Alexia without agraphia associated with right occipital lesion. A 78 year old, right handed man developed the syndrome of alexia without agraphia due to a right occipital thrombotic stroke. The cerebral dominance test strongly suggests that his right hemisphere is dominant. This is believed to be the first case of alexia without agraphia secondary to a right occipital lesion in a right handed person.


A sensitive test for tactile extinction: results in patients with parietal and frontal lobe disease. A simple test for detecting tactile extinction is described. In a population of parietal-damaged patients it yielded fewer false negatives than the classical clinical procedure. Contrary to expectations, lesions confined to the right frontal lobe produced no extinction, while those in right-handed, left frontal cases revealed ipsilateral extinction with the new test.


Electrical and mechanical responses in the platysma and in the adductor pollicis muscle: in normal subjects. In the platysma of 34 normal subjects the amplitude of the action potential and twitch tension and tetanic tension were lower, the contraction time of the isometric twitch was 1.4 times shorter, and the potentiation of twitch tension in a staircase and after tetanus was two to four times greater than in m. adductor pollicis. Differences in twitch kinetics and potentiation were related to the four times higher incidence of fast fibres in the platysma than in the adductor pollicis muscle, as determined by histochemistry. Ninety-five per cent confidence limits were established for comparison with patients with myasthenia gravis.


Mediastinal paraganglioma causing spinal cord compression. An invasive paraganglioma of the posterior mediastinum caused spinal cord compression in a 31 year old women. Electron microscopic examination of the paraganglioma invading the epidural space revealed numerous dense-cored granules in the cytoplasm of the tumour cells. We are reporting this case to present the ultrastructure of mediastinal paraganglioma, and to call attention to an unusual cause of spinal cord compression.


Familial idiopathic cerebral calcifications. Nine members of a family spanning three generations showed bilateral calcifications of the basal ganglia with autosomal dominant inheritance. Two members developed chorea, dementia, and a characteristic speech disturbance (palialalia) in the third or fourth decade. A third member possibly shows the initial stage of a similar syndrome. Six members with calcifications but without neurological signs are younger than 25 years. All nine patients had normal calcium and phosphorus, and no evidence of endocrinological or somatic abnormalities. Thie 'isiopathic' picture must be differentiated from hypoparathyroidism and pseudohypoparathyroidism.


The place of ganglion or root alcohol injection in trigeminal neuralgia. Of 157 patients with trigeminal neuralgia, referred for neurosurgery, 81 underwent 85 ganglion or root injections. The results, which are analysed with regard to pain relief and sensory loss, compare favourably with results from the literature of other forms of surgery, particularly open temporal root section.


Severe head injuries in three countries. Methods for assessing early characteristics and late outcome after severe head injury have been devised and applied to 700 cases in three countries (Scotland, Netherlands, and USA). There was a close similarity between the initial features of patients in the three series; in spite of differences on organisation of care and in details of management , the mortality was exactly the same in each country. This data bank of cases (which is still being enlarged) can be used for predicting outcome in new cases, and for setting up trials of management.


Cytophotometric mapping of neuronal changes in senile dementia. Results of a cytophotometric study have shown a widespread reduction in cytoplasmic RNA of nerve cells. It appears, therefore, that although certain aspects of the symptomatology of senile dementia may be accounted for by lesions in particular anatomical sites, the main part of the neurological disturbance is related to more broadly based changes in nerve cell metabolism affecting much, if not all, of the CNS.


Presenile dementia presenting as aphasia. A focal aphasic syndrome was the first and outstanding manifestation of a degenerative, presenile dementia in a 67 year old man. Computerised axial tomography showed a strikingly dilated left Sylvian fissure--particularly in its posterior aspect--in the presence of moderate diffuse cortical atrophy. The radiographic findings correlated well with the clinical data. This is the first report of an aphasic disturbance of language as the initial symptom is presenile dementia.


Fatal measles encephalopathy with retinopathy during cytotoxic chemotherapy. A 14-year-old boy receiving post-operative cytotoxic chemotherapy for a testicular rhabdomyosarcoma developed a fatal encephalopathy associated with retinal changes 2 months after an episode of acute measles. Post-mortem histological examination showed intranuclear inclusion bodies in the neurons and glial cells, but inflammatory cell infiltrations were absent. Electron-microscopic and immunofluorescent studies revealed intracellular masses of paramyxovirus nucleocapsid-like structures, which had the morphological and antigenic properties of measles virus. Recent reports have emphasized the possibility of occurrence of a similar encephalopathy in treated childhood leukemia. It is evident, however, that this potentially fatal complication must be borne in mind when measles is contracted during any form of cytotoxic treatment or immunosuppression. Retinal changes may be of value for the diagnosis during life. We propose the designation "measles encephalopathy during immunosuppression" (MEI) for this condition.


Crossed immunoelectrofocusing for identification of normal and abnormal cerebrospinal fluid proteins. A preliminary report. Isoelectric focusing is a valuable method for the analysis of cerebrospinal fluid (CSF) proteins. Its high resolving power has, however, created problems in identifying the large number of protein bands separated. In an attempt to identify these bands, two-dimensional crossed immunoelectrofocusing has been used, where isoelectric focusing is combined with rocket immunoelectrophoresis. By these methods 9 of the normal proteins in the acidic pH interval have been identified. In addition the unusual CSF protein abnormalities occurring in Marie-Sanger-Brown's ataxia and alcoholic cerebellar degeneration have been shown to represent increases of different microheterogeneous forms of transferrin.


Myopathy with hyperaldosteronism. An electron-microscopic study. In the case reported, an overproduction of aldosterone was accompanied by paretic attacks, a decrease in the serum potassium level, and in muscle tone and the deep tendon reflexes. The decrease of serum potassium level was consistent, but moderate, being to just below the normal lower limit. Loading with carbohydrate produced an attack, forearm ischaemic exercise resulted in less lactic acid production than normally. In the limb-girdle muscles there was also evidence of slight but permanent weakness. The results of histological and ultrastructural examination of a muscle biopsy are reported. It seems probable that the disturbance in the mineralo-corticoid metabolism led periodically to a decrease in the serum potassium, while in some muscle fibres the glycogen content increased and the SR became dilated and partially destroyed. In the attack-free periods tubular aggregates were produced, supposedly through an attempt at regeneration of the SR. During attacks portions of the muscle fibres were destroyed irreversibly and in consequence moderate permanent weakness resulted. Some spheromembranous degradation products which were observed might be regarded as remnants of degenerated tubular aggregates.


A quantitative technique for growing human adult skeletal muscle in culture starting from mononucleated cells. A quantitative and reproducible technique for establishing primary surface cultures from normal and diseased human muscle is described. Successful cultures were prepared from both fresh muscle and that stored up to 96 hr at 4 degrees C. The CPK activity of the muscle cells ranged between 0.5-3.0 micronmoles creatine per min per mg protein at 30 degrees C, thus indicating a high degree of differentiation. Spontaneous contractions were observed in 4 out of the 22 cultures established. Nerve cells were not required to achieve this level of differentiated function. No gross differences in plating efficiency, rate of myotube formation or CPK specific activity were found for the diseased muscle cells cultured so far. However, a 5--10-fold higher cell yield was obtained from muscles of patients with an inflammatory myopathy. The advantages of this technique for carrying out comparative studies on normal and dystrophic muscle cells are discussed.


HLA in multiple sclerosis. Relationship to measles antibody, mitogen responsiveness and clinical course. In our study of multiple sclerosis (MS) patients we have found significant increases in the A3, B7, and DW2 antigens. We have also studied immune responses in these same patients. There was elevation of measles antibodies in MS patients positive for A3, B7, and B18 as compared to MS patients without those antigens. The first study of mitogen responsiveness (31 patients) showed a decreased response in A3, and B7 positive patients. Study of a second and a larger group (62 patients), at a different time, failed to confirm this deficiency. We propose that there is a genetically linked (HLA) T cell deficiency in some MS patients and that this deficiency results in high humoral responses to measles antigens and an evanescent (or cyclical) reduced T cell response to mitogen.


Pathological changes in the optic chiasm of the cat following local injection of diphtheria toxin. The optic chiasm in 14 cats was injected stereotactically with small amounts of diphtheria toxin and the morphological changes were examined by light and electron microscopy. Phagocytosis was already well-marked at 3 hr after injection and massive at 1 week. Intercellular oedema was extensive in the first week and, though diminished, was still present after 1 month. The oedema was most marked in the subendothelial regions in the early stages but was found among the nerve fibres and glial processes in those animals which survived for longer periods. Demyelination and Wallerian-type degeneration were established at 3 hr after injection and both processes continued up to 2 months and beyond. Scarring and an absolute loss of nerve fibres were present in the longer-surviving animals. Unequivocal evidence of remyelination was not obtained.


Changing mortality patterns of motor neuron disease in Japan. The age-adjusted female death rate from motor neuron disease in Japan was noted to rise after 1952 and to fall rapidly since about 1960. A similar trend was also noticed in the males. Further study will show whether this was a part of a cyclical change or whether the mortality of the disease has entered a period of prolonged decline in that country. Death rates for neurological diseases in various countries were reported previously for 1953-58. Updating this study for 1966-71, a rising trend of deaths from motor neuron disease was identified in European countries, but the rate has been stationary in the United States. The rapidly changing patterns of the mortality seemed incompatible with a purely genetic causation of the disease. This indicates the need for extensive epidemiological studies to identify the extrinsic factors which induced such a trend, and were thus possibly the cause of the disease. In view of the results of the re-evaluation of the diagnosis in death certificates, mortality figures of motor neuron disease in females appeared reasonably reliable for an epidemiological study.


Hypocomplementaemic and normocomplementaemic multiple sclerosis. Genetic determinism and association with specific HLA determinants (B18 and B7). Seventy-five patients with multiple sclerosis (MS) were treated for complement components C3, after factor B, C4, and tested for HLA-A and B-determinants. Levels of IgG, IgA, IgD, IgE and titres of measles antibodies were also determined. Correlations between these immunological values and HLA determinants could be obtained in siblings, parents and/or children of the patients in 13 families. B18 frequency is strongly associated with the hypocomplementaemic group (x2 = 8.9). An association of B18 with the population of cases with low B levels is also found (x2 = 8.02). Familial data showed that low C3 and/or low B levels are associated with the HLA haplotyes, especially with those containing B18. A "complement abnormality susceptibility gene", linked to the HLA genes, is postulated. Infections are significantly more frequent in families of hypocomplementaemic MS, the existence of a genetic immunodeficiency affecting the synthesis of the complement components, linked to the HLA determinants. In 1 case studied in this article, a heterozygous C2 deficiency linked to HLA-A10, B18 was found and might confirm this hypothesis.


