Quantitative histological evaluation of early fracture healing of cortical bones immobilized by stainless steel and composite plates.

Internal fixation devices of less bending stiffness than conventional plates made of stainless steel or vitallium were compared with conventional plates in a study of fracture healing. The material for this investigation was a fine graphite fiber reinforced methyl methacrylate resin composite with a modulus of elasticity approximately ten times less than that of stainless steel. Osteotomies were performed on canine radii. Internal fixation was accomplished by means of a composite plate on the left side, and a stainless steel plate on the right. Clinical assessment, as well as biomechanical and quantitative histological techniques, were used to compare osteotomy healing of the two sides. At four months, all osteotomies had healed and the bioengineering tests showed radii from the two sides had equivalent strength. However, significantly less cortical porosity was found in the side with the composite plate (6.8 per cent), as compared to that of the stainless steel plated side (14 per cent). These results suggest that a less stiff fixation plate may have some advantage in the treatment of long bone fracture if there is no implant failure, and if union rates are equivalent.


Frozen thin-sections of rapidly forming bone: bone cell ultrastructure.

Frozen thin-sections of fresh medullary bone, which had been calcifying for 2 to 4 days, were prepared and examined in the electron microscope. The bone was obtained from male Japanese quail treated with estradiol valerate. Large numbers of 200-800 A electron dense granules, which consisted of 50-75 A subparticles, were seen within mitochondria. A population of electron-dense particles slightly smaller than ribosomes was also observed. Most granules were not present after conventional fixation, dehydration, embedding, sectioning and staining. Oother structures which were visible, also on the basis of their intrinsic electron density, were nuclei with regions which resembled condensed chromatin, ribosomes and rough endoplasmic reticulum. By the use of osmium tetroxide vapor staining, inner and outer membranes and cristae of mitochondria were delineated. Other membranous components were not detected. Since very little loss or dislocation of cell components can occur during the preparation of frozen thin-sections, the micrographs obtained may be a more accurate representation of cell ultrastructure.


Reversible extinction of the morphogen in bone matrix by reduction and oxidation of disulfide bonds.

Beta-Mercaptoethanol (beta-ME) or dithiothreitol (DTT) reduction extinguishes the capacity of bone matrix gelatin to produce new bone following implantation in a muscle pouch. If the reducing solution is used in concentrations of 50 mmoles/l or less, the extinction can be partially reversed by bubbling of oxygen through the solution for one hour. Sulfhydryl group blocking reagents prevent reoxidation of reduced bone gelatin, and restoration of the bone morphogenetic property (BMP). Unspecific borohydride reduction at 37 degrees destroys bone yield irreversibly, but at 2 degrees reduction of free aldehyde groups in bone gelatin does not prevent beta-ME and DTT reversible extinction. These observations are interpreted to suggest that the disulphide linkage may be an essential part of the biologically active conformation of either a non-collagenous bone morphogenetic polypeptide firmly bound to collagen or a collagen by-product entrapped within a water insoluble gel matrix.


Pathogenesis of gangrene following intra-arterial injection of drugs: a new hypothesis.

We have demonstrated the toxicity of diazepam and the safety of ketamine hydrochloride following intra-arterial injection in an anaesthetized animal model. The pathogenesis of gangrene following intra-arterial injection of drugs is unclear. Clinical reports and this experiment suggest that it only follows injection of highly membrane-soluble drugs. Early swelling and disruption of capillary endothelial cells were demonstrated after intra-arterial injection of diazepam and thiopentone. We believe that a theory of pathogenesis based on this finding is consistent not only with our experimental findings, but with known in vitro effects of membrane soluble drugs on cell membranes and the clinical features following intra-arterial injections in both human subjects and in animals.


Pulmonary shunting during anaesthesia in man.

Qs/Qt was determined during halothane and oxygen anaesthesia in 22 patients. All were believed to have no pulmonary dysfunction. A surgical operation was in progress and respiration was controlled. Qs/Qt was minimal in 15 of these patients (means 3.9 plus or minus 0.3%), indicating that anaesthesia and operation can be conducted in man without a significant increase of pulmonary shunting. The level of shunting was increased in the other seven patients. In neither group was Qs/Qt altered by the passage of time. Age varied between 23 and 61 years and was directly and significantly correlated to Qs/Qt (r=0.57,P less than0.01).


Body build and preoperative arterial oxygen tensions.

Arterial oxygen tensions were determined in 35 supine unpremedicated surgical patients. Correlations were sought for age, weight, and weight/height, and Pao2. A definite, clear cut linear reduction of Po2 with age was found but not for weight alone. A relationship with weight/height ratio was found. If the weight/height related reduction in FRC following induction is added to that, two potential factors can be seen to contribute to intra-operative hypoxaemia. In a further 20 patients who received phenobarbitone premedication only, arterial oxygen tensions were found to be above the predicted line for their age. This is taken as evidence against respiratory depression due to premedication with barbiturates.


Airway closure in pregnancy.

Closing capacity (CC; the lung volume at which dependent lung zones cease to ventilate, presumably as a result of airway closure) and standard lung volumes were measured in twenty-four normal women 21 to 29 years of age in the seated and supine positions. Measurements were made serially during pregnancy and once 6 to 8 weeks post partum (the control period). CC was unchanged during pregnancy, while functional residual capacity (FRC) fell by approximately 15%. The difference between FRC and CC (FRC-CC) was reduced during pregnancy, but in one of the subjects when seated, and in only two supine subjects did CC exceed FRC. FRC-CC was reduced in the supine position as compared to seated. The reduced FRC-CC during pregnancy offers a potential explanation for the observations of abnormally low arterial oxygen tensions (Pao2) during pregnancy in some women, and of reduced Pao2 in pregnant women in the supine as compared to upright position.


The myocardial effects of pancuronium.

The effect of pancuronium on myocardial contractility was studied in three different animal preparations. Pancuronium produced no change in isometric contraction of rabbit atrial or cat papillary muscle but displaced the acetylcholine dose-response curve to the right in the papillary muscle preparations, verifying a muscarinic blocking effect of this drug. In atropinized dogs in vivo pancuronium produced no significant change in the cardiovascular parameters studied. These studies show that pancuronium exerts its cardiovascular effects primarily by blocking muscarinic receptors in the heart.


Use of chloroquine in shock.

One group of dogs received single doses of intramuscular chloroquine and another group served as a control. The dogs were subjected to haemorrhagic shock and then retransfused with their own blood after two hours of shock. The chloroquine-treated dogs had normal PA pressures after correction of acidosis and significantly smaller increases in the pulmonary vascular resistance. The results are similar but less marked than those obtained with aspirin. Chloroquine inhibited in vitro platelet aggregation by 50% and was not associated with any increased bleeding. This may be an advantage when used in patients with multiple trauma or increased bleeding tendency.


Effect of isoflurane anaesthesia and surgery on carbohydrate metabolism and plasma cortisol levels in man.

The present study was undertaken to investigate in nine male surgical patients the effects of isoflurane anaesthesia alone on the carbohydrate metabolism by determining plasma growth hormone (GH), insulin, blood glucose, and cortisol, and to compare them with the effects of anaesthesia associated with surgical operations. Determination of plasma GH, insulin, cortisol, and blood glucose were made simultaneously before induction of isoflurane anaesthesia, after maintenance of anaesthesia for 15 minutes and 30 minutes and during and after conclusion of the operation. Plasma GH concentrations showed a significant elevation during isoflurane anaesthesia, and maintained a similar high level one hour after the start of the operation. An insignificant elevation in plasma insulin level and significant increases in blood glucose were noted during anaesthesia and operation. Plasma cortisol levels increased insignificantly during anaesthesia, but increased markedly during operation. Our observations would suggest that the increased blood level of GH and elevated blood cortisol play a part in the increase of blood glucose during isoflurane anaesthesia and surgical operations in man.


Anaesthesia for dwarfs and other patients of pathological small stature.

Sixty-nine anaesthetics were administered to 29 patients of pathological proportionate and disproportionate small stature. The anaesthetic course in most cases was uncomplicated. The few complications noted were similar in type and severity to those found in normal size patients undergoing similar anaesthesia and operative procedures. Achondroplastic dwarfs often develop neurological problems due to their bony deformities. General anaesthesia should be given preferential consideration in these patients. Non-achondroplastic dwarfs may have an associated odontoid dysplasia and if the neck is placed in flexion there is a potential risk of spinal cord damage. Tube size for proportionately small children is best estimated from body weight. No definite recommendations concerning proper tybe size in dwarfs can be given on the basis of the findings in the study.


Anaesthetic considerations in bronchial adenoma.

The patient with bronchial adenoma can present a puzzling diagnostic dilemma as well as challenging problems in anaesthetic management. Several aspects are reviewed in this report. Diagnostically these include chest roentgenographic findings and unique pulmonary function test. Problems in anaesthetic management include possible development of acute carcinoid syndrome, as this tumour is usually of the carcinoid variety. In addition, the tumour may act as a ball valve, causing uneven ventilation of affected lung with expiratory air trapping. Several factors may necessitate prolonged bronchial blockage during anaesthesia. These include a friable mass which may bleed profusely upon manipulation, infected and atelectatic parenchymal tissue beyond the obstruction, copious volumes of purulent secretions, and one lung ventilation during resection.


Multiple anaesthetics in a patient with phaeochromocytoma.

A patient with phaeochromocytoma was anaesthetized on four seperate occasions. Some of the problems associated with this disease are discussed and recommendations for anaesthetic management are made.


A simple dichromatic densitometer for repeated measurements of cardiac output in small animals.

The construction of a simple device for continuous monitoring and recording of plasma indocyanine green concentration in small animals is described. The apparatus is designed to hold a vascular bed such as the ear or the omentum and to transilluminate it with white light from a fiber optic bundle. The transmitted light is divided by a dichroic mirror. Appropriate filters select a narrow band of frequencies from each segment. There are two photovoltaic cells, one sensitive to the dye and the other insensitive to it. Both are approximately equally reactive to changes in transilluminence caused by changes in blood content or hematocrit and are relatively insensitive to changes in oxygen saturation of the transilluminated blood. Reproducible estimates of cardiac output have been obtained with the injection of 300 mug indocyanine green in a volume of 20 mul with the densitometer applied to the small intestine or to the ear of the animal. The device responds linearly to increasing plasma indocyanine green concentrations and can be calibrated with less than 0.1 ml of blood.


