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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 199 records · Page 11Linked to original sources
PubMed1997

Reproducibility and reliability of middle cerebral artery occlusion using a silicone-coated suture (Koizumi) in rats.

The best technical approach to rat middle cerebral artery occlusion (MCAO) using a nylon-monofilament suture remains unsettled, regarding the usefulness of coated or uncoated sutures. Three investigators with different degrees of experience: A, well skilled; B, 2 years of experience; C, a novice with 6 months of experience, each subjected 10 Sprague-Dawley rats to permanent MCAO using low-viscosity silicone-coated sutures with a mean diameter 0.468+/-0.013 mm (mean+/-S.D.) at the tip and 0.361+/-0.013 mm in the body. Post-mortem corrected infarct size 24 h after MCAO was similar among the three investigators: A, 204.7+/-33.2 mm3; B, 212.6+/-42.8, and C, 195.9+/-44.4. The coefficient of variation was 16.2% to 22.7%, and 19.4% for the three investigators. This study suggests that experimental stroke with silicone-coated sutures (Koizumi's method) provides good reproducibility and reliability, among investigators of varying experience.

Animals↗
PubMed1997

A system for the quantitation of DNA using a microtiter plate-based hybridization and enzyme amplification technology.

A quantitative hybridization technique for the detection of plasmid DNA by the action of a nuclease enzyme is described. The process utilizes the specific capture and detection of a sandwich hybridization, in a microtiter plate, that occurs in a single step. The detector probe is labeled with nuclease P1. The pH-dependent specificity of this enzyme for 3'-dinucleotides is used to generate a measurable signal by activating apo-glucose oxidase, which triggers an enzyme amplification cascade in the same microtiter plate. The sensitivity of the assay system is demonstrated in an assay of a mutated form of the human pancreatic ribonuclease gene inserted into the plasmid pUC 18. The system was able to detect 35 amol of target DNA in an assay composed of a 60-min hybridization and 20 min of signal generation. This use of nuclease P1 as the enzyme label and apo-glucose oxidase as the trigger for the amplification cascade results in an assay that is more sensitive than previously described enzyme amplification systems using colorimetric detection.

Colorimetry↗
PubMed1997

Racing-related factors and results of prerace physical inspection and their association with musculoskeletal injuries incurred in thoroughbreds during races.

OBJECTIVE: To describe and compare data from Thoroughbreds that sustained musculoskeletal injuries while racing with data from matched control horses. DESIGN: Matched case-control study. ANIMALS: 216 Thoroughbreds that sustained a musculoskeletal injury while racing and 532 horses from the same races that were not injured. PROCEDURE: Data regarding racing history, race-entrant characteristics, racing events determined by analysis of videotapes of races, and results of prerace physical inspections were determined for all horses. Injured horses were compared with control horses by using conditional logistic regression. RESULTS: Results of prerace inspection by regulatory veterinarians were significantly associated with injury. Odds of musculoskeletal injury, injury of the suspensory apparatus of the forelimb, and injury of the tendon of the superficial digital flexor muscle of the forelimb were 5.5 to 13.5 times greater among horses assessed to be at increased risk of injury by regulatory veterinarians on the basis of results of prerace inspection than for horses not considered to be at increased risk of injury. Odds of an abnormal finding in the suspensory ligament during prerace inspection were 3.4 times greater among horses that injured the suspensory apparatus than among control horses, and odds of an abnormal finding in the tendon of the superficial digital flexor muscle during prerace inspection were 15 times greater among horses that injured the tendon than among control horses. CLINICAL IMPLICATIONS: Regulatory veterinarians can identify horses during prerace physical inspection that have an increased risk of injury during races. Prerace physical inspections could be used to reduce the risk of injury to Thoroughbreds during races.

Animals↗
PubMed1997

A structurally novel transferrin-like protein accumulates in the plasma membrane of the unicellular green alga Dunaliella salina grown in high salinities.

The alga Dunaliella salina is outstanding is its ability to withstand extremely high salinities. To uncover mechanisms underlying salt tolerance, a search was carried out for salt-induced proteins. The level of a plasma membrane 150-kDa protein, p150, was found to increase with rising external salinity (Sadka, A., Himmelhoch, S., and Zamir, A. (1991) Plant Physiol. 95, 822-831). Based on its cDNA-deduced sequence, p150 belongs to the transferrin family of proteins so far identified only in animals. This, to our best knowledge, is the first demonstration of a transferrin-like protein in a photosynthetic organism. Unlike animal transferrins, p150 contains three, rather than two, internal repeats and a COOH-terminal extension including an acidic amino acid cluster. In intact cells p150 is degraded by Pronase, indicating that the protein is extracellularly exposed. The relationship of p150 to iron uptake is supported by the induction of the protein in iron-deficient media and by its radioactive labeling in cells grown with 59Fe. Accumulation of p150 is transcriptionally regulated. It is proposed that p150 acts in iron uptake other than by receptor-mediated endocytosis and that its induction permits the cells to overcome a possible limitation in iron availability under high salinities.