Ultrastructural and histological studies of brains of ferrets inoculated with subacute sclerosing panencephalitis: similarities to human disease. Similarities to human subacute sclerosing panencephalitis (SSPE) were revealed in a study of the brains of ferrets inoculated with a cell associated measles virus originally isolated from an SSPE patient. The similarities were greatest in animals that showed neurological signs 3-4 months after inoculation and had high titers of neutralizing antibodies against measles virus. These included dense core particles, nuclear bodies, alterations of basement membranes of small blood vessels, plasma cells, distorted myelin, and rod-like structures in some nuclei. Other abnormalities seen were Hirano bodies, tubular aggregates in cisternae of endoplasmic reticulum and clusters of cytoplasmic tubules. No cells containing viral inclusion bodies were observed by electron microscopy but cell cultures of the brains of these animals always yielded abundant measles virus nucleocapsids in typical SSPE multinucleated syncytia. These findings suggest that the ferret is a suitable animal model for the study of the pathogenesis of SSPE.


Fine structure of medulloepithelioma.

Fine structure of medulloepithelioma. A survey of published cases of medulloepitheliomas indicates that this tumor is highly malignant (average course 6 months), occurs in early childhood (average age 4,4 years) and has no sex predilection. Although it may originate in any part of the central nervous system, it is most common in the cerebral hemispheres. The first case studied with the electron microscope is reported here. The fine structure of the tumor is similar to that of the fetal neural tube in showing a primitive epithelium having uniform nuclei rich in chromatin but little cytoplasm and sparse organelles; it rests on a distinct basement membrane. The epithelial surface lacks cilia or microvilli and is covered with an irregular amorphous coat which is probably the cause of the light-microscopic misinterpretation of an inner limiting membrane. The lateral cell surfaces lack interdigitations but show extensive primitive forms of cell junctions. The case presented is also unusual in being the second case on record originating in the cerebellum and the first showing massive seeding along the spinal canal.


Inherited necrotizing myelopathy of Afghan hounds. Eleven examples of a naturally occurring, adolescent-onset spinal cord necrosis in Afghan Hounds were studied. Unusual and characteristic spinal cord lesions were necrosis and small vessel proliferation in the dorsal and ventro-medial spinal cord white matter extending from caudal cervical segments to cranial lumbar segments. Spinal cord gray matter and dorsal and ventral roots were preserved. Four dogs had histologically similar lesions in the superior olivary nucleus. The cause of these lesions was not determined by histopathologic or ultrastructural examination. Chi-square analysis of pooled sibships indicates a simple autosomal recessive mode of inheritance.


Reflex control of locomotion as revealed by stimulation of cutaneous afferents in spontaneously walking premammillary cats. 1. Stimulation of different hindlimb nerves in spontaneously walking premammillary cats was used in order to examine the effects of sensory input on the rhythmic motor output. 2. Stimulation of the tibial or sural nerve at low intensities caused the burst of activity in the triceps surae or semimembranosus to be prolonged if stimuli were given during the extension phase. When applied during the flexion phase, the same stimuli shortened the burst of activity in the pretibial flexors and induced an early onset of the extensor activity, except if stimuli were given at the very beginning of the flexion phase, when flexor burst prolongations or rebounds were observed instead. 3. These effects were related to activation of large cutaneous afferents in these nerves since the results could be duplicated by low-intensity stimulation of the tibial nerve at the ankle or by direct stimulation of the pad. 4. In contrast, activation of smaller afferents by high-intensity stimulation resulted prolongations of the flexor burst and/or shortenings of the extensor burst for stimuli applied before or during these bursts, respectively. 5. It was concluded that the large and small cutaneous afferents make, respectively, inhibitory and excitatory connections with the central structure involved in the generation of flexion during walking.


Swimming movements elicited by electrical stimulation of turtle spinal cord. I. Low-spinal and intact preparations. 1. Electrical stimulation applied within the dorsolateral funiculus of the spinal cord of an intact, unanesthetized turtle can elicit rhythmic limb movements similar to those observed during swimming. 2. A spontaneous display of hindlimb swimming movements is not observed in adult turtles whose spinal cord is transected at D2. Such swimming movements are observed in these "low-spinal" turtles in response to electrical stimulation applied within the dorsolateral funiculus caudad to the transection. 3. The repetition rate of these swimming movements can be altered by changing stimulus parameters, such as the frequency of electrical pulses. 4. The present results indicate that, in the turtle, a neural pattern generator contributing to the production of hindlimb movements during swimming is located mainly in structures caudad to the cervical enlargement of the spinal cord. These data support the hypothesis that a pattern generator for locomotion is largely resident within the spinal cord.


Determination of the optimum dietary proportions of lysine and tryptophan for growing rats based on growth, food intake and plasma metabolites. Weanling rats were divided into 24 groups and fed one of three levels of lysine and one of eight levels of tryptophan in a 3 X 8 factorial design to determine the optimum dietary proportions of lysine and tryptophan. The tryptophan "requirement" and the optimum lysine:tryptophan ratio were estimated for both adequate and subadequate lysine levels on the basis of weight gain, feed efficiency and changes in plasma levels of lysine, tryptophan and urea. The various criteria yielded similar estimates and indicated a tryptophan requirement of approximately 0.15% when lysine was adequate. The optimum lysine:tryptophan ratio was between 4 and 5 for the rapidly growing 3- to 6-week old rat.


Determination of the optimum dietary proportions of lysine and tryptophan for growing pigs based on growth, food intake and plasma metabolites. Weanling crossbred pigs were divided into 24 groups and fed one of three levels of lysine and one of eight levels of tryptophan in a 3 X 8 factorial design to determine the optimum dietary proportions of these two amino acids. Weight gain and feed efficiency, and changes in plasma levels of lysine, tryptophan and urea were the response criteria. The tryptophan "requirement" and the optimum lysine:tryptophan ratio were estimated for each of the three lysine levels. The data indicate a tryptophan requirement of 0.19% to 0.23% for the 3-week-old pig when the lysine level is adequate. For pigs of this age a lysine:tryptophan ratio of from 4 to 5 was about optimum.


Mechanism of lipid accumulation in rats fed wheat diets. Young, weanling rats fed wheat as a sole source of protein have been shown to develop periportal liver lipid infiltration. An attempt has been made to study the mechanism by which these lipid changes are produced. Weanling, male albino rats were fed three diets containing 10% protein based on wheat, wheat fortified with 0.2% lysine or casein, as control. Plasma and liver lipids, incorporation of [1-(14)C]acetate and [U-14C]glucose into hepatic lipids and triglycerides were studied after 6 weeks of feeding. Results of radioactive incorporation studies indicated that hepatic lipogenesis was depressed in rats fed wheat diets. However, adrenal cortical function as well as increased mobilization of lipids from adipose tissue was observed in these rats. Impaired secretion of lipids from liver to plasma is another factor which may be responsible for hepatic lipid accumulation in rats fed the lysine-deficient diet. Rats fed the lysine fortified wheat diet represented a more normal metabolic state though some features of protein deficiency were evident in this group too.


Potassium requirement of the growing rat. On the basis of maximum weight gain in weanling male rats fed a semipurified diet for 21 days, the requirement for potassium was found to be 0.23% of the diet. This compares with the NRC requirement of 0.18%. The higher requirement is believed to be due to the greater rate of growth, 6.6 to 7.0 g/day, compared with that obtained in older studies on which the NRC estimate was based. The higher potassium level also improved efficiency of food utilization.


Effects of zinc deficiency and zinc repletion during pregnancy on parturition in two strains of rats. The effects on parturition of a low zinc diet during pregnancy and of three levels of zinc repletion late in pregnancy were compared in two strains of rats, Sprague Dawley and Long Evans. Long Evans rats had a higher hematocrit and higher plasma protein levels than did Sprague Dawley rats. Long Evans rats also had heavier mammary glands and tended to deliver somewhat later than the Sprague Dawley rats. Weight gains during pregnancy and weights of the liver, spleen, adrenal glands, and pups did not vary between strains. No differences were detectable in the degree of stress at parturition between the unsupplemented females of the two strains. Injection of 300, 600, or 900 microgram zinc on day 18 of pregnancy increased female weight gains, pup weight, and spleen and mammary gland weights, and decreased hematocrit level. Three females in the unsupplemented groups died about the expected time of parturition; none died in the supplemented groups. Although there were some differences between the strains, the effects of a low zinc diet and the requirement for zinc for normal parturition were the same in the two strains. An injection of 900 microgram zinc on day 18 resulted in normal parturition in both strains.


Effect of high levels of dietary vitamin E on liver and plasma lipids and fat soluble vitamins in rats. The effect of low, moderate and high dietary vitamin E (ranging from 0 to 25,000 IU/kg diet) on the levels of alpha-tocopherol, total lipids, cholesterol and vitamin A in liver and plasma of rats fed for 8 and 16 months was studied. A logarithmic relationship was observed between dietary levels of vitamin E and the concentrations of this vitamin in liver and plasma. The total alpha-tocopherol in whole liver of rats fed different levels of dietary vitamin E for 16 months was approximately double in comparison to rats fed for 8 months. Totoal lipids in liver were significantly increased by excess vitamin E supplementation in rats fed for 8 months, but not in rats fed for 16 months. There was no significant change observed in liver cholesterol level at 16 months. Plasma total lipids and cholesterol were lowered by vitamin E deficiency and also by dietary levels higher than 2,500 IU vitamin E/kg diet in rats fed for 16 months. Liver vitamin A storage was 4.5 times higher in rats supplemented with vitamin E than in rats without any supplement, but the effect of excess dietary vitamin E was no different from that of normal level (25 IU/kg diet). The findings of our long-term study are compared with the results of other short-term studies and the implications are discussed.