Ontogenic pattern of dopamine, acetylcholine, and acetylcholinesterase in the brains of normal and hypothyroid rats.

The influence of neonatal thyroidectomy (Tx) on developmental changes in dopamine (DA), acetylcholine (ACh), and acetylcholinesterase (AChE) was studied in the whole brain of rats. In control animals, brain levels of ACh gradually increased and attained adult values at the 70th day. In contrast, AChE activity showed a rapid increase between the 7th and 30th days. Levels of DA were low during the early postnatal life but markedly increased to reach adult values of 1.47 mug/g at the 30th day, after which no further enhancement was noted. Neonatal Tx interfered with the normal growth of the animals, decreased brain weights, and markedly influenced the developmental pattern of both DA and ACh in the brain. The concentration of DA in 30-day-old hypothyroid rats was 46% of the control values. In contrast, brain ACh levels in Tx rats were consistently above those seen in controls, being significantly higher, by 49 and 64%, at 15 and 30 days, respectively. Activity of AChE in brains of hypothyroid animals was not significantly different from that in controls. Treatment of Tx rats with thyroid hormone virtually restored the levels of DA and ACh to values in control animals.


Time course of onset and decay of humoral natriuretic activity in the rat.

The natriuretic mechanism.tic activity shown in earlier cross-circulation experiments to develop in the blood of rats undergoing sustained vascular expansion has been further characterized. Following whole blood infusion and urine reinfusion of the donor rat, a cross-circulated isovolaemic partner exhibits a natriuresis of gradual onset, requiring 60-80 min to reach a peak (0.04-3.24 muequiv./min per gram kidney weight). The gradual feature of recipient natriuresis was unchanged by infusing the donor rat 1 h prior to cross-circulation. Once developed, the recipient natriuresis was sustained when fluid depletion by the renal response was prevented, but was reversible with a half-life of about 30 min on interruption of the cross-circulation; reconnection of cross-circulation promptly restored recipient natriuresis. No significant natriuresis (0.04-0.16 muequiv/min per gram kidney weight) occurred in the recipients if the donors in comparable cross-circulations were not infused. These findings confirm that a natriuretic activity develops in the blood as a consequence of vascular expansion, and reveal that the activity has a slowly developing and reversible action on the renal natriure


The effect of norethandrolone on organic ion transport by rat renal cortical slices.

Norethandrolone (NE) and other androgenic steroids have been shown to be renotropic in various species and have also been reported to have salutary effects in patients with diminished renal function. Renal cortical slices prepared from rats pretreated with NE showed an increased capability to concentrate p-aminohippuric acid (PAH). Pretreatment with NE failed to stimulate the transport of the organic base tetraethylammonium and the organic acid benzylpenicillin. Stimulation of PAH transport was observed after eight daily subcutaneous injections of NE. No stimulation was observed with shorter pretreatment intervals. When NE was given subcutaneously for 14 days at doses of 2.6 or 20 mg kg-1 day-1, significant stimulation of PAH transport was seen at all three dose levels but no dose-effect relationship was apparent. Stimulation of PAH transport was seen in female rats as well as castrated and intact males. In addition to its general anabolic properties, NE induces the synthesis of hepatic microsomal drug-metabolizing enzymes. For comparative purposes, therefore, the effect of pregnenolone-16 alpha-carbonitrile (PCN) was also investigated. This agent is a potent inducer of drug metabolism but is neither anabolic nor renotropic. When rats were pretreated with an inducing dose of PCN (75 mg kg-1 day-1 for 3 days), there was no significant stimulation of PAH transport. It would seem, then, that the stimulatory effect of NE on PAH transport is more closely associated with its generalized anabolic effect than with its ability to induce hepatic microsomal enzymes.


Kinetics of the red cell washout from coronary vessels of isolated feline hearts.

Twenty seven isolated feline hearts were perfused with cell-free oxygenated Ringer-Locke solutions. The concentration of red blood cells in samples of venous outflow collected from the coronary sinuses was determined by means of a Celloscope counter. Cellular concentrations decreased gradually as the perfusion time increased, and from 10(9) to 10(5) cells per millilitre after 300 ml perfusion. When the ventricular lumens were filled with residual blood (group I, 15 cats), several red cell peaks were superimposed on the smooth exponential decay curve of red cell washout. It is suggested that the peaks were caused by ejection of red cells from the ventricular lumens into communicating branches between the ventricular lumens and coronary capillaries. In cases of blood-emptied hearts (group II, 12 cats) these peaks did not occur, and mathematical analysis showed that summing three exponential functions could approximate the whole washout curve of red cells. This suggests that the coronary circulation may be described by three red cell compartments. The functional implication of this analysis for the microcirculation in the coronary vessels was discussed.


The development of sympathetic innervation and the functional state of the cardiovascular system in newborn dogs.

The present study in dogs indicates that the peripheral sympathetic fibers develop mostly after birth and reach a full maturity at about 2 months of life. The norepinephrine content of the heart, spleen, intestine, salivary glands, and adrenal glands increased from birth to 56 days of age. In contrast, the content of the stellate ganglia decreased during this period. In most of the organs studied, the uptake of [3H] norepinephrine developed in parallel with the norepinephrine content, except in the right atrium and salivary glands where it was fully developed soon after birth. During development, the systemic blood pressure increased from 40 to 100 mm Hg. Bilateral adrenal vessel clamping failed to induce a fall in blood pressure in growing dogs which indicates that the adrenal medulla or the baroreceptors did not fully compensate for the lack of peripheral sympathetic fibers and for the lower blood pressure in newborn animals. Although cardiac norepinephrine content was still very low in 10-day-old animals, cardiovascular responses to direct and reflex sympathetic stimulation were similar to those observed in 56-day-old animals. These results indicate that the sympathetic nervous system becomes functional before the fibers reach their full maturity.


Growth hormone and cortisol levels in the annual cycle of white-tailed deer (Odocoileus virginianus).

The annual cycles of growth hormone and cortisol levels in white-tailed deer were followed. No significant difference was found in the average cortisol levels in a large group of animals during the year. In contrast to cortisol, growth hormone (GH) investigated by heterologous bovine GH radioimmunoassay, seems to have a distinct annual rhythm. High levels of GH in plasma were found between casting and the first week of antler growth with the peak of 23.1 ng/ml (estimated in bovine GH equivalents) in the middle of April. From the middle of June until the middle of November a plateau averaging 3 ng/ml was found. The relationships between very rapid growth of a bone tissue and the influence of GH and sex hormones are discussed.


The effects of delta9-tetrahydrocannabinol on action potentials in the mollusc Aplysia.

The effects of delta9-tetrahydrocannabinol (delta9-THC) on action potentials were examined during intrasomatic recordings from the isolated buccal and parieto-visceral ganglia of Aplysia californica. When added to the saline solution bathing the preparation, the compound (in concentrations 10(-4) - 10(-5) M) caused a reduction in spike overshoot (15-20% of total amplitude) and increased the lability of responses to electrical stimulation. The somatic membrane appeared to be more affected than the axonal membrane. Diffusion barriers in the ganglion probably account for the high degree of variability in drug response, such that both of the characteristic changes were observed in only about 30% of the tests. This is the first report to describe effects of delta9-THC on invertebrate neurones. The results indicate that delta9-THC causes a depression in nerve cell excitability, and these data are consistent with reported effects of THC compounds in mammals.


The bronchodilator acitivity of an 11-deoxyprostaglandin (AY 23 578).

The bronchodilator activity of AY-23 578 was studied in vivo and in vitro techniques. In the conscious guinea pig, aerosols of AY-23 578, prostaglandin (PGE2) E2, and isoproterenol afforded significant protection against histamine-induced convulsions. In the anesthetized guinea pig, where changes in tracheal pressure were taken as an index of bronchoconstriction, AY-23 578, PGE2, and isoproterenol were equipotent in inhibiting the bronchoconstriction induced by histamine. AY-23 578, PGE2, and isoproterenol reduced or prevented neostigmine-, prostaglandin F2alpha- or carbachol-induced increases in pulmonary resistance, and decreases in dynamic compliance in the anesthetized cat. The activities of the former two compounds were qualitatively similar but less potent than isoproterenol. In both the guinea pig and the cat, the aerosol administration of effective bronchodilator doses of AY-23 578 did not exhibit any significant cardiovascular effects. Both AY-23 578 and PGE2 caused relaxation of the isolated guinea pig tracheal strip; PGE2 was about six times more potent than AY-23 578. It is concluded that AY-23 578 is an effective bronchodilator in both the guinea pig and cat.


The effect of cocaine on the responses of the differently innervated laryngeal and bronchial ends of the guinea pig trachea in vitro to clinically used bronchodilators.

Fluorescent histochemical studies indicate that guinea pig tracheal smooth muscle has sparse adrenergic innervation with the greatest nerve density being located at the laryngeal end. In the present study, log dose-response lines were obtained for dl-isoprenaline (ISO), l-adrenaline (ADR) l-noradrenaline (NOR), salbutamol (SALB), and orciprenaline on isolated tracheal chains prepared from both the laryngeal (L) and bronchial (B) ends of the trachea. Responses were obtained in the absence and presence of the Uptake1 blocker, cocaine (0.67 and 6.7 muM) which markedly potentiated responses to NOR and ADR but failed to significantly alter responses to ISO and SALB on L preparations. The degree of potentiation obtained on B preparations was significantly less for NOR and ADR and was not significant for the other agents. In addition, experiments were carried out on tracheal chains which developed their normal tone in the absence of carbachol, and also on preparations obtained from 6-hydroxydopamine treated animals. The present findings, based on selective potentiation of NOR and ADR, support evidence that the degree of adrenergic innervation to the guinea pig trachea is greater at the laryngeal end, and the results obtained with cocaine strengthen the argument that it has a pre-synaptic site of action.


Structure--activity relations for the acceleration of efflux of noradrenaline from adrenergic nerves in rabbit atria by sympathomimetic amines.