Algal Proteins↗
PubMed1997

Hemolytic anemia associated with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) is a useful tool in the treatment of a variety of neuromuscular disorders. Though IVIg therapy is generally safe, hemolytic anemia is a potentially serious complication that is often overlooked, and is currently not listed in product inserts. We analyzed 45 patients who received IVIg therapy, including 38 consecutive patients who received IVIg over a 13-month period. On 42 patients, direct antiglobulin testing was performed, searching for antibodies to the patients' own blood type. Of these 42 patients, 12 developed passive sensitization with antibodies to their own blood group antigens after receiving IVIg. Of these 12 patients, 11 patients developed hemolysis severe enough to lower the hemoglobin level by at least 1 g/dL. Of these patients, 3 required blood transfusion, and 1 had IVIg therapy truncated because of the hemolysis. Antibodies to blood group antigens are found in all commercial preparations of IVIg. Though most patients do not have clinically significant hemolysis, clinicians should be aware of this potentially serious complication. Careful monitoring of hemoglobin levels during IVIg therapy is recommended.

Anemia, Hemolytic↗
PubMed1997

Synthesis of early pregnancy factor using red deer (Cervus elaphus) as a delayed implantation model.

PURPOSE: This study measured serum early pregnancy factor (EPF) in pregnant red deer (Cervus elaphus) and ascertained whether EPF synthesis is associated with implantation. METHODS: Serial serum samples were taken from mated hinds up to 42 days postconception and analyzed for EPF activity using the rosette inhibition test. EPF activity was then correlated with calving records and stages of preimplantation development. RESULTS: EPF was detected in all pregnant animals, with a twin pregnancy giving increased EPF activity. Three animals gave an EPF response following fertilization but failed to continue beyond the preimplantation embryo stage. The increase in EPF synthesis previously associated with implantation in other mammals occurred at the blastocyst stage in red deer. CONCLUSIONS: EPF synthesis in red deer (Cervus elaphus) is consistent with the preimplantation period, as occurs in other mammals. However, the second phase of the biphasic increase in early pregnancy factor production is associated with blastocyst formation, not implantation.

Animals↗
PubMed1997

Response to the varicella vaccine in children with nephrotic syndrome.

Varicella vaccine was administered to seven children with corticosteroid-sensitive nephrotic syndrome. Immunization was not associated with any significant reactions or with increased frequency of relapse. The antibody response was, however, variable and a second dose was necessary before seroconversion was achieved in four patients. The findings indicate that immunization with varicella vaccine is safe in children with nephrotic syndrome in remission, but that a two-dose vaccine schedule should be considered.

Antibodies, Viral↗
PubMed1997

Characterization of complexes of oligonucleotides with polyamidoamine starburst dendrimers and effects on intracellular delivery.

This study evaluates polyamidoamine PAMAM "starburst" dendrimers (generation 3, Mr 6909) as a potential delivery vehicle for oligonucleotides. Complexes between dendrimer and phosphorothioate oligonucleotides were observed by agarose gel electrophoresis and were positive, negative, or neutral in charge depending on stoichiometry. Complexes were stable in 50% serum to variations in pH (3, 5, and 10) and ionic strength (0-500 mM). Ultrafiltration and gel filtration characterization indicated that the dendrimer:oligonucleotide complexes were primarily < 100 kD, although some larger complexes were formed at oligonucleotide excess. Use of dendrimers resulted in a 50-fold enhancement in cell uptake of oligonucleotide as determined by flow cytometry, and enhanced cytosolic and nuclear availability, as shown by confocal microscopy. These data support the further evaluation of dendrimers for oligonucleotide delivery in cell culture and in vivo.

Amines↗
PubMed1997

Susceptibility to anti-glomerular basement membrane disease is strongly associated with HLA-DRB1 genes.