Effects of fasting and feeding various diets on hepatic lipogenic enzyme activities in coho salmon (Oncorhynchus kisutch (Walbaum)). The influence of fasting and diet composition on the time sequence of changes in hepatic lipogenic enzyme activities in coho salmon was investigated. Young coho salmon fed a high-carbohydrate diet for 3 weeks were then fasted for 2, 6, or 23 days. Liver preparations were assayed for fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities. Fasting the fish for 2 or 6 days did not influence the activities of these enzymes; however, by the end of the 23-day fast the activities of all these enzymes had decreased. Changing the diet of the fish from high-carbohydrate to high-fat had only a minimal influence on the activities of the hepatic lipogenic enzymes after 7 to 14 days. Longer-term studies demonstrated that high-fat diets did eventually depress lipogenic enzyme activities. The effect of fasting and feeding on the level of lipogenic enzyme activities was observed only after several weeks, in contrast to hours in the rat. This may reflect a difference between poikilothermous and homoiothermous animals.


Lack of effect of ascorbic and citric acids on calcium metabolism of chickens. Five experiments were carried out in which various levels of calcium and ascorbic acid or citric acid were fed to adult male chickens, young chickens, or young coturnix. Observations were made on body weight, feed efficiency, plasma calcium and tibia mineral content. One percent dietary ascorbic acid had no adverse effect on body weight, tibia ash or tibia calcium content of adult male chickens over a 224-day period, even at calcium levels as low as 0.026% of the diet. In growing chicks, body weight and plasma calcium and tibia mineral content varied with the calcium level of the diet, but were not influenced by ascorbic acid even at 0.65% of the diet. Citric acid at the same molar level was also ineffective in altering calcium metabolism in growing chickens. Growing coturnix showed differences in growth and tibia ash content with 0.4% and 0.85% calcium, but there were no pronounced effects caused by dietary ascorbic acid. There is no evidence in this work that these relatively high levels of ascorbic acid or citric acid have any adverse effect on calcium metabolism because of their chelating properties.


Fatty acid and glucose metabolism in selenium deficient rats and lambs. Fatty acid analyses were done on tissues of lambs from ewes fed purified diets, and injected with selenium and/or vitamin E in a 2 X 2 factorial treatment. The concentrations of arachidonic acid averaged 9.3% of the total fatty acid content in semitendinosus muscle from lambs given vitamin E and selenium, but averaged 19.4% in this muscle from lambs given vitamin E without selenium. Arachidonic acid comprised 28.3% and 33.7%, respectively, of the total fatty acids in livers from selenium supplemented and deficient rats. Twice as much radioactivity from [1-(14)C]acetate was recovered in rat liver phospholipid arachidonate in selenium deficient rats as in selenium supplemented ones, indicating a greater turnover rate of this fatty acid in deficient rats. Fifty-five percent of dosed 14C-glucose (either [1-(14)C] or [6-(14)C]glucose) was recovered within 3 hours as 14CO2 from selenium deficient rats. This recovery dropped to one-half this value when these rats were fed a diet containing 0.1 ppm selenium for only 7 days. This increased glucose metabolism is suggestive of a greater metabolic rate in selenium deficient animals, which may be responsible for the differences observed in tissue fatty acid composition.


Quantitative requirement of the hatchling green sea turtle, Chelonia mydas, for valine, leucine, isoleucine and phenylalanine. Hatchling green sea turtles were fed purified diets containing 36% crude protein (N X 6.25) to determine the quantitative requirements for valine, leucine, isoleucine and phenylalanine. Expressed as percentage of total dry diet, the hatchling green sea turtle requires 1.3% valine, 1.6% leucine, 1.0% isoleucine and 1.0% phenylalanine (in the presence of 0.5% tyrosine). Within the range of isoleucine-leucine levels investigated, there was no apparent interrelationship between the quantitative requirements of these two amino acids. Growth rate was decreased at a high level of phenylalanine, 3.0% of the dry diet.


A biphasic response of rats to cobalt.

A biphasic response of rats to cobalt. The study was designed to confirm a previous, unexpected observation of a strong growth depressing effect of 1 microgram cobalt/g in rats fed lactalbumin based diets. The addition of 0.25, 0.5, and 1.0 microgram of cobalt/g to the basal diet containing 0.056 microgram/g depressed growth rates of rats progressively with increasing doses. This depression was overcome by increasing the cobalt supplement to 2 microgram/g, and additional weight gain was observed with 3 microgram/g. Higher concentrations were progressively toxic. Hemoglobin concentrations, hematocrits, and thyroid retention of intravenously injected sodium iodide all were lowest in rats fed the diet containing 1 microgram cobalt/g and increased with lower and higher concentrations of cobalt. The opposite was true for fasting serum glucose levels, which were elevated in rats fed the 1 microgram/g diet and low in rats fed the 3 microgram/g diet or control diet. This biphasic response to cobalt is consistent with the hypothesis that cobalt in low concentrations may have an essential function in the rat. However, an alternative explanation, an interaction of cobalt with a toxic constituent of the diet, has not yet been ruled out.


Maternal and fetal response to various suboptimal levels of zinc intake during gestation in the rat. Some effects of various degrees of zinc deprivation during pregnancy have been examined in dams and offspring. After mating, the dams were fed a biotin enriched, 20% sprayed egg white diet which contained less than 1 ppm zinc. Zinc was provided in the drinking water at one of the following concentrations: 1, 2, 3, 5, 11, or 25 mg/liter. Pups were taken by cesarean section on day 22 of gestation. The dams given insufficient zinc became anorexic, particularly during the latter third of gestation. Anorexia occurred earlier and was most severe at the lowest levels of zinc intake. The decreased food consumption resulted in energy deprivation and at the lowest levels of zinc intake, in protein insufficiency. The total weight gain and rate of weight deposition in the dams were both functions of the level of zinc provided. Fetal growth and extent of zinc deposition into the fetuses were both related to the amount of zinc provided. The responses of dams and fetuses to the extent of zinc deprivation were not equivalent, however. It appeared that there was a sparing of fetal growth at the expense of the dam at very low levels of zinc intake. Conversely, at higher, but still suboptimal levels of zinc, the fetuses still experienced growth retardation although the dams attained a normal weight deposition during gestation.


Ultrastructure of intestinal and diffuse type gastric carcinoma. Samples from 56 resected stomachs, including 28 cases of intestinal and 14 of diffuse type gastric carcinoma, were studied by electron microscopy. The main ultrastructural features of intestinal and diffuse type gastric carcinomas were described and compared to the ultrastructure of normal gastric mucosal cells and cells occurring in intestinal metaplasia of the gastric mucosa. Many similarities were demonstrated between intestinal metaplasia and intestinal type carcinomas. The cells of diffuse type carcinomas closely resembled the goblet cells of intestinal metaplasia. Microvilli, similar to those in the brush border of the intestinal columnar cells, could be demonstrated in the carcinomatous surface epithelium and occasionally also in individually spreading cells of the diffuse type carcinoma. Intracellular cysts with microvilli on the cyst wall were occasionally found in both types of carcinoma. The histogenetic origin of gastric carcinoma was discussed.


Pulmonary argyrophil cells at high altitude. The numbers of individual argyrophil cells and groups of argyrophil cells were compared in rabbits which had been born and had spent their entire lives at a height of 4300 m above sea level and in sea-level controls. In the bronchi and bronchioles there were more groups of argyrophil cells in the high-altitude rabbits (mean 10-23/cm2) than in the sea-level controls (mean 5-22/cm2). In the alveolar walls there were more individual cells in the high-altitude rabbits (mean 2-65/cm2) than in the sea-level controls (mean 0-72/cm2). These differences may be either inherited or acquired and in either case, it is suggested that the likely explanation for the differences is hypoxia. If acquired, the differences may be due to differentiation of argyrophil cells from a stem cell. The results provide evidence that individual argyrophil cells exist in the alveolar walls. They suggest that individual argyrophil cells and groups of argyrophil cells may have different functions according to their site.


Atypical glycogen deposits in a plasmacytoma: an ultrastructural study. A solitary, benign plasmacytoma, arising from the gum of the lower jaw of a dog, was studied by light and electron microscopy. Some of the tumour cell nuclei showed the characteristic clockface or cartwheel pattern of heterochromatin distribution similar to that found in normal plasma cells. Like normal plasma cells the tumour cells were endowed with rough endoplasmic reticulum but this was invariably dilated or visiculated. Glycogen deposits were found within mitochondria and within the dilated and vesiculated rough endoplasmic reticulum. The idea that these deposits were derived secondarily from glycogen deposits in the cytoplasm seems untenable because no glycogen particles were found in the cytoplasmic matrix. It would therefore appear that most, perhaps all, stages of glycogen synthesis occurred within the mitochondria and rough endoplasmic reticulum of some of these tumour cells.


The mechanism of fusion of hamster macrophages induced by antimacrophage serum. The mechanism of antihamster macrophage serum (AHMS)-induced fusion of hamster macrophages has been investigated using the serum alone or conjugated to ferritin or Sepharose beads. It has been shown that AHMS attaches to and is interiorised by hamster macrophages. When macrophages are brought into contact before AHMS bound to their surface is interiorised, fusion results. The results strongly support the hypothesis that macrophage fusion is the consequence os simultaneous endocytosis of particles or colloids. It is suggested that a similar mechanism underlies the formation of macrophage giant cells in granulomata where closely packed macrophages attach to and interiorise the denatured materials produced in the chronically inflamed environment.


Cytofluorograf detection of Plasmodium yoelii, Trypanosoma gambiense, and Trypanosoma equiperdum by laser excited fluorescence of stained rodent blood. Samples of rat blood infected with Plasmodium yoelii (3% parasitized erythrocytes), Trypanosoma gambiense, or Trypanosoma equiperdum (greater than 50 trypanosomes per microscope field at 400 X) were fixed with 0.5% glutaraldehyde in phosphate buffered saline, then stained with acridine orange (AO) at 10(-4), 10(-5), or 10(-6) M for 0 to 15 min at 5 C or 25 C and/or ethidium bromide (EB) at 0.05 mg/ml for 20 min at 25 C. Stained cells were analyzed with a laser Cytofluorograf (Bio/Physics Systems, Inc.) to determine if parasites could be detected and differentiated from blood cells by their fluorescent characteristics. Samples of uninfected rat blood with and without leukocytes and P. yoelii-infected blood without leukocytes were treated similarly. In addition, suspensions of T. gambiense and T. equiperdum without all blood cells were stained with AO or EB and analyzed with the Cytofluorograf, as were mixed suspensions of both trypanosome species. EB- but not AO-stained P. yoelii-infected erythrocytes had fluorescent characteristics different from most blood cells. Neither AO- nor EB-stained T. gambiense or T. equiperdum could be differentiated from host blood cells or from each other. The results are discussed with respect to the use of laser flow systems in the detection and analysis of bloodstream dwelling protozoan parasites.