Atria from reserpine-pretreated rabbits were exposed to pargyline to inhibit monoamine oxidase (amine oxidase (flavin-containing) EC 1.4.3.4) and subsequently incubated in (-)-[3H]noradrenaline to allow the cytoplasmic accumulation of amine in adrenergic nerves. The structure-activity relations for acceleration of efflux of cytoplasmic amine were examined. The most potent agents studied were (+)- and (-)-amphetamine, beta-phenethylamine, phentermine, and mephentermine. Ability to accelerate efflux was reduced by addition of phenolic hydroxyl groups, by phenolic methylation, by beta-hydroxylation, and by N-substitution. The structure-activity relations for acceleration of efflux differ notably from those for uptake, inhibition of uptake, or release of noradrenaline from adrenergic nerves, reported in previous studies. The ability and potency of a given phenethylamine derivative to accelerate the efflux of cytoplasmic noradrenaline is probably determined by such factors as the lipid solubility of the amine, the affinity of the amine for the uptake and efflux site(s) for noradrenaline, and competition for any reserpine-resistant intraneuronal binding sites.


Contractile responses of canine isolated pulmonary lobar arteries and veins to norepinephrine, serotonin, and tyramine.

Isolated helical strips of canine intrapulmonary lobar arteries and veins (about 4 mm in diameter) undergo dose-related tension development when exposed to increasing concentrations (10(-8) - 10(-3) M) of norepinephrine (NE), serotonin or 5-hydroxytryptamine (5-HT) and tyramine (Tyr). Venous segments were generally more sensitive while the maximum tension development was greater in the arterial strips, probably owing to their greater thickness. Both strips were more sensitive to 5-HT than NE and only responded to Tyr at high concentrations. Norepinephrine and 5-HT were nearly equally efficacious, whereas Tyr was less so. Responses to the latter were slow to develop, exhibited tachyphylaxis, and were greatly inhibited by phentolamine (10(-8) M), an alpha-adrenergic blocker. Exposure to cocaine (10(-5) M) enhanced submaximal NE responses, inhibited Tyr contractions and had no consistent effect on 5-HT responses. Phentolamine (10(-8) M) was also found to inhibit NE responses without altering 5-HT probably acts on other receptors. Tyramine may, in part, act directly on alpha-adrenergic receptors but may also release NE from surviving adrenergic nerve terminals in the preparation. Cocaine inhibits this effect and potentiates responses to lower levels of NE, presumably by blocking NE uptake into nerve terminals although a post-junctional action cannot be excluded.


Effects of testosterone metabolites on serum gonadotropin concentrations in immature male rats.

The ability of testosterone, androsterone, 5alpha-androstane-3alpha,17beta-diol, and 5alpha-androstane-3beta,17beta-diol to prevent the castration-induced rise in serum gonadotropin levels was investigated in immature male rats. Rats castrated at 30 days of age were treated once per day by subcutaneous injection of 12.5-100 mug of the steroid per 100 g body weight per day for 3 days, beginning on the day of castration. The animals were sacrificed 24 h after the last injection. Testosterone propionate, androsterone propionate, and 5alpha-androstane-3alpha,17beta-diol dipropionate were also tested at the approximate molar equivalent of 100 mug of the free alcohol form per 100 g body weight per day. Testosterone propionate and 5alpha-androstane-3alpha,17beta-diol were the only compounds tested that prevented the castration induced rise in luteinizing hormone (LH) concentrations. Testosterone propionate also inhibited the rise in follicle stimulating hormone (FSH) concentrations whereas 5alpha-androstane-3alpha,17beta-diol inhibited the rise in FSH in one but not in another experiment. These were the only compounds tested that affected serum FSH concentrations. The lower doses of testosterone tested significantly increased serum LH, but not FSH concentrations compared to castrate control animals. The highest dose tested partially inhibited the rise in serum LH concentrations. Both androsterone and androsterone propionate maintained ventral prostate weights. Although neither compound prevented the castration induced rise in serum LH, two groups receiving androsterone had serum LH concentrations significantly lower than the castrate control group. 5alpha-Androstane-3beta,17beta-diol and 5alpha-androstane-3alpha,17beta-diol dipropionate failed to maintain ventral prostate weights or prevent the rise in serum gonadotropin levels. These results indicate that 5alpha-androstane-3alpha,17beta-diol is capable of preventing the castration induced rise in serum LH concentrations in the immature male rat and thus may participate in the regulation of LH secretion in these animals.


Effects produced by local applications of harmaline in the inferior olive.

Local microinjections of harmaline evoked sustained rhythmic activity in the inferior olive of decerebrate cats. Harmaline appears to exert its action within restricted areas of the inferior olivary complex: the caudal halves of the dorsal and medial accessory nuclei. Since the highly synchronized activity generated by harmaline can be attributed to extensive electrotonic coupling between olivary neurones, it is postulated that such a coupling mechanism is weaker if not absent in the principal olive and in the rostral parts of the accessory nuclei.


Reversal of insulin resistance by ATP in hemorrhagic shock.

Hemorrhagic shock was produced by bleeding rats to a mean arterial pressure of 40 mm Hg (1 mm Hg = 133 N/m2), which was maintained for 2 h. Muscles from these animals ('shock' muscles) showed resistance to the stimulation of glucose uptake by insulin. Addition of 1 mM ATP-MgCl2 to the medium had no effect on basal glucose uptake in either group of muscles, but it permitted insulin to exert its stimulatory effect in 'shock' muscles. An optimal insulin effect on glucose uptake in 'shock' muscles incubated without ATP was observed at an insulin concentration of 0.2 Unit/ml. When 1 mM ATP-MgCl2 was added to the medium, optimal insulin effect in 'shock' muscles was observed at an insulin concentration of 0.007 Unit/ml. Increasing the concentration of ATP-MgCl2 to 2.5 mM in the medium resulted in an optimal insulin effect at an insulin concentration of ATP-MgCl2 to 2.5 mM in the medium resulted in an optimal insulin effect at an insulin concentration of 0.001 Unit/ml in 'shock' muscles. Following 1 h cubation in Krebs-HCO3 medium, intracellular ATP contents of 'shock' muscles were approximately 50% lower than in control muscles. Addition of 1 mM ATP-MgCl2 to the incubation medium had no effect on the intracellular ATP contents of either group of muscles following incubation; however, 2.5 mM ATP-MgCl2 elevated intracellular ATP contents of 'shock' muscles but had no effect in control muscles. Possible mechanisms for this reversal of insulin resistance by ATP-MgCl2 in shock are discussed.


Water, cations, and norepinephrine content of cardiovascular tissues of unilaterally nephrectomized dogs treated with deoxycorticosterone and NaCl.

Deoxycorticosterone pivalate (2.5 mg/kg) given intramuscularly on four occasions 10-15 days apart over a period of 45 days to unilaterally nephrectomized adult male mongrel dogs, receiving as drinking solution 0.9% NaCl in 5% dextrose, resulted in an average sustained rise in the mean arterial blood pressure of 30 mm Hg (1 mm Hg - 133 N/m2) in 60% of the animals. Hypertensive dogs had in their arterial tissues generally more sodium, potassium, magnesium, and calcium than the similarly treated but non-hypertensive dogs, but compared to the tissues of operated untreated or unoperated normotensive dogs, only sodium and calcium were significantly higher. The dogs who were similarly treated but did not develop hypertension had in their arterial tissues less sodium, potassium, and magnesium than operated untreated or unoperated normotensive dogs. Norepinephrine content in the branches of mesenteric arteries of all deoxycorticosterone- and NaCl-treated animals, irrespective of their blood pressure, was significantly lower, and in the myocardium significantly higher, than either the unoperated normotensive or operated but not further treated dogs. It is concluded, therefore, that in deoxycorticosterone + NaCl treatment the dogs which developed hypertension had more arterial sodium, potassium, magnesium, and calcium than those who were similarly treated but remained within the limits of normal blood pressure, and that there was no difference between hypertensive and non-hypertensive dogs in regard to their cardiovascular norepinephrine content.


Bile acid metabolism in mammals. VIII. Biliary secretion of cholylarginine by the isolated perfused rat liver.

In studies of cholic acid metabolism using the isolated perfused rat liver system, an unknown conjugate of cholic acid was observed. This conjugate comprised 15-27% of the biliary bile acids in these experiments, was less polar than cholylglycine on thin-layer chromatography using butanol, acetic acid, and water, and had an apparent molecular weight greater than that of cholyltaurine on gas-liquid chromatography. Amino acid analysis of the hydrolyzed conjugate demonstrated the presence of arginine. Perfusion studies with radioactive arginine, and mass spectrometric analysis proved that the conjugate was cholylarginine. Secretion of this conjugate does not represent a deficiency of available glycine and taurine.


The influence of (3H)taurocholate on the biliary excretion of (14C)acetylprocaine amide ethobromide.

The biliary excretion rates of [14C]acetylprocaine amide ethobromide (acetyl-PAEB) and [3H]taurocholate, either administered alone or in combination to adult male Wistar rats, were studied. Their renal pedicles were ligated, and the common bile duct and one jugular vein cannulated. Acetyl-PAEB, 20 mg/kg, and sodium taurocholate, 70 mg/kg, were infused over a 5-min period. Blood and bile samples were collected every 10 min for 60 min. Liver samples were taken at 10 and 20 min. Approximately 100% of the administered taurocholate was excreted within 50 min. The simultaneous administration of acetyl-PAEB did not significantly alter the taurocholate excretion. The amount of the acetyl-PAEB dose excreted in 1 h was 9.4%. This was increased significantly to 16.5% when taurocholate was given concomitantly. The concentration of acetyl-PAEB in the bile increased significantly when taurocholate was given, and the ratios of its concentrations in bile-liver and bile-plasma were also increased. Taurocholate did not alter the liver-plasma concentration ratio of acetyl-PAEB. It is suggested that the concomitant administration of taurocholate increased the biliary excretion of acetyl-PAEB by facilitating its secretion by the liver into the bile.


Rate of incorporation of CO2 carbon into glucose and other body constituents in vivo.

Specific activity curves of respired CO2 and of body glucose after intravenous NaH14CO3 as tracer and, in separate experiments, after [U-14C]glucose as tracer were employed to assess rate of interchange of carbon between HCO3 and glucose, and to calculate other rates of input and output for each of these substances. Solution for six rates attending the model was by integrals rather than by curve analysis. Fasting caused a twofold increase in rate of transport of CO2 carbon to glucose. Whereas in fed animals this rate was only 7% of the forward flow from glucose to CO2, it rose to 31% during fasting. Glucose carbon derived from CO2 rose from 3.7 to 20%. As expected, the rates of entry of new glucose to blood, and the conversion rate of glucose to products in body depots and to CO2 were reduced by fasting, whereas, the non-glucose input to CO2 was increased. Fasting was attended by a 20-fold increase in rate of conversion of CO2-derived carbon to hepatic glycogen and a fourfold increase to non-hepatic glycogen. Protein exceeded all whole-body depots for rate of acceptance of such carbon, and total lipids received an appreciable amount, but fasting caused no overall increase for either.


