[Effect of the contraction of other muscle groups on muscle strength, latency period and endurance].

The following investigation was undertaken in connection with Sechenov's idea on mutual influence of muscles performing different work. It deals with the influence on test muscle (TM) efficiency of other simultaneously working muscles (SWM). It was shown that tension of SWM or maintenance of complex postures exert a negative influence on the force and latency of the visual-motor reaction and the static effort endurance. The mechanism involved is external inhibition. After its extinction as a result of repeated combinations of both activities the degree of lowering of TM activity grows less and finally its improvement is observed as compared to data obtained in the absence of SWM contractions. It is suggested that when external inhibition is extinguished impulses arising in SWM reinforce and improve according to the law of dominant the functions of nervous centers regulating activities of the TM.


["Inhibition of inhibition" in neurons of the cerebral cortex].

Light flashes and single electrical stimuli applied to the nucleus ventro-posterolateralis and to the LGB evoked protracted IPSPs in visual and sensorimotor cortical neurons respectively. High-frequency stimulation of the midbrain RF suppressed these IPSPs which was manifested in a shortening of the inhibitory pause and in a decrease in the amplitude of the IPSPs up to their complete elimination (disinhibition). Activation of noradrenergic pathways by stimuli applied to the locus coeruleus or to the lateral hypothalamus led to the same result. The suppression of cortical IPSPs followed by facilitation of cortical unit firing in response to thalamic or peripheral stimulation seems to be an imprortant mechanism underlying arousal.


[Bilateral motor cortex effects on interneurons of the ventral horn of the lumbar segments].

The ventral horn interneurons in the spinal cord L6-7 segments were recorded in anesthetized cats during stimulation of the pericruciate cortex of both cerebral hemispheres. The majority of ventral interneurons are activated by volleys from the contralateral motor cortex and nearly half of them--by volleys from the ipsilateral cortex as well. Two kinds of firing patterns occurred: separate spikes and bursts of spikes. The latency of the 1st type firing was significantly greater than that of the 2nd one. There was a close relation of convergence of the afferent and corticospinal volleys on ventral horn interneurons: neurons activated by ipsilateral afferents only received synaptic influence only from the contralateral motor cortex whereas neurons with ipsilateral as well as contralateral inputs were activated by corticospinal volleys from both hemispheres. The interneurons with bilateral segmental and supraspinal connections seem to be involved in integrative action as important elements of the neuronal mechanism of bilateral motor coordination.


[Correlation between nonspecific and specific excitation in the cat somatosensory cortex during different modalities of stimulation].

Multiunit activity and EEG recorded with the same electrode from the somatosensory cortex in unrestrained cats, were compared. The obviously identical patterns of the EEG activation coincided with different multiunit patterns (acceleration or deceleration of frequency, modification of discharge order) depending on the stimulus modality (somatic, acoustic, direct RF stimulation) and on the foregoing background impulsation. This suggests that the EEG activation, although being basically unspecific, has specific features. The sensory information, apart from the known forms, seems to be coded in the form of diverse modes of functional activity of a neuronal population localized in a brain structure.


[Motor components of "caudate arrest"].

In chronic experiments on 4 defense-conditioned dogs maintaining a certain posture, the analysis of motor components of the "caudate arrest" (induced by high-frequency stimulation of the caudate nucleus) and their comparison with the characteristics of the myographic and motor components of normal cessation of the legs (i. e. in absence of the conditioning signal), showed the "caudate arrest" not to be a model for arrest of a voluntary movement. The caudate nucleus seems not to be involved structurally in the instrumental defense response but to belong to a parallel system controlling all stages of the response.


[Activity of several the mediator systems of the brain during hyperbaric oxygenation].

Dynamics of noradrenalin, adrenalin, dipeptide homocarnosine, GABA, hystidine, MAO activity (with noradrenalin as substrate), and homocarnosincarnosinsynthetase in the rat brain under hyperbaroxygenation, was studied. Exposure of the rats to 4 atm of oxygen for 1 hr leads to the 70--80% decrease of noradrenalin content in all brain areas. Adrenalin level does not change. MAO activity increases in hypothalamus remaining at the control level in cortex, decreases significantly in medulla oblongata, and complete inhibition of the enzyme activity occurs in the midbrain. The hyperbaric conditions cause no considerable changes in homocarnosine, GABA, and hystidine levels in all the areas under study. A profound decrease of homocarnosine content and inhibition of homocarnosine--carnosinesynthetase follows the convulsive phase of oxygen intoxication especially in the midbrain (69.9% and 50.3%, resp.).


[Mediator liberation at the neuromuscular junctions of rhythmically stimulated frog sartorius muscles].

Synapses of large fibers seem to have a more obvious initial increase followed by a greater decrease in quantum content (m) of EPPs than the small fibers. The total amount of neurotransmitter released during EPPs reproduction was much greater in the large fibres. The calculation of binomial parameters of transmitter release showed that n parameter repeated the dynamics of m, while the P parameter gradually increased. The initial uptake of P and increase of n was more obvious in verve endings of the large muscle fibres. The findings suggest an unequal length of synaptic contact.


[Convergence of corticofugal impulse projections onto superior colliculus neurons].

In unanesthetized immobilized cats, 82.75% of tectal neurons responded to direct electrical stimulation of different cortical areas. Stimulation of the associative and visual cortex was the most effective. On simultaneous presentation of light and electrical stimuli, facilitation of responses of the collicular neurons was prevalent. The role of striatal and extrastriatal effects of neocortex as well as the regularities of integration of retinotectal and corticofugal afferents upon the neurons of anterior colliculus, are discussed.


[Influence of the sympathetic nervous system on the electrical activity of the neuronally isolated cerebral cortex].

Bilateral transection of the pregangiolinic sympathetic cervical fibers and electrical stimulation of ipsilateral cranial and of the cervical sympathetic nerve originated reactions differing in strength and latency in intact hemisphere and in neuronally isolated neocortex, but having common origin mainly due to changes in the capacities of the delta--and theta--potentials. The direct nervous influences on electrical activity of the neuronally isolated neocortex through sympathetic fibers passing along the blood vessels, seems to be insufficient.


[Effect of inhibitors of the active transport of ions on the spontaneous and evoked electrical activity of parenchymal mammary gland receptors].

In the potassium-free saline spontaneous activity of the mammary gland parenchyma receptor increased within first 30--40 min., then decreased and, finally, ceased. Sensitivity of the receptor to the mechanical stimuli decreased gradually. After washing in normal saline the evoked and spontaneous activities recovered. Ouabain (5 . 10(-5)--10(-4) g/ml) exerted an effect similar to that of the potassium--free solution except that the impulse activity could not be restored by the washing in physiological saline.


[Arterial pressure responses to stretch and contraction of the gastrocnemius during stepwise interruption of its connections to the body].

In anesthetized cats, the pressoreaction of arterial pressure to stretch with weight of 3--4 kg and to contraction of the m. gastrocnemius due to direct 6--10--threshold electrical stimulation 50/sec, occurred due to reflex from the muscle receptors in 92--93%. 80--82% of the reaction was due to the afferents of the ischiatic nerve, and 11--12% to the afferents of vascular plexus. 7--8% were due to the blood outflow from the muscle and was unrelated to the stimulation.


[Role of adreno- and cholinoreactive structures of the hypothalamus in regulating blood coagulation and maintaining it in a fluid state].

Electrical stimulation of anterior and lateral hypothalamus as well as acetylcholin injection into the same areas activated the anticoagulating blood system whereas adrenaline injections activated the coagulating system. The electrical stimulation with certain parameters seems to involve cholinoreactive structures of the hypothalamus, shifting the blood potential towards hypocoagulation. The sitmulation of the paraventricular and ventromedial hypothalamic nuclei with the same current activated the blood coagulating system whereas stimulation of the preoptic lateral or medial areas, medial supraoptic nucleus of the hypothalamus induced no changes in the homeostatic system. The data obtained suggest that the regulation of the blood anticoagulating system involves the anterior hypothalamic area, the suprachiazmatic nucleus, and the rostral part of the lateral hypothalamic area.