Scanning electron microscopy of Eimeria tenella microgametogenesis and fertilization. Microgametes of Eimeria tenella were observed in cecal tissue from infected chicks killed six days after inoculation with oocysts. Development from the microgamont stage to maturity was followed. We observed three commonly found, but distinctly different, stages in developing microgametes while they were still associated with microgamonts. In the first, only the flagella could be seen protruding through the enveloping microgamont layer. In the second, both the bodies and flagella could be seen; the flagella had increased in size, and the bodies appeared bulbous. In the third, nearly mature microgametes were randomly arranged around the microgamont, and the manner of flagellar attachment to the bodies near the apical conjunction of the perforatorium was seen. A free microgamete and a macrogamete with one penetrating and two adhering microgametes were found. On flagellum and most of the body of the penetrating microgamete had entered the macrogamete. All micorgametes seen had two flagella.


Studies on growth, development, and infectivity of Philophthalmus hegeneri Penner and Fried 1963 in the chick. A reinvestigation of the growth curve of Philophthalmus hegeneri in chicks showed rapid growth for the first 17 days after infection. After this, the growth rate declined for multiple infections (two or more worms per eye), and after 20 days, adults in monometacercarial infections ceased appreciable growth and never attained reproductive maturity. These results are similar to those reported by Fried (1962), but here adults were approximately 0.5 mm shorter in all cases and were slower in producing mature eggs. When worms from 28 to 36 days old from monometacercarial infections were transplanted into multiple infections, normal growth occurred. Worms recovered from multiple infections and transplanted singly grew normally for at least 18 days but recovery rates were extremely low. When P. hegeneri adults over 20 days old from monometacercarial infections were transplanted singly with Philophthalmus megalurus adults, growth was not stimulated in either species.


Aerobic and anaerobic fermentation of glucose by Echinostoma liei. Echinostoma liei was incubated in vitro aerobically and anaerobically with various species of 14C glucose. From the recovery of isotope in the respired CO2, it appeared that glucose was incompletely oxidized. The major portion of the CO2 arose from the 3 and 4 carbons of glucose. In addition to CO2, a number of volatile fatty acids accumulated as end-products both aerobically and anaerobically. Lactate and succinate were also isolated. Of these, n-valerate was recovered in the highest concentrations. Qualitatively, the same products were demonstrated after both aerobic and anaerobic incubations, but quantitatively considerably more fatty acids accumulated anaerobically.


A lipogenic effect in intact male hamsters infected with plerocercoids of the tapeworm, Spirometra mansonoides. Plerocercoids of the tapeworm, Spirometra mansonoides, produce a potent growth stimulating substance which is active in several species of mammals. While most of the actions of the plerocercoid growth factor (PGF) are similar to those of growth hormone (GH), lipid metabolism is one area where their actions are not alike. This report demonstrates that plerocercoid infection not only stimulates growth of intact male hamsters but is lipogenic as well. The lipogenic effects of plerocercoid infection were demonstrated by increases in epididymal fat pad weights, serum triglycerides, cholesterol, and total lipid. The livers of the plerocercoid-infected hamsters also had more cholesterol and more lipid phosphorus than controls. Incorporation studies using [2-14C]acetate showed that infected hamsters incorporated significantly higher levels of the radionuclide in their livers and serum after 1 hr than the controls. The lipogenic effect of plerocercoid infection is distinctly unlike the reported lipolytic action of GH and the lack of any stimulation of [2-14C]acetate incorporation into the epididymal fat pads is unlike the reported acute actions of insulin as well.


A redescription of Eustrongylides tubifex (Nitzsch 1819) Jägerskiöld 1909 (Nematoda: Dioctophymatidae) from mallards (Anas platyrhynchos). Eustrongylides tubifex (Nitzsch 1819) Jägerskiöld 1909 is redescribed from six male and 10 female adult specimens from experimental infections in mallards (Anas platyrhynchos). Our redescription is compared with that of Jägerskiöld (1909) and those of the Russian investigators Kontrimavichus and Bakhmeteva (1960) and Karmanova (1968). Our redescription differs in the ranges of total body length, esophageal length, maximum width, spicule length and vagina length. The cuticular fringe and inner rim of small papillae of the male bursa are shown to be definitive species characters. A key to the species of Eustrongylides is included.


Immunity to Trichinella spiralis. VII. Resistance stimulated by the parenteral stages of the infection. In three experiments mice were given three intravenous injections of Trichinella spiralis newborn larvae produced in vitro. Following a challenge infection of newborn larvae the mice were shown to be on the average 85% resistant i.e., only 15% of the challenge larvae developed to encysted muscle stage larvae in these mice; when the challenge consisted of normal muscle larvae administered per os, the mice were 51% resistant. Neither the number nor longevity of adult worms in the intestines was affected by this immunization procedure.


Critical anthelmintic trials in ponies with four benzimidazoles: mebendazole, cambendazole, fenbendazole, and albendazole. The comparative efficacy of four benzimidazoles against gastrointestinal parasites of ponies was evaluated by the critical test method. Mebendazole (8.8 mg/kg), cambendazole (20 mg/kg), fenbendazole (5 mg/kg), and albendazole (2.5 and 5 mg/kg) given in single oral doses were highly effective against adult large strongylids (Strongylus vulgaris, S. endentatus, S. equinus) and adult small strongylids (genera identified in order of frequency: Cylicostephanus, Cylicocyclus, Cyathostomum, Triodontophorus, Poteriostomum, Oesophagodontus, Cylicodontophorus, Gyalocephalus, and Craterostomum). Limited data indicated that all benzimidazoles were completely effective against adult Oxyuris equi and 95 to 100% effective against the 4th stage larvae. There was activity also against the large roundworm, Parascaris equorum, although the low levels of infection and skew distribution among the test animals did not permit a definitive determination of efficacy. Habronema muscae, Draschia megastoma, and Trichostrongylus axei were found in digests of the stomach but none were recovered in the feces after treatment; percent efficacy for these species was not calculated. None of the benzimidazoles showed activity against stomach bots, Gasterophilus spp., and tapeworms, Anoplocephala spp. nor against immature large and small strongylids outside the lumen of the digestive tract.


Glochidiosis of salmonid fishes. I. Comparative susceptibility to experimental infection with Margaritifera margaritifera (L.) (Pelecypoda: Margaritanidae). This is the first report on the susceptibility of salmonid fishes to infection with the glochidia of the freshwater mussel Margaritifera margaritifera using known numbers of parasites under controlled conditions. The relative susceptibility of six species of salmonid fish, 20 to 80 mm in total length, to glochidiosis was determined by exposing fish individually to different numbers of parasites and plotting mortalities against these exposure levels at 70 days postexposure and also against the numbers of parasites recovered from fish 48 hr postinfection. The 70-day interpolated LE50 values (exposure concentrations of glochidia that killed 50% of the fish) for kokanee salmon (Oncorhynchus nerka kennerlyi), cutthroat trout (Salmo clarki), Atlantic salmon (S. salar), steelhead trout (S. gairdneri) and coho salmon (O. kisutch) were 17,500, 29,000, 35,000, 57,000, and 105,000, respectively. Chinook salmon (O. tshawytscha) was the most susceptible species. The LE50 values could not be estimated even at the lowest exposure levels because mortalities were too high. On the basis of the LE50 value, coho salmon was the most resistant species.


Ecology of the tick Amblyomma hebraeum Koch in the Eastern Cape Province of South Africa. I. Distribution and seasonal activity. In the Eastern Cape Province of South Africa larvae of Amblyomma hebraeum Koch occur in well-drained, shaded habitats, with a ground cover of grass. The life cycle is normally of 3 years duration. Peak larval activity occurs in the summer of the 1st year, peak nymphal activity in the spring of the 2nd year, and peak adult activity in the summer of the 3rd year. Larval activity shows no direct correlation with macroclimate. Adult activity is correlated with, in the following order of signficance, daylength, temperature, and rainfall. Nymphal activity appears to be regulated by the same factors.


Observations on the ontogeny of halarachnid mites (Acarina: Halarachnidae). Descriptions are given of protonymphal and deutonymphal instars of Orthohalarachne diminuata (Doetschmann 1944) and O. attenuata (Banks 1910), together with comparative data for larvae and adults. Some phylogenetic implications of comparative ontogeny in halarachnids are considered. Leg and palpal chaetotaxy of all instars of Pneumonyssus simicola, Banks 1901 is compared with that of the two Orthohalarachne species and with that characteristic of free-living dermanyssids. A neotenic pattern is indicated for the three species of halarachnids. Differences of probable generic significance in leg and palpal chaetotaxy are described for the three species mentioned and for Halarachne Allman 1847.


Adolescent Rorschach responses as a function of age at first institutionalization. To test the hypothesis that age of first separation from a home environment is a factor in the emotional health of institutionalized boys, Rorschach protocols of 82 residents of Saint Francis Vocational School, a facility for deprived nondelinquent nonretarded youth aged 10 to 18, were examined. Seven Rorschach variables were used as dependent variables of emotional status. It was found that boys who had first been institutionized before age 10 gave more color-dominant and pure color responses (p less than .005), and more responses with pathological overtones (p less than .005), than did youth first placed at ages 10 to 13 or ages 14 to 17. Fixation was proposed as the basis for the group differences.


The symbiosis scale: inkblot responses of children from symbiotically and non-symbiotically oriented families. Describes the development and subsequent attempts at validation of an objective measure of the concept of symbiosis based on children's responses to inkblot stimuli. It was hypothesized that children reared in symbiosis inducing versus non-symbiosis inducing family settings would obtain higher scores on the symbiosis scale. The hypothesis was supported in a first study involving 36 children evidencing neurotic and personality disorders (p less than .01), but was not supported in a second study involving 35 children of whom over 70 percent evidenced borderline psychotic or psychotic disorders. In a third study involving 27 neurotic and personality disordered children the scaled again differentiated between children from symbiotically oriented versus non-symbiotically oriented families (p less than .01).


