Two clinically discrete syndromes of transsexualism.

Transsexuals are defined as subjects who have a sustained feminine gender identity combined with a wish to alter their bodily appearance towards the feminine. The results of this study indicate that they can be differentiated into two clinically discrete groups. In an investigation of 29 transsexuals who sought a change of sex operation it was found that those who had experienced fetishistic arousal were significantly more likely to be older, to have experienced heterosexual intercourse, to be married and to show penile responses to pictures of men and women indicative of a more heterosexual orientation. They had less experience of homosexual contact to orgasm as compared transsexuals who had not experiennced fetishistic arousal , but this difference was not statistically significant. Frequency of cross-dressing, strenght of feminine gender identity and intensity of desire for a sex change operation did not discriminate the two groups. The fact that desire for a sex change operation may be associated with experience of fetishistic arousal could be one reason for the higher incidence transsexualism in men than in women.


Two transsexuals with 47-XYY karyotype.

Previous reports of sexual orientation and gender identity in subjects with XYY karyotype are reviewed. Two patients seeking a change of sex operation and found to have an XYY karyotype are described. It is argued that an XYY karyotype may predispose to a disturbed gender identity and possibly to the development of the transsexual syndrome.


Abdominal contrast tomography in the evaluation of the gall-bladder and biliary tract (with emphasis upon jaundiced patients).

Tomography of the right upper quadrant after the rapid intravenous infusion of a high dose of contrast medium is a valuable method of investigation of hepato-biliary disease. Gall-bladder wall opacification may be normal, but if the wall is thicker than 2 mm and if irregular, it indicates inflammatory or calculous disease. Gall-bladder area greater than 35 cm2 indicates bile duct obstruction. This also causes the ducts to appear as lucent bands within the opacified liver parenchyma. Secondary deposits in the liver may also become visible. Various patterns of these findings are described which suggest specific biliary abnormalities.


Lateral lumbar discography.

The technique of lateral lumbar discography is described and compared with that of posterior lumbar discography. Its safety is demonstrated in a series of 1500 patients, only four of whom developed complications of note. Of these four, three developed discitis and one a retroperitoneal haemorrhage, all of which settled with conservative treatment.


The effect of radiology electives on career choice at McMaster University.

Recruitment ot radiology is said to be affected by the extent to which radiologists participate in medical student teaching. At McMaster University, where radiologists make major contributions to the medical school curriculum, students appear to show little interest in radiology as a career. The characteristics, attitudes and career choices of students at McMaster who undertook elective periods in radiology between 1973 and 1976 were examined. Though students rated the elective experience very highly, none intended to become a radiologist. Half of the group wished to take up family practice, the proportion in the school as a whole being similar. This is consistent with policies of student selection and education at McMaster. Most of those choosing family practice did not change their career choice between entry to and exit from the school. Involvement of radiologists in the curriculum had no detectable positive influence on career choice.


Dosimetry of cathetron applicators in intracavitary therapy.

Theoretical computations have been done to obtain dose distributions in the paracervical and sagittal planes for various loadings of Cathetron applicators. Uterine catheters of various sizes and shapes and various loadings of ovoid catheters have been considered for the dosimetry. Experimental measurements have been made to verify the computed dose distributions. The computed dose distributions have also been compared with those of a conventional Manchester loading. Although the ratio of dose contribution to point A from vaginal sources to that from the uterine sources is found to be significantly different for Cathetron therapy from the conventional Manchester system, the isodose distributions in the paracervical plane are in good agreement. However, the differences in the isodose distributions in the sagittal plane indicates a higher dose to the rectal region for Cathetron therapy, which can be reduced by the use of rectal retractors.


Radiation damage to the rat spinal cord: the effect of single and fractionated doses of X rays.

The tolerance of the rat lumbar spinal cord to single and multiple doses of X irradiation has been studied using paralysis of the hind legs as the endpoint. The paralysis, which has an acute onset progressing from the first symptoms to full paralysis within two to three days, occurs within one year post-irradiation. Dose/effect relationships were estimated at one year. Experiments which were designed to study the effect of varying the overall treatment time between two equal doses of X rays showed that a large amount of recovery from irradiation damage occurred during the first 24 hours after irradiation (D2-D1 at 24 hours was 950 rad). No further recovery took place for another 15 days but at 32 days another wave of recovery seemed to be in progress (D2-D1 at 32 days was 1250 rad). The effect of varying the number of fractions independently of the overall treatment time was investigated. The tolerance of the cord increased rapidly as the number of fractions given in a six-week period was increased from four to 30. The slope of a Strandqvist-type plot of this data was about 0.4. The data for the spinal cord have been compared with similar data for late damage in the mouse lung. The latent period between irradiation and the onset of paralysis was also investigated. At high doses, when the probability of paralysis occurring was great, the latent period was independent of the dose. At lower doses which gave rise to a lower incidence of paralysis, the latent period was inversely related to the dose. A second type of paralysis occurred later than one year after irradiation. This had a very protracted development and occurred in unirradiated as well as irradiated animals.


A linear transform of the multi-target survival curve.

A completely linear transform of the multi-target survival curve is presented. This enables all data, including those on the shoulder region of the curve, to be analysed. The necessity to make a subjective assessment about which data points to exclude for conventional methods of analysis is, therefore, removed. The analysis has also been adapted to include a "Pike-Alper" method of assessing dose modification factors. For the data cited this predicts compatibility with the hypothesis of a true oxygen "dose-modification" whereas the conventional Pike-Alper analysis does not.


The origin of thrombi in the deep veins of the lower limb: a venographic study.

A series of 952 patients was examined by ascending venography; 812 with clinically diagnosed deep vein thrombosis (DVT) (group 1) and 140 with clinical features suggestive of pulmonary embolism (group 2). Thrombus was demonstrated in 401 (49.4 per cent) of group 1 and in 74 (53 per cent) of group 2 patients. A total of 535 limbs contained thrombus. In 493 (92 per cent) thrombus was present in the calf with either no further clot, or clot in continuity with that in more proximal veins. In the remaining 42 legs (8 per cent) thrombus either originated from multiple discontinuous sites in the legs and pelvis, or in proximal major veins without concomitant calf involvement. The clinical implications of these findings are discussed.


Surgical treatment of the severely ischaemic leg: I. Survival rates.

Over a 10-year period, 411 patients with atherosclerotic major artery disease causing severe ischaemia of the legs were treated by surgery. Their survival rate, assessed by the life table method, was 80 per cent at 1 year and 50 per cent at 5 years. Early and late survival rates were significantly worse in elderly patients, and in patients with extensive gangrene. Late survival rates were significantly worse in diabetics, and in patients with clinical myocardial ischaemia. Patients treated by arterial reconstruction showed a better survival rate than those treated by sympathectomy or amputation, though the latter groups contained more poor risk patients. Survival rates were not influenced by the technique of reconstruction.


Saphenous neuralgia: a complication of arterial surgery.

The saphenous nerve may be damaged during arterial surgery in the thigh as it emerges through the aponeurotic covering of the adductor canal. A clean cut of the nerve gives rise to anaesthesia, but an incomplete cut or tearing of the nerve, followed by its involvement in scar tissue, leads to saphenous neuralgia--a painful sensation in the area supplied by the nerve. Two hundred and fifty-seven arterial operations involving the course of the saphenous nerve in the thigh have been reviewed. Twenty-six of these operations were complicated by early failure of the arterial procedure necessitating amputation and have not been considered in assessing the incidence of damage to the nerve. One in five superficial femoral thromboendarterectomies and one in nine femoropopliteal bypass grafts were complicated by saphenous neuralgia. Profundaplasty was not followed by this complication. Appreciation of this troublesome symptom should lead to greater care of the nerve during surgery.


Revascularization of an arm for incipient gangrene after Blalock-Taussig anastomosis.

A case is reported of incipient gangrene of the right arm developing after a Blalock-Taussig (subclavian-pulmonary) shunt operation in an infant. The ischaemia was reversed by immediate common carotid-axillary artery-vein bypass, using a microvascular technique.


Adenocarcinoma of the oesophagus and of the oesophagogastric junction.

The clinical and pathological features of 52 adenocarcinomas invading the oesophagus and the oesophagogastric junction are reviewed. The relationship of these tumours to the presence of a concomitant hiatal hernia and the histogenesis of primary oesophageal adenocarcinomas are discussed. Adenocarcinomas of the cardio-oesophageal junction appear to have distinctive prognostic and pathological features and there may be a case for their classification into a separate category of alimentary neoplasms.


Results of Heller's operation for achalasia of the cardia.

A survey of 102 patients with achalasia of the cardia treated by cardiomyotomy is reported. The technique of operation was unchanged throughout and the patients were followed up for a maximum of 22 years. Only 6 patients (5.8 per cent) developed renewed symptoms of reflux and 7 patients (6.8 per cent) had peptic strictures. Over 80 per cent of the patients had no dysphagia or regurgitation postoperatively, but 61 per cent still complained of achalasic pain. The development of mucosal hernias after cardiomyotomy and the use of drinking times in the assessment of outflow at the cardia are discussed.


Acute hiatal hernia with oesophageal perforation following Heller's operation.

The unusual complication of acute hiatal hernia with oesophageal rupture following transthoracic oesophagomyotomy is described in 2 cases. Inadvertent disruption and widening of the oesophageal hiatus at the time of surgery coupled with increased intragastric and intra-abdominal pressure were the probable causes. The hiatus should be carefully inspected on completion of the myotomy and anatomical restoration performed if necessary in order to avoid this complication. Urgent surgical intervention, gastric fundal serosal patch repair and intravenous alimentation proved successful in the management of these patients.


Changes in metabolism of major food components in patients with intrathoracic replacement of the oesophagus with the stomach.

In 19 patients in whom the stomach had been used as an intrathoracic replacement after osephagectomy the absorption of fat, carbohydrate and protein was studied. There is no single pattern of disturbance of such absorption. Protein digestion and absorption occur earlier and more rapidly than in normal subjects, probably as a result of accelerated gastric emptying.


Heterotopic mediastinal goitre.

The unusual coexistence in a woman of 34 years of a cervical thyroid and a heterotopic mediastinal thyroid is recorded. Both thyroids had undergone non-toxic nodular enlargement. Recurrent enlargement was noted in the cervical gland 12 months after transpleural thoracic removal of the mediastinal goitre, whilst no corresponding change has so far been noted in the mediastinum. The literature on heterotopic thyroid is briefly reviewed and the diagnosis discussed.