[Effect of inspiratory resistance loading on temporal parameters of respiration in anesthetized cats].

In anesthetized cats, an increase in inspiratory resistance in conditions of growing hypercapnia entailed elongation of inspiration and of the whole respiratory cycle, as well as decrease of the volume threshold for cessation of inspiration. The latter occurred after bilateral vagotomy too, whereas no significant changes of the temporal parameters followed the increase in the resistance. The temporal rearrangements of the respiratory cycle seem to be due to the vagal effects, while the extravagal influences, probably the reflexes from the stretch receptors of intercostal muscles, are responsible for changes of the volume component in the relations characterizing the mechanism of cessation of inspiration.


[Glycerinized models of enterocytes and several of their properties].

The method for the preparation of glycerol-treated models of the enterocytes with preserved membrane has been described. Using such a simplified model of the enterocyte suspension allows membrane digestion and enzyme properties to be studied. Moreover, preserving the important properties of the native isolated cells the glycerol-treated enterocytes have a number of essential advantages as compared with other known preparations of the small intestinal mucosa. Some characteristics of the glycerol-treated models of the enterocytes have been described in the paper.


In vivo activity of spleen cells from untreated syngeneic mice against Ehrlich ascites carcinoma.

Inbred CFW/L1 or BALB/c male mice were injected intraperitoneally with 1 X 10(5) EAC cells. They died in 98.6 or 100%, respectively, within 100 days of observation. Intraperitoneal injection of 6 X 10(7) syngeneic spleen cells from 6--9-week-old CFW/L1 or BALB/c donors 2.5--4 h after tumour inoculation significantly prolonged MST and 16.7 or 23.5% of mice, respectively, survived for 100 days. Smaller amounts of spleen cells, thymus cells, mixed spleen and thymus cells, or spleen cells from older donors did not show this effect. Homogenized spleen cells were also inactive. Antitumour activity of spleen cells was still evident when they were isolated from irradiated (2 000R) donors or were given 24 h after tumour inoculation. Spleen cells used for in vivo studies showed spontaneous cytotoxic activity in vitro against EAC cells in the 51Cr-release cell-mediated cytotoxicity test. The possible participation of NK cells in the observed in vivo antitumour activity of normal spleen cells is discussed.


Norway rat haemoglobin phenotypes: which is the original?

On the basis of the incidence of haemoglobin alleles in different populations of rats, the hypothesis is discussed that the HbbB is phylogenetically "older".


The frequency of chromosomal aberrations in long-term irradiated mice and rats.

The frequency of chromosomal aberrations was studied in myelokaryocytes of mice and rats continuously irradiated for 90 days at a dose rate of 50R/day. The curves expressing the frequency of chromosomal aberrations in continuously irradiated mice and rats are biphasic. The first phase is similar for the two species and is characterized by an increase in the frequency of cells with chromosomal aberrations. In the second phase, the frequency of cells with chromosomal aberrations had stabilized at a level of 25--28% in rats, and in mice the values of aberrant cells were gradually increasing until the end of irradiation when they reached 40.1%. In contrast to it, the distribution of aberrations of the chromatid and chromosomal types did not change throughout the experiment in both animal species.


[Dermatoses provoked by opportunistic fungi].

In my exposé I confined myself to the moulds. Generally speaking, there are two groups of fungi. One group that often provokes diseases in otherwise normal subjects (fungi of parasitic-pathogenic character) and a second group that causes diseases in cases of lowered immunobiological resistance (fungi of saprophytic-opportunistic character). Though the biological conditions of the host are important, they are by no means the only prerequisites for the development of a mycosis. Just as important are the enzymatic qualities of the fungus. Ubiquitous moulds can become opportunists and provoke dermatoses under two conditions: (1) The fungus must possess keratolytic capabilities (2) its penetration and growth must be preceded by a lesion due to trauma, or bacterial or viral infection.


[Research of keratinophiles in the soil and their effects on human cutaneous pathology in the Lyons area].

Between 1967 and 1977, the systematic research of keratinophiles of the ground in a radius of 30--50 km around Lyon, has shown the ubiquitarian predominance of Microsporum nanum, which is probably the most ancient occupant of the ground. The most intensive areas of human and animal occupation in the Rhodanian tract show the predominance of Microsporum gypseum, which is scarcely found in man. Sporadic localizations, tightly limites, bound to cirulcation axes and international gathering, let us detect Microsporum cookei, Trichophyton verrucosum, Trichophyton mentagrophytes, Chrysosporium keratinophilum, and Keratinomyces ajelloi. However, in the last years, a progressive extension of recently imported kinds and a decrease in native kinds appears to have occurred.


[Otomycoses].

Otomycosis is a relatively frequent disorder (21.7% of the cases of external otitis) of fungi origin. Otomycoses can be discriminated from bacterial otitis by the following symptoms: itching, absence of otalgy, discharge and negative response to different local antibiotic therapies. Our study involves 148 cases of otomycosis and their therapy. Recovery was obtained in approximately 10 days.


[Phycomycoses].

Phycomycoses are opportunistic fungal diseases as far as mucormycosis is concerned, but for basidiobolomycosis and entomophthoromycosis, the adjective 'opportunistic' should be used with caution. Mucormycosis assumes cranial, pulmonary, gastrointestinal, disseminated, cutaneous and focal forms: the infection nearly always develops in a person whose resistance is lowered by a metabolic disorder, a blood dyscrasia, corticosteroid or immunodepressive therapy. It is a frequent complication in leukemia or diabetic acidosis. Basidiobolomycosis and entomophtoromycosis are caused by fungi which belong to the order, Entomophthorales. They are characterized in tissue by broad hyphae which are surrounded by eosinophilic material. These mycoses are treated by potassium iodide.


[Therapy of opportunistic mycoses].

The author presents the drugs that are available for the treatment of opportunistic mycoses: amphotericin B, nystatin, 5-fluorocytosine, miconazole and the newest imidazole derivative econazole. He presents his experience with econazole in 4 cases with deep mycoses. He speaks of the mode of application and the therapeutical limits of these products as well as of the favorable factors and the prophylactic measures to be taken.


[Parasitic adaptation phenomena of pathogenic fungi in human and veterinary medicine].

The pathogen species involved in medical and veterinary mycology can be divided into three categories according to their level of increasing adaptation to parasitism. Only the third category includes a few species (some dermatophytes) which can be regarded as genuine parasites. The opportunistic fungi belong to the first or the first two the third categories according to the given definition. The various possible factors of preadaptation or adaptation to parasitic life (physical factors, biochemical factors, avoidance of the immunological pressure and ecological factors) are discussed. Except for the species belonging to the first category the probably are efficient only if the host does not react normally.


[Opportunism in dermatophytes].

Dematophytes invade hosts when their state is suitable for the production of their pathogenicity. When the host's resistance is reduced, the prevalence of dermatophytoses can be extremely high or the symptomatology can be very unusual. It is suspected that the 'maladie dermatophytique' and pherhaps dermatophytic mycetoma develop in such situations. The fact is that the behaviour of dermatophytes does not differ from that of the so-called opportunistic fungi and in some cases it is possible to speak of dermatophytic asthenomycosis.


[Soil as a reservoir of opportunistic mycostic agents].

We studied the soil as a reservoir of vegetable detritus, keratinous materials of birds, terrestrial animals and micro-organisms. In the last group we can mention the bacteria and fungi. We classified the opportunistic fungi in three groups: (1) parasites of plants or growing on the vegetable detritus; (2) geophylic dermatophytes; (3) pathogenic fungi that in some cases behave like opportunistic ones. In each group we studied the opportunistic fungi of the soil, their relations with it chemical and physical composition, the mycoflora and the role of animal habitats.


[Alimentary nickel and contact eczema (author's transl)].

By atomic absorption spectrometry, nickel was analysed in many foodstuffs. The results of these determinations are given in detail. Nickel present in vegetables comes primarily from the soil but secondarily from stainless-steel cooking utensils.


[Ultrastructure of epidermolyses with junctional blister formation (author's transl)].

