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Biomedical subjects

S Nicol

Publications and source records attributed to S Nicol.

At least 37 records · Page 2Linked to original sources

Ca2+-dependent interaction with calmodulin is conserved in the synapsin family: identification of a high-affinity site.

The synapsins are a family of proteins associated with small synaptic vesicles that are implicated in synaptic maintenance and in the supply of vesicles for exocytosis. They are well characterized as substrates for protein kinases, and one class of synapsin, synapsin I, has been shown to bind, and be regulated by, calmodulin. A representative of the synapsin II class is now shown to bind calmodulin. Optical biosensor assays of Ca2+-dependent calmodulin binding to recombinant rat synapsin IIb indicated an apparent KD for calmodulin of 31 +/- 5 nM. Phosphorylation at Ser 10 increased the rates of calmodulin association (by a factor of 10) and dissociation (by a factor of 20). Fragment analysis and predictions from the sequence indicated two potential calmodulin binding sequences in the conserved central (C) domain. Peptides representing these sequences (residues 122-143 and 313-334 in synapsin IIb) were synthesized. Peptide 122-143 was found to bind calmodulin (KD 32 +/- 10 nM) and inhibit interaction of synapsin IIb with calmodulin. The interaction of peptide 313-334 was much weaker. Sequences similar to residues 122-143 are present in all published synapsin sequences. Calmodulin binding by synapsins seems not to be confined to mammals: a recombinant Drosophila synapsin 1 fragment containing part of the C-domain showed Ca2+-dependent binding to mammalian calmodulin. We conclude that calmodulin binding to synapsins is likely to be a general aspect of regulation of synaptic function.

Amine Oxidase (Copper-Containing)↗

Use of the respiratory stimulant doxapram in southern elephant seals (Mirounga leonina).

The use of doxapram to stimulate breathing was examined in southern elephant seals chemically restrained with ketamine and xylazine. Animals which were breathing spontaneously received doxapram (approximately 0.5, 1, 2, or 4 mg/kg) or saline into the extradural intravertebral vein. Doxapram caused a dose-dependent increase in the depth and rate of respiration which began within one minute, peaked after two minutes and lasted for up to five minutes. A dose of 2 mg/kg appeared to be safe and effective for the stimulation of respiration, while 4 mg/kg caused arousal and shaking. Doxapram (2 mg/kg) was tested on 14 occasions in animals which had developed apnoea during chemical restraint. Doxapram had no effect when administered into the extradural intravertebral vein and appeared to be of more benefit when administered directly into the lungs via an endotracheal tube, but it was not effective in all cases. There was evidence to suggest that the endotracheal tube prevented some of the animals from breathing. The effect of intubation and endotracheal doxapram administration was therefore examined in 19 apnoeic and 31 spontaneously breathing seals. Intubation induced apnoea in animals at low levels of chemical restraint and endotracheal doxapram was unreliable for the stimulation of breathing.

Animals↗

Chemical restraint of southern elephant seals (Mirounga Leonina); use of medetomidine, ketamine and atipamezole and comparison with other cyclohexamine-based combinations.

A study was conducted to assess the effectiveness of the alpha-2 agonist medetomidine for sedation of pre-moulting, mature female southern elephant seals (Mirounga leonina). Two animals were sedated with a single intramuscular dose of medetomidine (0.013 and 0.027 mg kg-1). A further two groups of five animals received medetomidine (0.017 mg kg-1) combined with ketamine (1.90 mg kg-1) and, 20 min later, either saline or the alpha-2 antagonist atipamezole (0.04 mg kg-1) intravenously. Medetomidine alone did not give sufficient restraint to permit intravenous access. The response appeared to be similar to previous findings with ketamine and xylazine. Administration of atipamezole had little effect upon the level and timecourse of restraint. Ketamine and medetomidine seem to offer few advantages over ketamine and xylazine or other cyclohexamine-drug combinations for routine chemical restraint of southern elephant seals.

