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Biomedical subjects

G Lawler

Publications and source records attributed to G Lawler.

9 recordsLinked to original sources

Rapid multivariate analysis and display of cross-reacting antibodies on human leukocytes.

We present an application which can rapidly determine the binding patterns of monoclonal antibodies on mixed populations of cells simultaneously in a single rapid analysis. It is an application of the tube identifier parameter (TIP) system which can provide fully correlated list-mode data of the entire patient phenotype in a single file. Using the phenogram analytical display, we are able to determine the cross-reacting antibodies for an entire antibody panel for each cell type. This information can be displayed in a single plot. Using light scatter gating to select different populations of lymphocytes, monocytes, and neutrophils, phenograms can be simultaneously generated. This provides a directly comparable means of displaying the positive and negative binding characteristics of each antibody on each cell population. Any marker combination that is abnormal will be identifiable in the phenogram. Additionally, by plotting the fluorescence distributions of each marker beside one another (termed overview), quantifiable differences in intensity can be determined. There are 3 major benefits of the proposed analysis. By using the TIP concept, several sets of antibodies can be compared simultaneously. Any light scatter gate can be used and this gate can be changed on one histogram or plot, yet apply to the total analysis. Data analysis is particularly rapid since the entire phenotype of a patient can be evaluated by performing a single rapid analysis.

Antibodies

Time interval gating for analysis of cell function using flow cytometry.

We propose a method which significantly shortens the time required for both the collection and analysis of data derived from multiple sample, flow cytometric kinetic assays. We have defined the term Time Interval Gating (TIG) to describe this method. TIG effectively allows one flow cytometer to concurrently monitor several samples over the course of a kinetic assay. Data for all samples are stored in a single FCS 2.0 compatible listmode data file which we refer to as the TIG data file. TIG is adaptable to most commerical flow cytometers. Standard listmode analysis software can be used to analyze the TIG data files and correlate any combination of tubes and/or time intervals from the assay. Results for the entire assay can be displayed on a single two parameter plot. This paper describes how TIG is applied to neutrophil oxidative burst measurement using a standard EPICS Elite flow cytometer. In this assay, 11 samples were each monitored for 30 min to identify the extent to which volatile organic chemicals (VOCs) inhibited the oxidation of DCFH in stimulated neutrophils. TIG makes the oxidative burst assay practical for high volume screening by reducing the overall flow cytometer and analysis time required by a factor of ten. In addition, TIG provides an organized approach to managing data acquisition on instruments equipped with automated sampling systems.

Flow Cytometry

An autoradiographic study of the uptake and distribution of iron by the brain of the young rat.

Rats aged 15, 28, or 42 days were injected intraperitoneally with iron-59 and were sacrificed at varying intervals. Total acquisition of iron-59 by the brain, when compared to levels of iron-59 in blood sampled 48 h after injection, diminished with increasing age at injection. Cerebral levels of iron-59 in animals injected at age 15 days did not change with postinjection interval despite rapidly decreasing serum levels of iron-59. Thus, iron acquired by the brain early in postnatal development becomes sequestered in that organ. However, autoradiography of the brains of animals injected at age 15 days showed definite changes over time in the anatomic distribution of the isotope. This suggests that mechanisms may exist for the translocation of iron from one area of the brain to another.

Aging

Effect of cytoskeletal geometry on intracellular diffusion.

A method is presented for determining the retardation of diffusion of particles inside cells owing to cytoskeletal barriers. The cytoskeletal meshwork is treated as a repeating periodic two-dimensional or three-dimensional lattice composed of elements of given size, shape, and spacing. We derive an analytic expression for the diffusion coefficient relative to that of the cytosol. This expression is evaluated by solving numerically an appropriate boundary-value problem for the Laplace equation. For the two-dimensional case, e.g., diffusion in a membrane, the results are quantitatively similar to those obtained by Saxton (1987. Biophys. J. 52:989-997) using Monte Carlo methods. The three-dimensional results are quantitatively similar to experimental results reported by Luby-Phelps et al. (1987. Proc. Natl. Acad. Sci. USA. 84:4910-4913) for the diffusion of dextran and Ficoll particles in Swiss 3T3 cells. By accounting for geometrical factors, these results allow one to assess the relative contributions of geometrical hindrance and of binding to the cytoskeletal lattice from measurements of intracellular diffusion coefficients of proteins.

Cytoskeleton

A comparison of changes seen on radiographs of rheumatoid arthritis patients in Australia and in China.

To test the hypothesis that rheumatoid arthritis in patients in China is milder in severity than that in patients in a western country, a comparison was made of 2 series of consecutive outpatients with definite or classic rheumatoid arthritis who were attending referral centers in Melbourne, Australia and Shanghai, China. This paper reports the findings on radiographs of the wrists and hands. Making allowances for age and duration of disease, changes were more frequent and severe in the Australian patient series, particularly at the metacarpophalangeal joints.

Adult

A comparison of rheumatoid arthritis in Australia and China.

A comparison was made of two series of consecutive outpatients with a presumptive diagnosis of rheumatoid arthritis (RA) attending referral centres in Melbourne and Shanghai. No significant differences were observed in disease onset, course, presence of antinuclear antibodies (ANA), or seropositivity. In the Australian series there was a higher frequency of nodules, Raynaud's phenomenon, carpal tunnel syndrome, and 'classical' in comparison with 'definite' disease, and a lower frequency of lymphadenopathy and hepatomegaly. Joint tenderness and soft tissue swelling tended to be more marked in the Chinese series, while deformity and limited range of movement were less severe. Drug therapy was similar overall but influenced by drug availability. Peptic ulceration was recorded in 28% of the Australian series but in only 6% of the Chinese; although 25% of the Chinese were receiving antacids and 6% antiulcerants. X-rays of hands and feet showed more severe disease in the Australian series. The older age group and longer duration of the disease in the Australian patients, who had more chronic and less active disease, may have influenced some of these results.

Anti-Inflammatory Agents

Acute median nerve compression by haemorrhage from acute myelomonocytic leukaemia.

A 61-year-old male receiving treatment for acute myelomonocytic leukaemia (AMML) developed weakness and sensory loss in the thumb, index and middle finger and half of the ring finger of the left hand as a result of a spontaneous haemorrhage into the carpal tunnel and forearm, an unusual cause of median nerve compression. These findings were confirmed by CT scanning and post-mortem examination. This is the first report of spontaneous haemorrhage occurring in a patient with AMML.

Acute Disease

Intravenous digital subtraction angiography in patients with carotid territory ischemia: a prospective trial.

To evaluate the place of intravenous digital subtraction angiography (IV-DSA) in the investigation of patients with carotid territory ischemia, we have compared the IV-DSA and conventional angiographic (CA) findings in 40 patients in a prospective study. Arterial disease was assessed by grading stenosis from zero (normal artery) to six (complete occlusion) and recording any luminal ulceration. In 59 of 66 bifurcations imaged by both techniques, the IV-DSA evaluation of any internal carotid artery origin disease was within one grade of the CA assessment, with three false negatives and four false positives. Luminal ulceration was less reliably predicted, and two clinically important middle cerebral artery lesions were missed by IV-DSA. In 11 patients who had carotid endarterectomy, there was a good correlation between surgical, CA, and IV-DSA findings, although some ulcerations were not detected by either angiographic technique. These results suggest that IV-DSA is a sensitive technique for detection of carotid bifurcation stenosis when the study is of good quality, but that intracranial lesions may be missed.

Carotid Artery, External