Junctional blister formation is the common feature of four clinically different types of inherited epidermolyses with atrophies but lack of scarring which, as a group, have been termed epidermolysis bullosa atrophicans. The Herlitz type is the most common one among them. Based on a material of 24 cases aged 2 days to 42 years at the time of biopsy, ultrastructural data on the pathomorphogenesis are reported. Blisters form in the dermo-epidermal junction area between the basal lamina and the basal cell plasma membrane. A well-developed basal lamina-anchoring fibrils complex covers the blister floor. Hypoplasia of hemidesmosomes precedes blister formation and is a constant finding in intact junction area without any other signs of disturbances. It is, therefore, regarded as a causal factor in the pathogenesis. Nail loss as a result of junctional separation within the nail bed, secondary changes in older blisters and formation of slowly healing granulation tissues are also reported.--Early diagnosis is made available by electron microscopy as shown in out early childhood cases. Genes coding for junctional epidermolyses seem to be far more frequent than those coding for the scarring or dystrophic types.


[Delayed hypersensitivity against staphylococcal antigens in guinea pigs (author's transl)].

Delayed type hypersensitivity against staphylococcal antigens could be induced in guinea pigs by injecting the animals with a staphylococcal homogenate in Freund's adjuvant in all four foot pads and the nuchal skin. Maximal skin reactivity, tested intracutaneously, was observed 21 days after sensitization. Highest stimulation of lymph node cells and peripheral blood lymphocytes was also obtained 21 days after sensitization. When comparing cell walls, cell materials (nonsoluble material obtained after the separation of the cell wall fraction) and soluble fraction (obtained after sedimentation of all nonsoluble material, the strongest skin test reactions occurred after testing intracutaneously with the cell wall fraction.


[Clinic and treatment of porphyria cutanea tarda (author's transl)].

Symptomatology and pathogenesis of porphyria cutanea tarda (PCT) are shortly reviewed. The different possibilities in the treatment of PCT are discussed with special reference to the phlebotomy according to Ippen and to the chloroquine administration according to the regimen described by Kordac and Semradova in 1974. 75 PCT patients were treated with chloroquine (Resochin, Nivaquine). After 9.3 +/- 3.4 months (means +/- SE) all patients excreted normal amounts of porphyrins, and the clinical symptoms disappeared. 14 of these patients relapsed after a mean period of 21 months after the withdrawal of chloroquine.


[Clinical aspects of epidermolyses with junctional blister formation (author's transl)].

The clinical symptomatology of epidermolysis bullosa atrophicans generalisata gravis (Herlitz' disease), epidermolysis bullosa atrophicans generalisata mitis (typus Disentis) and epidermolysis bullosa atrophicans localisata is described. These types belong to the non-scarring epidermolyses and show ultrastructurally junctional blistering.


Biological correlates of piracetam clinical effects in psychotic patients.

The purpose of this controlled clinical trial was to demonstrate possible correlations between changes in bioenergetic metabolism and psychotropic drug administration in the treatment of functional psychosis. The study included twenty-six patients, eleven with schizophrenia, three with chronic atypical depression and twelve with drug-resistant endogenous depressions. All patients were kept on continuous psychotropic medication for at least 3 weeks before starting the trial, and piracetam was given additionally in a fixed dosage of 2400 mg daily; the same number of identical capsules was given during the pre- and post-treatment placebo periods. Psycho-pathological evaluation of the patients was by the BPRS; clinical and biochemical data were evaluated statistically by the analysis of regression. The results show that in schizophrenic patients an improvement was observed in those cases who had improved biochemically, i.e. where the ATP values had increased. In drug-resistant depressions there was a rapid and significant clinical improvement after piracetam co-administration, and this went in step with a significant rise in ATP levels.


Multicentre general practitioner assessment of 'Tenormin' and methyldopa.

A large scale study in general practice was set up to investigate the effects of transferring hypertensive patients from treatment with usually less than 1 g daily of methyldopa to atenolol ('Tenormin') 100 mg daily. The results demonstrate an improvement in blood pressure control with atenolol treatment and a reduction in the incidence of side-effects. The simple dosage regime, combined with proven effectiveness and a relative lack of side-effects makes atenolol a useful treatment for the hypertensive patient.


Insulin requirements in diabetic patients treated with sulphinpyrazone.

Forty-one adult diabetic patients of either sex who had been controlled by insulin alone for at least one year were randomly allocated in a double-blind, between-patient study, to either sulphinpyrazone (600--800 mg daily) or an identnd at the end of it, no clinically or statistically significant change of the insulin needs of the patients was observed. It is concluded that no clinical interaction occurs between sulphinpyrazone (800 mg/day or 600 mg/day) and insulin when they are administered simultaneously for long periods. In the doses used the tolerability of sulphinpyrazone was very good.


Effect of glucocorticoid levels in vivo on growth hormone biosynthesis.

The rate of growth hormone (GH) biosynthesis in pituitary cells prepared from rats with different histories of glucocorticoid exposure was analyzed by a dual-labeling acrylamide-gel technique. Glucocorticoid deficiency, produced by adrenalectomy, reduces GH synthesis by approximately 50%. GH synthesis adrenalectomized rats treated with either natural or synthetic glucocorticoids, is restored to normal or above normal levels. Acute exposure (1 h) of cells to corticosterone in vitro does not produce a significant increase in GH synthesis. Adrenalectomized rats treated with steroid for one day show a small but detectable increase in GH synthesis, while treatment for 3--6 days results in progressively larger stimulatory effects. All of these results are similar to previous findings regarding glucocorticoid stimulation of GH synthesis in vitro.


Ecdysone 20-monooxygenase: characterization of an insect cytochrome p-450 dependent steroid hydroxylase.

Ecdysone 20-monooxygenase, the enzyme system that hydroxylates ecdysone at C-20 of the side-chain to form ecdysterone, has been characterized in the fat body of early last instar larvae of the tobacco hornworm, Manduca sexta, using a radioenzymological assay. Ecdysterone was demonstrated to be the product of the enzyme system by high-pressure liquid chromatography, gas-liquid chromatography and mass spectrometry. Differential centrifugation, sucrose-gradient centrifugation, electron microscopy and organelle-marker enzyme analysis revealed that ecdysone 20-monooxygenase activity is associated with the mitochondria. The enzymatic properties of ecdysone 20-monooxygenase are that it is most active in a 0.05 M phosphate buffer, is inhibited by Mg2+ and exhibits pH and temperature optima at 7.5 and 30 degrees C, respectively. The enzyme complex has an apparent Km for ecdysone of 1.60 x 10(-7) M and is competitively inhibited by its product, ecdysterone, with an apparent Ki of 2.72 x 10(-5) M. The cytochrome P-450 nature of this insect steroid hydroxylase was initially suggested by its obligate requirement for NADPH and its inhibition by carbon monoxide, p-chloromercuribenzoate, metyrapone and p-aminoglutethimide but not by cyanide. Difference spectroscopy revealed the presence of cytochrome P-450 in the fat-body mitochondrial fraction. A photochemical action spectrum of ecdysone 20-monooxygenase activity confirmed the involvement of cytochrome P-450 in this monooxygenase system.


Ontogeny of maternal behavior in the laboratory rat: early origins in 18- to 27-day-old young.

The responses of unweaned juveniles, 18 to 27 days of age, in brief tests with pups younger than 10 days were observed during initial exposure and at 4-6-day intervals. They showed no aversive responses and actively sought contact with the pups until 24 days when contact-seeking declined sharply. Young exposed to pups before 24 days continued to seek contact with them after 24 days showing an effect of the prior experience. Juveniles given a choice between young pups and a warm bowl chose the pups; given a choice between young pups and age mates, they chose the young pups until day 23, but chose the age mates after then. When housed continuously with young pups at 22 days of age, 5 of 9 retrieved and grouped pups with a latency of 1 day. Our results indicate that timidity or fear of novelty develops in rats in this situation about Day 24 and thereafter is a factor inhibiting the expression of positive social behavior toward pups.


Ontogeny of maternal behavior in the laboratory rat: factors underlying changes in responsiveness from 30 to 90 days.