Effect of dietary dieldrin on the liver and drug metabolism in the female Swiss-Vancouver mouse.

Female Swiss-Vancouver (SWV) mice, 13 weeks old, were exposed to dietary dieldrin for up to 10 weeks. Liver mass, hepatic microsomal protein and cytochrome P-450, and the in vitro metabolism of imipramine were determined at intervals. Dieldrin (5, 10, 15, and 20 ppm) caused hepatomegaly and increases in P-450; both effects were dose-related. All doses increased microsomal protein by about 30% (control value was 15.3 mg of protein per gram of liver). Maximal responses were attained by 2 weeks of exposure and maintained thereafter. Plateau liver masses at these respective doses were 111, 119, 133, and 162% of the control value (57.9 mg of liver per gram of body weight). Cytochrome P-450 was, respectively, 124, 142, 185, and 173% of the control value (0.93 nmol per milligram of microsomal protein). These changes decreased pentobarbital sleeping times by an average of 540% in animals fed 5, 15, or 25 ppm for 4 weeks. Similarly, the latency to the onset of anesthesia was increased by 26% at all doses. The N-oxidation and aryl-hydroxylation of imipramine increased with age, while demethylation decreased. The hydroxylation and demethylation of imipramine was increased after 2 and 4 weeks, respectively, of exposure to 20 ppm; N-oxidation was decreased. Longer exposure to lower doses caused similar changes. The changes in liver parameters and imipramine metabolism induced by 4 weeks exposure to 20 ppm were absent 6 weeks after exposure ceased.


Correlation between extracellular focal potentials and K+ potentials evoked by primary afferent activity.

There is a clear, positive correlation in amplitude between changes in potassium potentials (deltaEK) and focal potentials (deltaV) evoked by tetanic stimulation of afferent nerves in the cuneate nucleus and dorsal horn of cats under Dial anaesthesia or after decerebration. Data obtained with stimulations at various frequencies and intensities, or recording at different positions give a relatively constant slope of deltaV/deltaEK (varying between 0.2 and 0.6 in different experiments). These observations are fully consistent with the possibility that deltaV mainly reflects changes in extracellular potassium concentration caused by the release of K+ from active terminals. Differences in time course of deltaEK ANd deltaV evoked by single stimuli are a steep function of distance and therefore can be ascribed to the slowness of diffusion, without excluding the possibility of an early additional depolarizing effect by another mechanism.


Factors determining the decay of K+ potentials and focal potentials in the central nervous system.

Post-tetanic undershoots in extracellular focal potential (deltaV) and K+ potential (EK) can be recorded in the cuneate nucleus and dorsal horn of Dial-anaesthetized or decerebrate cat. They are seen best at depths where the largest deltaEK and deltaV are recorded and they increase with the frequency and duration of stimulation. The very different time courses of undershoots of deltaV and deltaEK indicate two hyperpolarizing influences: first, electrogenic pumping, and later, a reduced external K+ concentration. The importance of active K+ removal in determining the amplitude and duration of deltaEK and deltaV is illustrated by their marked potentiation (as well as the disappearance of post-tetanic undershoots) induced by a lowering of blood pressure or local application of strophanthidin.


Computation of aortic pulse wave velocity and aortic pulse wave velocity and aortic extensibility from pressure gradient measurements.

This study is concerned with the computation of aortic pulse wave velocity based on simultaneous recordings of the aortic pressure gradient and first-time derivative of aortic pressure. These variables were recorded by means of a double-lumen catheter introduced in the aorta of four anesthetized closed chest dogs, and connected to critically damped manometer systems. Results of aortic pulse wave velocity were then compared: (i) to the true phase velocity obtained from spectra of apparent phase velocity, and (ii) to the pulse wave velocity computed from the time shift between maximum slopes of the pressure wave. From the aortic valves to 37 cm down the aortic trunk, pulse wave velocity increased from 410-460 cm/s to approximately 600-800 cm/s. Based on the wave propagation equation presented of Bramwell and Hill (Bramwell, J.C., and Hill, A. V. 1922. Proc. R. Soc. 93, 298-306), volumetric extensibility coefficients were computed from pulse wave velocity data. Results indicated that, from the aortic valves to 37 cm down to the aorta, the mean volumetric extensibility decreased from 0.43-0.56% deltaV/cm H2O to 0.16-0.25% deltaV/cm H2O (1 cm H2O = 94.1 N/m2).


Temperature-induced changes in metabolism and body weight of cattle (Bos taurus).

The metabolic and body weight changes in two non-pregnant beef cows were studied during prolonged exposure to warm (20 +/- 3 degrees C, relative humidity 50-70%) and cold (-10 +/- 2 or -25 +/- 4 degrees C) temperatures. Other factors including daily food intake were held constant throughout each 8-week exposure. During cold exposures, metabolic rate, blood hematocrit, and plasma concentrations of glucose and free fatty acid were elevated and respiratory frequencies and skin temperatures decreased. Resting metabolic rates measured at 20 degrees C, i.e., without the direct influence of cold, were 83.4-95.3 litres 02 per hour when the cows were cold acclimated, at either -10 or -25 degrees C, and 30-40% greater than when the cows were warm acclimated. The resting metabolic response and the concomitant reduction in intensity of shivering is indicative of metabolic acclimation to cold in these animals of greater than 500 kg body weight. As well as the expected changes in body weight with changes in energy metabolism there were losses in weight (13-24 kg) during the first 3 days of each cold exposure. Weight gains occurred when the cold stress was abruptly removed. These short term weight changes were associated with changes in water intake and apparent shifts in body fluid content.


The effect of lobar obstruction on regional perfusion in the intact dog.

The effect of acute obstruction of the right lower lobes (RLL) on the relative perfusion of different lung regions was studied using Xenon-133 in anesthetized artificially ventilated supine dogs. When the RLL were obstructed at functional residual capacity (FRC) and the rest of the lung was inflated to a transpulmonary pressure of 10 or 20 cm H2O (1 cm H2O = 94.1 N/m2), relative perfusion increased within 10 s to the obstructed lobes by 59 and 92%, respectively. The increase was less marked but still present (17 and 42%, respectively) when obstruction was maintained for 15 min, at a time when arterial hypoxemia had occurred. Hence, there was increased perfusion to an obstructed hypoxic region. The perfusion distribution correlated with the difference in alveolar pressure between the obstructed lobes and the unobstructed lobes such that relative perfusion was always increased to the low alveolar pressure region.


Effect of succinylcholine on responses of neurons in the motor cortex to natural activation of muscle spindle primary endings.

In locally anesthetized cats, the effects of intravenous administration of succinylcholine (SCh) in sub-paralytic dosages on the responses of single neurons in motor cortex to small dynamic muscle stretches were studied. A large transient enhancement of these cortical responses with a time course corresponding to the peripheral action of SCh on muscle spindles was observed. This finding is discussed in terms of the hypothesis that muscle spindle primary endings may activate projections to motor cortex.


Re-incorporation of carbon atoms into plasma glucose in newborn dogs.

The ratio of the total turnover rate of glucose calculated with [2-3H]glucose as the tracer and the irreversible disposal rate of glucose, calculated with [U-14C]glucose as the tracer was found to be 1.35 +/- 0.28 SD (+/- 0.08 SEM) in dogs 1-33 days of age. This value was unrelated to age and to the level of glucose in the plasma. Accordingly, under basal conditions the overall re-incorporation of carbon atoms into newly released glucose in pups is nearly identical with that found in grown dogs.


The effect of metoclopramide on inhibition induced by purine nucleotides, noradrenaline, and theophylline ethylenediamine on intestinal muscle and on peristalsis in vitro.

Metoclopramide (N-(diethylaminoethyl)-2-methoxy-4-amino-5-chlorobenzamide) (Mcp) at concentrations of 0.1 and 1.0 muM partially and significantly reduced the relaxations induced by adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), and adenosine, was without effect on theophylline ethylenediamine whilst significantly potentiating noradrenaline on the atropine-pretreated (0.1 muM) taenia coli, rabbit ileum, and rat duodenum. Mcp (1.0 muM) decreased the inhibitory effects of ATP, ADP, and adenosine on peristalsis induced in the isolated guinea-pig ileum by a constant increase in intraluminal pressure, did not affect inhibition due to theophylline ethylenediamine, whilst it potentiated inhibition of peristalsis due to noradrenaline. It is proposed that this effect of Mcp may be a specific antagonistic action on receptors sensitive to the putative purinergic transmitter, ATP and ADP, and may be partly responsible for its observed facilitatatory action on peristalsis.


Isolation and characterization of Actinopolyspora halophila, gen. et sp. nov., an extremely halophilic actinomycete.

An actinomycete, isolated as a contaminant of a culture medium containing 25% NaCl, has been classified as Actinopolyspora halophila gen. et sp. nov. in the family Nocardiaceae. The morphology and biochemical characteristics of this organism distinguish it from other members of the family Nocardiaceae and other genera possessing a type IV cell wall. It requires high NaCl concentrations for growth and can grow in saturated NaCl. The lowest concentration permitting growth in liquid medium is 12%, and on solid medium, 10%. Colonies developing at lower salt concentrations contain holes resembling viral plaques. No growth occurred in a medium containing 30% KCl instead of NaCl. This organism can grow in simple media with NH4+ salts as nitrogen source and different sugars and other compounds as carbon source. Though it has a salt requirement almost as great as the extremely halophilic rods and cocci, it differs from these in containing diaminopimelic acid and in sensitivity to lysozyme; both properties suggest that it has a mucopeptide cell wall. It also contains some phospholipids common to other actinomycetes, but does not contain any phytanyl ether linked lipids characteristic of other extremely halophilic bacteria.


Fractionation of sulfur isotopes by continuous cultures of Desulfovibrio desulfuricans.

Sulfur isotope effects observed in lactate-limited continuous cultures of Desulfovibrio desulfuricans were, in general, similar to those reported for sulfate reduction by washed cells and batch cultures. There was a trend towards higher fractionation at low growth rates.


The relationship of acid-soluble glycogen to yeast flocculation.

