Clinical. 4. Naturally occurring risks.
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Carcinogens↗
Biomedical subjects
M Wright
Publications and source records attributed to M Wright.
Relationships between the structures of taxol and baccatine III derivatives and their in vitro action on the disassembly of mammalian brain and Physarum amoebal microtubules.
The in vitro disassembly of microtubules from mammalian brain and Physarum is inhibited by various derivatives of taxol and baccatine III. Structure-activity relationships of the taxol derivatives were identical for both mammalian brain and Physarum microtubules. This observation suggests that the site of action of taxol has been preserved during the evolution of these two different eukaryotic lines. The substituent at C-13 of taxol was required to prevent disassembly of brain microtubules with or without microtubule-associated proteins. In contrast, both taxol and baccatine III prevented the disassembly of Physarum microtubules to the same extent, showing that the substituent at C-13 was not required in the interaction with Physarum tubulin. The different effects of baccatine III and taxol derivatives indicate that measuring the disassembly of microtubules from different organisms could be a useful parameter in the search for derivatives exhibiting antiparasitic activity.
Alkaloids↗
Recent advances in the diagnosis and management of tumors of the central nervous system in children.
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Brain Neoplasms↗
Induction of polyploid nuclei in the plasmodium of Physarum polycephalum by platinum antitumor compounds.
The intranuclear mitosis of the plasmodial nuclei of myxomycetes permits the observation of defects in chromosomal repartition which would probably be lethal in other eukaryotic cells with open mitosis. We found that antitumoral platinum-amine compounds perturbed late mitotic events and induced the formation of giant nuclei which were polyploid in plasmodia of Physarum polycephalum. Using 26 platinum-amine complexes, we have shown that all antitumoral compounds induced the formation of polyploid nuclei for drug concentrations at least three times lower than the amount necessary to block the overall plasmodial growth, whereas platinum compounds without antitumor activity did not behave this way. DNA replication appeared to be quantitatively normal during formation of giant nuclei by antitumoral compounds. These observations suggest that platinum-amine compounds exert their antitumor activity by interfering with mitosis rather than by a gross inhibition of DNA synthesis.
Cell Nucleolus↗
Analgesic effects of butorphanol in horses: dose-response studies.
The analgesic effects of butorphanol (0.05, 0.1, 0.2, and 0.4 mg/kg), pentazocine (2.2 mg/kg), and butorphanol vehicle (0.04 ml/kg) were observed in 6 horses. These horses were instrumented to measure response objectively to painful superficial and visceral stimuli. The tested drugs were given IV according to a Latin square design. After preinjection base-line measurements were made, the analgesic effects were observed at 15 and 30 minutes and then at 30-minute intervals until postinjection minute 240. Analgesic effects of butorphanol were dose-related, with durations between 15 and 90 minutes. Duration of analgesia after pentazocine (2.2 mg/kg) was given was between 15 and 30 minutes. When compared with pentazocine, the 0.4 mg/kg dose of butorphanol provided a more intense and longer period of analgesia. A butorphanol dose of 0.2 mg/kg IV appears optimal. On a dose-body weight basis, the potency of butorphanol was 10 to 17 times that of pentazocine. Behavioral side effects were noted with both agents and were dose-related.
Analgesia↗
Effects of butorphanol, flunixin, levorphanol, morphine, and xylazine in ponies.
The analgesic and behavioral effects of butorphanol (0.22 mg/kg), flunixin (2.2 mg/kg), levorphanol (0.033 mg/kg), morphine (0.66 mg/kg), and xylazine (2.2 mg/kg), given IM were observed in 8 ponies. These ponies were instrumented to measure response objectively to painful superficial and visceral stimuli. Effects on the cardiopulmonary system and rectal temperature also were evaluated in 6 of these ponies. Observations were conducted before drug injection (base-line values) and after injection at 30, 60, 120, 180, and 240 minutes. Xylazine provided the highest pain threshold for the first 60 minutes and a sedative effect for 105 minutes. The effects for superficial pain and visceral pain persisted 3 hours and 4 hours, respectively. Morphine produced good analgesia for superficial pain (30 minutes), whereas butorphanol provided good effect for visceral pain (4 hours). A slight degree of analgesia for visceral pain was obtained after morphine (1 hour) and levorphanol (4 hours); flunixin did not induce analgesia. Butorphanol, levorphanol, and morphine stimulated motor activity. Behavioral effects did not occur after flunixin was given. Xylazine decreased systolic, diastolic, and mean blood pressures. Marked increases in these pressures, heart rate, and respiratory rate were observed after morphine was given. Changes of central venous pressure, rectal temperature, and blood gas values remained within base-line limits after both drugs were given. Butorphanol increased heart rates for 1 hour; flunixin and levorphanol did not alter any of the above values.