Gender-specific variances in sexual fantasy. Six sexual fantasy categories were derived by inductive content analysis, based upon the starting criterion that fantasy is a dynamic and interactional event. Detailed narrative descriptions of sexual fantasy in three conditions, including 'Daydream,' 'masturbatory,' and "During Sex Relations' were obtained from 48 male and 45 female volunteer graduate students. Detailed narrative descriptions of sexual fantasies were collected by administration of sexual fantasy questionnaires. While the intention was to empirically derive sexual fantasy categories which could be used for personality assessment of gender identity, the hypothesis predicted gender-specific variances in fantasy productions according to derived fantasy categories. Results indicated that significantly more females than males fantasized themselves as recipients of sexual activity from fantasized sexual objects, while males fantasized the sexual object as recipients of sexual activity. Marginal tendencies toward reversal of this gender pattern occurred in the 'Mastubatory' condition for males, and in the 'Daydream' sexual fantasy condition for females.


Personality characteristics related to cross-situational consistency of interpersonal distance. Explored the relation of personality dimensions to cross-situational consistency in interpersonal distance. Sixty-five male and 52 female undergraduates were given the Personality Research Form A and the Maudsley Personality Inventory as well as four forms of a measure of interpersonal distance preference which covered 10 different situations. The relationship between the personality dimensions and the consistency of interpersonal distance choice was measured by multiple regression. Neuroticism emerged as having the most reliable relation to consistency, confirming previous data in this area. Multiple Rs ranging from .36 to .53 indicated that consistency may be reliably related to personality dimensions and that conceptualizing consistency as an individual difference or moderating variable may partially explain the difficulty in predicting directly from personality dimensions as the situation varies.


Causal orientation and personal adjustment of hospitalized veterans. Continues a line of theory and research which sees human behavior as basically teleological. Groups of hospitalized male alcoholics, psychotics, and normals were administered the Causal Construct Scale, the Minnesota Multiphasic Personality Inventory, and the Shipley Institute of Living Scale. It was predicted that extent of pathology across experimental groups as well as general tendencies to abnormality would follow telic considerations. Intentional causal orientation was positively related and subtance causal orientation was negatively related to mental health. The impetus and pattern causal constructs failed to be predictive of personal adjustment.


Self-ideal discrepancy and acceptance of false personality interpretations. Effects of self-ideal discrepancy and favorability of content on subjects' acceptance of personality interpretations were studied. Subjects accepted more favorable than neutral statements and more neutral than unfavorable statements. A significant effect was found for self-ideal discrepancy and for the interaction between self-ideal discrepancy and content favorability. In contrast to moderate and low discrepancy subjects, high discrepancy subjects accepted more of the interpretations, accepted more unfavorable, and rejected more favorable interpretations. High discrepancy subjects also accepted more neutral interpretations than did low discrepancy subjects. High discrepancy subjects expected to receive more negative feedback than low discrepancy subjects, and also interpreted this feedback more negatively than did low discrepancy subjects, while scores for the moderate discrepancy subjects were consistently between these two groups.


Some Rorschach data concerning suicide.

Some Rorschach data concerning suicide. The Rorschachs of 59 effected suicides and 31 attempted suicides, all of which were collected within a period of 60 days prior to the critical event were categorized in terms of method used, and subjected to a computer scan to determine if any constellation of variables occurred with a greater frequency than in the protocols of three control groups, comprised of inpatient depressives, inpatient schizophrenics, and nonpatients. A constellation of 11 variables is reported, a composite of eight or more correctly identifies 75% of the effected group and 45% of the attempters while occurring with a relatively low frequency among controls. Data are also presented from a group of 33 records collected within five days after a suicidal attempt revealing that those records do not differ essentially from either of the two psychiatric control groups. The findings are discussed in terms of the problems of prediction, and in the context of the probable psychological structure of many suicide prone people.


Personality correlates of the abstract response on the Holtzman Inkblot Technique. Through the innovative use of a special set of Holtzman inkblots, several variables of the Personality Research Form were shown to be correlates of the Abstract response for 30 male and 33 female undergraduates. For males, positive correlations were obtained between Abstract and Achievement, Endurance and Sentience; while negative correlations were obtained between Abstract and Harmavoidance and Order, respectively. For females, Abstract was positively correlated with Dominance, Nurturance, Exhibition, and Social Recognition; and negatively correlated with Abasement and Affiliation.


Reliabilities and interrelationships of two HABGT scales in a male delinquent population. Reliabilities and interrelationships of the Adiense-Abience and the Psychopathology Scales of the HABGT were investigated in a population of 120 13-15 year-old male delinquents over a 40-week period. The delinquent boys were assigned to three conditions: individual tutoring and counseling; group tutoring and counseling; controls (no treatment). Both scales were found to have high test-retest reliability over all conditions (rs ranged from .85 to .93). Interscorer reliability among three scorers was also found to be very high. As expected, treatment had a differential effect on psychopathology and on adience-abience: the former was modifiable while the latter was resistant to change. Also as predicted, the two scales had a significantly higher degree of commonality before treatment intervention than after such intervention, but the relationship remained stable for the control group. Implications for clinical and research use are discussed.


Medical and nursing students: concepts of self and ideal self, typical and ideal work partner. Forty-three medical students and 78 nursing students each filled out four copies of the Interpersonal Check List. The subjects described self, ideal self as physician or nurse, and typical and ideal work partner. For each questionnaire the two summary scores Dom and Lov were computed. The results indicate a discrepancy between concepts of self and ideal self and the results also point to considerable disagreement between medical students and nursing students about their roles on the physician-nurse team.


Personality correlates of the Mosher Guilt Scales. Examined the relationship between sex guilt, hostility guilt, and morality-conscience guilt, and more traditional concepts in personality, to extend the construct validational work of the Mosher Guilt Scales. This was achieved by correlating the scores of the three guilt subscales with the 15 manifest needs of the Edwards Personal Preference Schedule. The results indicate that while there was some overlap between the guilt scores and the manifest needs, the association was usually a function of theoretically consistent relationships rather than duality of constructs. These findings, and the literature review of the Mosher Guilt Scales, are interpreted as supporting the continued use of the three guilt subscales as well as suggesting that guilt is a personality variable of considerable theoretical significance.


Children's beliefs in internal-external control and self-esteem as related to academic achievement. Previous work has shown high self-esteem to be related to an internal locus of control (LOC) orientation. Both have been shown to be related to academic achievement. It was hypothesized that LOC and self-esteem are each independently related to achievement, and that these relationships may vary according to the sex of the child and the measure of achievement used. Subjects were 113 ten-year-old, fourth grade children, 60 males and 53 females. They were administered questionnaire measures of LOC and self-esteem (Nowicki-Strickland and Piers-Harris). An internal LOC orientation was significantly related to greater academic achievement and high self-esteem. Males' LOC scores were related to grade point averages and not achievement test scores, while the reverse held for females. Differential socialization of females from males might account for the lack of a relationship between grades and LOC.


The occurrence of reinforcing activities in relation to locus of control, success-failure expectancies, and physical attractiveness. The Pleasant Events Schedule (mimeographed), which measures the retrospective frequency and value of positive reinforcement, was administered to 74 college students; and its relation to subjects' locus of control and success-failure expectancies and to their levels of physical attractiveness was evaluated. While results were less consistent for females than for males, significant relationships were obtained between each of these "person" variables and the various indices derived from the Pleasant Events Schedule. Not only do the findings reflect favorably on the construct validity of the various dimensions as measured, but the data carry implications for a more integrative study of depression.


A comparison of four measures of moral reasoning. Kohlberg's Moral Judgment Scale, Gilligan et al.'s Sexual Moral Judgment Scale, Maitland and Goldman's Objective Moral Judgment Scale, and Hogan's Maturity of Moral Judgment Scale, were examined for reliability and inter-scale relationships. All measures except the Objective Moral Judgment Scale had good reliabilities. The obtained relations between the Moral Judgment Scale and the Sexual Moral Judgment Scale replicated previous research. The Objective Moral Judgment Scale was not found to validly assess the Kohlberg stages. The Maturity of Moral Judgment Scale scores were strongly related to the subjects's classification on the Kohlberg stages, and the scale appears to offer a reliable, quickly scored, and valid index of mature thought, although the scale's continuous scores do not permit clear stage classification.


Watchman, what of the future?

Watchman, what of the future? Two Rorschachs were inadvertenly administered to the same client within a period of three months. Althoug the ensuing personality pictures were very similar, an important difference appeared. The first Rorschach report stopped with the client's present condition. The second report saw the protocol as an interim Rorschach, suggesting the possibility that positive changes could lie ahead, if the client were given the appropriate help. The point is made that unwittingly, examiners may do their clients harm by not thinking ahead, in a way which the Rorschach uniquely makes possible. The Rorschach record and graph are presented, along with the various evidences of potential change. In conclusion, a problem is raised concerning the obligation inherent in the examiner-client relationship.


Reactions of benzenesulfonohydrazides and benzenesulfonamides with hydrogen chloride or hydrogen bromide in acetic acid. Benzenesulfonohydrazides capable of yielding a sulfinic acid intermediate by virtue of a basic nitrogen atom in the second position of the hydrazide moiety produced thiosulfonates when treated with 1 N hydrogen chloride in acetic acid and produced disulfides when treated with 1 N hydrogen bromide in the same solvent. In two cases, a crystalline mixture of P-nitrophenyl p-nitrobenzenethiosulfonate and bis(p-nitrophenyl) disulfide was isolated from the hydrogen chloride reactions. No reaction product was obtained from either the hydrogen chloride or hydrogen bromide reaction with benzenesulfonohydrazides that were unable to form a sulfinic acid intermediate. Reduction of benzenesulfonamides to disulfides appeared to be possible only with hydrogen bromide in acetic acid. No thiosulfonate was isolated from the treatments of benzenesulfonamides with 1 N hydrogen chloride in acetic acid. p-Nitrophenyl p-nitrobenzenethiosulfonate and p-bromophenyl p-bromobenzenethiosulfonate exhibited some antimicrobial activities against Gram-positive bacteria. The latter compound also showed analgesic properties in the phenylquinone test.