A relationship between yeast flocculation and intracellular acid-soluble glycogen has been established which has been substantiated using flocculation mutants (mutants with altered capacities to flocculate) as well as a normal strain of Saccharomyces carlsbergensis. Sound evidence exists to implicate physiological differences in carbohydrate metabolism (glycogen storage) to this physical property of brewing significance.


Glycogen--a physiological determinant of yeast flocculation?

Evidence is provided to extend earlier observations that glycogen and flocculence levels vary concurrently in brewing yeast. The use of glycogen mutants, the alterations of growth conditions specifically to inhibit glycogen storage, and observations on glycogen decreases during endogenous metabolism have verified the above. A mechanism by which glycogen might exert its effect on flocculation is suggested.


Effect on microorganisms of volatile compounds released from germinating seeds.

Volatile compounds evolved from germinating seeds of slash pine, bean, cabbage, corn, cucumber, and pea were evaluated for their ability to support growth of microorganisms in liquid mineral salts media lacking a carbon source. Growth of eight bacteria was measured turbidimetrically and of six fungi as dry weight of mycelium. Volatiles caused increased growth of Pseudomonas fluorescens, Bacillus cereus, Erwinia carotovora, Agrobacterium tumefaciens, A. radiobacter, Rhizobium japonicum, Mucor mucedo, Fusarium oxysporum f. conglutinans, Trichoderma viride, and Penicillium vermiculatum but not of Sarcina lutea, Serratia marcescens, Chaetomium globosum, or Schizophyllum commune. Spores of Trichoderma viride showed higher germination in the presence of volatiles. Effects on growth were apparent only during the first 3 or 4 days after planting the seeds. Killed or dried seeds had no effect. The volatiles did not support microbial growth in the absence of nitrogen nor did they supply growth factors. Passing volatiles through KMnO4 or hydrazone reduced growth of the bacteria, indicating that oxidizable organic compounds, primarily aldehydes, were the active components. The volatiles were not absorbed by sterile soil, clay minerals, or water, but they were absorbed by non-steril soil and activated charcoal.


Exopolysaccharide depolymerases induced by Rhizobium bacteriophages.

Enzymes induced by two Rhizobium trifolii bacteriophages caused depolymerization of exopolysaccharides from most R. trifolii and R. leguminosarum strains tested, but did not, in general, attack the exopolysaccharides of R. meliloti, the slow-growing rhizobia, or Agrobacterium. Ca2+ and (or) Mg2+ were required for enzyme activity. In all strains tested, depolymerization of exopolysaccharide occurred when there was successful phage infection, but depolymerization also occurred with exopolysaccharides from nonsusceptible strains.


Mutualistic degradation of the lignin model compound veratrylglycerol-beta-(o-methoxyphenyl) ether by bacteria.

Complete degradation of the lignin model compound veratrylglycerol-beta-(o-methoxyphenyl) ether is accomplished mutualistically by a two-membered bacterial culture. Bacterial isolate E1, which has been tentatively identified as an Acinetobacter, grows on veratrylglycerol-beta-(o-methoxyphenyl) ether producing guaiacol (o-methoxyphenol) as a non-metabolizable, bacteriocidal by-product. When Nocardia corallina (strain A81) is also present in media containing veratrylglycerol-beta-(o-methoxyphenyl) ether as the only carbon/energy source, it is able to grow on the guaiacol produced from veratrylglycerol-beta-(o-methoxyphenyl) ether by isolate E1. Strain A81 alone does not grow on veratrylglycerol-beta-(o-methoxyphenyl) ether. In the absence of strain A81, isolate E1 is rapidly killed by accumulated guaiacol. In the presence of the Nocardia, isolate E1 maintains its viability.


Characterization of a reserve glucan from Megasphaera elsdenii.

A reserve glucan of Megasphaera elsdenii was studied by methylation analysis before and after treatment with isoamylase. The results of this study indicate that the glucan is of the amylopectin-glycogen type.


The fine structure of conidial development in the genus Torula. I. T. herbarum (Pers.) Link ex S. F. Gray and T. herbarum f. quaternella Sacc.

Conidiogenesis in Torula herbarum and T. herbarum f. quaternella was observed by scanning and transmission electron microscopy. Conidia of the former were shown to be made up of three equally sized cells capped by a distinctive, and easily recognizable, conidiogenous cell. Conidiogenous cells also arose terminally on erect hyphae and on prostrate hyphae. The single-layered conidial cell walls were differentiated into an inner hyaline zone and an outer electron-dense zone formed by the deposition of melanin. Conidiogenous cells lacked melanin at the apex and, before conidiation, the lateral walls were strengthened by a further deposition of melanin. The apex bulged outwards and was modified into a new multicelled conidium bearing another apical conidiogenous cell. Continued development of new conidia resulted in an acropetal chain which became disarticulated after cytolysis within the conidiogenous cell. The relative distinctions between holoblastic and enteroblastic development are discussed and it is concluded that the conidia should be referred to as blastoconidia.


Susceptibility of clinical isolates of Staphylococcus aureus to killing by oxacillin.

Sixty clinical isolates of Staphylococcus aureus have been screened for their relative susceptibility to the killing action of oxacillin. Only one of these strains was found to be exceptionally resistant to the bactericidal effect of this and other beta-lactam antibiotics. This ability to survive oxacillin inhibition of cell wall synthesis has been called "tolerance". The characteristics of the tolerant organism, which has been designated the Evans strain, in comparison with other isolates of S. aureus indicate that this form of resistance is not apparent from the minimal inhibitory concentration, is not related to an abnormal growth rate, and can be enhanced by treatment with N-methyl-N'-nitro-N-nitrosoguanidine.


Fine structure of the cell envelope layers of Flexibacter polymorphus.

Electron microscopy of the filamentous gliding marine bacterium Flexibacter polymorphus demonstrated that the cell envelope consists of an electron-dense intermediate layer located between two unit-type membranes: an outer membrane, presumably of lipopolysaccharide, and an inner cytoplasmic membrane. Separation of living filaments into single cells by lysozyme suggests that a peptidoglycan moiety, possibly corresponding to the intermediate layer, might be situated between the two membranes. Cell division proceeds by invagination of the cytoplasmic membrane and intermediate layer forming a transverse septum. Cells generally fail to separate after the division process, so that a common outer membrane encloses all of the cells in a single filament. There is a continuous layer of macromolecular cup-shaped elements ('goblets') attached to the outermost surface of the lipopolysaccharide membrane. Tangential thin sections, as well as negatively stained preparations of envelope fragments (produced by sonication of autolyzed cells), showed that the goblets are arranged in a close-packed hexagonal array. The presence of electron-dense structures located between the outer and inner membranes, and exhibiting the same periodicity as the goblets, suggests that some part of the goblets penetrates the outer membrane and extends across the periplasmic space to the dense intermediate layer or cytoplasmic membrane. Spontaneous autolysis in aging cultures is accompanied by the formation and release into the culture medium of large numbers of outer membrane vesicles coated with globlets. A tentative reconstruction of the envelope of F. polymorphus, based on the fine-structural data, is presented.


Humoral antibody response to cattle to formalinized Staphylococcus aureus vaccine.

Five cows were inoculated intradermally with formalinized Staphylococcus aureus suspension in Freund's complete adjunvant and the development of the humoral antibody response was followed as judged by the agglutination titer of sera, at various intervals post inoculation. Highest titers were observed at 78-87 days post inoculation. Agglutinating activity was found in IgM and IgG fractions (IgG1 and IgG2) of both serum and colostrum. The agglutinating activity of colostrum was significantly higher at 12 than at 24 and 36 h, post partum. However, no such activity was detected in either normal cow serum or colostrum against S. aureus.


Microbial petroleum degradation: application of computerized mass spectrometry.

An analytical procedure is presented for obtaining detailed characterization of petroleum hydrocarbons which undergo microbial degradation. The procedure includes column chromatographic separation and characterization of the resulting fractions by mass spectrometry and gas chromatography. The use of computerized low-resolution mass spectrometry is offered as a method for assessing microbial degradation of petroleum. This method provides information which cannot, at the present time, be obtained by other available analytical methods. Use of this method to evaluate degradation of a South Louisiana crude oil by a mixed culture of estuarine bacteria revealed that asphaltenes and resins increased by 28% after degradation, while saturates and aromatics decreased by 83.4% and 70.5%, respectively. Most of the normal and branched-chain alkanes were degraded (96.4%), but an increase in long-chain alkanes (C28-C32) after degradation was observed by gas-liquid chromatography. Susceptibility of cycloalkanes to degradation was less as the structure varied, i.e., 6-ring greater than 1-ring greater than 2-ring greater than 3-ring greater than 5-ring greater than 4-ring. Susceptibility of aromatic components to degradation decreased with increase in the number of rings, viz., monoaromatics greater than diaromatics greater than triaromatics greater than tetraaromatics greater than pentaaromatics. Aromatic nuclei containing sulfur were twice as refractory as non-sulfur analogs.


Gas metabolism in ovine rumen cultures on a nitrogen-deficient medium.

Inocula of rumen fluid from sheep were grown on a medium of low nitrogen content under an oxygen-free atmosphere containing N2. The cultures produced methane and carbon dioxide. Hydrogen gas was utilized and the partial pressure of N2 decreased by 24% in 48 h. Assuming this N2 to have been reduced to metabolically available nitrogenous compounds, these account for about 0.2% of the sheep's daily need.


Effect of glutamic acid on the fatty acid and lipid composition of Choanephora cucurbitarum.

The fatty acid composition of the total, neutral, sterol, free fatty acid, and polar-lipid fractions in the mycelium of Choanephora curcurbitarum was determined. The major fatty acids in all lipid fractions were palmitic, oleic, linoleic, and gamma-linolenic acid. Different lipid fractions did not show any particular preference for any individual fatty acid; however, the degree of unsaturation was different in different lipid fractions. Free fatty acid and polar lipid fractions contained a higher proportion of gamma-linolenic acid than did triglyceride and sterol fractions. Addition of glutamic acid to the malt-yeast extract and medium resulted in the biosynthesis of a number of long-chain fatty acids beyond the gamma-linolenic acid. These fatty acids, e.g., C22:1, C24:0, and C26:0, were never observed to be present in the fungus when grown on a malt-yeast extract medium without glutamic acid. Furthermore, thin-layer chromatographic analysis showed a larger and denser spot of diphosphatidyl glycerol from the mycelium grown on glutamic acid medium than from the control mycelium. The possible significance of this finding is discussed.