Thyroglossal cysts in children.

Of 69 cases of midline cervical swelling in children, the correct diagnosis was made in only 38 (55 per cent). Fifty cases of thyroglossal cyst or abscess were treated and 38 per cent suffered recurrence. Apart from failures in diagnosis, the main reasons for preventable recurrence were delay in surgery, failure to resect part of the body of the hyoid bone and a tendency to excise that portion of the duct above the level of the hyoid with insufficient surrounding muscle. In cases without florid abscess formation, the aim should be to perform a radical operation as soon as possible, then cure can be guaranteed at the first operation. Recurrence may occur many years after an apparent cure. Cysts in the submental region are not often recognized as being of thyroglossal duct origin.


Multiple congenital aneurysms in childhood: report of a case.

This paper reports the case of a girl who, at the age of 7 years, presented with a saccular aneurysm of a brachial artery. Over the following 8 years a further 15 aneurysm appeared, involving limb and visceral arteries and the aorta. Some, but not all, of these aneurysms have been operated upon. Complications included renovascular hypertension due to bilateral intrarenal aneurysms. She had been followed up for 15 years. Three other similar cases have been found in the medical literature, and these are also referred to. In two of these cases the affected persons also exhibited some of the other connective tissue anomalies associated with the Ehlers--Danlos syndrome. These were not present in our patient. The relationship between the syndrome of multiple congenital aneurysms and the Ehlers--Danlos syndrome is discussed.


Benign duodenocolic fistula.

Benign duodencolic fistula is a rare complication of a number of gastrointestinal diseases and it is seldom considered in diagnosis. Diarrhoea and weight loss are characteristic presenting features which may be masked by coexisting disease. Barium enema is the most useful diagnostic procedure. Prognosis is good if surgery is undertaken at an early stage after adequate correction of the metabolic consequences of the fistula, by administration of fluid, electrolytes and parenteral nutrition. This paper reports 4 cases of this condition and reviews the clinical features, investigation, aetiology and management.


Diagnosis and management of gastric carcinoid tumour with hepatic metastases.

The gastric carcinoid tumour is a rare variety of carcinoid characterized by atypical production of 5-hydroxytrytophane rather than serotonin. In our case it is likely that other polypeptides are the source of symptoms, though these are as yet unidentified. Since surgery was not feasible in the management of the hepatic metastases, we have used a non-operative technique of embolization to destroy the carcinoid secondaries and ameliorate symptoms. The patient tolerated this procedure well and improved dramatically, with remarkable diminution of liver size and the disappearance of all carcinoid symptoms. Destruction of hepatic secondaries without recourse to surgery has obvious advantages in severely ill patients. Careful attention should, however, be paid to the large quantities of pharmacologically active compounds released from the liver by the procedure.


Abdominal wound healing in jaundiced patients.

Abdominal wound healing was studied in 48 patients undergoing laparotomy for jaundice and 281 anicteric patients undergoing elective operations for cholelithiasis at the Sheffield Royal Infirmary during the period 1967 to 1976. Wound dehiscence or incisional hernia occurred in 27.1 per cent of jaundiced patients and in 4.3 per cent of anicteric patients (P less than 0.001). There was a slightly higher incidence of dehiscence and herniation in deeply icteric patients (plasma bilirubin greater than 170 mu mol/l), but patients who developed these complications did not appear to have a more severe degree of malnutrition or impaired liver function. The results of the study suggest that malignant disease may be an important factor in the pathogenesis of wound complications in jaundiced patients. Wound dehiscence or incisional hernia occurred in 59.1 per cent of patients with obstructive jaundice resulting from malignant disease but patients with jaundice resulting from biliary stones or benign pathology did not develop these complications.


Housing, health, and illness.

Cases referred to a community physician in his role as medical adviser to a housing authority were reviewed. A new system of classifying health problems was devised because conventional diagnostic classification was found to be inappropriate. The effectiveness of medical intervention was apparently low, since only 29 out of 612 (4.7%) applications for rehousing on medical grounds were successful. The effectiveness of the community physician's role was limited by the available resources and the number of cases he could take before the housing committee. It is proposed that the use of medical resources for intervention in such cases is acceptably efficient, though this proposal is based on value judgement rather than on economic grounds. Doctors should be concerned in improving housing conditions, which are still unacceptably poor in many parts of Britain, in the interests of improving general standards of public health.


Physiological aspects of menopausal hot flush.

Eighteen hot flushes experimenced by eight menopausal women were studied and compared with the effects of warming in six premenopausal women. The hot flushes were associated with an acute rise in skin temperature, peripheral vasodilatation, a transient increase in heart rate, fluctuations in the electrocardiographic (ECG) baseline, and a pronounced decrease in skin resistence. Although premenopausal women had greater maximum increases in skin temperature and peripheral vasodilatation, they showed a much smaller decrease in skin resistance and no changes in heart rate or ECG baseline. These findings suggest that the onset of the hot flush is associated with a sudden and transient increase in sympathetic drive. Further investigations may lead to the development of a more specific alternative to oestrogen for relieving menopausal hot flushes.


Axillary hyperhidrosis treated with alcoholic solution of aluminium chloride hexahydrate.

Sixty-five patients with axillary hyperhidrosis took part in a trial of treatment with a solution of 20% aluminium chloride hexahydrate in absolute alcohol, applied topically each night for a week and then whenever the patient thought it necessary. Excellent control of sweating was achieved in 64 patients, and occlusion of the area was found to be unnecessary. No troublesome side effects were reported. The results of this study indicate that 20% aluminium chloride hexahydrate in absolute alcohol is the treatment of first choice for patients with axillary hyperhidrosis.


Proctocolectomy without ileostomy for ulcerative colitis.

An operation has been developed that permits total removal of all disease-prone mucosa in ulcerative colitis but avoids the need for a permanent ileostomy. The colon and upper half of the rectum are excised and the remaining inflamed mucosa is stripped from the rectal stump down to the dentate line of the anal canal. A pouch is fashioned from a triplicated loop of terminal ileum. This is drawn down through the denuded rectum and an anastomosis created, via the per-anal approach, between the ileum just distal to the pouch and the mid-anal canal. A temporary ileostomy is made. Out of eight patients so treated, five were available for assessment, and four of them were highly satisfied with the result in improved health and function. The remaining three were awaiting closure of their ileostomies.


Comparison between subjective and ultrasound assessments of fetal movement.

Forty pregnant women participated in a study to compare subjective with ultrasound assessments of fetal movements. A real-time ultrasound scanner was used. Movements were recorded for 45 minutes in all cases. There was a significant positive correlation between the number of movements recorded by the two methods, but the 95% confidence limits were wide and no correlation was found in those patients who recorded fewer than 20 movements in the study period. Thus "false-positive" information may be obtained from purely subjective data, and in patients reporting low "kick counts" fetal activity should be assessed from real-time ultrasound recordings.


Frontal 'oculomotor" area in alert cat. I. Eye movements and neck activity evoked by stimulation.

(1) Stimulation within cat frontal lobe elicited saccadic eye movements whose maximum velocity was significantly greater than that of normal spontaneous saccades. (2) The majority (90%) of stimulated cortical points yielded eye movements whose directions and amplitudes were independent of the position of the eye in the orbit. The direction of these eye movements depended on the site being stimulated, with a discrete and orderly representation of directions existing within the cortex. (3) A lesser number of cortical points (10%) yielded centering movements whose directions and amplitudes depended on the position of the eye in the orbit, rather than on the site being stimulated. (4) Evoked neck muscle activation frequently preceded evoked eye movements by some 15--30 msec. This timing was compatible with a coordinated head-eye orientating response. (5) On the basis of the directions, and the latencies, of evoked eye movements, the cat frontal oculomotor area could be divided into two subregions, a 'medial' and a 'lateral', (6) The 'medial' area included the mesial wall of the hemisphere with a portion of the lower lip of the cruciate sulcus, and the medial wall of the presylvian sulcus. This area yielded contraversive eye movements with shorter latencies (average 45 msec). (7) The 'lateral' area included primarily the lateral wall of the presylvian sulcus. It yielded predominantly centering eye movements, and ipsiversive movements with longer latencies (65 msec). (8) The functional characteristics of the 'medial' area, as revealed by focal stimulation, resembled those of the monkey frontal eye field.


Frontal 'oculomotor' area in alert cat. II. Unit discharges associated with eye movements and neck muscle activity.

(1) Unit activity in front 'oculomotor' cortex was recorded extracellularly from sites where subsequent electrical stimulation, using threshold current (50 microamperes), could elicit both eye movements and simultaneous neck EMG acitivity. (2) Of 103 cells, 19% were related to either eye movements or neck EMG activity. Cells could be grouped into three categories: (a) Directional (D) cells (31%) discharged before and during saccadic eye movements, whenever the eyes followed a target in one specific direction. Spontaneous saccades, or vestibularly driven nystagmus, in either the light or dark, elicited no responses. (b) Conditionally directional (CD) cells (43%) discharged following (i) tracking saccades; (ii) spontaneous saccades and (iii) the quick phase of nystagmus, in all directions. There usually was a slight discharge preference for one given direction, and this preference was enhanced whenever visual tracking was restricted to the preferred direction. One-third of CD cells responded to stimulation of the contralateralal biventer cervicis neck muscle (min lat. 20 msec). (c) Neck EMG (N) cells (26%) discharged in association with, and preceding, changes in neck muscle activity. These cells also responded to stimulation of the contralateral biventer cervicis muscle (min lat. 10 msec). (3) For points in the lateral 'oculomotor' region (as defined by stimulation: see ref. 17), the directions of evoked saccades, and the directions of spontaneous saccades associated with unit discharges, were sililar. In the medial region 17, the directions of evoked saccades were roughly opposite to the directions of spontaneous eye movements favoured by unit discharges.


Unitary acitvity of ventrolateral nucleus during placing movement and associated postural adjustment.

