Canine dinucleotide repeat polymorphism at the VIAS-D23 locus.
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Alleles↗
Biomedical subjects
N A Robinson
Publications and source records attributed to N A Robinson.
An ostrich dinucleotide repeat polymorphism at the VIAS-OS2 locus.
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Alleles↗
The physician's role in worker's compensation.
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Humans↗
Milwaukee Prehospital Chest Pain Project--phase I: feasibility and accuracy of prehospital thrombolytic candidate selection.
This study prospectively determined the feasibility and accuracy of prehospital thrombolytic therapy candidate selection by base station emergency physicians. During a 6-month period, paramedics acquired and transmitted prehospital 12-lead electrocardiograms (ECGs) and then applied a thrombolytic therapy contraindication checklist. Emergency physicians interpreted prehospital ECGs and prospectively selected candidates for thrombolytic therapy. A safety committee of cardiologists reviewed prehospital ECGs, checklists and hospital records to determine accuracy independently. Six hundred-eighty stable adult prehospital patients with a chief complaint of nontraumatic chest pain were initially evaluated. Two hundred forty-one patients were excluded because of (1) unsuccessful electrocardiographic transmission (149), (2) transport to nonparticipating facilities (72), and (3) unavailable medical records (20). No prehospital thrombolytic therapy was administered in this study. Of 439 cases, 91 (21%) had the final diagnosis of acute myocardial infarction, 38 (8.7%) had diagnostic prehospital ECGs, and 12 (2.7%) were selected by emergency physicians as candidates for thrombolytic therapy. Seventy percent of patients with myocardial infarction had checklist exclusions for thrombolytic therapy. Prehospital evaluation increased mean scene time (paramedic arrival on scene to scene departure) by 4 minutes. The median time from chest pain onset to paramedic arrival in patients with myocardial infarction was 60 minutes. The estimated average time saved if prehospital thrombolytic therapy had been available was 101 +/- 81 minutes. The safety committee concluded that acceptable accuracy of emergency physician prehospital electrocardiographic interpretation, checklist and case selection was achieved. It is concluded that emergency physicians can accurately identify candidates for prehospital thrombolytic therapy.
Adult↗
Feasibility of prehospital r-TPA therapy in chest pain patients.
STUDY OBJECTIVE: The purpose of this study was to determine the number of eligible prehospital thrombolytic candidates and to estimate the potential time saved if field thrombolysis had been initiated in a series of prehospital chest pain patients. DESIGN AND SETTING: Prehospital 12-lead ECGs were obtained by paramedics during initial evaluation of chest pain patients and stored in the computerized ECG. Prehospital 12-lead ECGs, prehospital charts, and hospital charts then were reviewed retrospectively for final hospital diagnosis, prehospital and emergency department times, and historical exclusion criteria for prehospital treatment with recombinant tissue-type plasminogen activator (r-TPA). TYPE OF PARTICIPANTS: One hundred fifty-seven stable adult prehospital patients with a chief complaint of nontraumatic chest pain were enrolled. Six patients were excluded. Two had unretrievable 12-lead ECGs, and four refused paramedic transport and thus provided no further data. There were complete data on 151 patients making up the final study population. INTERVENTIONS: Prehospital care was unaltered except for acquisition of 12-lead ECGs. No prehospital thrombolytic therapy was administered during this study. MEASUREMENTS AND MAIN RESULTS: The incidence of r-TPA exclusion criteria was as follows: 45 patients (29%) were 75 years of age or older, 57 (38%) had chest pain for more than six hours, 24 (16%) had hypertension with blood pressure of more than 180/110 mm Hg, and six (4%) had a history of a cerebrovascular accident. The time from paramedic scene arrival to prehospital ECG (8.4 +/- 5.1 minutes) was significantly shorter than the time from ED arrival to ED ECG (24.2 +/- 21.6 minutes, P less than .001). Prehospital ECGs increased paramedic scene time over a retrospective control by 5.2 minutes. Mean time from prehospital ECG to ED ECG (potential time saved) was 50.2 + 22.4 minutes in all patients and 43.4 +/- 7.7 minutes in patients with a final diagnosis of acute myocardial infarction (P = NS). Thirteen of 151 patients (8.6%) had prehospital ECGs diagnostic for acute myocardial infarction; eight of these (5.3% overall) met criteria for prehospital r-TPA therapy. CONCLUSION: Prehospital 12-lead ECGs provide an ECG diagnosis 40 to 50 minutes earlier than ED ECGs. However, with current exclusion criteria, the number of prehospital r-TPA candidates is limited.