Mechanism of methacholine-induced rise in intraocular pressure in the dog. The mechanism of the methacholine-induced rise in intraocular pressure in the dog was studied to determine the basis of the relationship, if any, between lens thickness and intraocular pressure. The results rule out a vasodilator component in methacholine intraocular pressure elevation, and the tonometric recording of the elevation makes unlikely the involvement of methacholine stimulation of the rectus muscles of the eye. Thus, indirect evidence points to methacholine stimulation of ciliary muscle contraction with consequent thickening of the lens as responsible for its intraocular pressure-elevating effect and, hence, the ability of the response under investigation to specify the cycloplegic liability of a neurotropic antispasmodic agent.


Impurities in drugs I: Imipramine, desipramine, and their formulations. Nineteen lots of imipramine tablets and four lots of desipramine tablets were examined for impurities by TLC. Iminodibenzyl, desipramine, and 10,11-dihydro-5-[3-(methylamino-3'-dimethylaminopropyl)propyl]-5H-dibenz[b,f]azepine dihydrobromide (I) were found in some imipramine tablets, and iminodibenzyl and imipramine were found in some desipramine tablets, all at levels of less than 0.3% of label claim of the drug. Except for I, the identity of the impurities was established by comparison with known standards; I was synthesized and its composition was established by elemental analysis. All impurities, including I, were characterized by TLC, GLC, and mass spectrometry.


Chemical and spectroscopic analysis of a phenobarbital-ephedrine complex. A complex of phenobarbital and ephedrine was prepared and characterized. The complex was differentiated from physical mixtures of the two drugs by TLC and IR spectroscopy. NMR spectroscopy was used to verify the proportion of each drug in the complex and to confirm the existence of intermolecular binding. Mass spectrometry was employed to establish that all fragments characteristic of the individual drug entities could be isolated from the complex. Elemental analysis confirmed the chemical composition of the complex. A possible chemical structure for the complex was hypothesized on the basis of the chemical and spectroscopic data.


Relationship between protein binding of bilirubin, salicylic acid, and sulfisoxazole in serum of unmedicated and phenobarbital-treated rats. The relationship between the protein binding of bilirubin, salicylic acid, and sulfisoxazole in the serum of phenobarbital-treated and untreated rats was studied. The free fraction of bilirubin in serum varied about threefold between animals but was not related to the albumin concentration, the free fraction of salicylate, or the free fraction of sulfisoxazole. However, there was a strong positive correlation between the free fraction values of salicylate and sulfisoxazole. The free fraction value for each of these drugs showed a significant negative correlation with the serum albumin concentration. Treatment of the animals with phenobarbital had no apparent effect on the serum protein binding of bilirubin, salicylic acid, and sulfisoxazole.


Rapid GLC determination of therapeutic plasma glycerin levels. A new rapid and inexpensive method for the determination of therapeutic plasma glycerin concentrations is described. In this method, acetic anhydride and pyridine are added to 15 microliter of plasma. After brief incubation and centrifugation, an aliquot of the supernate is injected directly onto the 3% OV-1 column. A linear calibration curve was found in the 0.05--3-mg/ml range, with the precision of the assay estimated to be +/-5.5% (RSD). The method was used to determining preliminary pharmacokinetic data in the rabbit.


Colorimetric assay of benzocaine and some dosage forms. A colorimetric procedure for benzocaine and a number of its dosage forms was developed; it offers improvement in ease, speed, and sensitivity over the official method. The method is based on the formation of a red Schiff base between benzocaine and p-dimethylaminocinnamaldehyde in a nonaqueous acidic medium. At the maximum absorption of 544 nm, the Beer-Lambert law was adhered to over the 0.025--2.5-microgram/ml range. Best accuracy can be obtained for solutions containing 0.25--1.25  microgram/ml. The color was stable for at least 2 hr. Analysis of benzocaine in the dosage forms studied can be directly performed without prior drug extraction.


Solvent-dependent conformational system of hydroxyureas in octanol-water and in inhibition of ribonucleotide reductase. The carbonyl nitrogen IR absorption region of selected hydroxyureas was examined in octanol. The spectra indicated appreciably different absorptions prior to and after equilibration with water. Stability studies on the hydroxyureas indicated that the absorption differences were not due to chemical decomposition in the equilibration process but were due to solvent conformation and/or tautomeric dependency of the system. Preliminary in vitro inhibition of the enzyme ribonucleoside diphosphate reductase by selected hydroxyureas also indicated an apparent solvent dependency, which may involve the conformational and/or tautomeric properties of these agents. The implications of the solvent-dependent conformation-tautomeric system observed are discussed in relation to this property in the biological action of these agents.


Improved recovery of morphine from biological tissues using siliconized glassware. The adsorption of morphine onto glassware during analysis in aqueous solutions and biological tissues is a common problem, resulting in lower recoveries than expected. The problem can be remedied by siliconization of all glassware involved. The same glassware cannot be used repeatedly without incurring a significant loss of morphine.


Binding of pyridine derivatives to cytochrome P-450. The spectral binding constants, Ks, of pyridine, methylpyridine, and dimethylpyridines were determined. The Ks values of the compounds were discussed in terms of mechanisms of possible bonding to cytochrome P-450.


Determination of dextrorphan in plasma and evaluation of bioavailability of dextromethorphan hydrobromide in humans. A method is described for the estimation of dextrorphan, a metabolite of dextromethorphan, in plasma. The bioavailability of dextromethorphan hydrobromide after 30 mg po, as measured by the concentration of total (free and conjugated) dextrorphan in the plasma, was determined in six human volunteers with this procedure.


Effects of 3,4-dimethoxyphenethylamine derivatives on monoamine oxidase. The cactus alkaloid 3,4-dimethoxyphenethylamine and its naturally occurring N-methylated homologs inhibited the deamination of tyramine and tryptamine by rat brain monoamine oxidase. In contrast, the beta-hydroxylated derivatives of this series failed to inhibit the action of monoamine oxidase on both tyramine and tryptamine.


Alkaloids of Papaver orientale L.

Alkaloids of Papaver orientale L. According to the alkaloid profiles, five different chemotypes (A, B, C, D, and E) were classified in Papaver orientale L. with haploid chromosome number n = 14. Chemotype A had only oripavine; chemotype B contained oripavine and thebaine; chemotype C had isothebaine in addition to oripavine; chemotype D contained oripavine and alpinigenine; and chemotype E had oripavine, thebaine, and alpinigenine. In all chemotypes, oripavine was either the sole alkaloid or the single major alkaloid.


Preparation of spin-labeled opiates: morphine and codeine. The preparation of 6-spin-labeled codeine and morphine is described. Treatment of either 6-chlorocodide or 8-bromocodide with 4-amino-2,2,6,6-tetramethylpiperidino-1-oxyl free radical in dimethylformamide afforded 6-spin-labeled codeine. Similar treatment of 6-chloromorphide afforded 6-spin-labeled morphine. Exclusive formation of the 6-isomer in these reactions is explained by halide-ion-catalyzed isomerization of the 6-halo opiate to the 8-halo isomer followed by a normal SN2' displacement of the halogen. Both spin-labeled compounds displayed weak in vivo analgesic activity and did not bind appreciably to receptors in brain homogenate.


Radiochemical GLC assay for nortriptyline in human plasma. A novel method was developed for the assay of nortriptyline in plasma. After nortriptyline was extracted, it was acetylated with 3H-acetic anhydride; the quantity of 3H-acetylnortriptyline in the extract was determined by radiochemical GLC. The method is capable of assaying 5 ng of nortriptyline/ml of plasma. The instrumentation was assembled from commercially available components.


Pharmacokinetic evidence for improved ophthalmic drug delivery by reduction of instilled volume. The bioavailability of topically applied pilocarpine nitrate was studied as a function of instilled volume. As the instilled volume decreased, the fraction of dose absorbed increased. The relationship between fraction absorbed and instilled volume was not direct, but appropriate adjustment of instilled volume and concentration should permit substantial dosage reductions without sacrifice of drug concentration in the eye. The implications of these findings from both a therapeutic and toxicity standpoint are discussed.


Sulfur-containing derivatives of amphetamine: thioureas, methanesulfonamides, and trifluoromethanesulfonamides. N-Methylthiourea, methanesulfonamide, and trifluoromethanesulfonamide derivatives of amphetamine, 4-nitroamphetamine, and 4-aminoamphetamine were synthesized. The N-methylthiourea derivative of amphetamine, as well as the triethylammonium salt of the dithiocarbamate, produced significant depressor effects in normotensive dogs. N,N'-Bis(methanesulfonyl)-1-methyl-2-(4-aminophenyl)ethylamine and N-trifluoromethanesulofonyl-1-methyl-2-phenylethylamine, but not N-methanesulfonyl-1-methyl-2-phenylethylamine and N-trifluoroacetyl-1-methyl-2-(4-trifluoromethanesulfonamido-phenyl))ethylamine, showed significant antiobesity effects in rats.


Release of drugs from ointment bases II: In vitro release of benzocaine from suspension-type aqueous gels. The in vitro release of benzocaine, suspended in an aqueous gel, through silicone rubber membranes was studied to test an extension of existing mathematical models. The theoretical treatment proposed is intended for experimental systems involving release, through a non-porous membrane, of a drug whose concentration is a few times (larger than or equal to 3) greater than its solubility in the vehicle. For either micronized (2micrometer) or macrosize (125 micrometer) drug, the Q (amount released) versus t1/2 (time1/2) plots were not linear until substantial time had elapsed. Excellent agreement was found between the experimental points and theoretical plots, generated by a computer fit to experimental data of an equation derived from a reported vehicle-boundary diffusion layer model. The values of the solubility and of the diffusion layer model. The values of the solubility and of the diffusion coefficient of benzocaine in the gel, calculated by the present mathematical treatment from release data, were in agreement with literature data. The particle size of released benzocaine did not influence the release pattern, thus confirming release in the present conditions to be diffusion rather than dissolution controlled. The present method is applicable for determining the solubility and diffusion coefficient of drugs in vehicles in cases not contemplated in current release theories.