The activity of neurons in the ventrolateral nucleus of the thalamus (VL) was analyzed in the cat during placing movements of both the right and left forelimbs. The purpose was to determine if thalamic neuron discharge patterns could be related to movement and/or to postural changes. Placing tests were conducted on animals maintained in a standing position and partially restrained by a hammock. Each of the forelimbs rested on a flat surface containing a strain gauge which allowed the stance forces to be measured. Two mobile plates, one on the left and one on the right, were used to elicit a contact placing reaction. The response was composed of an isometric phase, during which the body weight was shifted from the stimulated limb to the opposite forelimb while the stimulated limb was gently pushed backwards, and a movement phase during which the stimulated paw actually accomplished the placing reaction. (1) About half the recorded neurons (47/86) in the VL region demonstrated a change in activity, generally an increase of discharge frequency, during placing of the right of left forelimb. (2) Almost all the reactive units (45/47) responded to contralateral placing. Two units changed their activity with ipsilateral placing only, whereas 18 units were active during placing of both forelimbs. The discharge pattern of cells activated during ipsilateral placing was considered as related to the isometric postural adjustment of the contralateral limbs. (3) Cells reactive during contralateral tests were located preferentially in the ventrolateral part of VL. Units reactive during ipsilateral tests (postural units) were also clustered in the ventrolateral half of VL which is the zone controlling limb musculature. Some of the 'postural units' were identified as receiving afferents from cerebellar nuclei and projecting to motor cortex. (4) Changes in discharge frequency were observed during either the isometric phase, the movement phase, or both. The same type of patterns were observed during contralateral and ipsilateral placing. About half of the cells responding during the contralateral placing movement did so throughout the entire duration of the movement, and were not specifically related to either the flexion or the extension phase of the placing. (5) The timing of the discharge of VL units with respect to the isometric phase and to the movement phase of the motor sequence varied from cell to cell. No topographic arrangement of neurons with the same pattern of discharge could be found within the nucleus.


Some properties of extrastriate visual units in the cortex of the rabbit.

Receptive fields and trigger properties of 306 units in the visual cortex of the rabbit have been examined in detail. Reconstruction of the electrode tracks revealed that 276 of these recordings were made from cells located in the striate cortex, whilst the remaining 30 were found to lie in cortex lateral to the striate field. These latter units have been termed 'extrastriate'. Five penetrations involved both striate and extrastriate units enabling a direct comparison of their properties to be made. The most outstanding feature of the extrastriate units was their huge receptive field sizes (up to 80 degrees X 130 degrees) and high rates of spontaneous activity (usually between 10 and 20 imp./sec). None of these cells responded well to stationary stimuli and most preferred moving targets. Responses could be elicited regardless of the nature of stimulus-to-background contrast and were constant over a wide range of stimulus sizes. No cells were found which were orientation selective. Approximately half the extrastriate units were direction selective, the majority preferred anterior movement in the visual field. Movement in the counter-preferred direction generally resulted in suppression of the spontaneous discharge. In contrast to this the receptive fields of cells in the striate cortex were small, and were often sensitive to features such as stimulus size, orientation, and contrast, in addition to movement and direction of movement. The similarity between one class of extrastriate unit, and units recently observed in the pretectum of the rabbit is pointed out.


Effects of undernutrition on glial maturation.

Rats of Wistar strain were conceived and breast-fed until the 25th day by mothers maintained on a low protein (5%) and low caloric (21 calories/day) diet, producing a severe deficiency in weight body growth (more than 50% at the 10th day) and of the weight of the central nervous system (40% on the 15th day) both in the cerebral hemispheres and the spinal cord. Histological and biochemical analysis of the central nervous system shows: (1) Glial proliferation is insufficient and delayed, the number of glial cells is reduced by 50% on the 10th day in the cuneatus and gracilis tracts and the density of the glial cells is reduced by 50% in the corpus callosum at the 19th day. (2) Maturation of the glial cells is greatly retarded, especially in the corpus callosum a structure which matures late. On the 19th day, the majority of the cells in this structure still have a glioblastic appearence, whereas in the normal rat, at this age the majority of the glial cells are oligodendrocytes. (3) These abnormalities of glial maturation agree well with the delay of the increase of DNA, RNA and protein measured in the spinal cord and cerebral hemispheres. (4) There is a defect in myelination assessed by estimation of the density of the myelin fibres, and a definitive reduction in the caliber of the spinal tracts.


Reward, attention and the dorsal noradrenergic bundle.

The resistance to extinction seen after lesion to the dorsal noradrenergic bundle has been suggested to arise from a deficit in internal inhibition or a 'perseverative' type of deficit. This hypothesis is tested by examining the ability of 6-hydroxydopamine-treated animals to inhibit a previously developed preference for saccharine solution as a result of poisoning with lithium chloride. Unimpaired taste aversion is found, arguing against a deficit in the ability to inhibit a prepotent response. An alternative explanation of the dorsal bundle extinction effect (DBEE), that of alterations in attention, is tested by acquisition and reversal of a successive light-dark discrimination. Both acquisition and reversal are severely impaired, suggesting that the treated animals have difficulty in attending to a specific stimulus in the environment when this is required in order to structure behaviour appropriately, and thus being consistent with a role for the dorsal bundle in the control of attentional processes.


The dorsal and medial raphe projections to the substantia nigra in the rat: electrophysiological, biochemical and behavioural observations.

Electrophysiological experiments have been performed in urethane anaesthetized rats to investigate the projections from the dorsal (DRN) and medial raphe nuclei (MRN) to the substantia nigra. The biochemical and behavioural effects following discrete electrolytic lesions in the dorsal and medial raphe have also been investigated. Stimulation of the DRN produced predominantly inhibition of spontaneous activity of single neurones in the substantia nigra though some neurones were also excited. Bilateral stimulation of the substantia nigra produced antidromic spikes in DRN and MRN neurones. Lesions of the DRN and MRN produced a significant reduction in substantia nigra 5-HT concentration. Additionally, DRN lesions reduced striatal 5-HT, while MRN lesions reduced hippocampal 5-HT. Both lesions increased substantia nigra HVA concentration but did not affect DA concentration. Neither DRN nor MRN lesions affected striatal HVA, although DA levels were significantly elevated after 14 days. Animals with DRN lesions explored more than controls or MRN-lesioned animals. However, this behaviour was transient and was not observed after 14 days. On the other hand, MRN-lesioned animals were significantly hyperactive. These observations suggest that the substantia nigra receives a direct monosynaptic inhibitory input from the DRN and MRN and that these pathways use 5-HT as a neurotransmitter serving to tonically inhibit dopaminergic neurones. While 5-HT and dopamine appear to be involved in the control of motor behaviour, the precise relationship between these serotoninergic and dopaminergic systems in this respect is unclear.


Storage and release of acetylcholine in the isolated superior cervical ganglion of the rat.

The storage and release of acetylcholine and choline were studied in the isolated superior cervical ganglion of the rat by a radioenzymic method. The acetylcholine and choline contents were 202.2 +/- 5.1 and 624.7 +/- 20.2 pmole/ganglion, respectively. The transmitter tissue store was unaffected during 1 h of superfusion in choline--Krebs solution, while a 20% decrease was exhibited after 2 h and then remained approximately stable. Conversely, choline content declined to 50% within 1 h and further to 37% of the original level by 4 h. About 24% of the choline assayed in the intact preparation is located in the connective sheath. Preganglionic nerve stimulation at 10--20/sec or potassium stimulation (40 mM KCl) invariably decreased the transmitter tissue stores by 25--45%; such a depletion is independent of the presence or absence of external choline. By contrast, the presence of choline proved to be a prerequisite for the efficient release of acetylcholine from eserinized ganglia during continuous 10/sex stimulation. A drastic depression in the acetylcholine release is described which is related to the time of preincubation of the ganglia with eserine prior to stimulation. Indeed, a 30 min exposure to eserine, compared with a 5 min period, resulted in a 4-fold decrease in the steady output rate. Under optimal conditions, the initial volley output at 10/sec was 1.3 X 10(-4) of the releasable transmitter pool and 1.9 X 10(-4) during the steady-state output. These results are discussed in the light of the electrophysiological knowledge of the quantal release process at the ganglionic synapse.


Substance P release from the rat substantia nigra.

The characteristics of substance P release have been investigated in the rat substantia nigra, in vitro, using a sensitive radioimmunoassay method. The spontaneous efflux of substance P represented approximately 0.5% of tissue stores released per minute. Addition of potassium to the superfusion medium produced a concentration-dependent increase in substance P release which was linear over the range 15--60 mM potassium. The potassium-evoked release of substance P was almost totally abolished by removal of calcium from the superfusion medium, and was linearly related to an increase in calcium concentration with a corresponding decrease in the magnesium concentrations over the range 0.1--3.0 mM calcium. Veratridine (50 micrometer) also evoked the release of substance P in a calcium- and tetrodotoxin-sensitive manner. Superfusion of substantia nigra slices with GABA produced a concentration-dependent inhibition in the K+-evoked release of substance P which could be abolished by continuous superfusion with picrotoxin. Bicuculline was less effective than picrotoxin in blocking the effects of GABA. The GABA agonist muscimol also produced an inhibition of substance P release, whereas baclofen was without effect. These results support the concept that substance P may function as a neurotransmitter within the substantia nigra, and suggest that GABA may have a role in the regulation of substance P release.


Messages conveyed by spinocerebellar pathways during scratching in the cat. I. Activity of neurons of the lateral reticular nucleus.

(1) Signals transmitted to the cerebellum by the spino-reticulocerebellar pathway (SRCP) during scratching were studied. For this purpose, the activity of neurons of the lateral reticular nucleus (LRN), which are the last-order neurons of the SRCP, was recorded during scratching in thalamic cats. Scratching was evoked by stimulation of the pinna. LRN neurons were identified antidromically by stimulation of the hindlimb area in the cerebellar anterior lobe. In most experiments, animals were immobilized with Flaxedil, and stimulation of the pinna resulted in fictitious scratching, i.e., in periodical reciprocal activity of flexor and extensor motoneurons typical of actual scratching. (2) During both actual and fictitious scratching, the discharge frequency of LRN neurons was rhythmically modulated in relation with the scratch cycle. Most LRN neurons fired in short high-frequency bursts of spikes which coincided (completely or partly) with the extensor phase of the cycle. In this respect the SRCP differs from the ventral spinocerebellar tract (VSCT) which is maximally active in the flexor phase of the cycle. (3) The firing pattern of LRN neurons during fictitious scratching was similar to that during actual scratching. Therefore, the rhythmical burst firing of LRN neurons is determined mainly by the central mechanisms and not by the rhythmical sensory input. (4) Rhythmical modulation of LRN neurons disappeared after transection of the ipsilateral lateral funiculus of the spinal cord in which spinoreticular fibers are located. On the other hand, considerable reduction of rhythmical activity in descending brainstem-spinal pathways after contralateral hemisection of the spinal cord did not affect the discharge pattern of LRN neurons. These two facts indicate that the SRCP conveys mainly messages about activity of the central spinal mechanisms, and that influences of supraspinal motor centers.on LRN neurons and on spinoreticular neurons are of minor importance. (5) Axonal terminations of LRN neurons are distributed rather evenly over the hindlimb area in the anterior lobe of the cerebellum. Therefore, messages about the events, which happen within the spinal cord in the vicinity of the extensor phase of the cycle, arrive at every point of the hindlimb area.


