the course of a clinical research study.

Adult↗
PubMed1987

Is hypercapnia necessary for the ventilatory response to exercise in man?

1. Continuous recordings of arterial pH, ventilation, airway CO2 and heart rate were made during rest and during 3-4 min periods of rhythmic leg exercise in four renal patients with arteriovenous shunts. 2. The patients were anaemic (haemoglobin 6.5-9.0 g/dl) but had a normal ventilatory response to exercise as judged by the ratio of the change in ventilation to the change in CO2 production. 3. Breath-by-breath oscillations in arterial pH disappeared for the majority of the exercise period in each patient. 4. Changes in mean arterial pH and end-tidal CO2 tension with exercise were inconsistent between subjects but consistent within a given subject. On average, mean arterial pH rose by 0.011 pH unit. Changes in end-tidal CO2 tension reflected changes in mean pHa by falling on average by 1 mmHg (0.13 kPa). 5. Hypercapnia and acidaemia were not found to be necessary for the ventilatory response to moderate exercise.

Adult↗
PubMed1987

Physical and morphological characteristics of eucaryotic ribosomes and lipopolysaccharide complexes.

Lipopolysaccharides (LPS) from Pasteurella multocida or Brucella abortus were complexed with Aspergillus fumigatus ribosomes by mixing and fixation for 3 days in 3.8% formaldehyde. To investigate the nature of their physical association, ribosomes, LPS, and ribosome-LPS complexes were (i) centrifuged in CsCl gradients to determine buoyant densities, (ii) examined by electron microscopy, and (iii) monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Ribosomes were found to bind to LPS from either P. multocida or B. abortus, producing complexes with densities of 1.45 to 1.50 g/ml. The buoyant density of the fixed ribosomes was 1.54 g/ml, and the buoyant densities of the fixed P. multocida and B. abortus LPS were 1.41 and 1.35 g/ml, respectively. Electron microscopy showed that formaldehyde-fixed ribosomes were attached to the LPS. Complexing of ribosomes to LPS may be of importance as a potentiator or carrier for experimental subunit vaccines.

Antigens, Bacterial↗
PubMed1987

Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study.

In 1980, a consensus chemotherapy intergroup study for advanced malignant mesothelioma was initiated based on a collaborative agreement among the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG), and the Southeastern Cancer Study Group (SECSG). The purpose of the study was to evaluate cyclophosphamide (500 mg/m2 day 1), imidazole carboxamide (250 mg/m2 days 1 through 5), and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (50 mg/m2 day 1) v cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) in a randomized prospective clinical trial involving 76 fully evaluable patients with advanced stages II to IV malignant mesothelioma. A total of nine responses (12%) were documented, including three complete and six partial responses. There was no significant difference in response duration or survival between treatment arms. Leukopenia (greater than 2,000/microL) was observed in 46% of patients treated with the three-drug combination and 38% of patients receiving the two-drug combination. The variables of performance status 0-1 and the absence of prior chemotherapy/radiotherapy were significant with respect to favorable impact on survival. We conclude, based on the minimal benefit observed, that the combination of cyclophosphamide and doxorubicin with or without imidazole carboxamide does not warrant further investigation in patients with advanced-stage malignant mesothelioma.

Adult↗
PubMed1987

Persistent sensitivity to ethanol following a single dose of parenteral sustained-release disulfiram.

A pilot study of a new injectable sustained-release formulation of disulfiram was performed in two alcoholic volunteers. Both subjects were treated with a single subcutaneous dose of disulfiram (1g or 2g). An oral alcohol challenge (0.15g/kg) was administered before the disulfiram was injected, and similar posttreatment alcohol challenges were repeated on days 7, 14, 21, and 28. Subjects were observed at five minute intervals for a period of 90 minutes after all alcohol challenges. Subjective responses were monitored, as well as heart rate, blood pressure, skin temperature, and the concentration of ethanol and acetaldehyde in the breath. Persistent and statistically significant changes were observed in the subjective and objective responses to alcohol during the posttreatment period. These responses to the alcohol challenges were consistent with disulfiram-ethanol reactions resulting from the persistent pharmacologic effects of the parenteral sustained-release disulfiram.

Adult↗