Anesthetics, Dissociative↗

Antagonism of some cyclohexamine-based drug combinations used for chemical restraint of southern elephant seals (Mirounga leonina).

This study examined the use of 4 antagonists of chemical restraint in mature female southern elephant seals (Mirounga leonina) that were restrained with ketamine and diazepam, ketamine and xylazine, or tiletamine and zolazepam. The antagonists were: 4-aminopyridine, yohimbine, doxapram and sarmazenil. The effects of the antagonists on the animal's time to first movement forward and recovery, heart rate, respiratory rate and venous blood gas and pH values, and level of chemical restraint were recorded. Sarmazenil (1.0 mg/kg) and doxapram (5.0 mg/kg) partially antagonised 50:1 ketamine: diazepam (ketamine = 3.0 mg/kg, diazepam = 0.06 mg/kg) and tiletamine and zolazepam (tiletamine = 0.5 mg/kg, zolazepam = 0.5 mg/kg). However, the rapid recovery after low doses of anaesthetics means that antagonism is usually unnecessary, and it may increase the likelihood of shaking. Routine antagonism of ketamine and xylazine (ketamine = 3.0 mg/kg, xylazine = 0.5 mg/kg) is more useful given its usually delayed recovery time and potential for thermoregulatory problems. For this purpose yohimbine (0.06 mg/kg) offered advantages over doxapram in giving a smoother recovery with less aggression. 4-aminopyridine (0.2 mg/kg) prolonged chemical restraint by 100:1 ketamine:diazepam (ketamine = 3.0 mg/kg, diazepam = 0.03 mg/kg) and ketamine and xylazine, and should be contraindicated. Doxapram (5.0 mg/kg) was the most useful general antagonist for all groups of drugs but shaking was seen and a lower dose is recommended.

4-Aminopyridine↗

Use of midazolam, pethidine, ketamine and thiopentone for the restraint of southern elephant seals (Mirounga leonina).

Thirty-two pre-moulting female southern elephant seals (Mirounga leonina) were heavily sedated with midazolam (0.04 mg/kg) combined with pethidine (4 mg/kg). This combination made it possible to give the seals intravenous injections and was rapidly antagonised by naloxone. After sedation with midazolam and pethidine, 2 to 3 mg/kg intravenous thiopentone or ketamine induced light immobilisation for approximately five minutes and allowed the animals to be intubated. Prolonged deep levels of restraint were achieved after sedation with midazolam and pethidine by repeated intravenous doses of approximately 1.5 mg ketamine/kg at 10 minute intervals, to maintain restraint for 60 minutes.

Animals↗

Evolution of marsupial and other vertebrate thyroxine-binding plasma proteins.

Binding of radioactive thyroxine to proteins in the plasma of vertebrates was studied by electrophoresis followed by autoradiography. Albumin was found to be a thyroxine carrier in the blood of all studied fish, amphibians, reptiles, monotremes, marsupials, eutherians (placental mammals), and birds. Thyroxine binding to transthyretin was detected in the blood of eutherians, diprotodont marsupials, and birds, but not in blood from fish, toads, reptiles, monotremes, and Australian polyprotodont marsupials. Globulins binding thyroxine were only observed in the plasma of some mammals. Apparently, albumin is the phylogenetically oldest thyroxine carrier in vertebrate blood. Transthyretin gene expression in the liver developed in parallel, and independently, in the evolutionary lineages leading to eutherians, to diprotodont marsupials, and to birds. In contrast, high transthyretin mRNA levels, strong synthesis, and secretion of transthyretin in choroid plexus from reptiles and birds indicate that transthyretin gene expression in the choroid plexus evolved much earlier than in the liver, probably at the stage of the stem reptiles. NH2-terminal sequence analysis suggests a change of transthyretin pre-mRNA splicing during evolution.