Messages conveyed by spinocerebellar pathways during scratching in the cat. II. Activity of neurons of the ventral spinocerebellar tract.

(1) The activity of neurons of the ventral spinocerebellar tract (VSCT) during scratching was studied in thalamic and decapitate cats. The neurons were identified antidromically either by stimulation of the hindlimb area in the anterior lobe of the cerebellum (in thalamic cats) or by stimulation of the contralateral ventrolateral funiculus of the spinal cord (in decapitate cats). The scratch reflex was elicited by stimulation of either the pinna (in thalamic cats) or the cervical spinal cord (in decapitate cats). In most experiments, animals were immobilized and the activity of VSCT neurons was recorded during fictitious scratching. (2) During both actual and fictitious scratching, the discharge of VSCT neurons was rhythmically modulated in relation with the scratch cycle: neurons fired in bursts separated with periods of silence. Phases of activity of different neurons were unevenly distributed over the scratch cycle: most neurons fired within the limits of the flexor phase of the cycle. (3) The firing pattern of VSCT neurons during fictitious scratching was similar to that during actual scratching. Therefore, rhythmical burst firing of VSCT neurons is determined mainly by central mechanisms and not by a rhythmical sensory input. (4) The firing pattern of VSCT neurons in decapitate cats was similar to that in thalamic cats. Therefore, rhythmical burst firing of VSCT neurons is determined mainly by the central spinal mechanism and not by supraspinal motor centers. (5) The VSCT neurons which fired in long bursts during the greater part of the flexor phase were usually activated during the latent period of scratching, while those firing later in the cycle were usually either inhibited or not affected during this period. (6) The antidromic response in most VSCT neurons could be evoked from a large number of points in the hindlimb area of the cerebellar anterior lobe, both in the vermis and in the pars intermedia. Due to such extensive branching of axons, each point of the cortex receives signals from neurons firing in different phases of the cycle. But axons of VSCT neurons firing in long bursts during the greater part of the flexor phase terminate more extensively in the pars intermedia, while axons of neurons firing later in the cycle terminate more extensively in the vermis. (7) The functioning of the VSCT is essentially similar to that of the spino-reticulocerebellar pathway (SRCP). Both pathways convey messages about activity of the central spinal mechanism generating the motor output pattern of scratching, but the VSCT is active mainly in the flexor phase of the scratch cycle and the SRCP in the extensor one. A hypothesis is advanced that these pathways monitor activity of different groups of spinal interneurons.


Behavioral and anatomical consequences of small intrastriatal injections of kainic acid in the rat.

The effects of bilateral injections of kainic acid into the anteromedial neostriatal region were examined behaviorally and anatomically in two groups of rats. Behaviorally, kainic acid injections resulted in a severe impairment of delayed alternation retention, while the ability for visual discrimination remained unaffected. Anatomically it was found that axons traversing the injected area remain able to transport horseradish peroxidase. Furthermore, histological examinations of the injected regions revealed a heavy loss of neurons and a decrease of histochemical staining for specific acetylcholinesterase. Silver impregnation showed slightly disorganized, but continuous, axons in bundles of the capsula interna. On the other hand, the axonal network throughout the neuropil of the injected area was markedly diminished. No conspicuous change was found in myelin staining or in the intensity or catecholamine fluorescence. The anatomical results suggest that kainic acid appears to affect only perikarya of the neostriatum and the axons originating from these perikarya, whereas passing axons seem to remain intact. Thus, the observed behavioral impairment must be attributed to changes in the neostriatum itself. It is concluded that the neostriatum has 'complex' or 'cognitive' functions and that some mental symptoms in Huntington's chorea may be attributed to a dysfunction of this part of the brain.


X-ray diffraction and electron microscope study of osteons during calcification.

To obtain information on the changes in the inorganic bone fraction during calcification, low- and wide-angle X-ray diffraction techniques and electron microscopy have been applied to single osteon samples. The samples were cylindrically shaped and their axes corresponded to the axes of the Haversian canals. The selection was made according to the degree of calcification and the orientation of collagen bundles and inorganic particles. Osteons at both the initial and final stages of calcification were chosen. Arrangements of fiber bundles and inorganic particles in successive lamellae characteristic of three types of osteon were selected, that is, longitudinally structured osteons, transversely structured osteons, and alternately structured osteons. The results indicate that in osteonic lamellar bone there are two types of inorganic particles: (1) granules arranged in linear or needle-shapred entities with maximum width 40-45 A, which are regularly distributed at the level of the main band of the collagen fibrils where their maximum length reaches the length of the main band itself; that is , about 400 A; and (2) very long crystallites, with a diameter of 40-45 A, which grow with their crystallographic c-axis parallel to the collagen fibrils and cover much more than a major collagen period.


[The shell of the quail's egg: ultrastructural and crystallographic study (author's transl)].

The egg-shell of Japanese quail was studied by several techniques. Semithin sections (1 micron thick) of non-decalcified shell were observed by normal and polarized light microscopy. Thin sections of non-decalcified shell, examined by transmission electron microscopy, permitted us to observe the forms and dimensions of crystals of calcite within different layers of the shell: mammilary layer, layer of cones, palissade layer and surface crystal layer. There appears to be two distinct zones in the layer of cones as well as in the superficial crystal layer. Electron microdiffraction revealed the orientation of calcite crystals in the columns. Some crystal defects (twins?) were described and the possibility of their artefactual formation during ultramicrotomy is discussed. Localization of Ca, Mg, P and S were made by X-ray microanalysis of semithin sections. This technique shows that shell membranes, and chiefly the true cuticle, are also mineralized but, in these layers, minerals are not crystallized. Otherwise the distribution of Mg is not uniform throughout the shell thickness; it is less concentrated in the external zone of the layer of cones. These results together with observation of developing shells by scanning electron microscopy allowed us to propose a scheme for shell organization of the quail egg. This organization was related with decalcification which occurs during hatching.


A macromolecular inhibitor of in vitro calcification of tendon matrix.

Bovine and human tendon tissue do not induce calcification in vitro. However, extraction of those tissues with 3% Na2HPO4 converts them to calcifiable matrices. The supernatant fraction derived from the extraction contains a nondialyzable, perchloric acid soluble component that inhibits calcification of the extracted matrix. This inhibitory substance is characterized by a molecular weight in the range of 85,000-100,000. Exposure to pronase or hyaluronidase did not alter the inhibitory potency but did render the inhibitor dialyzable. Commercial sources of hyaluronic acid, chondrotitin-6-sulfate, chrondroitin-4-sulfate, dermatan sulfate, heparin and lysozyme did not inhibit calcification of the extracted matrix. Phosvitin, a phosphoglycoprotein is a potent inhibitor. Although phosvitin and the tendon extract also inhibit calcification of previously calcified matrix, they have no detectable effect on the rate of decalcification. We conclude that the mechanism of inhibition is characterized by a degree of specificity and that phosvitin and a macromolecular component of tendon tissue blocks conversion of an intermediate matrix-bound CaP complex to crystalline apatite. It seems reasonable that the tendon inhibitor could function in situ and possibly in vivo to control calcification of tendon tissue.


Phosphophoryns-major noncollagenous proteins of rat incisor dentin.

Freshly excised rat incisors were immediately cleaned and demineralized in 0.5 M ethylene diaminetetracetic acid at pH 7.5. The extracts were freed of calcium, diffusible phosphate and low molecular weight polypeptide components by dialysis in membranes with cut-off of 3500 molecular weight. The extract was resolved into at least 7 protein components by chromatography on DEAE-cellulose at pH 8.2. The composition of each protein component was determined. Two proteins, rich in serine, phosphorous and aspartic acid were unlike any proteins attributed to enamel, and hence were considered to be components of incisor dentin. These were the principal non-collagenous components of the teeth. Further purification was carried out under dissociative conditions on Sepharose CL-6B gel filtration columns in 3.0 M guanidine hydrochloride. The two phosphoproteins have mol wts, by this method, of 71,000 and 65,000, respectively, and differ in content of apolar amino acids, although both contain greater than 70 residue % of seryl (or phosphoseryl) and aspartyl residues. The name "phosphophoryns" is proposed to describe these dentinal proteins. The insoluble collagenous matrix remaining after the original demineralizing extraction was degraded with cyanogen bromide. Several non-collagenous protein components were released as well as the typical collagen derived peptides. Two collagen phosphoprotein complex peptides were also isolated, demonstrating as in bovine dentin, the probable direct covalent interaction of a dentin phosphoprotein with hte collagen of the mineralized matrix.


The female carrier of haemophilia--a problem for the anaesthetist.

Three case histories reflect the difficulties of pre-operative assessment and management of female obligatory carriers for Factor VIII or Factor IX deficiency (haemophilia). The dangers of operation in these individuals is emphasized in view of the often confusing laboratory and clinical findings in this group of patients. A protocol is presented which, if used by the anaesthetist, will provide for logical and safe diagnostic and therapeutic approaches for these patients.


Epiglottitis and pulmonary oedema in children.

We have presented three patients with epiglottitis who developed pulmonary oedema during the course of treatment with nasotracheal intubation and antibiotics. The exact mechanism for the development of pulmonary oedema in these patients is not known. Possible mechnisms are changed in the physical factors controlling the movement of fluids across the capillary-alveolar membrane, transitory bacteraemia and endotoxinaemia, or myocardial depression by the antibiotics and the anaesthetic agent. The pulmonary oedema had a benign course and responded to mechanical ventilation and increased airway pressure.


Plasma vasopressin levels during cardiopulmonary bypass with and without profound haemodilution.