Analgesia↗
Clinical. 2. Eating your defences.
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Dietary Fiber↗
Inactivation of the beta-adrenergic receptor in skeletal muscle by dithiols.
The effect of sulfhydryl compounds on binding of the beta-adrenergic antagonist (-)-[3H]dihydroalprenolol [(-)-[3H]DHA] to a microsomal fraction from rabbit skeletal muscle was examined. Inhibition of binding by a variety of adrenergic agonists and antagonists and the effects of these agents on adenylate cyclase were consistent with the beta-adrenergic receptor in this tissue being of the beta 2-subtype. Binding of (-)-[3H]DHA was reduced by incubating the membranes with dithiols such as dithiothreitol (DTT), 1,3-dimercapto-2-propanol and 1,4-dimercaptobutane; monothiols were much less potent. DTT-induced decline in (-)-[3H]DHA binding resulted primarily from a decrease in receptor number. Inactivation was partially reversed by the oxidant H2O2. Binding sites could be locked in the inactivated state by incubating DTT-treated membranes with the alkylating agent iodoacetamide. Both beta-adrenergic agonists and antagonists protected against inactivation. Adenylate cyclase activity in the membranes was increased by DTT. The enzyme was rapidly inactivated by H2O2, and this could be partially reversed by DTT. It is concluded that the beta-adrenergic receptor of skeletal muscle contains an essential disulfide moiety which can be inactivated by reducing dithiols. Adenylate cyclase, on the other hand, contains at least one essential sulfhydryl which is preserved by dithiols.
Adenylyl Cyclases↗
Density and ultrastructure of mast cells in lung vessels of aging rats exposed to and recovering from chronic hypoxia.
A decrease in pulmonary vascular responsiveness in aging animals during exposure to chronic hypoxia has been previously reported; however, morphological documentation is lacking. Lungs from young (3-5 months) and aging (12-14 months) Sprague-Dawley rats, exposed to and recovering from chronic hypoxia, were morphometrically analyzed at the light-microscopic level for changes in perivascular mast cells, and at the electron-microscopic level for cellular alterations. While young rat lungs showed proliferation of mast cells around elastic and muscular pulmonary arteries and arterioles, perivascular mast cell density in lungs of aging rats was significantly greater than in young rat lungs. At the ultrastructural level, perivascular mast cells in aging hypoxic rats showed numerous profiles of cellular extensions that contained remnants of discharged secretory vesicles. The results suggest that increased proliferation of perivascular mast cells as well as increased secretory activity of vasoactive substances in aging animals might represent a humoral determinant of the hyporesponsiveness of pulmonary vessels that occurs with increasing age during chronic hypoxia.
Aging↗
Characterization of the thymidine kinase of Physarum polycephalum.
Thymidine kinase [ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21] has been purified more than 3,500 fold from microplasmodia of Physarum polycephalum. Properties of the enzyme were determined on preparations purified 1,400 fold. Thymidine was transformed to dTMP while a stoichiometric quantity of ATP was transformed to ADP. 5-Iododeoxyuridine, 5-bromodeoxyuridine, and 5-fluorodeoxyuridine acted as competitive inhibitors for the thymidine substrate while 5-bromodeoxyuridine could be used as a substrate. In contrast uridine did not inhibit the enzymatic activity while deoxyuridine was a very poor competitive inhibitor in agreement with the observation that deoxyuridine could not be used as a substrate. Two apparent Michaelis constants were found for thymidine. Only the highest Michaelis constant could be decreased in the presence of increasing concentrations of ATP. Among the various nucleoside mono, di, or triphosphates studied only ATP and to a less extent dATP could be used as phosphate donors. A non competitive inhibition for thymidine was observed with dTTP. dTMP, dTDP, and dTTP acted as competitive inhibitors for ATP. None of the nucleoside mono, di, or triphosphates studied showed an activatory effect at low concentrations of ATP, even in the presence of dTTP. However, dUTP and dGDP acted as competitive inhibitors for ATP.