Amino Acid Sequence↗

Chorionic villus sampling for fetal Rh typing: clinical implications.

OBJECTIVE: The prenatal Rh typing of red blood cells obtained by chorionic villus sampling was performed with an immune rosette technique. STUDY DESIGN: Ten Rh-negative pregnant women undergoing chorionic villus sampling at 9 to 11 weeks' gestation were studied at a large referral hospital. RESULTS: Accurate Rh phenotyping may be done on red blood cells obtained from chorionic villi weighing 2 to 8 mg. The preparations were shown to be greater than 90% fetal in origin as demonstrated by radial immunodiffusion quantitation of fetal hemoglobin-containing cells. Of the 10 fetuses typed in the first trimester nine of the pregnancies were carried to term. In all cases typing of red blood cells confirmed the antenatal fetal red cell typing. CONCLUSIONS: This study shows that antenatal Rh phenotyping may be performed as early as 9 to 11 weeks' gestation. This technique may be used in the management of pregnancies complicated by Rh incompatibility.

Blood Grouping and Crossmatching↗

Negative association between schizophrenia and rheumatoid arthritis.

Persuasive evidence has accumulated demonstrating a strong negative association between rheumatoid arthritis and schizophrenia at the population level. Explanations for this phenomenon have taken into consideration immunological, biochemical, and genetic factors. In this article, we examine these and other factors in closer detail. We then propose hypotheses at the molecular level that might account for the negative association between the two diseases. These hypotheses may provide clues for our colleagues in molecular biology as they search for candidate genes, "anti-genes," and molecular mechanisms relevant to schizophrenia.

Arthritis, Rheumatoid↗

Gas exchange during high-frequency ventilation in the pigeon (Columba livia).

We studied the effect of high-frequency ventilation (HFV) on the gas exchange of tracheotomized pigeons. The pigeons were artificially ventilated using a piston pump, which alternately connected the pigeons' airways to a constant-flow source. Two-minute periods of HFV were interposed between long periods of normal ventilation. The effect of HFV was assessed by the recorded changes in the PO2, PCO2 and pH of arterial blood and from the changes in the composition of the gas in the interclavicular air sacs. The results showed that HFV can augment gas exchange when the tidal volume (VT) is less than the volume of the anatomical dead space (VD). However, normal arterial gas composition can only be maintained if respiratory frequency is high (greater than 20 Hz). At the normal panting frequency of pigeons (7.8 Hz), gas exchange can thus only be maintained if tidal volume is approximately 125% of the dead space. When panting the VT must be greater than the VD. This finding agrees with the results of recent work showing flush-out- or compound-panting in birds: i.e. if, during panting, VT approaches close to the VD, intermittent interruptions, by taking deeper breaths in order to ensure a supply of fresh air to the lungs, are necessary.

Animals↗

Distribution of nicotinic binding sites with respect to CRF and neurophysin immunoreactive perikarya within the rat hypothalamus.

These studies determined the differential autoradiographic distribution of [125I]alpha-bungarotoxin versus [3H]nicotine relative to the histochemically defined perikarya for neurophysin and corticotropin releasing factor (CRF). Specific [3H]nicotine binding sites occurred in relatively greater density within the neuropil surrounding PVN and SON compared to within the nuclei. In contrast, the highest density of [125I]alpha-BTX sites codistributed with neurophysin immunoreactive perikarya within these nuclei.

Animals↗

Active cation transport and Na+K+Mg ATPase of the monotreme erythrocytes.

The erythrocytes of the echidna (Tachyglossus aculeatus) and platypus (Ornithorhynchus anatinus), which are practically devoid of intracellular ATP content (1), were examined for active Rb86 influx and for the presence of Na+K+Mg ATPase. We found that intact erythrocytes of both species possess the ability to actively transport cations. Ouabain sensitive Rb86 influx in the echidna was approximately 0.17 mumoles/ml cells x hr, whereas the platypus exhibited a higher value of 0.43 mumoles/ml cells x hr. Surprisingly, ouabain sensitive Na+K+Mg ATPase activity of isolated membranes was high amounting to some 15 to 25 fold higher than the human erythrocyte counterpart determined under identical conditions. These findings suggest that a trace amount of ATP is sufficient to maintain active cation transport across the monotreme cell membranes.