In cardiopulmonary bypass the effect on plasma vasopressin levels of the addition of whole blood to the pump priming solution was measured. Six patients (Group I) had blood added to the lactated Ringer's solution for the prime, and six patients (Group II) had only lactated Ringer's solution. Neither group had significant changes in plasma vasopressin levels until surgical stimulation occurred. Comparable significant elevations occurred during bypass in both groups. Greater decreases in haematocrit and urinary K+ and greater increases in urinary Na+ occurred in Group II. The degree of haemodilution does not appear to effect plasma vasopressin levels but may alter the degree of electrolyte shift.


Arterial pressure and deltoid muscle gas tensions during cardiopulmonary bypass in man.

The results of this study demonstrate that standard techniques of conducting cardiopulmonary bypass produce low muscle oxygen and high muscle carbon dioxide tensions and, thus, little perfusion of skeletal muscle. Our findings also show that PmO2 and PmCO2 do not return to pre-bypass levels until the mean arterial blood pressure exceeds 12 kPa (90 torr) during bypass and that utilization of vasopressor drugs during bypass maintains the pressure; but at the expense of muscle blood flow. The data indicate that both high mean blood pressure and high flow are necessary during bypass to ensure skeletal muscle perfusion and suggest, when combined with preliminary animal findings, that this type of bypass perfusion may prove to be superior to standard techniques in hastening recovery after cardio-pulmonary bypass.


Effects of certain antibiotics on isometric contractions of isolated rat heart muscle.

The direct effects of potassium-penicillin-G, kanamycin, streptomycin and chloramphenicol on isometric contraction of isolated rat heart muscle were examined. Potassium-penicillin-G did not depress myocardial contractility but rather increased it. Those increases are not due to penicillin itself but due to a small amount of K+ in potassium-penicillin-G. Kanamycin and streptomycin did show not only direct myocardial depressants effects but concentration-dependent depressions. The depression produced by kanamycin could be restored to normal by adding Ca++ to the bath solution. Chloramphenicol did not show any significant concentration-dependent depression in our studies. We conclude that it is important to be aware of the potential depression of cardiac function by antibiotics, particularly in patients who have diminished cardiac reserve and who are undergoing surgical procedures under anesthesia which may also depress cardiac function.


The effect of halothane anaesthesia on liver regeneration.

The effects of halothane and diethyl ether on the regenerating liver following 70 per cent hepatectomy were studied in Fisher/344 (F) rats. Our aim was to discover whether halothane administered repeatedly and over prolonged periods could influence the liver regenerative process or hepatocyte function. We also wished to know if the effects of halothane differed from those of diethyl ether. We found: 1. Prolonged halothane or diethyl ether anaesthesia did not inhibit liver mitotic activity, even if administered repeatedly. 2. The effects of halothane and diethyl ether on liver cell division were identical. 3. With reference to liver regeneration, halothane is as safe as diethyl ether when administered during extensive hepatectomy.


Effects of halothane on the pharmacokinetics of lidocaine in digitalis-toxic dogs.

Following the production of digitalis toxicity in dogs as manifested by ventricular tachycardia, the pharmacokinetics of lidocaine treatment of the arrhythmia were determined during pentobarbitone anaesthesia and pentobarbitone-halothane anaesthesia. The elimination rate constants, beta and Ke, and the biological half life T1/2beta were statistically significantly increased during halothane anaesthesia. The volume of distribution was unchanged. The results indicate that the therapeutic loading dose of lidocaine need not be altered during halothane anaesthesia but if a constant infusion is used, the rate of infusion would have to be decreased four fold to avoid toxic plasma levels of lidocaine.


Halothane for status asthmaticus in the intensive care unit--a case report.

A case report is presented demonstrating the beneficial beta2 stimulating effect of halothane in a patient with status asthmaticus unresponsive to adequate conventional therapy. Twenty-four hours after the commencement of therapy, 0.5 per cent of 1.0 per cent halothane was administered for one hour with sustained reductions in peak inspiratory airway pressure and increases in dynamic and static effective compliances.


The influence of fentanyl on an alfathesin infusion technique.

The effects of fentanyl (1 microgram/kg) supplementing an alfathesin infusion technique were assessed in a double blind study in 53 healthy unpremedicated female patients undergoing therapeutic abortion as outpatients. The addition of fentanyl reduced the tachycardia, tachypnoea and hyperventilation seen in those patients receiving alfathesin alone, without unduly prolonging recovery time. Two patients receiving alfathesin alone developed marked coughing or laryngospasm. Fentanyl would seem to be a desirable addition to an alfathesin infusion technique in unpremedicated patients presenting for outpatient anaesthesia.


Protein composition of rat bile.

In order to characterize the protein composition of rat bile, the bile duct was cannulated in 250 g male Wistar rats and biliary proteins were examined over 48 h. Total protein secretion was monitored by the Cu2+--Folin differential test while individual proteins were characterized by sodium dodecyl sulfate (SDS) and non-SDS polyacrylamide gel electrophoresis. The relative contribution of various proteins was evaluated by densitometric scanning of the stained gels. It was observed that both total biliary protein secretion and the protein polypeptide profiles remained constant throughout the 48h. This is in comparison with biliary bile-acid secretion which fluctuates markedly during this time period both in quantity and composition. It is concluded that biliary secretion is probably not related to the biliary secretion of bile acids.


Analysis of spermidine and spermine in rat liver. Effect of hypophysectomy on polyamine concentrations.

A simple, rapid, reproducible assay for tissue polyamines using a standard unmodified amino-acid analyzer is described. This technique will allow accurate measurement of the polyamines from as little as 10 mg of liver in less than 1 h. We have used this method to establish the optimum conditions for the extraction of polyamines from liver and to study the effects of hypophysectomy on polyamine content of rat liver. Hypophysectomy caused a fall in RNA, protein, putresine, and spermidine content prevented the normal increase in spermine in rat liver seen with increasing age.


Effect of the basic amino-acid side chain length and the penultimate residue on the hydrolysis of benzoldipeptides by carboxypeptidase B.

The kinetic parameters Km and k cat/K m have been determined for the carboxypeptidase B (CPB, EC 3.4.12.3) catalyzed hydrolysis of benzoylglycyl-DL-homolysine and benzoylglycyl-L-homorginine. Plots of these data and those for Bz-Gly-Orn and Bz-Gly-Arg (Wolff, E. C., Schirmer, E.W. & Folk, J. E. (1962) J. Biol. Chem. 237, 3094-3099) and Bz-Gly-Lys versus the length of the side chain of the basic amino acid indicate that unlike trypsin (EC 3.4.21.4) (Seely, J. H. & Benoiton, N. L. (1970) Can. J. Biochem. 48, 1122-1131) CPB has a higher bending affinity for a guanidino group than for an amino group at the side chain of the substrate C-terminus. On the other hand, CPB is similar to trypsin (ibid) in that the best substrate would have a side chain length between those of lysine and arginine. Studies with Bz-MeGly-Lys and Bz-Ala-Lys showed that the former is very slowly hydrolyzed by CPB but that the latter is a good substrate with a high affinity for the enzyme, indicative of considerable participation of the Calpha-methyl group of alanine in the binding of the substrate to the enzyme.


Mechanisms for activation and inhibition of carboxypeptidase A catalyzed hydrolyses of peptides and esters.

3,3-Diphenylpropanoate (DPP) activates the carboxypeptidase A catalyzed hydrolysis of benzoylglycyl-L-phenylalanine (BzGly-L-Phe) (Ka = 2.1 x 10 (-3) M) and inhibits ester hydrolysis uncompetitively (K1 =2.1 X 10 (-3) M). A common modifier binding site located adjacent to the peptide and ester substrate binding sites is proposed. The forms of the pathways proposed for activation and inhibition are remarkably similar.


L-Ascorbic acid and lysosomal acid hydrolase activities of guinea pig liver and brain.

The effects of L-ascorbic acid deficiency on guinea pig hepatic and brain lysosomal hydrolases were examined. In general, hepatic beta-N-acetylhexosaminidase, beta-D-glucoronidase, alpha-D-galactosidase, alpha-D-mannosidase, and acid phosphatase were elevated in scorbutic animals. This appears to be independent of the starved state. Brain beta-D-glucoronidase and acid phosphatase followed a similar pattern to that observed with the liver enzymes, but brain beta-N-acetylhexosaminidase was not affected by L-ascorbic acid decreased the activity of hepatic beta-N-acetylhexosaminiadase was unaffected by dietary treatments although the activity of beta-N-acetylhexosaminidase A tended to increase in the scorbutic animals. Subcellular fractions were obtained from the three groups of animals and the recoveries of protein, beta-N-acetylhexosaminidase, and glucose-6-phosphatase estimated.


Conformational studies on wheat embryo 5S RNA using nuclease S1 as a probe.

Ribosomal 5S 32 P-labelled RNA was isolated from imbibing wheat embryos and digested with nuclease S1, a single-strand specific nuclease. The products of enzymic digestion were separated by polyacrylamide gel electrophoresis and identified by fingerprint analysis of their RNase T1 digestion products. The results indicate that the most sensitive portion of the molecule, and hence, the region containing the least helical structure, is close to the 5'-terminus. Similarly, the most resistant portion of the molecule is close to, but does not include, the 3'-terminus. These findings are discussed in relation to proposed models for the secondary structure of 5S RNA.


Wheat embryo ribonucleates XI. Conserved mRNA in dry wheat embryos and its relation to protein synthesis during early inhibition.

It has been found that bulk poly(A)-rich RNA from dry wheat embryos is broadly heterodisperse when examined by polyacrylamide gel electrophoresis. The poly(A)-rich RNA from dry wheat embryos has been translated in a cell-free protein-synthesizing system from the same commerically supplied, roller-milled wheat embryos. Compatiable with the electrophoretic heterodispersity observed for poly(A)-rich RNA, the radioactive products of its cell-free translation, when examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis, have mobilities that are broadly coincident with the many dye-stained (nonradioactive) proteins present in wheat extracts. With due allowance for the limitations of the cell-free system, which is known to translate, selectively, lower molecular-weight species of mRNA, it has been concluded that the conserved poly(A)-rich mRNA in dry wheat embryos probably has the translational capacity required to account for the highly eclectic protein synthesis that we have observed during early (40-min) inhibition of viable wheat embryos.


Increased purine nucleotide binding, altered polypeptide composition, and thermogenesis in brown adipose tissue mitochondria of cold-acclimated rats.