Male and female rats that were nonhandled or that were handled from weaning, and that had intact or impaired olfaction (intranasal zinc sulfate), were sensitized through continuous pup exposure commencing at 30, 45, 60, or 90 days of age. Nonhandled males and females were alike in latencies to become maternal at Day 30 but thereafter latencies of females became shorter and latencies of males lengthened; by 90 days males had markedly longer latencies than females and only 1/3 became maternal. Handling facilitated sensitization at 30 days among males and females but only among males at 45 and 60 days. Intranasal zinc sulfate reduced latencies of both males and females at all ages tested, but appeared most effective after 45 days of age. Gender differences in latencies persisted in adult animals even after combined treatments. Results indicate that both timidity and olfaction inhibit the onset of maternal responses to pups in virgin males and females, but they differ in relative importance by age and gender.


Ontogeny of ultradian and nocturnal activity rhythms in the isolated albino rat.

The activity of isolated rats from 6 to 25 days of age was analyzed at 10-min intervals. Ultradian peak activity rhythms, with a rough 1-2-hr periodicity, developed between 9 and 12 days of age, and reached an extreme at 15 days. Ultradian periods of attenuated activity were however detectable even in 6-day-olds. Isolated rats at 15 days of age displayed greatly accentuated profiles characterized not only by heightened activity levels, but by an extreme cyclicity. These subjects spent most of their time oscillating between periods of marked activity and marked inactivity. Both the average and total duration of these extreme periods were greater in 15-day-olds than any of the other ages. Free-running nocturnal activity rhythms were also observed to develop in isolated rats tested in continuous darkness by the 15th day.


Approach and departure patterns generated in the domestic chick by intermittent white light.

Newly hatched domestic chicks were given extended free access to 7 rates of intermittent white light between .5 and 24 flashes per sec. Inspection of the data showed approaches and departures directed toward the light that increased in number and formed an orderly pattern as the rates neared 4 per sec and as the chicks exposed to this rate became older. Also, no differences were found in the amount of time chicks remained next to the various rates during each approach but only in the amount of time they remained away during each departure. The bearing of these results on the proposal that flicker phototaxis might stem from the neural excitation produced through photic driving was discussed along with relating further evidence to recent work in imprinting.


Postnatal undernutrition in rats: attempts to develop alternative methods to food deprive pups without maternal behavioral alteration.

Two methods were investigated as attempts to undernourish rat pups without the disturbances in maternal behavior that accompany the procedures used to date for this purpose. In the 1st method, a litter of 12 pups was raised by both a lactating mother and a "sensitized" female. The sensitized female was provided under the assumption that she could correct for the deficit in maternal care when 1 mother raises a large litter. The results showed that the pups raised by the 2 females were constantly removed by the females from each other's nests; the females engaged in constant fighting and showed altered maternal behavior. As a consequence the pups lost more weight than control underfed young. The 2nd method consisted of removing 6-8 nipples from virgin females which were mated 10 days later. After delivery these females raised litters of 6 pups. Their maternal behavior was equal to that of unoperated controls, and at weaning the pups had 20-50% less body weight. This method could be useful to study undernutrition effects on behavior, without confounding experimental variables.


The effect of visual deprivation on pattern recognition in the rat.

In 2 experiments the performances of light-reared (LR) and dark-reared (DR) 90-day-old rats were compared on a variety of transfer tests following acquisition of 3 pattern discriminations. Significant differences due to rearing condition were found in performance on a discrimination involving horizontal separations between pairs of vertical contours. No such differences due to rearing were observed during either acquisition or transfer testing of a discrimination involving pairs of mirror image oblique contours. Significant differences due to rearing were observed in acquisition of a discrimination between a checkerboard pattern and a similar pattern containing an irregularity and in performance on a subsequent series of transfer tests. The results suggest that the spatial integration necessary to discriminate basic as well as complex relational properties between linear elements involves mechanisms which require experience for their development and maintenance.


Deficits in fixed-interval performance following prenatal and postnatal lead exposure.

Female rats were exposed daily to 750 mg/kg of lead acetate via a restricted watering schedule for 70-80 days prior to mating and then throughout pregnancy and nursing. At weaning, litters from half of the lead dams were placed directly on treatment for the duration of the experiment. These manipulations yielded 3 groups: Group Pb/Pb, offspring exposed during pre- and postweaning  periods; Group Pb/C, offspring exposed only during preweaning periods: and Group C/C, control offspring. Beginning at 42-49 days of age, postnatal, offspring were shaped to bar press under a fixed-interval, 1-min schedule (FI1) and then given 20 sessions, each 45 min in length. Analyses revealed that Group Pb/Pb received fewere reinforcements across sessions than the other 2 groups, which did not differ. However, when the Pb/Pb offspring did receive reinforcement, they exhibited the scalloped pattern of responding characteristic of fixed-interval schedules.


Long-term effects of preweaning taurine injections in rats: interactions with strain and gender.

A comparison was made of MR, MNR, and RCA strains that had been injected with either 62.5 mg/kg of taurine or comparable volumes of physiological saline between postnatal Days 8 and 20 and later tested at 100 days of age in an open field and 1-way shock avoidance situations. Taurine-injected rats displayed significant elevation in defecation score in the open field. In addition a significant Treatment X Strain interaction was due to the larger defecation numbers displayed by the taurine-injected MR rats relative to the saline-injected MR rats.


Ontogenesis of human brainstem evoked potential amplitude.

Brainstem evoked potentials (BEP's) were studied in human subjects ranging in age from birth to adulthood. The BEP's were recorded from the surface of the scalp referenced to either ear while brief clicks were delivered binaurally through earphones. Separate analyses of variance were computed for the peak-to-peak amplitude of each component of the BEP. Significant age effects were observed documenting the strong relationship between human brainstem development and amplitude changes in the BEP. The independent maturation of these structures was reflected by the significant interaction between age and peaks. Despite small fluctuations in the maturational curve of each peak, strong linear and quadratic trends were apparent. The research presented here provides evidence of significant amplitude changes in the BEP accompanying human development. These findings indicate that brainstem maturation is not yet complete at birth and that the components believed to represent spatially separate generators in the auditory system show distinct maturational stages.


Ontogenetic study of the Miwh gene in mice.

Ontogenetic and adult behavioral tests were conducted on an extreme non-agouti strain of mice carrying the Miwh mutation. Except for startle response, no significant differences were seen in any aspect of the preweaning reflex and neuromuscular tests. The lack of startle response seen in Miwh/Miwh and Miwh/+ mice can be attributed to abnormalities found in the inner ear of these genotypes. Among adult mice, significant differences were found in the open field and visual cliff tests.


Studies of insulin binding in children using human erythrocytes in small amounts of blood.

We have demonstrated specific insulin binding by the erythrocytes (RBCs) of children. Complete binding studies were done using as little as 5 ml of blood. The receptors exhibited competition-inhibition curves and nonlinear Scatchard plots similar to those reported for insulin target tissues, such as the hepatocyte and the adipocyte. Compared with those from adults, the RBCs from children had significantly greater numbers of insulin receptors per cell (P less than 0.05). The total insulin bound by the RBCs from both children and adults, however, was not different over the physiologic range of insulin concentrations. Cord blood RBCs showed greater numbers of receptors per cell than did those from either children or adults; however, the affinity for insulin was similar in both groups. The total amount of insulin bound by cord blood was significantly greater than that in either children (P less than 0.01) or adults (P less than 0.05) over the physiologic range of insulin concentrations. The method used to measure insulin binding by erythrocytes and relatively little intra- and interassay variability, and there was little diurnal variation in binding. Storage of heparinized blood at 4 degree C for 24--36 h had no effect on insulin binding by the RBCs. We conclude that the measurement of insulin binding by RBCs from small volumes of blood may be particularly useful in the study of infants and children with disorders of carbohydrate metabolism to elucidate the role, if any, of abnormal receptor function in their condition.


Serum protein-bound hexose in diabetes: the effect of glycemic control.

