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Biomedical subjects

M Harrington

Publications and source records attributed to M Harrington.

At least 55 records · Page 3Linked to original sources

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↗

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↗

Reproductive outcome.

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Air Pollutants, Occupational↗

Characterization of myogenic cell lines derived by 5-azacytidine treatment.

Three myogenic clonal cell lines were isolated from C3H 10T1/2 C18 cells (10T1/2) treated with 5-azacytidine (5-aza-CR). These lines reproducibly underwent fusion at confluence into functional myotubes capable of contracting in response to acetylcholine. The degree of fusion could be increased two- to threefold if the cells were grown on gelatin-coated dishes. All of the cell lines lost some of their myogenic potential after repeated passaging and the percentage of colonies capable of forming muscle was not increased by permissive media containing 2% horse serum. The 10T1/2 cells expressed only the BB form of creatine phosphokinase but all of the myogenic clones expressed additionally the MM and MB forms of the isozyme after fusion. The overall genomic level of 5-methylcytosine was decreased in some but not all of the cell clones tested. Comparisons between the 10T1/2 cells which never form muscle without 5-aza-CR treatment and clonal derivatives of committed cell types might be of value in understanding the molecular basis of the commitment process.

Animals↗

Thermal stability of cowpea mosaic virus components: differential scanning calorimetry studies.

Differential scanning calorimetry studies show that the thermal stability of cowpea mosaic virus (CPMV) is pH dependent in the pH range 5 to 8. The four different components of CPMV, top (protein shell devoid of RNA), middle (virus particle containing the smaller RNA), bottom upper and bottom lower (virus particle containing the larger RNA), are stable up to 64-70 degrees at pH 5.0 and up to 43-46 degrees at pH 8.25. These components did not exhibit any difference in their thermal stability between pH 6.0 and 8.0.

Calorimetry, Differential Scanning↗

1H, 13C, and 31P nuclear magnetic resonance studies of cowpea mosaic virus: detection and exchange of polyamines and dynamics of the RNA.

1H and 13C NMR studies on cowpea mosaic virus (CpMV) revealed that polyamines are present in the middle (M) and upper bottom (BU) components obtained by CsCl density gradient centrifugation but not in the top (T) component; the lower bottom (BL) component contains trace amounts of polyamine. Dialysis of the BL component against spermidine led to incorporation of spermidine which gave rise to NMR peaks very similar to those observed with the natural M and BU components. NMR results conclusively demonstrate that polyamines in the M and BU components of CpMV are exchangeable with cesium ions and the exchange process is pH dependent. They also provide experimental support for the hypothesis that the BU to BL conversion results from the displacement of polyamines and possibly other natural counter ions of the RNA by cesium ions [G. Bruening, (1977), In "Comprehensive Virology" (H. Fraenkel-Conrat and R. R. Wagner, eds.), Vol. 11, pp. 55-141. Plenum, New York]. No sharp peaks, attributable to mobile amino acid side chains, were seen in spectra of an intact CpMV particle or its empty protein shell (T component). 31P NMR spin-lattice relaxation time and nuclear Overhauser effect parameters, which are sensitive to high-frequency motions, suggest that the RNA and, when present, the bound polyamine undergo internal motions with correlation times in the nanosecond range.

Carbon Isotopes↗

Intestinal parasites in metropolitan Toronto day-care centres.

In 1981, 900 children (aged 3 months to 10 years) and 146 staff attending 22 day-care centres in metropolitan Toronto chosen at random provided a stool specimen in a survey for intestinal parasites. Of the children, 4% to 36% were infected in 20 of 22 centres. Overall, 19% of the children and 14% of the staff had intestinal parasites: 8.6% and 4.0% respectively had Dientamoeba fragilis, and 7.8% and 2.0% respectively had Giardia lamblia. The highest prevalence of dientamebiasis was in the 7- to 10-year-olds, whereas giardiasis was detected most frequently in the 6-year-olds. Infection with intestinal parasites was not correlated with age, sex, duration in the day-care centre, dog ownership, travel history, gastrointestinal symptoms or the proportion of children in the day-care centre who were born in less developed countries. Immigrant children and children of parents born in industrialized countries (including Canada) were more likely to be infected than were children born in Canada of parents from the developing world. Dientamebiasis was associated with cat ownership. Thus, intestinal protozoa--in particular, D. fragilis and G. lamblia--are endemic in Toronto day-care centres.

Canada↗

Penetrating injury of the spinal cord.