Aged↗
Toxicity and kinetics of [3H]microcystin-LR in isolated perfused rat livers.
Isolated rat livers were perfused for 60 min with either 0.3 or 0.5 microgram/ml (initial volume, 119 ml) of [3H]microcystin-LR at a constant flow of 10 ml/min in a recirculating system. During the 60-min exposure, toxin caused stimulation of glycogenolysis, liver engorgement, and cessation of bile flow. Electron micrographs of liver showed dilation of bile canaliculi and the space of Disse. loss of sinusoidal lining architecture, and decreased hepatocyte intercellular contacts. Although hepatocytes did not exhibit overt necrosis, mitochondria were hydropic, occasionally encircled by whorls of rough endoplasmic reticulum, and desmosomal tonofilaments were decreased on the plasma membrane lateral surface. Isolated mitochondria displayed inhibition of state 3 respiration and a 50-60% decrease in the respiratory control index, characteristic of hydropism. Distribution of radiolabel was 1.7% to bile, 79% to perfusate, and 16% to liver. Two to four percent was recovered in perfusate that leaked from the surface of the liver. Of the radiolabel found in bile and perfusate, 78 and 100% were associated with parent toxin, respectively. The radiolabel in liver, associated with the cytosolic fraction (S-100), corresponded to parent toxin (15%) and to a more-polar component(s) (85%). The elimination half-life from perfusate was 130 +/- 10 min (0.5 microgram/ml) and the hepatic extraction ratio 0.07 +/- 0.01. Although the calculated hepatic extraction ratio was low, there was a significant accumulation of microcystin in the liver. Many toxic effects of microcystin in the perfused liver mimicked those observed in the whole animal, suggesting that this model can be used as an alternative to whole animals for screening of potential therapeutic agents.
Animals↗
Association of microcystin-LR and its biotransformation product with a hepatic-cytosolic protein.
Microcystin-LR (MCYST-LR), a cyclic peptide hepatotoxin, associates with high-molecular-weight, liver cytosolic components. Repetitive cycles of heat denaturation and pronase digestion released 80 +/- 6% of the bound radiolabel from these components, parent toxin (22%), and two biotransformation products, with high-performance liquid chromatography (HPLC) retention times of 6.7 (52%) and 5.6 (13%) min. Both parent and the biotransformed (6.7 min) toxin appeared to be covalently bound to a monomeric protein of molecular weight 40,000 (protein plus radiolabeled toxin). Binding and biotransformation reactions were time- and temperature-dependent and did not require endogenous molecules less than 6,000 daltons. The binding appeared to be saturable with a maximum of 20 pmol MCYST-LR bound per mg protein. The binding protein(s) and biotransformation activity were present in rat liver, brain, kidney, heart, lung, small intestine, large intestine, testes, skeletal muscle, and to a lesser extent, in fat. Okadaic acid, a specific protein phosphatase inhibitor, showed a concentration-dependent inhibition of [3H]MCYST-LR binding to hepatic cytosol. The molecular weight and organ distribution of the binding protein(s), and inhibition of binding by okadaic acid were consistent with one of the binding sites being the catalytic subunit of protein phosphatase type 2A.
Animals↗
Hepatotoxicity of microcystin-LR in fed and fasted rats.
The LD50 (25 hr, i.p.) for microcystin-LR in fed rats (122 micrograms/kg) was significantly higher than that in fasted rats (72 micrograms/kg). At doses of 100, 150 and 200 micrograms of microcystin-LR per kg, the median times to death were 31.9, 18.2 and 11.2 hr for fed rats, and 1.8, 1.7 and 1.5 hr for fasted rats. A sublethal dose of microcystin (50 micrograms/kg) afforded protection to fasted, but not fed, rats against a subsequent lethal dose (200 micrograms/kg) challenge given 72 hr later. Biochemical and ultrastructural changes resulting from microcystin-LR (100 micrograms/kg, i.p.) were compared in fed and fasted rats 1 hr after injection. In both groups, liver weight and serum levels of sorbitol dehydrogenase and glucose significantly increased. Plasma membranes, isolated from livers of fed or fasted rats, exhibited similar toxin-induced changes in associated cytoskeletal elements. Liver mitochondria from toxin-treated, fasted rats exhibited complete inhibition of state 3 respiration, while those from toxin-treated, fed rats had ADP/O ratios and respiratory control indices comparable to control values. The primary event responsible for enhanced microcystin hepatotoxicity in the fasted state has not yet been identified. Depletion of glycogen stores and a decreased respiratory capacity may, however, play significant roles in this degenerative process.