Metabolism of N-ethyl-3-piperidyl benzilate in rats. The metabolic fate of N-ethyl-3-piperidyl benzilate (I) and its potential metabolites 3-piperidyl benzilate (II), N-ethyl-3-hydroxypiperidine (III), and 3-hydroxypiperidine (IV) was studied. Incubation of I with rat liver homogenates resulted in the formation of II and III. Only a trace of unchanged drug appeared in urine after intraperitoneal injection of I. Approximately 9% of the injected dose of I was excreted in urine as III and 2% in the form of metabolites that produced III after acid hydrolysis. After intraperitoneal injection of II in rats, 18% of the dose was excreted in urine as IV. Approximately 26% of the injected dose of III was present in urine as the unchanged drug, and 63% of the dose was excreted in the urine in the form of conjugates that produced III on acid hydrolysis. Urine of rats injected with IV contained approximately 50% of the injected dose as the unchanged drug and 50% of the dose in the form of a conjugate that produced IV on acid hydrolysis. The identity of the metabolites in extracts from urine was established by GLC-mass spectrometry. It is concluded that hydrolysis was one metabolic pathway for I and II. The major routes of elimination of these compounds are not yet known and may include excretion in feces or metabolic transformations resulting in the degradation of the piperidine ring.


Effects of agitation on size distribution of particulate matter in large-volume parenterals. The particle-size distributions of six types of large-volume parenterals subjected to different degrees of agitation were determined using an automatic particle counter. Data acquired from each solution, which had been maintained in a stored condition, subjected to agitation by inverting 20 times, and then mechanically shaken for 30 min, produced a linear relationship between log N greater than D and log D. Both the slope (K) and the number of particles per milliliter exceeding 1 micrometer in diameter (N greater than 1) exhibited a dependence on the degree of agitation. Their combined effect indicates that agitation by 20 hand inversions removed particulate matter from the surface of the container, which increased the total number of particles in solution (greater than 1 micrometer) but did not significantly alter the relative size distribution. Agitation for 30 min, however, disintegrated agglomerates and produced a particle-size distribution with a greatly increased number of particles whose diameters were less than 1 micrometer and a corresponding decrease in the number of particles exceeding 1 micrometer in diameter. The particle-size distribution of a parenteral solution determined by this in situ instrumental method was, therefore, dependent upon the degree of agitation to which the parenteral was subjected prior to examination.


Comparative pharmacokinetics of coumarin anticoagulants XXV: Warfarin-ibuprofen interaction in rats. The effect of ibuprofen on the pharmacokinetics and anticoagulant action of racemic warfarin was determined in a crossover study on male Sprague-Dawley rats. At average plasma concentrations of 24-83 mg/liter, ibuprofen decreased the biological half-life and increased the total clearance of warfarin. It also increased the anticoagulant effect produced by a given plasma concentration of total (free and protein-bound) warfarin. These effects of ibuprofen appear to be a consequence of its displacing effect on warfarin in plasma.


Interrelation between two anticomplement cobra venom factors isolated from crude Naja naja cobra venom. Two moieties occurring in crude Naja naja cobra venom were found to possess anticomplement activity. Both materials possessed similar molecular weights and specific activities but dissimilar elution profiles upon ion-exchange chromatography. The anticomplement activities of these materials were maintained upon digestion with neuraminidase, and their elution profiles from cation-exchange chromatography became identical after this treatment. It was concluded that the differences between the two anticomplement materials were due to their different sialic acid contents.


Functional modification of indole binding site with indomethacin congeners. Indomethacin and four congeners were shown by equilibrium dialysis to interfere with the binding of L-tryptophan at the primary indole binding site on defatted human serum albumin. Incubation of albumin with 1-(p-bromoacetamidobenzovl)- and 1-(m-bromoacetamidobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid functionally modified this site, decreasing the availability of the site for the binding of L-tryptophan. Incubation in the presence of a large excess of L-tryptophan resulted in the partial protection of the site from modification by 1-(m-bromoacetamidobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid.


Rectal absorption of nitrofurantoin.

Rectal absorption of nitrofurantoin. The adsorption in humans of nitrofurantoin from seven suppository bases was studied using urinary excretion measurements. Rectal absorption was poorer than GI absorption. The administration of 400 mg of nitrofurantoin in a polyethylene glycol-polysorbate 80 suppository base and in a polyethylene glycol-silica suppository based provided an adequate urinary concentration of nitrofurantoin. Persons who cannot tolerate orally administered nitrofurantoin due to gastric upset could receive nitrofurantoin therapy rectally.


Determination of energy change associated with dissolution of a solid. The dissolution of a solid immersed in a solvent was considered as a consecutive process, consisting of a primary surface interaction leading to the production of a new surface at the solid-liquid interface, solvation of the solid at the interface, and transfer of the solvated solid into the bulk of the solution. The energy changes involved in each step were studied for the dissolution of m-tolylacetamide in hexane and heptane. An energy diagram was constructed according to the proposed dissolution mechanism. The heats of dissolution determined from the energy diagram agreed well with those obtained experimentally.


Absorption kinetics of procainamide in humans. Plasma procainamide concentrations following the administration of 500 mg of procainamide hydrochloride via intravenous infusion, conventional capsules, and sustained-release tablets were compared in 11 healthy male volunteers. Two-compartment open modeling of the plasma levels from the intravenous infusion experiments yielded mean Kel, k12, and k21 values of 0.0162, 0.0542, and 0.0233 min-1, respectively. The bioavailability of the oral preparations (versus intravenous) averaged 83% for the capsule and 79% for the sustained-release tablet. Calculations using a previously reported method suggested that absorption was a first-order process with mean ka's of 0.0336 and 0.0039 min-1 for the capsule and sustained-release tablet, respectively. The sustained-release formulation exhibited delayed release and adequate bioavailability.


Inhibition of catechol O-methyltransferase and transfer RNA methyltransferases by coralyne, nitidine, and related compounds. Inhibitory activity against both catechol O-methyltransferase and transfer RNA methyltransferases was observed among the antileukemic alkaloids coralyne, nitidine, and related synthetic alkoxy analogs. Inhibition of both classes of enzymes seems to have a similar profile. The role of water solubility of these compounds with regard to their enzyme inhibitory activity was noted.


Pharmaceutical applications of solid dispersion systems: X-ray diffraction and aqueous solubility studies on griseofulvin-polyethylene glycol 6000 systems. The X-ray diffraction method was used to characterize physiochemical properties of griseofulvin dispersed in polyethylene glycol 4000 and 6000. Results indicate a negligible or very limited solid solubility of griseofulvin in the pulverized solid dispersions. Pulverization and aging had pronounced effects on the X-ray diffraction spectrum. Results from aqueous solubility studies of griseofulvin in various concentrations of polyethylene glycol 6000 further indicate weak or insignificant interactions between the drug and the carrier. Mechanisms are postulated to account for the reported marked enhancement of dissolution rates and oral adsorption of griseofulvin dispersed in these carriers.


Carbon disulfide. I. The metabolism of inhaled carbon disulfide in the rat. The pharmacokinetics of inhaled carbon disulfide (CS2) vapor was evaluated in rats. Estimates of free CS2 and its nonvolatile, acid-labile metabolites (AL CS2) were made in a variety of rat tissues after an 8-hour inhalation exposure to CS2 vapor (2 mg/l of air). At the end of the exposure, all tissues examined contained appreciable amounts of the native solvent and AL CS2. Elimination of CS2 from the rat during the postexposure period was rapid and occurred primarily via the lungs. Excretion of AL CL2 occurred primarily via the kidneys and was prolonged with respect to that of free CS2. Accumulation of these metabolites upon repeated exposures and their presence in all tissues examined suggest that they may play a role in the toxicity of CS2.


The site and the mechanism of phenoxy-benzamine potentiation of the pressor response to oxytocin and vasopressin: in vivo and isolated aortic strips studies. In intact rats, alpha adrenergic receptor blocking agents, phenoxybenzamine (PBZ) and phentolamine potentiated the pressor response to oxytocin and vasopressin (VP). In the presence of PBZ or phentolamine blockade, the dose-response curves of oxytocin and VP were shifted to the left, resulting in an apparent doubling of the pressor potency of the neurohypophysial peptides. The beta adrenergic blocking agent, propranolol had no significant effect on the pressor response to oxytocin or VP. Combined PBZ and propranolol blockade did not alter the potentiating activity of PBZ. The PBZ-potentiating effect seems to be specific to the neurohypophysial peptides, since the pressor response to angiotensin was not potentiated by PBZ. The  potentiating effect of PBZ on VP could be demonstrated in isolated rat aortic strips. This clearly indicated that the site of action of PBZ is directly on the vascular smooth muscle. However, in aortic strips, the effect of PBZ was seen only if norepinephrine (NE) was also added to the bathing medium. NE alone had no significant effect on the contractile response to VP. The requirement of both PBZ and NE for the potentiating effect suggests that an interaction between these two agents is involved in the PBZ potentiation of VP response. The possibility that NE and not PBZ is the direct agent causing the potentiation of VP response is discussed.


Requirements for angiotensin tachyphylaxis in smooth muscles. The ability of angiotensin II (AII) and of seven N-terminally modified peptide analogs to induce tachyphylaxis in isolated preparations of the rat uterus and the guinea-pig ileum was found to correlate well with the degree of amino group protonation. No correlation was found between tachyphylaxis and the affinity for the rat uterus receptors, as measured by the reciprocals of ED50 values. Dissociation between the tachyphylactic property and receptor affinity in the rat uterus was also evident by lowering the calcium concentration in the medium, which resulted in increased tachyphylaxis without significant changes in ED50 values. In the guinea-pig ileum, tachyphylaxis correlated with the reciprocal of ED50, but there was a better correlation with amino group protonation. [6-Pyrazolylalanine] AII was approximately as tachyphylactic as AII in both smooth muscles studied, indicating that protonation of the histidine side-chain may not be important for the manifestation of tachyphylaxis. The recovery of the guinea-pig ileum for AII tachyphylaxis was not affected by repeated treatments with BaCl2, but it was partially impaired by [Suc1]AII, des-Asp-AII, bradykinin and histamine.


Leakage of dl-propranolol from cerebrospinal fluid to the bloodstream in the rabbit. Intracerebroventricular (i.c.v.) injection of 500 microgram of dl-propranolol in the conscious rabbit in a rise in mean arterial pressure followed by a small but significant fall (3.2 +/- 1.4 mm Hg between 2 and 4 hours after injection), as has been observed by others. The same dose injected i.v. resulted in a lowering of mean arterial pressure of 6.0 +/- 2.4 mm Hg between 2 and 4 hours after injection. After i.c.v. injection there was a rapid rise in plasma propranolol concentration. Ten minutes after i.c.v. injection the concentration of 80% of the level reached after giving the same dose i.v. After i.c.v. injection there was significant blockade of cardiac beta adrenoreceptors for at least 2 hours. This blockade was determined from the degree of attenuation of isoproterenol-induced tachycardia in rabbits subjected to presynaptic sympathetic nerve block with guanethidine and to vagal block with methscopolamine. Because of the rapid leakage of propranolol from cerebrospinal fluid to plasma it is not possible by means of the technique of i.c.v. injection of the drug to differentiate between central nervous and systemic mechanisms contributing to the lowering of blood pressure.