We describe 2 cases of penetrating injury of the thoracic spinal cord complicating stab wounds of the chest. Both patients exhibited the Brown-Séquard syndrome, with disturbances of sphincters as well as motor and sensory changes; both developed meningitis. The diagnosis and management of these patients are discussed.

Adult↗

Fibrinolytic response to trauma.

The fibrinolytic response to trauma was investigated in 23 patients. Patients were triaged upon arrival in the emergency center into three groups; group I-patients with significant trauma who maintained normal vital signs, had a good prognosis, and tolerated the trauma well (mean injury severity score 8, range 4 to 12); group II--patients with significant trauma and transient episodes of hypotension, hypoxia, or acidosis who recovered (mean injury severity score 22, range 9 to 38); and group III--patients with profound or continued hypoxia and hypotension who eventually died of the trauma (mean injury severity score 41, range 30 to 50). Serial measurements of prothrombin time, activated partial thromboplastin time, and platelet count; concentrations of fibrinogen, plasminogen, and fibrin degradation products; and assays of euglobulin fraction fibrinolytic activity on plasminogen-free and plasminogen-rich fibrin plates were obtained on all patients. Coagulation studies documented a trauma-related coagulopathy that correlated with the degree of trauma. Plasminogen concentrations were initially depressed in all three groups; however by 24 hours group III patients were noted to have significantly elevated plasminogen concentrations while group I and group II patients had normal plasminogen concentrations. Fibrinolytic activity measured on plasminogen-free and plasminogen-rich fibrin plates was initially increased in all three groups with group III patients demonstrating the greatest increase. Over the succeeding 14 hours fibrinolytic activity returned to baseline values in group I and group II patients while group III patients demonstrated no detectable fibrinolytic activity for the remainder of the study period. This absence of fibrinolytic activity and increase in plasminogen concentrations in group III patients is thought to be caused by depletion of the intravascular plasminogen activator with the subsequent development of a hypofibrinolytic state.

Blood Coagulation↗

Lung function in acromegaly.

Lung function has been assessed by spirometry, body plethysmography, flow volume loops and single breath transfer factor in thirty patients with acromegaly. Having excluded eight patients with kyphosis and/or clinical or radiological evidence of pulmonary venous hypertension we have found a significant correlation between duration of acromegaly and lung size as assessed by total lung capacity. Excluding the same eight patients we have found evidence of small airways narrowing in eight patients, seven of these eight had had acromegaly for nine years or longer, and the duration of acromegaly was significantly longer in the patients with small airways narrowing than in those without. In the absence of other recognized causes it is possible that small airways narrowing in acromegaly is caused either by the increased whole blood volume with pulmonary vascular engorgement, or by increase in size of the soft tissues of the small conducting airways. Six of the eight patients with kyphosis and/or pulmonary venous hypertension also had evidence of small airways narrowing. Thus fourteen of the thirty patients with acromegaly had small airways narrowing. Five men had evidence of extra thoracic airway narrowing and in four the duration of acromegaly was ten years or longer. We conclude that the increase in total lung capacity, the incidence of small airways narrowing and the incidence of upper airway narrowing are all related to the duration of acromegaly. It seems that once duration exceeds eight years patients are very likely to develop abnormalities of lung function either primarily from the effects of acromegaly on the airways and lung or secondarily from the associated cardiovascular and thoracic skeletal abnormalities. It seems probable that the small airways and upper airway narrowing contribute to the morbidity and mortality of this disease. This study provides further evidence that acromegaly should be treated early.

Acromegaly↗

Rotavirus infection in hospitalised children: incidence and impact on healthcare resources.

BACKGROUND AND AIMS: In anticipation of vaccine development this study sought to determine the incidence, disease burden and associated financial burden of rotavirus (RV) infection, in hospitalised children. METHODS: Prospective observational study in two Dublin paediatric centres. RESULTS: Of 663 confirmed infections, 485 (73%) patients were hospitalised with community acquired (CA) RV; 178 (27%) cases were hospital acquired (HA) RV. A total of 243 (50%) children were < 12 months of age, with peak incidence in the 6 to < 12 month age group. CA RV resulted in utilisation of 2,305 bed days, with a median bed stay of three days (range 1-91), representing a minimum cost of Euro176,637 per year to the hospitals. When nosocomial spread and secondary cases are included, this increases to Euro258,695 per year. CONCLUSION: CA RV infection accounted for 1% of all admissions during the study period at a minimum cost of Euro728.40 per case. A safe and effective vaccine could reduce morbidity and advantage children by allowing redeployment of healthcare resources to other critical areas.

Child↗