Cultural, morphological, and physiological characteristics of Thermomonospora fusca (strain 190Th).

The cultural, morphological, and physiological properties of Thermomonospora fusca (strain 190Th) are described. Its physiological properties show that this species is primarily a carbohydrate-degrading actinomycete which can use a wide range of plant sugars and polymeric carbohydrates as sources of carbon and energy. The culture does not use proteins or amino acids for carbon and energy, or as a nitrogen source. A few organic acids are utilized. Ammonia is the preferred nitrogen source. The culture has trace nutrient requirements which include biotin and an undetermined number of amino acids. These and other physiological characteristics are discussed in relation to the roles that T. fusca carries out as a saprophytic bacterium in nature. Its cultural and morphological properties are discussed in relation to the taxonomic status of this species in the literature.


The influence of acridine dyes and caffeine on recovery from ultraviolet damage in Eudorina elegans.

Caffeine and the acridine dyes, acridine orange and acriflavine, were used to examine the repair potential in Eudorina elegans following ultraviolet irradiation. Acridines blocked photoreactivation primarily as a result of absorption of photoreactivating wavelengths, but acridines did not influence dark survival. Therefore, an acridine-sensitive excision-resynthesis-repair process is absent in Eudorina. Caffeine decreased both dark and light survival, the latter only after relatively high doses of ultraviolet light were used for inactivation. The caffeine-sensitive repair process appears to function most actively when the organisms are engaged in DNA synthesis, indicating that a postreplication-repair system exists in Eudorina. However, the data suggest that a repair system not associated with the DNA synthetic phases may also exist.


Infrared color photomicrography of soil microorganisms.

The infrared color photomicrography technique for detecting unstained microbial cells in soil is revised for use with Kodak's recently introduced Ektachrome infrared film. Thes new version of the film required achromatic objectives instead of apochromats, and the use of a blue filter in addition to the previously required red filter. These filters also improve the visual focus capability of the operator. It was found that dry soil smears can be photographed as either immersion oil or aqueous mounts. Several makes of bright-field transmitted-light microscopes gave similar results. Phase microscopy, however, produced deteriorated image quality although the proper 'false' colors were produced.


Congenital displacement of temporal cortex into the central spinal canal.

This is a report of the first recorded observation of displacement of temporal cortex into the central spinal canal in an infant with Arnold Chiari malformation, platybasia, aqueductal atresia, hydrocephalus and meningomyelocele. The combination of an absent right cerebellar hemisphere and malformed fourth ventricular roof provided the anatomical background for this unique event.


Patterns of memory performance in the neurologically impaired aged.

The specific behavioral manifestation associated with the different disorders producing the syndrome of dementia have remained poorly investigated. We examined the memory performance of three distinct groups of patients with dementia secondary to Alzheimer's disease (AD) multiple-infarctions (MID) and vertebrobasilar insufficiency (VBI) on the ten subtests of the Wechsler Memory Scale (WMS). Statistical methods of analysis were used to maximize the differences between the groups. Univariate statistical procedures revealed that the AD group performed significantly and consistently lower than the two cerebrovascular groups. There were no significant differences between the two cerebrovascular disease groups, even though the MID group tended to perform consistently more poorly than the VBI group. For heuristic and conceptual purposes as well as to determine which combination of the ten WMS variables produced the "best" statistical model differentiating the groups the data was analyzed by multivariate techniques. A discriminate function analysis obtained a 100% valid positive hit rate in discriminating among the three groups. One hundred percent diagnostic accuracy was also obtained in discriminating between MID and AD as well as AD and VBI. The two cerebrovascular groups tended to overlap in their probability distributions with an 81% hit rate. Different predicitive statistical models were identified to differentiate the various diagnostic groups. It was possible to discriminate the three diagnostic groups by different patterns of memory performance.


A model for the future care of acute spinal cord injuries.

This is a review of the total care of those acute spinal cord injury patients in Ontario during the years 1969 and 1970, from extrication and transportation following the accident to death, or the completion of primary definitive rehabilitation. Information was extracted from the available ambulance records, the patients and many of the responsible physicians were interviewed personally. The study was detailed and intensive and included a review of each patient's hospital records in each hospital up to discharge from the rehabilitation programme into the community, or to a chronic care unit. The data was compiled in accordance with a detailed and lengthy questionnaire developed for this study. The incidence of acute cord injuries in Ontario in 1969 and 1970 amounted to 244; in 1969, 15.9 per million population and in 1970, 13.6 per million. As in other studies road accidents took first place, followed by falls from a height; sports injuries ranked third and 65.7% of these were caused by diving into shallow water. Age incidence, and incidence by month, day of week and time of day were identified. Fridays and Saturday afternoons in July and August are particularly hazardous. The study continued to the end of 1974 by which time 34 deaths had been recorded. Peak incidence of death occurred within fourteen days of injury. The most common cause of death was respiratory in origin. Geographical distribution was identified and the type of hospital treating the acutely injured patient. Fourteen percent of persons with spinal column injury suffered progressive or sequential spinal cord damage both prior to and following medical contact. The incidence of pressure sores and genitourinary sepsis and calculosis was high in all types of hospitals. The effect of operative treatment was noted in cases of complete quadriplegia and paraplegia. Of the 133 survivors who undertook a rehabilitation program, 84% returned to their homes and 59% achieved gainful employemnt or ongoing education. The cost was determined of general hospital services and rehabilitation programmes. A new model for the care of the spinal cord injury patients in Ontario was proposed.


Technical report: method of fixation of subluxed or dislocated cervical spine below C1-C2.

A method of internal fixation of adjacent vertebrae that have been dislocated or subluxed has been presented. In the author's hands and in the hands of associates this has proven to be a satisfactory method of fixation in this type of injury. It has the advantage over many other posterior techniques that only two verbebrae are fixed together.


Secondary epileptogenesis in frog forebrain: effect of inhibition of protein synthesis.

Secondary epileptogenesis was induced in the hippocampal cortex of the paralyzed bullfrog by means of localized, unilateral, intermittent electrical stimulation (kindling). Stimuli were designed to yield a brief but definite after-discharge. In control animals a progressive increase in after-discharge duration occurred at the 1 degree (stimulated) site and then at the 2 degrees site (contralateral hippocampus). Spontaneous epileptiform potentials (SEP's) occurred between stimuli, eventually independently on both sides. Cycloheximide (50 mg/kg) caused 88-99% reduction in protein synthesis, measured by 14C-leucine incorporation into brain protein. Cycloheximide-treated animals revealed no evidence of progressive prolongation of after-discharge duration when subjected to the kindling procedure (p = 0.1205 X 10(-7)). SEP's were reduced in the cycloheximide-treated animals, and confined to 1 degree hemisphere (p = 0.6 X 10(-10)). Since cycloheximide did not disturb normal electrogenesis or disrupt the after-discharges, this experiment distinguishes processes dependent upon electrical events from those requiring macromolecular synthesis. Protein synthesis seems critical to the emergence of spontaneous and autonomous epileptiform behavior of neural aggregates.


Primary and "transfer" seizure development in the kindled rat.

An investigation was made of both primary and "transfer" kindling as they occur in ipsilateral limbic sites. Primary kindling was found to involve progressive growth of afterdischarge (AD), propagation and convulsive behavior. It was noted that AD growth did not take place gradually but occurred in sudden, large increments. "Transfer" (a significant acceleration of secondary kindling) was found at every secondary limbic site. It was associated with the early appearance of full-blown AD's, super-normal propagation, and well-developed seizures. The post-transfer interference of primary site function previously reported by Goddard et al was also found, but it occurred in significant amounts only after transfer kindling of the amygdala. It is believed that the data offer some support for both of the hypothetical mechanisms of transfer which have been proposed.


Split-brain rat: transfer and interference of kindled amygdala convulsions.

Rats were subjected to varying degrees of commissurotomy, followed by implantation of a bipolar electrode into each amygdala. After the kindling of six convulsions at one electrode (primary site), the procedure was applied to the contralateral amygdala (secondary site). Convulsions were observed to develop more rapidly, independent of the degree or kind of transection. After 6 secondary site convulsions, the primary site was re-tested and convulsion-triggering was blocked, except in animals with transection of the rostral portion of the corpus callosum (CC). Collectively, the data indicate: (i) amygdala kindling develops a lasting trace which operates through the midbrain or brainstem; (ii) kindling from a second site utilizes this trace; (iii) a series of 6 convulsions produces negative after-effect which manifests itself at the convulsion level via the anterior CC; (iv) the anterior CC is important in determining the laterality of the forelimb clonus; and (v) the inter-amygdala propagation of after-discharge is blocked by the combined sectioning of the anterior CC and the anterior commissure.


Kindling: secondary epileptogenesis, sleep and catecholamines.

Seizure development and transference phenomenon were investigated in hippocampal and amygdaloid kindled cats. The behavioral and electrographic findings during the kindling procedures showed that motor seizure development in hippocampal seizures occurred with the emergence of independent discharging in the amygdala, globus pallidus and contralateral hippocampus. Furthermore, secondary site convulsions developed upon the first stimulation of these structures in the hippocampal group but only after over a month of hippocampal stimulation in the amygdaloid group. It was, therefore, concluded that role of the amygdala and globus pallidus in hippocampal seizure development was more essential than that of hippocampal stimulation in amygdaloid seiqure development. The common findings between the hippocampal and amygdaloid kindled animals were the systematic progression to seizures, the all-or-nothing nature of the electrical response and the relative permanency of the seizure susceptibility. Seizure susceptibility increased during slow wave sleep and decreased during REM sleep. These latter findings were examined with preliminary data of brain bioassays of catecholamines.


Sleep, subcortical stimulation and kindling in the cat.

A longitudinal study of the effects of sleep on amygdaloid kindling showed that kindling disrupted normal sleep patterns by reducing REM sleep and increasing awake time. Few interictal spike discharges were observed during the awake stage, while a marked increase in discharge was observed during the light and deep sleep stages. No discharges were observed during REM sleep. During the immediate post-stimulation period the nonstimulated amygdala showed a much higher rate of spike discharge. On the other hand, there was an increase in spike discharge in the stimulated amygdala during natural sleep without preceding amygdaloid stimulation. Amygdaloid stimulation at the generalized seizure threshold during each sleep stage resulted in a generalized convulsion. The influence of subcortical electrical stimulation on kindled amygdaloid convulsions was investigated in a second experiment. Stimulation of the centre median and the caudate nucleus was without effect on kindled convulsions, while stimulation of the mesencephalic reticular formation at high frequency (300 Hz) reduced the latency of onset of kindled generalized convulsions. Stimulation of the nucleus ventralis lateralis of the thalamus at low frequency (10 Hz) prolonged the convulsion latency, and at high current levels blocked the induced convulsion. Stimulation in the central gray matter at low frequency (10 Hz) also blocked kindled amygdaloid convulsions.