To determine whether the carbohydrate content of serum proteins is related to overall glycemic control, we studied serum protein-bound hexose and glycosylated hemoglobin [HbA1(a+b+c)] in 37 ambulant diabetic patients and 32 nondiabetic controls. Protein-bound hexose was correlated with HbA1(a+b+c) in the diabetic patients (r = 0.36, P less than 0.025). The mean protein-bound hexose level of the diabetic patients was greater than that of the controls (190.8 versus 174.7 mg/dl, P less than 0.01), but diabetic patients with HbA1(a+b+c) less than 12% had a mean protein-bound hexose similar to the controls. In nine of the diabetic patients, mean protein-bound hexose and HbA1(a+b+c) were significantly reduced during a period of intensive outpatient care, while two major serum glycoproteins, haptoglobins and alpha-1-antitrypsin, were unchanged. Our findings support the hypothesis that increased glycosylation of serum proteins may occur in diabetes mellitus; this abnormality in serum protein-bound hexose may be corrected by close attention to overall glycemic control.


Nonenzymatic glucosylation of serum proteins in diabetes mellitus.

The extent of nonenzymatic glucosylation of serum protein in control and diabetic subjects was measured by a chemical procedure using thiobarbituric acid. A mean value of 0.81 (+/- 0.21 SD) nmol glucose per milligram serum protein was observed in the control group. Diabetics displayed elevated levels of glucosylated serum proteins, up to 4 nmol glucose per milligram protein. Glucosylation of serum protein correlated strongly with fasting blood sugar (r = 0.71), percent hemoglobin A1 (r = 0.79), and percent glucosylated albumin (r = 0.99). There was no overlap between control and diabetic groups, i.e., within 3 SD of the mean of controls. These studies indicate that the assay for glucosylated serum protein appears to be an especially sensitive indicator of the degree of hyperglycemia in diabetes.


Effect of acetate on hypoglycemic seizures in mice.

In order to determine the effects of acetate on signs and symptoms of hypoglycemic seizures, Swiss Webster albino mice were injected intraperitoneally with solutions of NaCl, NaHCO3, NH4Cl, Na-acetate, or NH4-acetate, followed by subcutaneous injection of 7 U of insulin/kg body wt. Administration of Na- or NH4-acetate delayed and reduced the incidence of hypoglycemic reactions. Reinjection with Na-acetate or repeated injections with NH4-acetate caused a return to normal behavior patterns for 60 and 75%, respectively, of the affected hypoglycemic experimental animals. Injections of control animals with NaHCO3 or NH4Cl showed that the results were not due to alkalosis or acidosis. Acetate administration significantly increased plasma acetate and citrate, but not glucose, lactate, beta-hydroxybutyrate, or acetoacetate concentrations. The results indicate that intraperitoneal administration of acetate directly acted to prevent signs of hypoglycemia from occurring and reversed its manifestations when they were present. The protective effect of acetate suggests that it may serve as a fuel for the brain.


Spontaneous diabetes in the gnotobiotic BB/W rat.

To determine the influence of infectious agents on the initiation of diabetes in the spontaneously diabetic Bio-Breeding/Worcester (BB/W) rat, susceptible rats were raised in a germ-free environment. Between 2 and 3 mo of age, 3 of 12 pups became diabetic. Histologic examination of the pancreas revealed insulitis or end-stage islets. Culture and smears from various tissues were negative for bacteria or parasites. Serum vital antibody titers for all known rat viruses were undetectable. These data suggest that the diabetic syndrome of the BB/W rat is not dependent on recognized infectious agents.


Changes in glucagon levels after four to five weeks of glucoregulation by portable insulin infusion pumps.

Near-normal glucoregulation was maintained in five patients with juvenile-onset diabetes mellitus for 4--5 wk with a preprogrammed, continuous, subcutaneous insulin infusion using a portable battery-powered infusion pump. This form of therapy significantly lowered immunoreactive glucagon (IRG) levels below those observed while on conventional insulin treatment at several times during the 24-h profile. The maximum IRG levels were also reduced in all five subjects. Thus, a flexible system of insulin delivery, as is provided by certain open-loop pump systems, can overcome inappropriate glucagon secretion that occurs with conventional insulin therapy.


Decreased sympathetic vasomotor tone in diabetic orthostatic hypotension.

In normals, subcutaneous blood flow in the ankle region, measured by means of the 133Xe washout technique, decreases about 45% when the position of the ankle is changed from cardiac level to 50 cm below the heart. A sympathetic vascular axon reflex is responsible for this flow reduction. A normal response [mean blood-flow reduction, 49% (range, 40 to 64%)] was found in seven diabetics without neuropathy. In nine diabetics with autonomic neuropathy (beat-to-beat variation in heart rate less than or equal to 15 min-1 during hyperventilation), the reduction in blood flow on lowering of the ankle was also normal. A significant deterioration of the response was found in six diabetics with autonomic neuropathy, including orthostatic hypotension, in whom blood flow increased 23% (range, -35 to +77%). Autoregulation of blood flow, i.e., constancy of blood flow in the ankle region on lowering and elevating of the ankle 20 cm below and above cardiac level was intact in the patients with orthostatic hypotension, indicating a normal vascular smooth muscle function. In conclusion, in diabetic patients with orthostatic hypotension, the subcutaneous axon reflex is absent. This may be one of several factors responsible for their orthostatic hypotension.


A simplified method using somatostatin to assess in vivo insulin resistance over a range of obesity.

Twenty-one nondiabetic subjects, their weights ranging from 56 to 165 kg, received an infusion of glucose (420 mg/min), insulin (0.77 mU/kg/min), and somatostatin (500 microgram/h) for 150 min. A steady state level of plasma insulin and glucose was attained after 90 min. Endogenous insulin secretion determined by C-peptide measurement, and glucagon secretion remained suppressed throughout the period. With similar steady state levels of plasma insulin (SSPI) maintained in all subjects, the height of the steady state plasma glucose concentration (SSPG) was considered an index of total body sensitivity to insulin-mediated glucose uptake. A positive correlation between SSPG and the degree of obesity, as determined by the body mass index (BMI), was demonstrated (r = 0.70, P less than 0.001). No correlation was found between SSPI and BMI. The fasting plasma insulin concentration correlated with BMI (r = 0.82, P less than 0.0001) and SSPG (r = 0.80, P less than 0.0001). This method provides a simple safe measure of total body insulin resistance over a wide range of obesity and is independent of endogenous insulin secretion.


Bimodality of glycosylated hemoglobin distribution in Pima Indians: relationship to fasting hyperglycemia.

Glycosylated hemoglobin (HbA1) concentrations were determined in 300 Pima Indians aged 15 yr and older. Frequency distributions of HbA1 were unimodal in the 15--24-yr-old age group, but were bimodal in those aged 25 yr and over. The bimodality indicated that the subpopulation with diabetes could be identified by the presence of elevated HbA1 levels. This group was comprised primarily of subjects who also had fasting plasma glucose levels of less than or equal to 140 mg/dl, but subjects with impaired glucose tolerance without fasting hyperglycemia had HbA1 levels that were not significantly higher than those with normal glucose tolerance. The prevalence of diabetic retinopathy was much higher in the subgroup with elevated HbA1 levels and increased with increasing HbA1 level. HbA1 levels and triglyceride concentrations showed only a modest association. HbA1 determinations provided no advantage over fasting or post challenge glucose levels in the diagnosis of diabetes.


The effects of different conditions of organ culture on the survival of the mouse pancreas.

The effects of different conditions of organ culture on the viability of murine pancreatic tissues and, particularly, of pancreatic islets, was assessed by morphologic and histochemical analyses. High oxygen tension (1300 mm Hg), found previously to allow successful allogeneic thyroid transplantation, was toxic to pancreatic tissue. Low temperature (22 degrees C) was associated with better islet preservation than high temperature (37 degrees C). Hydrocortisone did not reduce the survival of pancreatic islets and did appear to preserve the acinar components. Fetal and neonatal pancreas responded similarly to the various organ culture conditions. These results have potential importance in guiding future transplantation experiments.


Changes in glycoproteins of liver plasma membranes from rats treated with D-galactosamine.