Animals↗

Metabolic properties of low ATP erythrocytes of the monotremes.

The erythrocytes of the monotremes, having a trace amount of ATP, can metabolize glucose to lactate at a rate comparable to human and other mammalian erythrocytes. The echidna energy metabolism is unique in that adenosine can stimulate glycolytic carbon flow, resulting in a nearly 20-fold net synthesis of ATP.

Adenosine Triphosphate↗

Ventilatory and circulatory changes during cold exposure in the Pekin duck Anas platyrhynchos.

Inspired ventilation (VI), O2 uptake (VO2), body temperature (TB), arterial blood pressure and arterio-venous differences in blood gases and pH were measured in ducks. Anas platyrhynchos, during exposure to variable ambient temperature (Ta) +20, 0 and -20 degrees C. A stable TB was maintained at all Ta's VO2 increased from 12.07 ml O2 (STPD) X kg-1 X min-1 at 20 degrees C to 28.95 ml O2 X kg-1 X min-1 at 20 degrees C. The ventilatory requirement (VI/VO2) changed from 0.468 L X mmol-1 at 20 degrees C to 0.322 L X mmol-1 at -20 degrees C corresponding to a change in overall O2-extraction from 28.5 to 41.4%. The increase in VI during cold exposure resulted from an increased tidal volume while breathing frequency was unchanged. This caused a smaller fraction of the total inspired air being dead space ventilation during cold exposure. The changed ventilatory requirement was largely the result of an increased parabronchial O2-extraction, whereas the altered ventilatory pattern accounted for a smaller part (21%) of the decreased ventilatory requirement. Arterial and venous O2 content and PaO2 changed little with cold exposure while PVO2 increased significantly. Calculated values for cardiac output increased from 173.7 ml X kg-1 X min-1 at +20 degrees C to 431.4 ml X kg-1 at -20 degrees C. From a thermoregulatory point of view it seems significant that the increased heat production during cold exposure is followed by an increased oxygen extraction in the lungs and in increased cardiac output, rather than by a further elevation of ventilation.

Animals↗

Erythrocyte phosphates and hemoglobin function in monotremes and some marsupials.

Hematologic values, red blood cell (RBC) organic phosphate composition, hemoglobin function, and hemoglobin composition have been determined on blood from the monotremes, the duckbill platypus and the echidna, and three species of marsupials, the Tasmanian devil, the wallaby, and the brush-tail possum. Blood from the platypus had a RBC count of 8.63 X 10(6)/mm3, a mean corpuscular volume of 49.1 millemicron3, and a white blood cell count of 26.0 X 10(3)/mm3. The RBCs from the monotremes and the three marsupials exhibited hemoglobin polymorphism, each with three hemoglobin components. Addition of ATP, 2,3-bisphosphoglycerate (2,3-P2-glycerate), or inositol pentakisphosphate (inositol-P5) to phosphate-free hemoglobin from each species decreased hemoglobin oxygen affinity; the order of effect of these compounds was ATP less than 2,3-P2-glycerate less than inositol-P5. The RBCs of all species had concentrations of 2,3-P2-glycerate ranging from 6.02 mumol/ml RBCs in the wallaby to 10.39 mumol/ml RBCs in the possum. The RBCs from the three species of marsupials had concentrations of ATP ranging from 0.24 mumol/ml RBCs in the possum to 0.80 mumol/ml RBCs in the Tasmanian devil. The level of ATP in RBCs of the platypus and echidna were 0.06 and 0.03 mumol/ml RBCs, respectively.

Adenosine Triphosphate↗