Rapid increases in atractyloside-insensitive binding of purine nucleotides (ADP or GDP) and in a polypeptide of 32 000 occur in brown adipose tissue mitochondria of the rat during acclimation to cold. The increased binding is apparent within 1 h and reaches a maximum after 3--7 days of exposure to 4 degrees C. The increase in the 32 000 peptide occurs more slowly and reaches a maximum after 2--3 weeks. There is a simultaneous decrease in a polypeptide of 96 000, apparent after 1 day and reaching a maximum after 1--2 weeks. Results are interpreted in terms of the appearance of an increased amount of the purine nucleotide-sensitive proton conductance pathway in association with the development of an enhanced thermogenic capacity of brown adipose tissue mitochondria during acclimation of the rat to cold.


Cytosol protein-independent translocation of isomeric spin-labelled radioactive lipids from isolated guinea pig liver microsomal to mitochondrial membranes.

Intermembranous translocation of membrane-bound radioactive lipids covalently labelled with 5-, 12, and 16-doxyl stearic acid was studied. Guinea pig liver microsomal membranes containing known amounts of isomeric spin-labelled radioactive phosphatidic acid, phosphatidylcholine, and diglycerides were incubated with unlabelled mitochondria; reisolated mitochondria contained around 28-31% of microsomal labelled lipids above the microsomal contamination. The effect of adding crude or 'pH 5.1' 105 000 X g cytosol supernatant on the amount and composition of translocated labelled lipids was studied. While the translocation of labelled phosphatidylcholine was slightly stimulated by the addition of these cytosol supernatants, no significant increase of the amount of translocated labelled phosphatidic acic and diglycerides was observed by this addition. In view of these results,  a probable mechanism for the cytosol protein-independent translocation of lipids  between biological membranes is proposed.


The evolution of 5S RNA secondary structures.

We have applied the Pipas-McMahon algorithm based on free energy calculations to the search for a 5S  RNA base-pair structure common to all known sequences. We find that a 'Y' shaped model is consistently among the structures having the lowest free energy using 5S RNA sequences from either eukaryotic or prokaryotic sources. Compaison of this 'Y' structure with models which have recently been proposed show these models to be remarkably similar, and the minor differences are explicable based on the technique used to obtain the model. That prokaryotic and eukaryotic 5S RNA can adopt a similar secondary structure is strong support for its resistance to change during evolution.


Effect of radiosensitizing agents on electron transport systems.

Experiments have been carried out to study the interaxtion between chemical radiosensitizing agents and model electron transport systems. Using an NAD(P)H:O2 oxidoreductase enzyme as such a model, it was demonstrated that radiosensitizers can act as intermediates in the transfer of electrons from NADH to O2, even in the presence of classical inhibitors of electron transport, with anefficiency related to both their redox potentials and their radiosensitizing abilities. This work which was further confirmed in mammalian mitochondria and microsomes as well as in a cultured cell system indicated that these sensitizers can accept electrons from a variety of organelle systems. This action was shown to be related to the concentration of reduced pyridine nucleotides present both in vivo and in vitro. Of the electron-affinic agents tested, those whose redox potential was more negative than -0.39 V may possibly serve as better radiotherqpeutic mediators.


Lipid compositional manipulation in Acholeplasma laidlawii B. Effect of exogenous fatty acids on fatty acid composition and cell growth when endogenous fatty acid production is inhibited.

A variety of potential inhibitors of de novo fatty acid biosynthesis have been tested for activity in Acholeplasma laidlawii B. Two compounds, avidin and N,N-dimethyl-4-oxo-2trans-dodecenamide (CM-55), an antimicrobial fatty amide, strongly inhibit de novo biosynthesis without nonspecific toxic effects at moderate dosages. Avidin is the more potent inhibitor, abolishing de novo fatty acid synthesis and greatly reducing the chain elongation of exogenous fatty acids at level of 25 U/l. CM-55 gives complete inhibition of de novo biosynthesis only at low temperatures and inhibits exogenous fatty acid elongation to a variable extent. However, CM-55 is still a more potent antilipogenic agent in this organism than is the fungal antibiotic cerulenin. Cells cultured with avidin grow only when one or more exogenous medium- or long-chain fatty acids are added to the growth medium. The extent of cell growth under these conditions depends primarily on the physical properties of the exogenous fatty acid(s). In general, fatty acids giving diacylglycerolipids of very high or very low fluidity are unsuitable growth substrates, while those whose diacylglycerol derivatives are of intermediate fluidity support fair to good cell growth.


A study of the localization of high mobility group proteins in chromatin.

High mobility group (HMG) proteins from fetal calf thymus and mouse brain chromatin were purified and compared electrophoretically. The four major HMG proteins characteristic of fetal calf thymus chromatin (HMG's 1, 2, 14, and 17) were also found to be present in mouse brain chromatin. Nuclei from these two eucaryotic tissues were digested with DNase I and micrococcal nuclease and the acid-soluble proteins solubilized by the two nucleases in both tissues were analyzed on starch gels. Limited digestion of fetal calf thymus nuclei with DNase I led to the solubilization of a substantial fraction of proteins HMG-1 and HMG-2 together with smaller amounts of H1. In addition, limited digestion with micrococcal nuclease released approximately 70% of HMG's 1 and 2 and variable amount of H1 into the soluble fraction. The observation that HMG proteins 1 and 2 are selectively solubilized under conditions in which active genes have been shown to be preferentially digested in various other cell types suggests their selective association with chromatin regions which are transcriptionally competent.


The structure and maturation of intermediates in bacteriophage T7 DNA replication.

Concatemeric DNA from T7-infected cells consists of phage genomes in a linear head-to-tail arrangement. Adjacent genomes within a concatemer overlap for the length of the terminal repetition. Fast-sedimenting T7 DNA contains single-stranded regions at roughly unit-lentth intervals but these interruptions are heterogeneously distributed and do not occur at the genetic termini. Mutations in either bacteriophage genes 9, 18, or 19 (required for DNA maturation and packaging) lead to the synthesis and persistence of DNA with fewer interruptions than normal.


A new double-labelling procedure for determination of amino acid composition: application to bacteriorhodopsin.

A new double-labelling procedure for amino acid analysis which requires only routine chromatographic equipment is described. When 1-fluoro-2,4-dinitro[3H]benzene is reacted with a mixture of 14C-labelled amino acids followed by reaction with the same 14C-labelled amino acid mixture diluted with an unlabelled sample of amino acids, the 3H:14C ratio in the resulting 2,4-dinitrophenyl (DNP) amino acid derivatives of the diluted sample will be increased in proportion to the quantity of unlabelled amino acid in the diluted sample. This procedure gave reliable results when applied to the known proteins insulin and lysozyme. The procedure is most advantageous when applied to amino acids which are unstable during acid hydrolysis or present in low molar fractions. When applied to the analysis of the bacteriorhodopsin in Halobacterium cutirubrum, this procedure showed the presence of one histidine residue and four tryptophan residues per mole protein but no cystine or cysteine; in general, the analyses obtained were consistent with those originally reported by Oesterhelt, D. and Stoeckenius, W. (1971) (Nature (London) New Biol. 233, 149-152) for bacteriorhodopsin of H. halobium.


Electrogenic sodium-dependent glycine transport in sheep reticulocytes.

Na+-dependent glycine transport has been studied in reticulocyte-enriched fractions of blood obtained after massive bleeding of sheep. The activity is dependent on the sodium electrochemical potential and the membrane potential. The sodium chemical gradient was varied by changing either external or internal Na+ and the membrane potential, by addition of valinomycin. Similar results were obtained with resealed reticulocyte ghosts. Under conditions optimal for sodium pumping (intracellular Na+ greater than 50mM), ouabain inhibited glycine uptake prior to any measurable change in the cellular Na+ suggesting that in these cells an electrogenic sodium pump is sufficiently active to contribute to the membrane potential. Na+-dependent glycine transport undergoes a marked decrease during long-term incubation at 37 degrees C. During this time, the cells maintain their integrity and ATP content but undergo maturation as evidenced in the decrease in cells with reticulocyte morphology.


Biochemical and genetic approaches to the study of mammalian mitochondrial tRNAs.

The possible existence of mammalian mitochondrial asparaginyl-tRNA has been examined using a variety of approaches. [3H]Asparagine was incorporated into protein by mitochondria of the Chinese hamster ovary (CHO) cell line Asn-7, which has a temperature-sensitive cytosolic asparaginyl-tRNA synthetase, either in the presence of cycloheximide or at a nonpermissive temperature. Isolated mitochondria of CHO thymidine kinase minus (TK-) cells also incorporated the amino acid into protein. In each case, the number and electrophoretic mobility of the proteins was the same as mitochondrially synthesized proteins of CHO TK- cells labelled with [35S]methionine. A tRNAAsn could be charged in isolated CHO TK- cell mitochondria and the asparaginyl-tRNA was found to elute before its cytosolic counterpart on an RPC-5 column and to have a higher mobility on polyacrylamide slab gels run under denaturing conditions. This is the first demonstration of a unique mitochondrial asparaginyl-tRNA.


The nuclear magnetic resonance determination of the conformation of saccharides bound in subsite D of lysozyme.

The binding of the trisaccharide (2-acetamido-2-deoxy-D-muramic acid)-beta(1 leads to 4)-(2-aceta-mido-2-deoxy-D-glucosyl)-beta(1 leads to 4)-(2-acetamido-2-deoxy-D-muramic acid) to subsites B, C, and D in lysozyme has been studied by 1H nuclear magnetic resonance methods. In particular, the coupling constant between H1 and H2 of the reducing saccharide bound in subsite D has been determined. The coupling constant for the bound saccharide indicates that the dihedral angle between C1 and C2 for the reducing saccharide is not significantly changed upon binding to lysozyme. This result is discussed in terms of other evidence for the role of distortion of the saccharide bound in subsite D in the lysozyme-catalyzed hydrolysis of cell wall oligosaccharides.


The toxicity of ochratoxin to ruminants.

Among the mold toxins the most toxic ochratoxin, ochratoxin A, commonly occurs in many grains, other feedstuffs, and in soil but in low concentrations. The amount required to produce acute toxicity in ruminants makes such occurrences unlikely. Toxic effects are more likely to occur in chronic low-level intoxication. The lethal single oral dose in cattle is high, probably being a few milligrams more than 13 mg/kg. The lethal level produced by repeated feeding to goats was 3 mg/kg. Ochratoxin A occurred in cows milk and urine but only when massive doses were ingested. Abortion or fetal death, though occurring in rodents, are unlikely to be induced in cattle.