D-Galactosamine administration to rats (400 mg/kg) by intraperitoneal injection induced biochemical alterations in liver plasma membranes. Alterations were studied 4, 16 and 24 h after D-galactosamine injection. Plasma membrane 5'-mononucleotidase activity decreased to 40% of control values. Carbohydrate composition was significantly changed. After 24 h D-galactosamine administration, the diminution in plasma membrane sialic acids and hexoses reached 30% of control values. As detected by SDS-acrylamide gel electrophoresis, high molecular weight glycoproteins of D-galactosamine-treated plasma membranes were modified. Moreover, the incorporation of [35S]-sulfate into membrane glycoproteins decreased after D-galactosamine administration (40--60% of control). The present results show that biochemical alterations in rat liver plasma membranes appear soon after D-galactosamine injection. Marked changes are observed in cell surface glycoproteins, especially in sialoglycoproteins and sulfated glycoproteins.


Vagovagal stimulation of pancreatic-polypeptide secretion by graded distention of the gastric fundus and antrum in man.

Previous studies have shown that pancreatic polypeptide (PP) secretion is regulated by efferent, vagal stimulation. In the present study the afferent part of a vagovagal pathway has been investigated in two different ways: (I) Graded fundic distention: in 8 patients with duodenal ulcer ballon distention with 150 ml of the fundus and the body of the stomach increased PP concentrations in plasma from 19 (17--26) to 41 (35--48) pmol/l, median and interquartile range. Distention by 300 and 600 ml did not further increase PP concentrations. After denervation of the fundus by proximal gastric vagotomy, no increase in PP levels was observed during distention with 50 and 300 ml whereas distention by 600 ml was followed by a small increase. (II) Graded antral distention: balloon distention with 50, 100 and 150 ml of the antrum increased plasma PP concentrations in 7 healthy subjects and 14 duodenal ulcer patients. Maximal PP response was achieved by distention with 100 ml, healthy subjects: from 14 (12--23) to 40 (26--44) pmol/l, and duodenal ulcer patients: from 25 (13--38) to 47 (22--63) pmol/l, median and interquartile range. It is concluded that a gastropancreatic reflex stimulating PP secretion through a long vagovagal pathway is present in man, and that this mechanism probably is involved in the initial PP response during a meal.


Inhibition of bombesin-stimulated gastric acid secretion by secretin, glucagon and caerulein in patients with duodenal ulcer.

The inhibitory effects of intravenous infusions of secretin, glucagon and caerulein on the gastric acid response to bombesin were studied in 8 duodenal ulcer patients. Bombesin was found to be a very potent stimulator of gastric acid secretion in patients with duodenal ulcer. There were no significant differences in acid outputs per 15-min period between bombesin infused in a dose of 0.9 microgram/kg/h and pentagastrin infusion administered in a maximal dose, at a rate of 6.0 microgram/kg/h. Secretin (1 U/kg/h), glucagon (30 microgram/kg/h) and caerulein (0.1 microgram/kg/h) produced significant decreases in gastric acid secretion evoked by bombesin given in a dose of 0.9 microgram/kg/h. Percentages of inhibition were 48.6, 45.2 and 35.5, respectively. It is supposed that secretin and glucagon given in pharmacological doses are capable of interfering with the action of gastrin released from antrum by means of bombesin on the parietal cell by noncompetitive kinetics. Caerulein administered in a pharmacological dosis, however, can inhibit the effect of gastrin released by bombesin on the parietal cells by a competitive kinetic.


Influence of bile on kinetic behavior of colonic epithelial cells of the rat.

The acute effect of bile deprivation on colonic epithelial cell proliferation in Sprague-Dawley rats was investigated and compared with its effect on jejunum and ileum. 2. days after the creation of bile fistula, tritiated thymidine was injected and animals sacrificed 1 and 24 h later. Compared with control untreated animals, sham-operated restrained rats had a reduced labeling and mitotic index of the colonic epithelial cell population as well as a slower migration of cells to the lumen. Colonic cell proliferation in animals deprived of bile flow was reduced a further 50%. Moreover, no evidence of cell migration or appreciable decline in grain density was seen over 24 h in bile fistula rats. Alterations in cell proliferation in both sham and bile fistula treated rats became less marked as one proceeded proximally to the small bowel. Therefore, significant alterations in cell kinetics result when normal bile flow is interrupted, suggesting its importance in the regulatory control of colonic cell proliferation.


Effect of an elemental diet (Vivonex) on the absorption abnormalities and histological appearances of the jejunum in untreated adult coeliac disease.

The effect of an elemental diet (Vivonex) together with a gluten-free diet on the absorption of water, sodium and chloride in the jejunum was studied in 4 patients with untreated adult coeliac disease before and after a 1-month course of therapy. The morphology of the jejunum was also studied by jejunal biopsy taken at the same time as the intestinal perfusion. The results were compared with those obtained in 4 patients with adult coeliac disease treated with a gluten-free diet alone. No marked improvement was noted in the transportation of water, sodium and chloride after either treatment with Vivonex and a gluten-free diet or after a gluten-free diet alone, and no marked histological changes were found. Clinical improvement occurred in both groups of patients, in that the diarrhoea improved in all patients and they generally felt better. There appears to be no additional advantage of using an elemental diet with a gluten-free diet in the initial management of adult coeliac disease.


Cimetidine and salbutamol combined inhibition of gastric acid secretion in the dog.

The effects of salbutamol and cimetidine, alone and in combination, on pentagastrin-stimulated gastric secretion have been studied in conscious dogs with gastric fistulae. Salbutamol 24 nmol/kg.h alone and cimetidine 4 mumol/kg.h alone inhibited acid up to 69%, cimetidine 8 mumol/kg.h produced up to 87% inhibition and the combination of cimetidine 4 mumol/kg.h and salbutamol 24 nmol/kg.h almost totally inhibited acid (up to 99%). The pharmacokinetics of these inhibitions were studied and salbutamol and/or cimetidine caused a complex uncompetitive inhibition of pentagastrin-stimulated acid. The inhibitory combination of the two drugs was additive.


Lysosomal changes and enterocytic copper deposits in Wilson's disease.

In 4 siblings, of whom 2 had symptoms of Wilson's disease, electron microscopy showed that the number and size of lysosomes in the enterocytes were increased compared with controls. Electron-dense aggregates, observed near the lysosomes in the 2 symptomatic patients and 1 other sibling, were shown, by means of a microanalytical method, to contain copper. These findings could suggest a possible role of the small intestine in Wilson's disease.


Reduced insulin binding to hepatic plasma membranes in D-galactosamine-treated rats.

Six to 12 hr after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV Load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40--60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosamine-treated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.


Effect of experimental hyperinsulinaemia on intracellular glucose metabolism of isolated adipocytes.

Glucose oxidation and lipogenesis were studied in isolated adipocytes from control and non-obese, experimentally hyperinsulinaemic rats. In cells from the hyperinsulinaemic animals oxidation of either [1(-14) C]- or [6(-14) C] glucose was increased in the presence or absence of insulin, at substrate concentrations from 0.1 to 20 mmol/l. Glucose incorporation into total triglycerides and fatty acids was also increased. These enhanced rates of glucose metabolism were due to increased activity of the glucose transport system in addition to increased activity of intracellular glucose metabolism. Therefore, these data indicate that insulin can influence long term glucose homoeostasis by augmenting the overall cellular capacity for glucose metabolism at several loci.


The effect of unabsorbable carbohydrate on gut hormones. Modification of post-prandial GIP secretion by guar.

Five healthy volunteers and 6 diabetics were given a mixed test meal on two occasions--once with and once without 10 g guar flour. Addition of guar caused a 47% decrease in maximum post-prandial GIP levels, a 48% decrease in blood glucose and a 48% decrease in plasma insulin in normal subjects. In diabetics, addition of guar caused a 30% reduction in maximum post-prandial GIP and 58% decrease in blood glucose. Four normal and 6 diabetic subjects were given a predominantly carbohydrate meal, again with and without 10 g guar. Addition of guar caused a 78% decrease in blood glucose and a 59% decrease in plasma insulin in normal subjects. In diabetics addition of guar caused a 71% decrease in maximum post-prandial plasma GIP and a 68% decrease in blood glucose. Lowering of post-prandial blood glucose, plasma insulin and GIP levels by guar was statistically significant in every case. Addition of guar to the predominantly carbohydrate meal caused a decrease in total plasma GLI in both normal and diabetic subjects but reached statistical significance only in the normal subjects. There was a highly significant correlation (r = 0.83; p less than 0.0005) between peak post-prandial insulin levels in normal subjects and the corresponding plasma GIP concentration. The reduction of GIP or GLI secretion may, therefore, be partly responsible for the smaller rise in plasma insulin observed in normal volunteers when guar is added to meals.