Anti-glomerular basement membrane (anti-GBM) disease is caused by autoimmunity to a component of glomerular basement membrane. The major autoantigen has been identified as the NC1 domain of the alpha 3 chain of type IV collagen, and patients are characterized by the presence of specific autoantibodies to this molecule. In common with other autoimmune disorders, there is a strong association with HLA genes, with up to 80% of patients inheriting an HLA-DR2 haplotype. To examine the genetic basis of susceptibility to anti-GBM disease in more detail, the HLA-DRB and DQB alleles inherited by 82 patients were analyzed using sequence specific oligonucleotides. This identified a hierachy of association of DRB1 genes with anti-GBM disease, including susceptibility (DRB1*15, DRB1*04), neutral (DRB1*03) and protective (DRB1*07) alleles. Analysis of inherited haplotypes, particularly DRB1*04 and DRB1*07 carrying haplotypes, provided further evidence that the primary association was with genes at the DRB1 locus. Comparison of the sequences of the positively and negatively associated alleles showed that polymorphic residues in the second peptide binding region of the HLA Class II antigen binding groove segregated with disease. This work supports the hypothesis that the HLA associations in anti-GBM disease reflect the ability of certain Class II molecules to bind and present peptides derived from the autoantigen to T helper cells.

Alleles↗
PubMed1997

[Diffusion-weighted magnetic resonance tomography: a highly promising MR technic for the early recognition of cerebral ischemia].

PURPOSE: The aim of this study was to show the temporal and spatial evolution of ischaemia over time using diffusion-weighted magnetic resonance imaging, and to correlate the extent of ischaemia with the postmortem infarct size after 24 hours. MATERIAL AND METHODS: In 8 rats focal cerebral ischaemia was induced by intravascular occlusion of the middle cerebral artery. The evolution of the ischaemic lesion was examined over 180 min with an experimental MR scanner. RESULTS: Diffusion-weighted magnetic resonance imaging displayed a hyperintense area in the lateral part of the putamen as early as 5 min after the onset of ischaemia. The mean volume of ischaemia on diffusion mapping after 5 min was 62.5 +/- 12.9 microliters and increased to 224.4 +/- 48.5 microliters after 180 min. This correlated well with the corrected infarct volume at postmortem examination (194.0 +/- 23.1 microliters, r = 0.72, p < 0.05) using the TTC staining. CONCLUSION: Diffusion-weighted magnetic resonance imaging is a reliable tool in the early diagnosis of cerebral ischaemia. Due to the non-invasiveness this method can be used for therapy monitoring and might help to develop new therapeutic strategies.

Animals↗
PubMed1997

Comparative pharmacokinetics, tissue distribution, and tumor accumulation of phosphorothioate, phosphorodithioate, and methylphosphonate oligonucleotides in nude mice.

The goals of this study were to systematically compare the pharmacokinetics and tissue distribution of phosphorothioate (PS), methylphosphonate (MP), and phosphorodithioate (PS2) oligonucleotide analogs; 15-mers of sequence d-TAC GCC AAC AGC TCC (5'-3') complementary to the AUG region of K-ras were radiolabeled with carbon-14. Oligomers were administered as a single dose in the tail vein of nude mice harboring a K-ras-dependent human pancreatic tumor (CFPAC1). The kinetics of PS, PS2, and MP oligomer availability in the bloodstream was followed. Concentration versus time profiles for all oligomers were biphasic, indicative of a two-compartment model. A rapid distribution phase with t1/2 alpha values of 1 minute or less and an elimination phase with average t1/2 beta values of 24-35 minutes were observed. Volumes of distribution (Vd) were 3.2, 4.8, and 6.3 ml for PS2, MP, and PS, respectively, in comparison to 3.6 ml for sucrose, a fluid-phase marker. Relative tissue drug levels obtained at 1 and 24 hours after administration were kidney > liver > spleen > tumor > muscle. Total kidney and liver oligonucleotide accumulation was approximately 7%-15% of the initial dose, with tumor accumulating 2%-3%. Intact compound was recovered from all tissues, including tumor, as assessed by high-pressure reversed-phase HPLC coupled to radiometric detection. Integrity of the oligonucleotides ranged from 73% in blood to 43%-46% in kidney and liver. Kidney and liver appear to be the primary sites of metabolism. These results demonstrate widespread tissue availability of these compounds and suggest their development as potential antitumor agents.

Animals↗
PubMed1997

Delayed triphenyltetrazolium chloride staining remains useful for evaluating cerebral infarct volume in a rat stroke model.

Sixteen of 24 Sprague-Dawley rats with permanent middle cerebral artery occlusion for 24 hours were subjected to immediate or 8-hour delayed 2,3,5-triphenyltetrazolium chloride (TTC) staining (n = 8 at each time point); the other 8 animals were subjected to immediate or 8-hour delayed measurement of succinate dehydrogenase activity (n = 4 at each time point). The TTC staining was of good quality good in all animals, and the infarcted region could be distinguished easily from normal tissue. There was no significant difference in corrected infarct volume between the two groups (263.8 +/- 43.1 versus 264.4 +/- 54.8 mm3 [mean +/- standard deviation]). The activity of succinate dehydrogenase was not significantly different when normal or infarcted tissue was measured immediately after death or with an 8 hour delay, although less activity was detected at both time points in the infarcted tissue. These results demonstrate that an 8-hour delay of TTC staining is reliable for evaluating brain infarct volume in a rat stroke model and this probably is attributable to the slow deterioration of mitochondrial enzyme activity in nonischemic brain over this time period.

