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Biomedical subjects

M Harrington

Publications and source records attributed to M Harrington.

At least 19 recordsLinked to original sources
PubMed1992

Polyhydroxy and polyethyleneglycol (meth)acrylate polymers: physical properties and general studies for their use as electrophoresis matrices.

A new series of materials have been tested for their suitability as electrophoresis matrices. The mechanical and optical properties of gels composed of polyethyleneglycol (meth)acrylate esters or polyhydroxy (meth)acrylate esters in water and in various concentrations of organic solvents are described. Several crosslinkers including polyethyleneglycol and polyhydroxy di(meth)acrylates, piperazine diacrylate, and bisacrylamide were used in these studies. Electrophoretic migration and separation of a series of protein standards through polyethyleneglycol methacrylate (PEGM) 200, PEGM 400, and glyceryl methacrylate is demonstrated. Further, copolymerization of all of the monomers with acrylamide was performed and the distribution of monomer incorporation into the polymer network calculated. All monomers and copolymers that were examined by IR spectroscopy showed greater than 99% polymerization. These results justify their further study for biomolecule separations.

Cross-Linking Reagents↗
PubMed1992

Polyethyleneglycol methacrylate 200 as an electrophoresis matrix in hydroorganic solvents.

The properties of gels composed of poly(polyethyleneglycol methacrylate) and copolymers of polyethyleneglycol methacrylate and acrylamide were studied. These novel electrophoresis matrices are amphigels (swellable in water and organic solvents) that have unprecedented organic solvent compatibility. Hydrophobic proteins which are poorly solubilized in aqueous detergent systems (e.g., zein) are well-resolved in these gels with hydro-organic solvents. This is especially relevant for isoelectric focusing, to avoid using either ionic detergents that may interfere with the focusing, or urea that may cause carbamylation of proteins. Variations of crosslinker, buffer, and solvent systems in these gels were explored.

Electrophoresis↗
PubMed1992

Human cerebrospinal fluid protein database: edition 1992.

Two-dimensional electrophoresis maps of human cerebrospinal fluid proteins are presented in the form of labeled images. 931 protein spots are identified in spinal fluid from a normal volunteer. Distinct spots that represent variants of the same protein, especially posttranslational modifications, are estimated to reduce the 931 different spots to < 200 different proteins. 248 spots of 29 protein groups have been identified and are indicated on enlargements of specific gel regions. The distribution of protein abundance, mass, charge and shape characteristics of these normal 931 spinal fluid spots are graphically profiled. Analysis of the shape parameter "vertical height: width ratio" reveals that a ratio > 3.5 correlates with glycoproteins, enabling their identification simply by image analysis. Proteins that are not present on the normal map, but appear in spinal fluid in patients with schizophrenia and Creutzfeldt-Jakob disease are illustrated on additional maps.

Cerebrospinal Fluid Proteins↗
PubMed1992

The role of 99Tcm-HMPAO white cell imaging in suspected orthopaedic infection.

Accurate diagnosis is essential for the effective management of suspected bone infection. Current imaging techniques have had limited success and further work is required. Although white cell labelling techniques have been available for many years the radiopharmaceuticals employed have disadvantages, particularly in their availability and suitability for imaging. These problems have been overcome by the use of 99Tcm-HMPAO as an in vitro leukocyte labelling agent. The aims of this study were to assess retrospectively its role and accuracy in imaging orthopaedic infection and to compare the results with three-phase bone imaging. 30 patients with suspected bone infection underwent three-phase methylene diphosphonate (MDP) bone imaging and labelled leukocyte imaging on separate occasions. 16 bone scans were positive for infection, of which 14 were subsequently confirmed, and there were no false negatives. There were no false positive white cell studies and only one infection was not identified. 99Tcm-HMPAO white cell imaging has been shown to be an accurate technique for the diagnosis of bone infection but should be performed only following a positive finding on three-phase bone scanning, since the latter is highly sensitive but significantly less expensive, making it a more appropriate screening procedure.

Adolescent↗
PubMed1992

Leukocyte scanning with 111In is superior to magnetic resonance imaging in diagnosis of clinically unsuspected osteomyelitis in diabetic foot ulcers.

OBJECTIVE: To compare the accuracies of MRI and leukocyte scanning in diagnosing clinically unsuspected osteomyelitis in diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A prospective study of 16 diabetic foot ulcers in 12 patients, including both ambulatory and hospitalized patients, was performed at a university medical center. Pedal images were obtained by leukocyte scanning with [111In]oxyquinoline and MRI. Definitive diagnosis of osteomyelitis then was determined by bone biopsy for culture and histology. RESULTS: Biopsy-proven osteomyelitis was present in 7 (44%) of the 16 foot ulcers. The diagnosis was suspected clinically in 0%. Leukocyte scanning was 100% sensitive, whereas MRI was only 29% sensitive in diagnosing osteomyelitis in diabetic foot ulcers. Specificities were 67 and 78%, respectively. The positive and negative predictive values (70 and 100%, respectively) for the leukocyte scan also were greater than those of MRI (50 and 58%, respectively). CONCLUSIONS: Leukocyte scanning is superior to MRI in detecting clinically unsuspected osteomyelitis in diabetic foot ulcers.