Basement membrane thickness, insulin antibodies and HLA-antigens in long standing insulin dependent diabetics with and without severe retinopathy.

The study was designed to show whether there was any relation between muscle capillary basement membrane thickness, HLA-antigens, anti-insulin antibodies and proliferative retinopathy. Electron microscopic measurements of muscle capillary basement membrane thickness were performed on muscle biopsies from 15 insulin-dependent diabetics and severe proliferative retinopathy, 24 insulin-dependent diabetics with minimal retinopathy and 18 age- and sex matched non-diabetics. All the patients had had diabetes for 20 years or more. None had biochemical or clinical evidence of diabetic nephropathy. Basement membrane thickness was measured according to the methods of Siperstein and Williamson. Muscle capillary basement membrane thickening occurred in 32 of 39 diabetics, using the Siperstein method, but patients with proliferative retinopathy did not exhibit thicker basement membranes than patients with no or minimal changes in the retina. There were apparent differences in HLA-antigens between diabetics with and without proliferative retinopathy, but they did not reach statistical significance. There was no correlation between muscle capillary basement membrane thickness and the quantity of insulin antibodies. The results indicate that factors other than basement membrane thickening and genetic factors in the HLA-region, are responsible for the development of proliferative retinopathy.


Absorption kinetics of subcutaneously injected insulin. Evidence for degradation at the injection site.

The absorption of subcutaneously injected insulin was examined by injecting semisynthetic [3H] insulin in anaesthetized pigs and subsequently analysing the tissue excised from the injection site. Contrary to previously accepted views, a significant proportion of insulin was degraded at the injection site. The disappearance of intact [3H] insulin from the injection site followed a monoexponential function with a half-time of 59 min.


[Statistical findings on the variability of chemo-antibiotic resistance in minor Salmonella strains particularly frequent in the Piedmont area].

462 Strains of Salmonella spp. were tested; they had been arranged in species according to the frequency of appearance in Regione Piemonte: 358 of them were isolated in the period 1975-'76 and 104 in 1977. The susceptibility of the two groups considered to 40 antibiotics was determined. The results obtained evidenced significant variations of this parameter.


[Epidemiological aspects of salmonelloses in Turin. II: The presence of Salmonella in surface waters and sewerage waters of Turin].

The Authors have examined several sets of superficial water and of sewerage waters (respectively 44 and 27) in the metropolitan area of Turin in search of Salmonella bacteria.


[Routes of spread of the current rabies epizoonosis in Europe].

The present report describes the spreading paths of the rabic epidemic that is rapidly reaching Italy from Central Europe. The epidemiologic situation of neighbouring countries is examined and the sanitary measures undertaken in Europe against epidemic are compared.


[Sensitivity of human and pigeon erythrocytes to rubella virus].

Human cord blood and adult red blood cells (rbc) and pigeon rbc were compared for sensitivity to rubella virus hemagglutination by a new method, consisting of the direct counting of free and aggregate red blood cells by using an hemocytometer chamber. With this method, more reliable than the "pattern test", hemagglutination is quantitated by the "aggregation index" (A.I.). Pigeon rbc were more sensitive than human rbc; cord blood and trypsinized adult human rbc showed the same sensitivity. However the kinetics of hemagglutination, evaluated by A.I. after different incubation times, were essentially the same with the three rbc types.


[Epidemiological aspects relating to the determination of fosfomycin sensitivity: results of a study on 300 strains isolated in a hospital milieu in Turin].

The AA. evaluated the sensitivity to Fosfomycin and to other commonly used antibiotics of 105 bacterial strains isolated from hospital environment and 195 from pathological materials. They also studied the problem of bacterial resistence to Fosfomycin considering the frequency of "inner colonies" and of bacterial cross-resistance to other antibiotics.


[HBsAG in feces, urine and saliva].

After some observations about the tests of the research exposed in the literature, authors illustrate the tests for 142 patients divided into 5 groups: a) patients affected with acute viral hepatitis; b) patients affected with praegressa acute viral hepatitis; c) relatives of patients with acute viral hepatitis; d) volunteers; e) patients affected with chronic uraemia under dialisis periodic treatment. After the testing control, authors, conclude with an hipotesis: a possible epidemic function of faeces, urine saliva, in the passage of the acute viral hepatitis.


[Transient enterotoxemia following tooth extraction: observations on the Limulus test].

The incidence of endotoxemia (with limulus assay) in a group of patients undergoing dental extraction of both normal and diseased teeth was determined. Transient endotoxemia was found in 7 caes, without incidence of bacteremia.


[Distribution and anomalies of coronary arteries in tetralogy of Fallot (author's transl)].

Anomalies in the course and distribution of coronary arteries may complicate the surgical correction of tetralogy of Fallot (TF). With the aim of preventing possible serious, and even lethal, cardiac events caused by the injury of aberrant vessels, 119 patients with TF were subjected to selective coronary angiography. Apart from demonstrating anastomoses between the coronary and bronchial arteries in 31 cases, small fistulas between the coronary arteries and pulmonary artery (in 14 cases) and hypoplasia of the entire coronary tree in 1 case, this investigation revealed anomalies in the origin of coronary branches in 11 cases. In some cases the first septal branch was absent and the diagonal branches were poorly developed. An injury to the coronary system, following the closure of the interventricular septal defect, may possibly explain the onset of a "left anterior hemiblock" after total correction of TF. Selective coronary angiography in small children presents no riskes provided it is correctly performed. In our cases no complications arose.


[Case of L. monocytogenes meningitis in the non-neonatal period].

A case of Listeria monocytogenes meningitidis in a little girl of Envie (Cuneo) is reported. The epidemiologic study has shown the presence of significatively high antibodies titers also in the sera of other members of the family.


[Clinical and epidemiological criteria of evaluation of the exercise test (author's transl)].

Exercise test diagnostic and prognostic value depends on the purpose for which is performed and on the population studied. In typical angina patients the test is usefull for choosing between medical and surgical therapy and for evaluating treatment efficacy. In patients with atypical chest pain a diagnostic value is recognized. In asymptomatic subjects results of a number of epidemiological studies suggest that this test is recommended only in selected groups or for research purpose. In the appendix definitions of epidemiological measures used in screening tests evaluation are given with examples.


[Effort test on a treadmill in peripheral arteriopathic obstructions (author's transl)].

20 males, 48 to 66 of age, whose 10 normal and 10 with chronic arteriopatic obstruction at inferior limbs, were submitted to effort on a treadmill for 5 minutes or until pain. The clinostatic systolic aterial pressure was obtained in the four limbs before and at fixed intervals of time from the exercise. Arterial pressure increases after effort in the normal limbs; the length and the amount of the systolic pressure decrease after exercise are in correlation with the degree of the arterial involvement. The exercise on treadmill seems useful when the clinical and other diagnostic data are inadequate for a reliable diagnosis and to evaluate the progression of the arteriopathy through a non-invasive, and easy to repeat, method. The possible mechanisms of the pressor decrease in the arteriopatic limbs are discussed.


[Left atrial myxoma revealed by saddle occlusion of the aortic carrefour (author's transl)].

A case of a left atrial myxoma revealed a saddle occlusion of aortic carrefour is reported. The embolus has been surgically removed and histology allowed to recognise its myxomatous nature, suggesting source for left atrial cavity. Cardiac catheterisation and angiocardiography confirmed the presence of atrial tumor, which has been successfully excised. Embolisation is referred to villous, friable surface of the neoplasm. Employment of echocardiography in patients with arterial emboli from unknown etiology is highly recommended.