Animals↗
Effects of hypertension on the intercellular contacts between smooth muscle cells in the rat thoracic aorta.
A qualitative and quantitative study was made of the contacts between muscle cells in the media of the thoracic aorta of hypertensive and normotensive Sprague-Dawley rats. In ultrathin sections, the type and number of contacts per 100 microns cell perimeter and per 100 cell profiles were determined using an image analysis computer. The intercellular contacts in both groups were in the form of simple appositions, interdigitations, intermediate junctions and nexus junctions. In the hypertensive group, there was a reduction in the number of simple appositions and intermediate junctions, but the nexus junctions (which provide intercellular communication) were increased in density. Interdigitations demonstrated no change. Decreased intercellular cohesion may play an important role in the mechanisms by which hypertension predisposes degeneration of the media with progression to ectasia, aneurysm formation and dissection.
Animals↗
The influence of egg sequence position on fertility, embryo viability, and embryo weight in broiler breeders.
A study was undertaken to determine whether fertility, early embryo viability, and the weight of the egg, shell, and embryo are influenced by the position of an egg in a laying sequence. One hundred and three Indian River broiler breeder hens were housed individually in cages at 21 wk of age. Beginning at 43 wk of age, each hen was inseminated once per week, with 50 microL of fresh undiluted pooled semen from Indian River broiler breeder males. Beginning at 45 wk of age, and for the following 45 days, all eggs laid were collected. Eggs were collected hourly for 8 h after "lights on" and a final daily collection was made 14 h after lights on. Each egg was classified as "first-of-sequence" or "subsequent". Eggs were weighed and placed in a forced-air incubator twice per week. After 168 h of incubation, the eggs were removed from the incubator, weighed and assessed for fertility and embryo viability status. The embryo was also weighed. Shell weight was recorded after 3 to 4 days of air drying. Egg weight was significantly greater in first-of-sequence compared with subsequent eggs. First-of-sequence eggs exhibited significantly smaller Day 7 embryos (on a percentage basis), lower shell weight (on a percentage basis), and significantly less egg weight loss during the 7 day incubation period (absolute and percentage basis) than did subsequent eggs on a sequence. Least squares (LS) means for fertility did not differ significantly between first (87.02%) and subsequent (89.56%) eggs.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Tissue distribution, excretion and hepatic biotransformation of microcystin-LR in mice.
The distribution, excretion and hepatic metabolism of [3H]microcystin-LR (sublethal i.v.) were measured in mice. Plasma elimination was biexponential with alpha- and beta-phase half-lives of 0.8 and 6.9 min, respectively. At 60 min, liver contained 67 +/- 4% of dose. Through the 6-day study the amount of hepatic radioactivity did not change whereas 23.7 +/- 1.7% of the dose was excreted; 9.2 +/- 1.0% in urine and 14.5 +/- 1.1% in feces. Approximately 60% of the urine and fecal radiolabel 6 and 12 hr postinjection was the parent toxin. Hepatic cytosol, which contained 70 +/- 2% of the hepatic radiolabel (1 hr through 6 days), was prepared for high-performance liquid chromatography analysis by heat denaturation, pronase digestion and C18 Sep Pak extraction. At 1 hr, 35 +/- 2% of the radiolabel was insoluble or C18 Sep Pak-bound; 43 +/- 3% was associated with a peak of retention time (rt) 6.6 min, and 16 +/- 3% with the parent toxin (rt 9.4 min). After 6 days, 8 +/- 1% was C18 Sep Pak-bound or insoluble; 5 +/- 0% occurred at rt 6.6 min, 17 +/- 1% with parent and 60 +/- 2% was associated with rt 8.1 min. Two other peaks, rt 4.9 and 5.6 min, appeared transiently. Analysis of hepatic cytosol by desalting chromatography under nondenaturing and denaturing conditions revealed that all of the radiolabel was associated with cytosolic components, and 83 +/- 5% was bound covalently through 1 day. By day 6 the amount of covalently bound isotope decreased to 42 +/- 11%. This is the first study to describe the long-term hepatic retention of microcystin toxin and documents putative detoxication products.