Biopsy↗
PubMed1991

Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline.

OBJECTIVE: The prevalence of osteomyelitis in diabetic foot ulcers is unknown. Early diagnosis of this infection is critical, as prompt antibiotic treatment decreases the rate of amputation. We therefore assessed the prevalence of osteomyelitis in 35 diabetic patients with 41 foot ulcers. We compared results of roentgenograms, leukocyte scans with indium In 111 oxyquinoline, and bone scans with the diagnostic criterion standards of bone histologic and culture findings. Leukocyte scans were repeated at 2- to 3-week intervals during antibiotic treatment. DESIGN: Cohort study. SETTING: Institutional and private, ambulatory and hospitalized patients. PATIENTS: Consecutive sample of 54 diabetic patients. Thirty-five patients with 41 foot ulcers were included. RESULTS: As determined by bone biopsy and culture, osteomyelitis was found to underlie 28 (68%) of 41 diabetic foot ulcers. Only nine (32%) of the 28 cases were diagnosed clinically by the referring physician. Underscoring the clinically silent nature of osteomyelitis in these ulcers, 19 (68%) of 28 occurred in outpatients, 19 (68%) of 28 occurred in ulcers not exposing bone, and 18 (64%) of 28 had no evidence of inflammation on physical examination. All patients with ulcers that exposed bone had osteomyelitis. Of the imaging tests, the leukocyte scan had the highest sensitivity, 89%. In patients with osteomyelitis, the leukocyte scan image intensity decreased by 16 to 34 days of antibiotic treatment and normalized by 36 to 54 days. CONCLUSION: The majority of diabetic foot ulcers have an underlying osteomyelitis that is clinically unsuspected. Leukocyte scans are highly sensitive for diagnosing osteomyelitis in diabetic foot ulcers and may be useful for monitoring the efficacy of antibiotic treatment. We recommend that diabetic patients with foot ulcers that expose bone should be treated for osteomyelitis. Diabetic patients with foot ulcers that do not expose bone should undergo leukocyte scanning, which eliminates the risk of bone biopsy in diagnosing osteomyelitis and allows for the diagnosis and treatment of this well-known but often silent precursor of lower extremity amputation.

Diabetes Mellitus, Type 2↗
PubMed1991

Synergistic effect of human lactoferrin and recombinant murine interferon-gamma on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex.

Mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) have been used as a leukemic mouse model. In the present study, purified iron-saturated human lactoferrin (LF) and recombinant murine (rmu) interferon-gamma (IFN-gamma), alone or in combination, were used to influence disease progression in virally infected mice. DBA/2 mice were injected i.v. with FVC-P, and were treated s.c. with 100 micrograms LF at day 7, and/or rmuIFN-gamma at 5 x 10(4) units/day for 3 days beginning at day 6 after viral infection. Mice were assessed for survival, and also 14 days after virus inoculation, the mice were killed and spleen extracts were assessed for spleen focus forming virus (SFFV) titers by spleen focus forming unit (SFFU) assay, SFFV mRNA and genomic DNA expression, and natural killer (NK) cell activity. Treatment with LF or rmuIFN-gamma alone had little or no effect on SFFU numbers or SFFV mRNA or genomic DNA expression. However, dramatically decreased SFFV titers and levels of SFFV mRNA and genomic DNA were observed in mice treated with the combination of LF and rmuIFN-gamma. NK cell activity decreased by FVC-P was returned to normal levels by LF and rmuIFN-gamma. The combined treatment also enhanced the survival rates of FVC-P-infected mice. The results suggest synergistic suppressive effects of LF with rmuIFN-gamma on disease progression in FVC-P-infected mice. This information might be of significance as a potential therapy for patients with leukemia and those infected with retroviruses.

Animals↗
PubMed1990

Regional procurement and export of hepatic allografts for transplantation.

A team dedicated to hepatic procurement exclusively for export to distant centers was established at The Mount Sinai Hospital in New York. Between January 1987 and March 1988, 20 livers were retrieved and sent to five institutions in the U.S. and Canada for implantation. These procedures were carried out in concert with local cardiac and renal procurement teams; 12 hearts and 34 kidneys were used from these 20 donors. Functional results of both the livers and the other organs were in line with nationally reported standards. The multi-organ procurement procedure was streamlined as a result of the coordination which developed between the teams. Savings in time and travel expense by skilled personnel were realized; in five cases no alternative hepatic procurement team was available. With the ability to preserve livers for increasingly long periods, this type of program will assume greater importance in the future.