The prevalence of serum antibodies to Toxoplasma gondii in Ontario mammals.

The prevalence of seropositive reactions to Toxoplasma gondii was studied in farm animals, companion animals, wild rodents and birds. Of the animals tested, 17% of cattle, 65% of sheep, 45% of pigs, 9% of horses, 33% of dogs and 20% of cats were seropositive by the Sabin-Feldman dye test. In addition 11% of mice (Mus musculus), 5% of deer mice (Peromyscus), 3% of rats (Rattus norvegicus) and less than 2% of sparrows (Passer domestcus) were seropositive. All samples from short-tailed field mice (Microtus pennsylvanicus), squirrels (Sciurus carolinensis), chipmunks (Tamias striatus), meadow jumping mice (Zapus hudsonius) and starlings (Sturnus vulgaris) were seronegative. The significance of these findings in relation to the epizootiology of toxoplasmosis in Ontario is discussed.


Intranasal exposure of the Richardson's ground squirrel to Western equine encephalomyelitis virus.

Adult Richardson's ground squirrels were infected with western equine encephalomyelitis virus by intranasal instillation. Mortality followed the instillation of a minimum threshold of 4.7 logs of virus while infection was produced by a dosage of 2.3 logs. The incubation period was from four to seven days, being preceded by a viremic phase. Signs were depression, ataxia and paralysis of the limbs. Highest titres of virus were recovered from the brain and histopathological changes involving the central nervous system included meningitis, vasculitis, perivascular cuffing, gliosis, neuronophagia and neuronal degeneration. The virus was also found in a variety of extraneural tissues. Lesions in extraneural tissues included necrosis of brown fat and an apparent increase in number of Kupffer's cells in the liver. The lymphoid tissue was involved indicating a possible source for viremia. The duration and magnitude of viremia were ample enough to provide virus source for arthropods. The potential for transmission of the virus independent of arthropods was discussed in view of the pathogenesis demonstrated in the experimental infections.


Experimental lead intoxication in dogs: a comparison of blood lead and urinary delta-aminolevulinic acid following intoxication and chelation therapy.

Intravenous lead administration to dogs produced an acute syndrome of lead intoxication charcterized by depression, vomiting, anorexia and weight loss. The effect of chelation therapy with calcium disodium ethylene diamine tetraacetate, penicillamine or both was determined by serially monitoring changes in blood lead and urine delta-aminolevulinic acid. Following therapy, blood lead values were significantly lower in chelated dogs than non-treated lead exposed dogs on days 7 and 10. Urine delta-aminolevulinic acid at day 7 was significantly higher in untreated lead exposed dogs than in other groups. There was no significant difference in blood lead or urine delta-aminolevulinic acid between lead intoxicated dogs which underwent the indicated chelation therapy protocols. There was, however, a trend for higher urinary delta-aminolevulinic acid excretion in those intoxicated dogs undergoing calcium disodium ethylene diamine tetraacetate therapy as opposed to those undergoing penicilamine therapy. There was no significant correlation between blood lead and urinary delta-aminolevulinic acid previous to lead exposure. However, after lead exposure significant correlation was present at days 4, 7, 10 and 14. Certain lead exposed dogs following chelation therapy were noted to have normal blood lead levels but elevated urinary delta-aminolevulinic acid suggesting that blood lead does not always correlate with metabolic effects of lead in the body. Urinary delta-aminolevulinic acid was therefore recommended as an additional laboratory parameter which improved assessment of lead exposure in dogs, particularly in determining adequacy of chelation therapy.


Bovine abortion associated with Anaplasma marginale.

During the period from June 1974 to June 1975, five bovine fetuses between seven to nine months old were received for necropsy from four different counties of the S. Paulo State, Brazil. All of them were from brucellosis-free herds. Necropsy revealed slight liver enlargement generally accompanied by capsular petechial hemorrhages. Enlargement and congestion of the spleen, epicardial and endocardial petechiae were present in three fetuses and one of them had lungs with some hemorrhagic lobules. Cardiac blood films of all the fetuses stained by the Pappenheim's panoptic method showed Anaplasma marginale in two to 20% of red corpuscles. When stained with acridine orange and immunofluorescent methods blood films of the first fetus specifically showed A. marginale.


Rapid radioimmunoassay of progesterone in unextracted bovine plasma.

A rapid radioimmunoassay for determining progesterone levels in unextracted bovine plasma has been developed. Two antisera have been tested, anti-deoxycorticosterone-21-hemisuccinate human serum albumin and antiprogesterone-11-hemisuccinate bovine serum albumin. The usefulness of an antiserum for rapid assays has been based on its agreement with assays of organic extracts or chromatographically purified extracts of selected bovine samples. To avoid large blank effects and non-specific interference, a plasma volume of 20 microliter that provided adequate sensitivity was not exceeded. All correlations between rapid assays, assays using organic extraction or assays after chromatographic purification were greater than 0.9 and showed regression slopes approximating unity. It was concluded that individual lots of antisera should be evaluated thoroughly before use in a rapid assay.


Status of trichinosis in bears in the Atlantic provinces of Canada 1971--1976.

During 1971 to 1976 inclusive, 73 black bears, Ursus americanus and one polar bear, Thalarctos maritimus, originating in the Atlantic Provinces of Canada were examined for the presence of trichinosis. The polar bear was infected but all of the black bears were negative.


Studies on the occurrence and significance of bovine respiratory syncytial virus in Saskatchewan.

Seventy-six percent of 49 blood samples from Saskatchewan cattle had serum antibodies against bovine respiratory syncytial virus. Experimental infection of one week and seven month old calves with bovine respiratory syncytial virus (Iowa strain) caused transient fever, mucopurulent nasal discharge and coughing but no macroscopic or microscopic lesions attributable to bovine respiratory syncytial virus.


Zinc, cadmium, and iron interactions during intestinal absorption in iron-deficient mice.

Zinc absorption from a test dose of (65Zn) zinc chloride was increased in mice with a high capacity to absorb iron induced by a low-iron diet. When radiolabelled zinc chloride in concentrations varying from 0.025 to 0.30 mM was perfused through open-ended duodenal loops of mice fed this diet, the proportion of zinc taken up from the lumen and transferred to the body was greater from lower than from higher doses. The addition of iron to the perfusate inhibited zinc uptake and transfer, and zinc had a similar effect on iron absorption. Cadmium, a potent inhibitor of iron uptake in mice fed a low-iron diet, impaired zinc uptake under these dietary conditions. These results suggest that in dietary-induced iron deficiency there are analogous mucosal binding sites for the uptake of iron and zinc. There also appear to be mutually exclusive binding sites for the absorption of these metals: radiolabelled iron absorption from an intragastric test dose was enhanced in mice with a high capacity to absorb iron produced by bleeding, whereas the absorption of zinc was not increased.


Reflex effects of thoracic aorta wall stretch on regional vascular resistance.

In anesthetized, vagotomized cats with both carotid arteries occluded, a stretch of the walls of the thoracic aorta, performed without obstructing aortic flow, induced a significant reflex increase in arterial pressure (35 +/- 2-26 +/- 1 mmHg; systolic-diastolic). This pressure increase was accompanied by significant increases in peripheral resistance in the superior mesenteric (+30%), renal (+23%), and external iliac (+23%) vascular beds. The increase in iliac resistance observed in the skinned leg was comparable with that observed in the contralateral intact limb. All these vascular responses were drastically reduced by the administration of phenoxybenzamine. After alpha-adrenergic blockade no signs of reflex vasodilatation could be detected during aortic stretch in any of the vascular beds examined.


Development of cardiovascular responses to sympathomimetic amines and autonomic blockage in the unanesthetized fetus.

The cardiovascular effects of phenylephrine or ephedrine alone and after autonomic blockade was studied in the chronically cannulated fetal lamb (100-145 days), the newborn lamb, and adult sheep. As gestation advanced, phenylephrine and ephedrine produced an increasing pressor response before and after pretreatment with atropine (1 mg/kg). Compared with the fetus, the magnitudes of the pressor responses were somewhat greater in the newborn and much larger in the adult. Both drugs produced a reflex bradycardia in the unatropinized fetus which in the case of ephedrine was followed by a tachycardia. Pretreatment with atropine resulted in an immediate tachycardia after ephedrine but not after phenylephrine administration. Pretreatment with phentolamine (0.15 mg/kg) produced about a 55% inhibition of the phenylephrine pressor response in both the fetus and adult, suggesting a linear relationship between body weight and number of alpha-adrenergic receptors. Pretreatment with metoprolol blocked the tachycardia associated with ephedrine administration to unatropinized fetuses. In summary, the increase in the magnitude of the pressor response to phenylephrine suggested development of the receptor-effector system. The greater development of the response to ephedrine suggested that there was an increasing amount of noradrenaline being released with advancing gestation.


Assessment of ether anesthesia in normal and spinal cats using gas--liquid chromatographic analysis of blood.

A new gas-liquid chromatographic method was developed for the determination of diethylether in whole blood. Ether was quantitated by peak area ratio analysis with n-propanol as the internal standard using a flame ionization detector. Blood ether concentrations were determined in cats undergoing inhalational anesthesia by ether in oxygen. In normal spontaneously breathing cats, anesthesia began at ether concentrations of about 0.6 g/l, and respiratory arrest occurred at 2.4 g/l and above. Mean arterial blood pressure was well maintained throughout the entire anesthetic range. In spinal artificially respired animals, mean arterial blood pressure correlated inversely with blood ether concentration. The data suggest that decline in blood pressure may be a useful sign of ether toxicity in spinal cats.


The role of displacement of the mitral annulus in left atrial filling and emptying in the intact dog.

The variations in ventricular-atrial mitral annular position during the cardiac cycle and the simultaneous changes in left atrial silhouette area (obtained by angiography after injections of contrast material into the main pulmonary artery) were investigated in six experiments on intact dogs with chronically implanted intracardiac markers. Frame-by-frame measurements of the angiograms (120 frames/s) were used to determine, under various hemodynamic conditions, the duration, magnitude, and average rate of the mitral annular motion and of the simultaneous changes in left atrial area during atrial filling (ventricular systole) and atrial emptying (early in ventricular diastole). The mitral annulus was seen to move towards the ventricular apex during systole and towards the atrium early in diastole with the duration, average rate, and magnitude of displacement (although varying widely) showing good statistical correlations (P less than 0.0005-0.005) with the changes in projected left atrial area. These findings suggest that the duration, rate, and magnitude of atrial filling and emptying may be, in the intact heart, determined by the movements of the atrioventricular junction.