Generality of the kindling phenomenon: some clinical implications.

The purpose of the present investigations was to explore the generality of the kindling phenomenon and its applicability to clinical situations. Whether local brain stimulation, electroconvulsive shock (ECS), or metrazol the consequence of periodic administration of convulsive agents was found to be the same; in each case repeated application of the agent resulted in the gradual development and intensification of convulsive symptoms (kindling). Moreover, in each case the resulting intensification was not specific to the agent being used and seemed to increase the responsiveness to convulsive agents in general. In the present studies this interaction was seen in the form of an intensified alcohol withdrawal syndrome observed 18 days after cessation of a series of metrazol injections, amygdaloid stimulations, of ECS. Thus, it appears that one of the hazards of the convulsive therapies is that they may induce enduring changes in brain function which leave the patient in a state of increased susceptibility to a variety of potentially convulsive agents.


Recurrent spontaneous seizure state induced by prefrontal kindling in senegalese baboons, Papio papio.

In our earlier study of amygdaloid kindling in Papio papio (Pp), the development of partial complex seizure and of focal motor seizure was correlated with bifrontal theta discharge and increasing Rolandic spike discharge respectively and the final stage was characterized by primary generalized convulsive seizure. Since the latter seizure pattern is known to originate from the frontal focus in man, the frontal cortex became suspect in the development of the final stage seizure pattern. Daily prefrontal stimulation showed that Pp can be kindled from this site, culminating in a recurrent spontaneous seizure state identical to that induced by amygdaloid kindling in this species. However, our observation did not support our original assumption regarding the genesis of primary generalized convulsive seizure. Prefrontal and amygdaloid kindling are significantly different with respect to morphology, distribution and propagation of after discharge and interictal spike discharge, and speed and pattern of clinical seizure development. Most intriguingly, inter-ictal behavioral aberration associated with depth EEG changes was observed only in the prefrontal animals and not in the amygdaloid animals.


Chronic obstructive pulmonary disease in two cities of contrasting air quality.

Spirometric tests of 3280 Ottawa residents in 1969-71 and 2208 Sudbury residents in 1972-73 showed that the mean ratio of forced vital capacity to forced expiratory volume in 1 second was lower in Sudbury, where sulfur dioxide concentrations in the air tend to be appreciably higher than in Ottawa. This difference was significant for both males and females considered separately, and held true when age and smoking habits were taken into account. The prevalence of symptomatic chronic bronchitis was significantly higher in Sudbury males than in Ottawa males, but no such difference could be detected in females.


Photosensitivity: results of investigation in 250 patients.

Between January 1972 and December 1974, 250 patients were referred for investigation of possible photosensitivity to a university-associated clinical research unit for photobiology. In addition to an appropriate history and clinical examination, phototesting was carried out with a solar simulator, monochromatic light and fluorescent light directed to patch-tested areas of skin. Photosensitivity was not demonstrated in 110 patients (44%). Among the laboratory-confirmed photosensitivities, diagnoses included polymorphous light eruption (4.4%), erythropoietic protoporphyria (3.6%), porphyria cutanea tarda (2%), photoallergic contact dermatitis (5.6%), persistent light reaction (4%),  systemic drug phototoxicity (1.2%), phototoxic contact dermatitis (2%), solar urticaria (0.8%) and photoaggravated dermatoses (7.6%). It is important to establish a precise etiologic diagnosis in patients with photosensitivity in order to treat the disorder specifically or effectively or both.


The child and the snowmobile.

From November 1970 through March 1975, 41 children in Manitoba required hospitalization for treatment of injuries sustained in snowmobile accidents. The commonest injuries were fractures of a leg. In general, the injuries were severe, and in many instances the fractures were unusualy and uncommonly seen in children. Most often the child had been driving the snowmobile and all injuries were a result of driver error or misadventure; none was due to malfunction of the snowmobile. Recommendations to minimize the number and severity of snowmobiling injuries in children include an education program for both adults and their children, use of lightweight cowling to protect the legs, incorporation of a governor on the throttle to prevent excessive speeds, and use of a restraint for children travelling as passengers on the snowmobile. Children should always wear tight clothing when around snowmobiles.


Models of learning disability: their relevance to remediation.

A scheme of classification is suggested for physicians faced with clinicians' numerous and varied prescriptions for remedial management of children with learning disabilities. Three explanatory models of the causes of learning disability -- the difference, deficit and delay models -- and two strategies of management -- the process-oriented and goal-oriented -- are delineated. Remedial methods are classified according to their implicit explanatory model and the clinician's adherence to the process-oriented or goal-oriented approach. A pragmatic conservative, goal-oriented strategy is advocated, in which individualized instruction is tailored to the child's current abilities and learning requirements.


Carpal tunnel syndrome: a complication of arteriovenous fistula in hemodialysis patients.

Symptoms of compression of the median nerve in the carpal tunnel developed in two patients in whom an arteriovenous fistula was created to alleviate chronic renal failure through hemodialysis. Anatomic changes in the wrist area due to the fistula are probably important in the development of this syndrome, and pre-existing uremic peripheral polyneuropathy may also be important in the early development of local symptoms of nerve damage.


Coronary arteriography in patients with impending and evolving myocardial infarction.

To determine whether characteristic pathologic alterations in coronary arteries are associated with impending and complicated evolving myocardial infarction, the angiographic and hemodynamic findings in 47 acute coronary patients were compared to those of 49 patients with chronic stable angina. Subtle differences in angiographic and hemodynamic alterations were found in these two groups of patients. These differences were more pronounced in patients with evolving myocardial infarction with less than--15 per cent lactate extraction. The risk of coronary arteriography was surprisingly low. Myocardial metabolic function studies demonstrating less than--15 per cent lactate extraction were considered an indication for emergency coronary arteriography in preparation for contemplated coronary bypass surgery.


Ventricular patterns in acute myocardial infarction.

Ventricular dysfunction attendant with acute myocardial infarction results in considerable morbidity and mortality. Acute changes in morphology and physiology underly ventricular dysfunction. The ventricular morphologic changes of AMI differ from those of chronic coronary heart disease only in their temporal characteristics. The pathophysiologic changes are the result of the interaction of several variables. These include infarct size, compliance of both the infarcted and normal myocardium, contractility, heart size, filling pressure, and afterload. Through an understanding of the role played by each of these variables, a better comprehension of events following AMI may be obtained and a more rational basis utilized for selection of therapy.


Tachyarrhythmias associated with acute myocardial infarction: diagnosis, frequency, and significance.

Every known type of tachyarrhythmia may be associated with acute myocardial infarction, and it is extremely important to recognize clinically significant tachyarrhythmias versus relatively benign tachyarrhythmias. The individual tachyarrhythmias have been discussed in detail with pertinent illustrative examples included.


Heart failure in acute myocardial infarction.

In recent years, our understnading of heart failure complicating acute myocardial infarction has expanded considerably. Although it is not always possible to control cardiac decompensation in this situation, rational therapy has evolved with the improved recognition of the hemodynamic alterations in heart failure and the factors contributing to ventricular performance. Furthermore, a more secure physiologic basis now exists for the early identification of such patients and the development of additional therapeutic techniques.


The effects of prolonged beta-adrenoceptor blockade on heart weight and cardiac intracellular potentials in rabbits.

Estimates were made in vivo in rabbits of the relative beta-receptor blocking potency and duration of action of propranolol and practolol. In further experiments groups of litter mates were injected twice daily with approximately equi-active amounts of propranolol or practolol, or with saline, for several weeks. The heart weights of the treated animals were significantly lower than those of the controls, the water contents were higher, and the dry weight differences were highly significant; -16.8% after 2 mg/kg bd propranolol for six weeks and -33.8% after 10 mg/kg practolol. (The treated animals grew less rapidly than the controls; when corrected for body weight these figures were -11.9% and -20.4%, respectively.) In the practolol group, but not the propranolol group, the duration of the atrial intracellular potentials was prolonged. There was no evidence that the prolonged treatment with either drug had a negative inotropic effect, or reduced positive inotropic responses to isoprenaline.


Electrophysiological significance of rapid atrial pacing as a test of atrioventricular conduction.

Although rapid atrial pacing is frequently used as a test of atrioventricular conduction, no studies have compared this method with other conduction parameters. The purpose of this study was to compare the results of rapid atrial pacing with refractory period measurements utilizing the extrastimulus technique. Determination of the refractory periods of the atrium, A-V node, and His-Purkinje system were accomplished in 41 patients undergoing diagnostic cardiac catheterization, and the results compared with rapid atrial pacing to the point at which A-V Wenckebach occurred (WP). The results showed significant correlation (P less than 0.01) between the WP and functional refractory period (FRP) of the A-V node (r=0.89, FRP=865-2.6 WP), and significant correlation between the WP and the effective refractory period (ERP) of the total A-V conducting system(r=0.81, ERP=729-2.6 WP). The relationship between WP and the refractory periods also allowed prediction of the occurrence of physiological His-Purkinje block during introduction of premature atrial contractions and the site of the effective refractory period of the total A-V conducting system. This study establishes a close relationship between these methods and confirms the usefulness of rapid atrial pacing as a reliable test of A-V conduction in man.


Effect of transmembrane potential on the manifestations of ouabain toxicity in sheep cardiac Purkinje fibres.

The effect of membrane potential on the manifestations of ouabain-induced alterations in the electrical activity of shortened sheep cardiac Purkinje fibres was studied by a microelectrode technique. The level of membrane potential was modulated by passing intracellular polarizing current. It was found that the toxic electrical effects induced by exposure to ouabain vary according to the level of membrane potential.


Ventricular fibrillation threshold and vulnerable period in the isolated perfused rat heart.