Epinephrine and recovery from punishment. Motor activity of adrenal demedullated and sham-operated rats was suppressed by punishing footshocks. In subsequent no-punishment sessions, the demedullates more rapidly recovered normal spontaneous activity levels. Only the rate of recovery differentiated demedullates from shams: they were equally suppressed on the day of punishment and at the beginning of the first no-punishment session. Further, spontaneous activity levels were the same in demedullates and shams which were not punished. Administration of epinephrine to the punished demedullates prevented the more rapid recovery. In intact rats, dl-propranolol and SK&F 64139 (7,8-dichloro-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride), an inhibitor of adrenal phenylethanolamine N-methyltransferase, affects recovery in the same way as demedullation. Neither phenoxybenzamine nor d-propranolol had this effect. These results suggest that epinephrine is important in modulating behavioral adaptation to aversive experiences.


Motor nerve terminal facilitatory action of SQ 20009: an inhibitor of cyclic nucleotide phosphodiesterase. Facilitatory effects of SQ 20009 [1-ethyl-4-(isopropylidenehydrazine)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid, ethyl ester, HCl] were investigated at the frog sartorious neuromuscular junction. A dose-dependent increase in miniature end-plate potential frequency occurred without changes in miniature end-plate potential amplitude. Significant increases in the amplitude and the rate of rise of the end-plate potential and reduction in the incidence of end-plate potential failures were observed in magnesium blocked muscle. The increase in end-plate potential amplitude and rate of rise appeared calcium dependent. No significant changes in passive membrane resistance or muscle membrane sensitivity to acetylcholine were observed. Twitch studies employing direct and indirect stimulation of the rat diaphragm preparation demonstrated a preferential facilitation of the indirect response rather than a direct action on the muscle fiber. The facilitatory effect of SQ 20009 on evoked and spontaneous release were of approximately equal orders of magnitude, suggesting that the drug may affect a common mechanism in the two release processes.


Effects of morphine and haloperidol on the electrical activity of rat nigrostriatal neurons. The action of opiates on electrical activity in nigrostriatal neurons was compared with the actions of known dopamine receptor agonists and antagonists in order to clarify the effects of opiates on postsynaptic dopamine receptors in the striatum. The systemic administration of either morphine or haloperidol increased the rate of spontaneous firing of neurons in substantia nigra. The injection of either drug directly into the caudate nucleus of the striatum also increased the firing rates of nigral neurons. The administration of the opiate antagonist, naloxone, blocked or reversed the action of systemically or locally applied morphine on firing rates, but not those of haloperidol. The dopamine receptor agonists, dopa and apomorphine, decreased the firing rate in nigral neurons and also reversed the stimulation of firing rates by morphine. The agonists were only partially successful in reversing the effects of haloperidol. The differences in the ability of naloxone and dopa to reverse the stimulated firing rates produced by morphine or haloperidol support the hypothesis that opiates do not act directly on the postsynaptic dopamine receptor in the striatum.


The analgesic action of baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. When administered to mice, baclofen induced dose-related antinocisponsive activity in the stretch, hot plate and tail-flick tests. Although high doses also impaired motor coordination, as measured by the rotating rod test, the following observations suggest that the pronounced antinocisponsive effect of higher doses did not reflect a reduced capacity to respond to perceived pain: motor impairment, having shorter onset of action, was fully developed before the appearance of any analgesic action; mice made completely tolerant to the motor effect were still analgesic; and other agents which severely impaired rotating rod performance did not necessarily show antinocisponsive activity in the hot plate test. The mechanism of action of baclofen is not similar to that of morphine since naloxone did not antagonize the analgesic effect of baclofen, and cross-tolerance between morphine- and baclofen-induced analgesia could not be demonstrated.


Alteration of delta 9-tetrahydrocannabinol-induced teratogenicity by stimulation and inhibition of its metabolism. Treatment of pregnant mice with delta 9-tetrahydrocannabinol (THC) significantly increased the incidence of in utero deaths. SKF-525A pretreatment increased the incidence of THC-induced in utero deaths. THC also significantly reduced the body weight of surviving fetuses. Phenobarbital treatment antagonized THC-induced reduction of fetal body weight, but did not reduce resorption rate. Administration of THC, 50 or 200 mg/kg, did not induce fetal anomalies. However, both SKF-525A and phenobarbital treatment potentiated THC-induced cleft palates. SKF-525A treatment plus THC produced 36% cleft palates. Phenobarbital treatment plus THC produced 77% cleft palates. Pretreatments altered the level of tetrahydrocannabinol plus metabolites found in plasma, placenta, fetus and amnionic fluid. In general, SKF-525A increased levels and phenobarbital decreased levels. Two chemically reactive metabolites of THC are proposed, 9,10-epoxyhexahydrocannabinol and an 11-oxo derivative. SKF-525A pretreatment increased the concentration of both of these metabolites. Phenobarbital treatment increased the levels of the proposed 9,10-epoxyhexahydrocannabinol. Possible covalent binding of THC was observed. An active metabolite theory may apply to the teratogenic properties of THC.


[Morphological, cytological, and biochemical changes of Anguilla anguilla L. gills deprived of Stannius corpuscles (S. C.) (author's transl)]. In the silver female eel (Anguilla anguilla L.) maintained in fresh water, surgical removal of Stannius corpuscles (SC) resulted in: a) A significant increase of wet weight of gill cells and the dry weight of gill filaments expressed as function of body weight. b) A proliferation and a hypertrophy of chloride cells shown by a significant rise of cell volume expressed as a precentage of the epithelial volume. c) An increase of the calcium (Ca) binding protein activity in the total branchial mucosa. These modifications are not observed when eels are maintained in Ca-free water. The results are discussed in relation to the Ca fluxes across gills in eels deprived of SC and gill morphological changes during sea water adaptation.


Determination of the biliary tree capacity of the rat in its distended and nondistended state using 35 S-sulfobromophtalein glutathione (35 S-BSP-GSH) as a marker. The biliary tree capacity of the rat in its nondistended and distended state has been previously determined as the volume of bile collected between the time of intravenous injection of a marker substance and the time at which the concentration of this marker in bile reached one-half maximal excretion rate. 1. According to this procedure modified methods are presented in this study using 35S-sulfobromophthalein glutathione as a test substance for the calculation of both the normal and the distended biliary tree. These approaches are based on the assumption that first measurable radioactivity, which follows the intravenous administration of the dye (most probably with no or only very little delay) indicates the time of appearance of the injected marker in the right and left hepatic duct. 2. The measured nondistended capacities are much smaller in comparison to those reported up until now. 3. The distended biliary tree was determined in two different ways. In one set of experiments, 35S-sulfobromophthalein glutathione was injected intravenously 2-3 sec, in another set 60 set, before termination of a 15 min biliary obstruction. The latter procedure was introduced to avoid transit time problems. Both experimental conditions revealed significantly different values for the distended state (69.8 +/- 7.1 vs. 56.9 +/- 6.7 microliter/rat liver).


Enhanced non-electrolyte uptake in vitro by the dog jejunal mucosa in the cholera-toxin-induced secretory phase. A characteristic secretory response in the dog jejunumis observed following three hours' perfusion with cholera toxin. When this mucosa in the secretory phase is examined in vitro, the steady-state accumulation of phenylalanine and beta-methyl-glucoside is considerably enhanced. Since the initial rates of influx of these substrates are unchanged and the tissue ion contents are the same as normal, it is concluded that the increase in steady-state uptake may be attributed to a change in the rate of efflux of the substrates across the baso-lateral membrane of the cell. This change might be related to the reported collapse of the intercellular channels when the intestine is in a secretory state.


Nursing home patients' perception of nurses' affective touching. Within a sample of 99 elderly white patients in two nursing homes, E used the Comfort when Touched Inventory to measure Ss' perception of comfort-discomfort from affective touching by white nurses, and investigated the relationship of inconsistencies in perception to sex, age, and care classification. Results from alpha factor analysis with varimax rotation suggested that S would most likely perceive discomfort if an older male nurse affectively touched S; if a male nurse touched or held S's hand; or if a nurse, male or female, placed his/her arm around S's shoulders. Results from correlation procedures suggested that inconsistencies in perception were related only to sex; female Ss more than male Ss were likely to perceive discomfort from affective touching by nurses, especially if the nurse was a male.


Situational effects on the identification of emotions in children. Naive judges were asked to observe infants independently and judge their emotions at 5 sec intervals under three different conditions. Two experiments were conducted to produce the different conditions. In Experiment I, 9- and 12-month-old infants of both sexes (N = 40) were exposed to a series of situations each designed to provoke a specific emotion (Condition 1). Although the judges were not informed as to which emotion each situation sought to provoke, one may assume that they received clues from the situations themselves. In Experiment II, 13- to 17-month-old infants of both sexes (N = 16) were individually placed on a large table (8' X 6') on which they could explore or play in the presence of their mothers (Condition 2). The judges were tota-ly without guidelines as to what emotion to expect. For Condition 3 in the same experiment the table was transformed into a visual cliff, and the judges were told that the generally expected emotion was fear. The judges reached significant agreement for the emotions of interest and anger in Conditions 1, 2, and 3; for distress only in Condition 1; for joy only in Condition 3; and no agreement for fear in any condition.


Sex chromosome abnormalities and cognitive performance: III. Field dependence, frame dependence, and failing development of perceptual stability in girls with Turner's syndrome. The Rod-and-Frame Test (RFT) was administered to Turner girls (N = 45), their normal sisters (N = 19), and to nonsiblings with primary amenorrhoea and growth retardation as seen in Turner girls (N = 15). The test was scored by the traditional method which gives a measure of field dependence, as well as by a new method that gives a measure of frame dependence and response inconsistency. The traditional method showed Turner girls to be extremely field dependent. The new method showed that the so-called field dependence in Turner girls was due to response inconsistency, rather than to significant frame dependence. It is concluded that response inconsistency is a characteristic of RFT performance in Turner girls, probably reflecting failing development of "perceptual stability".