Transmucosal potential-difference profile in rat upper gastrointestinal tract. A simple model for testing gastric effects of pharmacologic agents.

Transmucosal potential difference in the rat upper gastrointestinal tract is described by a simple in vivo technique. Values for potential difference between blood (reference) and lumen (in millivolts) were the following: esophagus, -13.7 +/- 1.6 (mean +/- SE); forestomach (rumen), -39.2 +/- 0.8; stomach fundus, -39.1 +/- 0.4; pylorus -26.6 +/- 0.6; and duodenum, -9.2 +/- 0.4. These values (excluding rumen) are strikingly similar to those obtained in man. Aspirin, taurocholic acid, and alcohol all produced falls in gastric potential difference very similar to those found in man. The rat appears to be a promising and convenient model for screening gastric effects of certain pharmacological agents before use in man.


Some effects of the ionophore X-537A on the isolated rat tail artery.

The effects of micromolar concentrations of the ionophore X-537A (RO 2-2985) were studied using isolated preparations of the rat tail artery. The ionophore causes complete release of catecholamines from adrenergic nerves, which is the sole cause of the transient contractile response. The amines are released by a nonexocytotic process which seems to be related to the ability of X-537A to act as an efficient transmembrane carrier of Na+, k+, and H+. The ionophore also causes an almost complete and irreversible loss of the cocaine-sensitive component of metaraminol uptake by the tissue. X-537A dissipates the transmembrane concentration gradients of Na and K in the smooth muscle component of the preparation. This effect is unrelated to the release of endogenous catecholamines, and it can also be observed after the Na pump has been inhibited with ouabain. It is fully reversible, though not readily, and it can be induced repeatedly. In catecholamine-depleted strips, X-537A dissipates the transmembrane Na+ and K+ gradients without causing any change in tension. Stimulation of the rate of O2 consumption by X-537A in catecholamine-depleted tissue is reversible, and it is unaffected by ouabain and (or) removal of external Ca2+.


Changes in the hyperthermic responses of rats to daily injections of morphine and the antagonism of the acute response by naloxone.

Core temperatures of unrestrained male rats were measured by rectal probe over a 4-h period following seven daily subcutaneous injections of morphine sulphate in doses of 5, 20, or 80 mg/kg. With the smaller doses, rapid hyperthermia occurred and was maximal after 20 mg/kg; with 80 mg/kg, two of eight rats had immediate hypothermia, with the group response being a small, delayed hyperthermia. The results with repeated administration of morphine give statistical validity to earlier findings suggesting that peak hyperthermia increased and occurred progressively sooner after each injection of morphine. In groups of naive rats a single injection was given of saline or of 1, 10, or 40 mg naloxone hydrochloride per kilogram in saline. In these rats saline led to a slight increase in core temperature; when the first injection was one of the three doses of naloxone, no transient increase was seen. In nine other groups each of the three doses of naloxone was given 15 min before each of the morphine doses. All three doses of naloxone significantly reduced the hyperthermia induced by 5 and 20 mg morphine sulphate per kilogram, but this was less apparent in the group treated with 80 mg/kg, although naloxone at 40 mg/kg prevented any increase in temperature for over 3 h. The results obtained in this study demonstrate that morphine-induced temperature changes and perhaps stress-induced changes can be suppressed by naloxone.


The effect of taurine on kindled seizures in the rat.

Recently, it has been reported that taurine, an amino acid with anticonvulsant properties, does not suppress experimental seizures generated by the "kindling" technique. This finding seems somewhat paradoxical since taurine antagonizes other sorts of experimental convulsion and since kindled seizures are easily suppressed by other anticonvulsant drugs. Further tests were therefore conducted during which taurine's anticonvulsant effects were assessed: (1) when kindling stimulation was dropped to near-threshold levels; (2) when cortical as well as limbic kindled foci were stimulated; (3) when developing as well as fully kindled seizures were involved; and (4) when taurine was introduced directly into the ventricles of the brain. Even in these tests which were specifically designed to favour the appearance of anticonvulsant effects, no taurine antagonism of kindled seizures was found.


Effects of arachidonic acid and indomethacin on the in vitro release of prostaglandins by aortic strips of spontaneously hypertensive rats.

Aortic strips removed from spontaneously hypertensive (SH) rats and preincubated with arachidonic acid (1.0 X 10(-5) g/ml) for 15 min produced two times more prostaglandin (PG) like material than aortae unexposed to the precursor of PG biosynthesis. The stimulating effect of arachidonic acid was largely inhibited by indomethacin (1.0 X  10(-5) g/ml). Also, the release of PG-like material by aortic strips derived from SH rats treated with an intravenous injection of indomethacin (10 mg/kg) was inhibited by 74% compared with the control tissues. These results raised the possibility that the in vivo conversion of arachidonic acid by large arteries of SH rats may contribute to the hypotensive effect of this PG precursor in SH rats.


Inability of glucagon to increase glomerular filtration rate in dogs with experimental cirrhosis and ascites.

In marked contradistinction to the normal dog, to the dog with renal hypoperfusion, or to the chronic caval dog with ascites, the intravenous infusion of glucagon at 5 microgram/min to dogs with experimental portal cirrhosis and ascites does not increase glomerular filtration rate or renal blood flow. In eight experimental dogs who did not respond to glucagon, a marked natriuresis was observed in response to furosemide and a marked renal vasodilator response was seen following the intraarterial infusion of acetylcholine. Because plasma immunoreactive glucagon levels are increased fivefold in cirrhotic dogs, it is suggested that continuous high levels of this peptide render the animals insensitive to the effects of an exogenous infusion.


Motoneuronal after-potentials and extracellular divalent cations.

In cats under Dial anesthesia, microiontophoretic injections of Co2+ or Mn2+ outside lumbosacral motoneurones regularly diminish the postspike hyperpolarizing after-potential (AHP) without any clear reduction of the deplorarizing after-potential (ADP). Comparable injections of Sr2+ have the opposite effect of augmenting the AHP. These results indicate that the AHP is indeed initiated by an influx of calcium linked to the action potential, but the ADP is unlikely to be mainly a manifestation of a calcium inward current.


Dantrolene blocks intracellular calcium release in smooth muscle: competitive antagonism of thromboxane A2.

Dantrolene sodium has been shown to block the release of intracellular calcium in skeletal muscle. It has been proposed that dantrolene blocks the movement and (or) action of a natural calcium ionophore. In a rat vascular preparation dantrolene was found to inhibit pressor responses to noradrenaline and angiotensin but not those to potassium with an IC50 concentration within the therapeutic levels in man. Imidazole, an inhibitor of thromboxane A2 (TXA2) synthesis, had similar actions to dantrolene. Interactions between imidazole and dantrolene suggested that dantrolene may be a competitive antagonist of TXA2 in muscle. We report the first demonstration of an effect of dantrolene sodium on smooth muscle contractility and suggest that TXA2 is an essential modulator of vascular reactivity. A similar role has been shown for TXA2 in platelets.


Antagonism of substance P induced facilitation of central neuronal activity by 2,4-dinitrophenol and depressant agents.

2,4-Dinitrophenol, pentobarbital, thiopental, methoxyflurane, and halothane more often antagonized the facilitatory effects of substance P than of acetylcholine on the activity of spinal dorsal horn neurons (of unanesthetized decerebrated and spinalized cats) as well as interpeduncular and cerebral cortical cells (of either rats anesthetized with methoxyflurane, nitrous oxide, and oxygen or 'cereveau isolé' rats). The results of the studies indicate that the excitatory effects of substance P on central neurons are extremely sensitive to anesthesia.


The effect of glucagon on intestinal lymph flow in rats.

Intravenous injection of a bolus of 5 microgram of glucagon to rats with an intestinal lymph fistula produces a marked, transient rise in lymph flow and protein output from the fistula. The effect is presumably the result of brief enhancement of splanchnic blood flow.


Flow correlation of loop of Henle potassium influx.

Potassium influx in short loops of Henle was assessed using end proximal to early distal perfusion with potassium-free saline. Over a wide range of perfusion rates influx was highly correlated with collected flow rates. The magnitude of the influx was comparable with the delivery rate of potassium to the early distal site seen during free flow, over a narrower range of collected flow rates.


Loss of chloramphenicol production in strains of Streptomyces species 3022alpha treated with acriflavine and ethidium bromide.

An assay procedure was developed to detect chloramphenicol production in large numbers of Streptomyces species 3022alpha isolates, and was used to screen colonies from cultures exposed to acriflavine and ethidium bromide. There was a significant rise in the proportion of low- and non-producing strains in the treated cultures. Since the organism developed resistance to acriflavine but not ethidium bromide, the effects of the latter agent were examined in more detail. Loss of chloramphenicol production was not due to mutation, nor to differential sensitivity to the drug among producing and non-producing natural variants. The response of cultures varied with age, and at least three strain types--high-, low-, and non-producers could be distinguished. A study in shaken cultures of selected isolates from the screening process established the general reliability of the screening method and showed that the assay probably sometimes failed to distinguish between low- (15-20 mg/iota) and non-producers. It indicated that the non-producer class consisted of some very low (up to 4 mg/iota) producers as well as fully negative strains, and it confirmed indications from the screening results that a non-producing isolate obtained by acriflavine treatment accumulated aromatic amines and was probably blocked in the pathway for chloramphenicol biosynthesis.


The effect of growth temperature on the fatty acid composition of Thamnidium elegans Link.

The fatty acid composition of a slightly psychrophilic fungus, Thamnidium elegans, has been determined and compared with other mucoraceous fungi. The growth temperature strongly influences the degree of unsaturation of lipids, as reported for other organisms, but in T. elegans both the quantitative and qualitative profiles of the fatty acids are affected. At low temperature, T. elegans contains both alpha- and gamma-isomers of linolenic acid. The alpha-isomer is reported here for the first time in a mucoraceous fungus. Besides the biosynthesis of alpha-linolenic acid at the low temperature, T. elegans shows an increase in synthesis of a relatively unknown fatty acid in fungi, i.e. octadecatetraenoic acid (18:4delta 6,9,12,15). The significance of the occurrence of both the isomers of linolenic acid as a response to temperature and in relation to fungal phylogeny is discussed.