Ventricular fibrillation threshold (VFT) measurements were obtained in the isolated perfused rat heart. Detailed morphology of the vulnerable period (VP) could be described by stimulating repeatedly at increasing levels of stimulus energy. Addition of lignocaine to the system caused an elevation of VGT, but also led to a delay of the VP to the end of the QT interval. The implications of these findings for the understanding of VFT measurements are discussed.


The effect of therapeutic doses of lidocaine hydrochloride on the effective refractory period of the right ventricle in man.

The effect of lidocaine on the effective refractory period of the right ventricle (EVRP) was measured in 10 patients using the extra stimulus technique of progressive introduction of premature stimuli until a response could not be elicited. In four patients lidocaine produced a significant decrease in the EVRP, in a further four patients there was no change, and in the remaining two patients lidocaine produced a significant increase in the EVRP. The effect of the drug on the EVRP could not be correlated with the serum potassium levels. The reasons for the variable effect of lidocaine are attributed to the different action of lidocaine on different components of conduction within the ventricle.


Relationship between ST-segment elevation and local tissue flow during myocardial ischaemia in dogs.

The relationship between electrocardiographic ST-segment changes and local tissue flow recorded from idential sites in the myocardium was determined by inserting platinum electrodes into the left ventricular wall of anaesthetized dogs. Local myocardial blood flow was measured during graded coronary constriction by recording tissue hydrogen desaturation rate. In the detection of ischaemic ST-segment elevation, intramural recordings proved to be more sensitive than corresponding epicardial recordings. Significant ST-segment elevation could only be detected by reducing local myocardial flow below 50% of control; by further reduction ST-segment elevation increased in proportion to the reduction in myocardial flow. Thus, significant myocardial ischaemia might exist without electrocardiographic alterations.


Myocardial distribution of coronary blood flow in the isolated supported heart preparation.

The regional distribution of myocardial blood flow was studied by use of radioactive microspheres (15 micro-meters [mum]) under control conditions and during an intracoronary infusion of norepinephrine (2mug/min). In control experiments endocardial blood flow was generally greater than epicardial flow; during administration of norepinephrine the endocardium received significantly less blood flow. It is proposed that normally the endocardium is well perfused, but under conditions of stress, eg, norepinephrine infusion in the presence of a constant coronary blood flow, decreased endocardial blood flow results.


Oxygen demand and collateral vessels of the heart. Factors influencing the severity of myocardial ischaemic injury after experimental coronary artery occlusion.

Epicardial electrocardiographic maps were used to assess the effect of heart rate, myocardial contractility, and oxygen need on the severity of myocardial ischaemic injury after acute coronary artery occlusion in dogs. The experimental data indicate statistically significant dependence of the severity of ischaemia on heart rate, contractility, and oxygen need of the heart. These dependences are highly influenced by the spontaneous collateral vessels of the heart.


Comparison of the handling of norepinephrine in the myocardium of adult and old rats.

The handling of norepinephrine was compared in the myocardium of adult and old rats. Endogenous norepinephrine levels were significantly lower in the hearts of old animals. Following intravenous injection of 3H-norepinephrine [3H-NE] the initial uptake was slightly higher in the old animals; subsequently, however, there was a more pronounced and prolonged fall in 3H-NE specific activity in the myocardium of the old rats. The increased turnover rate was associated with normal catecholamine synthesis. Studies of the subcellular distribution of 3H-NE showed an inability of the myocardium from ageing rats to retain norepinephrine in the storage granules with subsequent loss of the soluble fraction.


Static mechanical properties of the developing and mature rat aorta.

The static mechanical properties of the aorta have been examined in rats, aged between 4 weeks and 2 years. Internal radius, relative wall thickness, circumferential incremental strain, and circumferential incremental elastic modulus have been measured at pressures between 1.33 and 33.3 kPa (10 and 250 mm Hg). The results show that the value of the incremental elastic modulus does not change after 12 weeks. Changes observed in younger animals are related to alterations in relative wall thickness. The findings correlate with previously observed chemical and morphological changes. Studies of muscle function indicate that the smooth muscle of the media does not contribute significantly to the static elastic properties of the vessel wall.


The dynamic and static elastic response of the abdominal aorta of the dog.

The dynamic and static elastic response of the abdominal aorta was studied in beagle dogs of similar age and weight. The dynamic response was measured in situ by means of an optical transmission wedge resting on the exposed vessel to record the pulsatile changes in wall displacement and the pressure pulse recorded at the same site via a hypodermic needle. The static response was recorded (1) in situ by observing the change in radius which occurred with a change in the mean blood pressure, (2) post mortem using both transmission wedge and radiographic techniques. The change in radius (deltaR) for a change in pressure (deltaP=20 mm Hg[2.67kPa]) was calculated for both the dynamic and static cases. It was found that the aorta was stiffer for the dynamic case, the extent of the stiffening being dependent on the mean pressure. At pressures less than 80 mm Hg (10.64 kPa) the dynamic/static deltaR ratio was 1.8 decreasing to 1.1 at 160 mm Hg (21.28 kPa). This behaviour is interpreted in terms of smooth muscle relaxation and the subsequent transference of circumferential tension to collagen.


Pathological effects of intra-arterial blood transfusions in dogs.

During storage, large cellular aggregates and clots formed in venous blood but not in arterial blood. Contrary to previous opinions, the intra-arterial transfusion of blood containing aggregates and clots did not cause focal brain damage and the presence of aggregates was not essential for the post-transfusion development of cerebral petechial and other minor haemorrhages.


Pulmonary vasoconstriction produced by protamine and protamine-heparin complex in the isolated cat lung perfused with blood or dextran.

Injections of protamine sulphate, protamine-heparin complex, and the supernatant from this mixture produced a rise in pulmonary artery pressure during constant flow perfusion in the isolated cat lung. The rise in pressure occurred with both blood and dextran perfusates. This suggests that the pulmonary vasoconstriction produced by protamine may be partly due to a direct action on the pulmonary vasculature or to the release of vasoactive substances from the lungs.


Estimation of non-autonomic and autonomic components of iliac bed vascular resistance in renal hypertensive rabbits.

Iliac bed vascular resistance (IVR) was measured before and after pharmacological block of the autonomic effectors in unanaesthetized renal hypertensive and normotensive rabbits with previously implanted Doppler flowmeters. This permitted partitioning the resting IVR into a non-autonomic component (ie, steady-state IVR after block) and an autonomic component (ie, resting IVR minus non-autonomic IVR). When IVR was measured at the same mean arterial pressure (MAP) before and after block in each animal, the increase in estimated non-autonomic IVR accounted entirely for the rise in resting IVR in renal hypertensive rabbits. However, if IVR measurements after block were made at a lower MAP than before block, the estimated non-autonomic and autonomic components were both significantly increased in renal hypertensive rabbits. It is concluded that in the latter experiment non-autonomic IVR in renal hypertension was underestimated, whilst the autonomic component was overestimated. The rise in non-autonomic IVR in renal hypertension was partly due to structural changes in the iliac bed, since IVR remained higher in hypertensive than in normotensive rabbits after abolishing smooth muscle tone with vasodilator drugs.


Kinetic-microarchitectural correlations in the bone marrow of the mouse.

Transverse histologic sections of bone marrow obtained from mice that were sacrificed by perfusion fixation at intervals following tritiated thymidine injection were studied by means of radioautography. A kinetic gradient was demonstrated across the marrow section, with the highest proliferative rate in the subendosteal region. Megakaryocytes were shown to originate from the rapidly proliferating subendosteal cells. The immediate proliferating precursors of mature granulocytes were slowly proliferating cells found predominantly in the central region of the marrow. It was concluded that in the steady state there must be a migration of cells from the subendosteal region to the central region with concomitant growth retardation of the migrating cells.


The induction of transient increases in mitotic rate in murine tissues following prolonged intravenous infusions of hydroxyurea.

Intravenous infusions of hydroxyurea were established in mice and maintained for periods up to 48 hr. The influence of different rates of hydroxyurea infusion on the number of viable cells gathered in S phase was studied in eight different mouse tissues. An infusion rate which was sufficiently slow not to block thymidine incorporation completely, resulted in gathering of cells in S phase while offering some protection against hydroxyurea-induced cell death. The duration of the period of DNA synthesis following release from hydroxyurea inhibition appeared to be shortened in some tissues. After the release of hydroxyurea blockades maintained for 12-24 hr, each of the tissues showed sharp increases in mitotic activity and peak mitotic index values were as much as twenty times greater than values found in tissues of control animals. An important finding was that the time of maximal mitotic activity for different tissues after release of blockade could differ by many hours.


The predominant role of the spleen in lymphocyte recirculation. I. Homing of lymphocytes to and release from the isolated perfused pig spleen.

Lymphocyte recirculation through the isolated pig spleen was studied by means of a perfusion system which kept the organ alive for a prolonged period of time. By changing the perfusate to a leucocyte-enriched or cell-free perfusate and taking serial arterial and venous samples, the numbers of lymphocytes which homed to or were released from the spleen were measured. In all experiments more lymphocytes homed than were released per minute. There was no apparent difference when autologous or allogeneic cells were used. The number of lymphocytes released depended on the number of lymphocytes homed previously. During the phase of constant release up to 3-3 X 10(6) lymphocytes were released per gram spleen per minute. From these values it can be extrapolated that up to 270 X 19(9) lymphocytes recirculate through the isolated pig spleen per day. Based on kinetic data from other species it is estimated that in the entire pig a total number of 300-400 X 10(9) lymphocytes recirculate per day. Thus, it can be concluded that the spleen is the most important organ for lymphocyte recirculation in the pig.


The influence of a granulocytic inhibitor(s) on hematopoiesis in an in vivo culture system.

The in vivo diffusion chamber (DC) technique for mouse marrow culture was used to determine the effect of a granulocyte inhibitor on the proliferation of the pluripotent stem cell(CFU-s) and the granulocyte progenitor cell (CFU-c). Granulocyte conditioned medium was injected intraperitoneally into mice bearing DCs during the initial 48 hr of culture. The early injections of inhibitor resulted in a significantly reduced number of granulocytic progeny formed within the DCs while there was no growth inhibition of mouse fibroblasts cultured under identical conditions. The reduced cell production was due in part to a significant reduction in the self-renewal rate of the CFU-c while no apparent direct effect was observed upon the growth of the CFU-s within the same cultures. These data suggest that the granulocytic inhibitor(s) acted to reduce the proliferation within the CFU-c population and thereby diminished the amplification potential inherent in the initial cell inoculum.