Animals↗
PubMed1997

The specialist learning disability nurse in Wales.

This paper reflects on the development of services for people with learning disabilities within the United Kingdom and focuses on the role of the specialist nurse. The nurse's contribution to the care of this client group has been the subject of debate and controversy for a number of years. Developments within the learning disability filed in Wales in particular are explored, with the All Wales Strategy for People with Learning Disabilities providing the background and context for these developments. An example of how specialist nurses from around Wales came together in order to share good and best practice is discussed. The conclusion is that the specialist learning disability nurse has a great deal to offer, but must be prepared to work together with other professionals as well as service users and their families.

Humans↗
PubMed1997

Acute ischemic stroke therapy. A clinical overview.

Acute ischemic stroke therapy has two basic therapies, dissolving the intravascular occlusion by thrombolytic therapy and protecting the brain from the harmfull cellular, and metabolic consequences ofischemic injury by neuroprotective therapy. It seems most likely that the methods that will be used to treat the acute ischemic stroke patient will be multiple, likely a combination of thrombolytic therapy for early reperfusion and neuroprotective therapy for maintaining vitality. In the last decade, a number of advances in the field of imaging and pharmacology have been made which should provide meaningful improvement for the management of acute ischemic stroke patients in the near future. This update summarizes recent clinical trials and emphasizes the question of risk versus benefit for the acute ischemic stroke therapies being developed.

Acute Disease↗
PubMed1997

Carvedilol inhibits aortic lipid deposition in the hypercholesterolemic rat.

The effects of carvedilol, a vasodilating beta-blocker with antioxidant activity, and nifedipine, a calcium channel blocker, were investigated on aortic lipid deposition and the accumulation of monocytes and foam cells at the sites of atherosclerotic lesions in rats subjected to a hypercholesterolemic diet. Fifty rats were randomly assigned to the following experimental groups: (1) regular rat chow (n = 5); (2) regular rat chow supplemented with a high-cholesterol diet (1% cholesterol and 1% cholic acid; n = 15); (3) a high-cholesterol diet plus nifedipine (n = 15), and (4) a high-cholesterol diet plus carvedilol (n = 15). Animals were maintained on these diets for 12 weeks. None of the treatment groups had blood pressures that were outside the normotensive range, and no significant differences in plasma lipid levels were observed among the high-cholesterol diet and drug-treated groups. There was a significantly lower lipid content (p < 0.001) in the thoracic aortas of the nifedipine-treated (211 +/- 23 nmol/mm2) and carvedilol-treated (182 +/- 23 nmol/mm2) groups compared to cholesterol-fed controls (242 +/- 27 nmol/mm2). Furthermore, carvedilol-treated animals showed significantly less (p < 0.001) lipid accumulation than did the nifedipine-treated animals. The number of monocytes and foam cells were decreased in both drug-treated groups compared to animals receiving high-cholesterol diets without drug treatment. The results demonstrate that treatment with carvedilol or nifedipine can significantly inhibit lipid deposition in the aorta and reduce monocyte and foam cell accumulation, and that carvedilol is significantly more effective than nifedipine in inhibiting lipid deposition.

Adrenergic beta-Antagonists↗
PubMed1997

Characterizing the target of acute stroke therapy.

BACKGROUND: The development of effective therapies for acute ischemic stroke presumes the existence of potentially salvageable ischemic tissue when therapy is initiated because it is widely assumed that the effectiveness of most acute stroke therapies under development is related to reducing ultimate infarct size to promote functional improvement. Such salvageable ischemic tissue was previously labeled the ischemic penumbra and must be distinguished from irreversible injury. SUMMARY OF REVIEW: Pathological identification of irreversibility (infarction) appears to lag behind the actual development of this condition, and reversible injury after focal ischemia should be differentiated from infarction. Imaging and biochemical markers apparently can provide clues for distinguishing potentially salvageable from irreversibly injured ischemic tissue in experimental and clinical stroke. Recent positron emission tomography and MRI studies suggest that these clinically available imaging technologies will be useful for determining the presence of ischemic penumbra in individual stroke patients. The progression from potentially reversible to irreversible injury after focal brain ischemia has many potential mechanisms that may be synergistic and vary among individuals. CONCLUSIONS: Delineating and prioritizing these mechanisms provides the opportunity to develop multiple potential acute stroke therapies that ultimately will be used in combination, perhaps directed by imaging technology.

Acute Disease↗