Animals↗
Effects of progesterone and human chorionic gonadotrophin administration five days postinsemination on plasma and milk concentrations of progesterone and pregnancy rates of normal and repeat breeder dairy cows.
Treatment with a progesterone-releasing intravaginal device between days 5 and 12 after estrus elevated (p less than 0.05) plasma progesterone concentrations between days 6 and 8 in comparison with controls. Treatment with injectable progesterone (200 mg) on days 5, 7, 9 and 11 postestrus did not increase plasma progesterone concentrations over controls. The administration of 1500 IU human chorionic gonadotrophin (hCG) on day 5 after estrus resulted in a sustained increase (p less than 0.01) in plasma progesterone concentrations from day 8 until day 20 when measurements ceased. Pregnancy rates, as a result of artificial insemination (AI) at the pretreatment estrus, in these treatments (n = 12-14 each), were unaffected by any of the treatments and ranged from 57.1 to 75.0% at 45-60 days post-AI. In a field trial, of 36 repeat breeder cows treated with 1500 IU hCG 5.5 days after insemination, 47.2% were pregnant at 60 days, whereas 39.5% of saline-treated controls were diagnosed pregnant. Treatment with hCG significantly (p less than 0.05) increased milk progesterone concentrations over controls on days 14 and 20 after insemination.
Administration, Intravaginal↗
Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats.
The toxic effects of microcystin-LR, a cyclic heptapeptide isolated from the cyanobacterium Microcystis aeruginosa, were studied in the fasted rat model and in subcellular fractions from fasted, toxin-treated and control rats. Hepatotoxic effects of a lethal dose (100 micrograms/kg) were examined 15-90 min post-injection. Elevations of serum enzymes, particularly sorbitol dehydrogenase, specific for liver mitochondria, correlated with hepatic damage. Electron micrographs showed progressive cellular disruption, including dilation of rough endoplasmic reticulum, incorporation of cellular components into cytolysosomes, hydropic mitochondria devoid of electron-opaque deposits, loss of desmosome-associated intermediate filaments, disruption of sinusoidal architecture and, ultimately, lysis of hepatocytes. The appearance of hydropic mitochondria correlated with loss of coupled electron transport. Changes in plasma membrane-associated cytoskeletal filaments correlated with loss of desmosome tonofilaments. In contrast to in vivo exposure to microcystin-LR, in vitro exposure to toxin had no effect on mitochondria or cytoskeletal filaments, suggesting that the toxic effects observed in vivo were indirect and may be dependent on bioactivation of the toxin or a cascade of events not supported in in vitro models.
Adenosine Diphosphate↗
Characterization of chemically tritiated microcystin-LR and its distribution in mice.
Chemically tritiated microcystin-LR (spec. act. 194 mCi/mmol), purified to greater than 95% by C-18 reverse-phase high performance liquid chromatography, exhibited the same retention time and ultraviolet absorption profile as unlabeled toxin. Acid-hydrolyzed [3H]-toxin yielded tritiated glutamate and beta-methylasparate. Stability of the nonexchangeable [3H]-toxin in saline and urine was greater than 93% after 42 days stored at 22 degrees, 4 degrees or -20 degrees C. In blood, the breakdown of toxin was temperature- and time-dependent (63% at 22 degrees C, 28 days). Unlabeled toxin was stable for greater than 42 days stored at either 4 degrees or -20 degrees C in saline. The LD50 (mouse, i.p.) of [3H]-microcystin-LR and unlabeled toxin was the same [75 micrograms/kg (65-90) and 65 micrograms/kg (53-80), respectively]. From 3 to 90 min after i.p. injection of 70 micrograms/kg [3H]-microcystin-LR there was a slow absorption of toxin from the peritoneal cavity and efficient accumulation in liver. The elimination half-life of the plasma concentration curve was 29 min. Tritium distribution in tissue at death or 6 hr post injection was similar for all doses (13-101 micrograms/kg). At 101 micrograms/kg, liver contained 56 +/- 1%, intestine 7 +/- 1%, kidney 0.9 +/- 0.2% and carcass 10 +/- 1% of the injected dose. Heart, spleen, lung and skeletal muscle contained less than 1% of the radiolabel.