Humans↗
PubMed1989

Effects of recombinant human colony stimulating factors (CSF) (granulocyte-macrophage CSF, granulocyte CSF, and CSF-1) on human monocyte/macrophage differentiation.

Purified recombinant human granulocyte-macrophage (rhuGM)-CSF, rhuG-CSF, and rhuCSF-1 were evaluated for their capacity to influence the differentiation of U-937 cells and normal human monocytes. The human U-937 cell line represents an early stage of monocytic differentiation. It was found that rhuGM-CSF and rhuG-CSF, but not rhuCSF-1, induced phenotypic changes consistent with monocyte/macrophage differentiation in U-937 cells. After 3 days of culture in the presence of either rhuGM-CSF or rhuG-CSF, a small but significant proportion of U-937 cells were able to reduce nitroblue tetrazolium. Nitroblue tetrazolium reduction, however, was maximally induced when rhuGM-CSF and rhuG-CSF were added in combination. These changes were accompanied by increased alpha-naphthyl acetate esterase activity, acquisition of macrophage morphology, Mo-1 Ag expression, and decreased cell proliferation. rhuGM-CSF alone also induced expression of the c-fms proto-oncogene (CSF-1 receptor) in U-937 cells and this expression was enhanced by the combination of rhuGM-CSF and rhuG-CSF. In cultured normal human peripheral blood monocytes, representing a late stage of maturation, rhuGM-CSF and rhuCSF-1 differentially increased Mo-1 and My-4 Ag expression, respectively, whereas rhuG-CSF was without effect. Our results suggest that the interaction of GM-CSF, G-CSF, and CSF-1 may play a fundamental role in the early and late stages of the human monocyte/macrophage differentiation process.

Antigens, Surface↗
PubMed1988

Coloration of silver-stained protein bands in polyacrylamide gels is caused by light scattering from silver grains of characteristic sizes.

This study investigates the physical basis of color effects in the detection of proteins in polyacrylamide gels by silver staining. Specifically, the hypothesis that different colors may correlate with the development of silver grains of characteristic sizes was investigated by electron microscopy. Protein bands that stained brown, yellow, and blue were excised from stained gels and prepared for electron microscopy by thin-sectioning. In each case, the size distributions of globular silver grains were determined directly from the electron micrographs. We found that blue bands have larger silver grains (with diameters of 40-100 nm) than yellow (21-39 nm) or brown bands (17-35 nm). On the basis of these and other observations, a general mechanism is proposed whereby chemical specificity of electrophoretically separated proteins is expressed in color-specific silver staining.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

HDL particle associated proteins in plasma and cerebrospinal fluid: identification and partial sequencing.

The proteins from plasma HDL particles isolated by immunoaffinity chromatography on anti-apolipoprotein A-1 affinity columns have been analysed and purified by high resolution two dimensional gel electrophoresis. Two of the lipoprotein-associated proteins found in the HDL plasma fraction, previously referred to as NA1 and NA2, have also been found in cerebrospinal fluid. After separation by 2DGE, these two proteins were transferred to PVDF membranes, stained and cut out for N-terminal sequencing. The partial sequences (11 and 13 amino acids) obtained for the two HDL particle associated proteins do not match any of those included in the December 1987 National Biomedical Research Foundation (NBRF) database, and there are no significant sequence similarities.

Amino Acid Sequence↗
PubMed1987

Localization of radioiodinated monoclonal antibody in colorectal cancer. Initial dosimetry results.

HT-29-15 is an IgG1 monoclonal antibody reacting with a neuraminidase-sensitive determinant on a cell-surface antigen (molecular weight, 200,000 daltons) present on the colon cancer cell line HT-29. HT-29-15 was selected for a tumor localization study because the antigen was shown to be present, by immunohistochemical staining, in a high percentage of primary and metastatic colorectal cancers. HT-29-15 labeled with iodine 131 was given intravenously over a dose range of 0.2 to 10.0 mg to 23 patients with colorectal cancer. No significant toxicity was seen. Imaging of hepatic metastases was successful from days 5 to 7. Analysis of tissue radioactivity by biopsy showed that the tumor-liver ratio increased from day 1 to day 7, suggesting more rapid clearance of antibody from normal tissue than from tumor. Thus, tissue biopsy specimens and scintigraphy have shown that imaging of metastatic colorectal cancer is possible with monoclonal antibody HT-29-15. Tissue biopsy specimens are essential for demonstrating specificity of localization. Scans alone provide insufficient evidence of specific localization by monoclonal antibodies. Simultaneous infusion of a nonreactive control antibody would be necessary for specific localization to be demonstrated unequivocally.

Animals↗
PubMed1987

Reproductive outcome.

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Air Pollutants, Occupational↗