Cations, Divalent↗
A data management tool for reporting productivity.
Hospital-based occupational therapy departments in the 1980's must be able to report productivity levels in terms of cost-effectiveness. Only the most efficient programmes are likely to succeed in this era of budgetary constraints. A data retrieval model. operating in a hospital-based occupational therapy department is described. The model reports departmental productivity and data for making cost estimates related to direct and indirect patient care by diagnostic category. In addition, the system shows individual therapists' input and output. This data system has made possible monthly management statements that provide an overview of productivity and indicate the complexity of occupational therapy services for specific diagnostic categories within an acute-care paediatric hospital.
Efficiency↗
Cervical tracheoesophageal fistula.
Four unusual cases of cervical tracheoesophageal fistula (TEF) are presented. The incidence, diagnosis and treatment of cervical TEF are discussed. Surgically, if the location is above the level of T2 a cervical approach may be utilized. The cases included a cervical "H" type TEF occurring in an adult. Congenital "H" type TEFs frequently occur in the neck. An adult presenting with a cervical "H" type TEF, having as an infant undergone repair of a thoracic TEF, is unique. Two layer closure of both trachea and esophagus with strap muscle interposition is preferred. The other cases include a TEF secondary to metastatic breast carcinoma, one associated with a stomal recurrence, and an acquired TEF following laryngectomy. Metastatic breast carcinoma resulting in a TEF is reported for the first time. Malignant TEF's are usually secondary to carcinoma of the esophagus, lung, or thyroid. Best palliation is achieved either by esophageal intubation, by colon bypass, or by gastric pull-up with esophageal exclusion. Stomal recurrence with TEF following laryngectomy is treated with one-stage resection and reconstruction with a pectoralis major myocutaneous flap and gastric pull-up. A patient 5 years post-laryngectomy illustrates an acquired non-malignant cervical TEF, a category which includes fistulas due to trauma, tracheotomy, or endotracheal tubes, instrumentation, and inflammatory disease. Prompt surgical closure as in congenital cases is the treatment of choice although select cases require medical therapy.
Adult↗
Pharmacologic effects of ketamine and its use in veterinary medicine.
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Amphetamine↗
Acid-base and electrolyte values in dogs with acute gastric dilatation-volvulus.
Twenty dogs with acute gastric dilatation-volvulus (GDV) and 37 clinically normal dogs had arterial blood drawn for analysis of pH and blood gases. There was no statistically significant difference between values from the 2 groups. By calculation of the anion gap and by assessing arterial bicarbonate concentration, it appeared there were concomitant and offsetting factors, resulting in normal values for pH, blood gases, and anion gap in dogs with GDV. The results obtained indicated that sodium bicarbonate therapy should not be used in dogs with GDV.
Acidosis↗
Induction of heat-shock proteins at permissive growth temperatures in the plasmodium of the myxomycete Physarum polycephalum.
When synchronous plasmodia of the myxomycete Physarum polycephalum were submitted to temperature shifts from 22 degrees C to 32 degrees C, the highest physiological temperature, protein synthesis was increased during at least 10 h. Moreover during 2 h, four proteins (69, 74, 82 and 105 kDa) showed a transient increase of their synthesis, independently of the period of the temperature shift during the cell cycle. The stability of these proteins and the susceptibility of their synthesis to actinomycin suggested that they corresponded to four different proteins. Temperature shifts from 22 degrees C or 29 degrees C to 37 degrees C, a non-physiological temperature, demonstrated that the 69-kDa, 74-kDa, 82-kDa and 105-kDa proteins were identical to the four heat-shock proteins which could be detected in Physarum. Although the physiological significance of these heat-shock proteins remained unclear, comparison between the extent of their synthesis and the length of the mitotic delays induced by various temperature shifts ruled out a direct relationship between mitotic delays and synthesis of the 74-kDa, 82-kDa and 105-kDa proteins.
Fungal Proteins↗