Animals↗
Effect of treatment with progesterone on pregnancy rate and plasma concentrations of progesterone in Holstein cows.
Progesterone-releasing intravaginal devices inserted into the vaginas of dairy cows between d 5 to 12 (n = 28) or d 10 to 17 (n = 27) after insemination increased pregnancy rate to 60 over 30% in untreated control cows (n = 30). Plasma progesterone concentrations were increased during both progesterone treatments. Subtraction of the estimated contribution of exogenous progesterone indicated that endogenous, luteal progesterone was reduced during d 10 to 17 but not during d 5 to 12. Supplemental progesterone increased pregnancy rate but suppressed endogenous production of progesterone when administered during d 10 to 17 after insemination.
Administration, Intravaginal↗
Polyphosphate kinase from Propionibacterium shermanii. Demonstration that polyphosphates are primers and determination of the size of the synthesized polyphosphate.
Polyphosphate kinase from Propionibacterium shermanii was purified to 70% homogeneity and shown to be a monomeric enzyme of molecular weight 83,000 +/- 3,000. It was demonstrated that short chains of polyphosphate serve as primers by using [32P]polyphosphate, 6-80 residues in length for synthesis of long-chain polyphosphate glucokinase, the radiolabel was found to be at the end of the polymer, proving that the mechanism of elongation of polyphosphate by polyphosphate kinase is strictly processive. Only 1 out of 3-8 of the polyphosphate chains contained the primer, indicating that there is a second unknown pathway of initiation which does not involve the polyphosphate primer. The termination of polyphosphate synthesis was investigated. With polyphosphate as a primer, the majority of the synthesized polyphosphate was 750 residues in length. With phosphate, in place of the polyphosphate primer, the major portion was about 2,000 residues in length but there was a large span of chain lengths down to 300. Termination is influenced by pH, temperature, and the concentration of the polyphosphate primer, with the chain length decreasing as either the temperature or the concentration of primer is increased.
Adenosine Triphosphate↗
Polyphosphate kinase from Propionibacterium shermanii. Demonstration that the synthesis and utilization of polyphosphate is by a processive mechanism.
The mechanism of synthesis of inorganic polyphosphate by polyphosphate kinase (EC 2.7.4.1) from Propionibacterium shermanii is shown to be processive. Analysis of the synthesized polyphosphate on polyacrylamide gels, which resolve on the basis of molecular weight, proves that the elongation reaction occurs without dissociation of intermediate sizes of the polymer from the enzyme. As a consequence, only high molecular weight polyphosphates are synthesized. The mechanism is processive both in the presence and absence of basic protein. It has been shown previously that basic proteins stimulate the synthesis of polyphosphate (Robinson, N.A., Goss, N.H., and Wood, H.G. (1984) Biochem. Int. 8, 757-769). In addition, using a similar method, it is shown that the reverse reaction, the utilization of polyphosphate to phosphorylate ADP, occurs by a processive mechanism. Accordingly, polyphosphates formed by polyphosphate kinase in the cell would be entirely high molecular weight.
Kinetics↗
Cardiac angiosarcomas. A review and a case report.
Forty-five cases of cardiac angiosarcomas were reviewed, and the data were compared with those of a 1968 review of 41 other cases which revealed these tumors to be typically located within the right atrium as large symptomatic masses and to be rapidly fatal, with the diagnoses usually determined only at autopsy. The relationship of these tumors to Kaposi's sarcoma was also examined. The findings paralleled those of the previous review. Additionally, the following points emerged: With the aid of newer imaging techniques, localization, biopsy diagnosis and resection of the atrial tumors are now being achieved more often, with some improvement in survival. Like angiosarcomas of other organs, atrial angiosarcomas exhibit highly variable histologic patterns, which often overlap those of Kaposi's sarcoma, and may also present metastatic patterns simulating widespread Kaposi's sarcoma or malignant melanoma. In reported cases of classical, endemic, or epidemic Kaposi's sarcoma, cardiac lesions are uncommon and typically are small, asymptomatic, restricted to the epicardium/or pericardium and, thus, are clearly different, both clinically and pathologically, from the atrial tumor group. The justification for designating cases of the latter group as "primary cardiac Kaposi's sarcoma" is open to debate. A case report illustrates many of the above points.
Adult↗