[A rare case of Friedreich's atoxia with cardiac involvement: the torsade de pointe (author's transl)].

The Authors describe a case of Friedreich's ataxia complicated by an unusual arrhythmia, torsade de pointes, the only manifestation of cardiac involvment in this patient. Then some hypothesis of etiopathogenetic mechanism of this rhythm disturbance in patients affected with Friedreich's ataxia are proposed.


[Changes in precordial movements in non-ischaemic heart disease patients after i.v. administration of isoproterenol and dopamine. Comparison between normal and cardiopathic subjects (author's transl)].

18 patients with non-ischemic heart disease have been studied with reference to the kinetocardiographic changes before and after i.v. administration of dopamine (DOP) (Revivan) or Isoproterenol (ISP) (Aleudrin). For this purpose a simultaneous registration of ECG (lead D2), Kinetocardiogram (KCG) in K25 and K45 was performed. Volume curves were considered as a normal features of KCG, curves showing systolic outward movements during the ejection phase were classified as pathologic. The reduction or disappearance of the systolic movements during the drug administration, were considered as kinetic improvement, the increase of their site was judged as kinetic worsening. During the infusion, 17 KCGs maintained a normal morphological pattern; out of 19 pathological KCGs, 4 did not show any change, and 15, 5 reached a complete normalization. It is pointed out the overlap of the precordial kinetics in the ventricular hypertrophies and in the normal subjects (kinetic improvement), and the possibility to differentiate a systolic outward movement due to synergic contraction of hypertrophied ventricle from a systolic outward movement to be reffered to a diskynetic contraction in the myocardial ischemia (kinetic worsening).


Radiologic assessment of resectability and prognosis in esophageal carcinoma.

Utilizing double-contrast technique it is possible to detect the earliest malignant lesions of the esophagus even when the carcinoma is confined to the mucosa. In patients with carcinoma, it is also important to attempt to grade and classify the lesion in order to predict its resectability and prognosis. The resectability of a lesion is determined by the depth of invasion and by the presence or absence of lymph node metastases. The significant factors are the length of the lesion, its gross morphology, the character of its margins, and the depth of ulceration. Unfortunately, the depth of invasion is not necessarily directly related to the prognosis. In some carcinomas confined to the submucosa, lymph node metastases are already present, and these patients have a poor prognosis. The presence of lymph node metastases in early carcinoma can be suggested by the gross morphology of the lesion, its length, irregularity of the surface, and the presence of a complex lesion. Careful analysis of the radiographic features of the carcinoma can be valuable for the assessment of resectability and prognosis.


Delayed esophageal perforation after pneumatic dilatation for the treatment of achalasia.

Two cases of delayed esophageal perforation following a pneumatic dilatation for the treatment of achalasia are presented. Esophagrams obtained immediately after pneumatic dilatation failed to reveal a perforation. Increasing symptoms prompted repeat contrast studies, at which time an esophageal perforation was demonstrated. The occurrence of delayed esophageal perforation after pneumatic intrumentation is emphasized. An ischemic etiology for this delayed perforation is postulated.


Spontaneous closure of esophageal tear in Boerhaave's syndrome.

An unusual case of spontaneous rupture of the esophagus is reported in which the patient survived without surgical closure or drainage procedure. The site of perforation and subsequent closure are documented radiologically.


Unusual leiomyoblastoma of the stomach.

Only about 250 cases of benign gastric leiomyoblastoma of the stomach have been reported. Most occur in the smooth muscle of the antrum, and may be intramural, intraluminal, or exogastric in position. A pedunculated gastric leiomyoblastoma occurs less frequently, and those containing radiographically identifiable calcifications are extremely rare.


Angiographic evaluation of the abnormal endoscopic pancreatogram.

Out of 1,269 pancreatograms, 122 were abnormal. Angiography was performed in these patients. Fifty-five were found to have pancreatic carcinoma. In the remaining 67 patients a false positive angiographic diagnosis of either chronic pancreatitis or pancreatic cancer was made in 11%. In one patient a hemangioma was diagnosed as a pancreatic cyst. The remaining 58 patients all had normal pancreatic angiograms in spite of gross ductal abnormality on endoscopic retrograde cholangiopancreatography (ERCP). All these patients were followed for an average of 19 months and showed no clinical evidence of pancreatic disease. It is suggested that angiography should be considered a complementary examination to ERCP and is particularly useful to exclude carcinoma when the pancreatogram is abnormal.


Ultrasonographic demonstration of the pancreatic duct.

During a 4-year period, 375 patients with clinically suggestive pancreatic disease were examined with gray scale ultrasound. In 14 patients, the pancreatic duct itself was demonstrated. All of these had clinical or laboratory evidence for, and radiologically or surgically proven, pancreatic duct obstruction. Etiology of the obstruction was either tumor, chronic pancreatitis, pancreatic abscess, pseudocyst, or stricture of the duct at the papilla of Vater. Two patients had Crohn's disease of the duodenum.


Ultrasonic characteristics of pancreatic tumors.

The ultrasonic features of 40 pancreatic tumors were analyzed. The tumors were categorized by texture, attenuation, shape, size, and location. Secondary effects of pancreatic duct visualization, biliary stasis, splenic vein involvement, metastases, and ascites were reviewed. Thirty of thrity-one adenocarcinomas had a similar ultrasonic texture consisting of a background of faint, low-level echoes with varying amounts of superimposed coarse echoes. Tumors are detectable prior to enlargement or distortion of the pancreas. Secondary features were present in 94% of the adenocarcinomas. Significant information regarding the possibility and complexity of resection can be provided.


Primary common bile duct carcinoid.

Endoscopic retrograde cholangiography was performed in a 32-year-old man with recurrent episodes of painless jaundice. There was demonstration of a large intraluminal mass causing partial obstruction of the common bile duct. The lesion proved to be a primary carcinoid tumor of the bile duct.


Spontaneous disappearance of gallstones.

A case of spontaneous disappearance of gallstones in a 55-year-old woman is presented. Examination of biliary lipids after the stones had disappeared revealed supersaturated bile with cholesterol. This suggests that the stones migrated from the gallbladder to the small intestine via the biliary ductal system.


Recurrent appendicitis: reexamination of a controversial disease.

The existence of recurrent appendicitis as a true disease entity is still disputed. The controversy surrounding recurrent appendicitis is discussed. This disease is thought to represent repeated inflammation of a nonperforated appendix. Case material supporting this concept is presented. The barium enema can provide evidence of the diseased appendix.


Simultaneous double obstruction of the proximal colon: a case report.

A rare case of simultaneous obstructions of the proximal colon secondary to an obstructing carcinoma of the transverse colon and an ascending colon volvulus at the hepatic flexure is presented. Their probable interrelationship and resulting radiographic features are discussed.


Pneumoperitoneum occurring during double-contrast enema.

A case of pneumoperitoneum occurring during double-contrast barium enema is described. Cases reported to date indicate that colonic rupture during a double-contrast enema is likely to result in exit of air rather than barium from the colon. The diagnostic implicatons of this observation are considered. The potentially high pressure generated by bulb-type inflators is discussed, and caustion is advised against overdistending the colon during double-contrast enemas.


Retroperitoneal lipomatosis--report of two cases with an unusual distribution.

Two cases of retroperitoneal lipomatosis with an unusual distribution are reported. In the first case the fat was confined to the perirectal soft tissues and the sigmoid mesentery, whereas in the second case it was peripancreatic and extended into the small bowel mesentery. The lipomatous nature of these retroperitoneal masses was suggested by the lucency of the fat on the plain abdominal roentgenograms. These cases were studied prior to the availability of computed tomography, so that the diagnoses were confirmed by surgical exploration, which may have been avoided by this currently available noninvasive technique.


Infusion tomography and ultrasonography of the gallbladder in the diagnosis of acute cholecystitis.

Sixty-three patients with the clinical suspicion of acute cholecystitis were examined with infusion tomography of the gallbladder. Ultrasonography was performed in 51 of these cases. The technique and diagnostic principles of both methods when used in combination is stressed. Thus in a case of gangrenous cholecystitis when opacification of the gallbladder wall may not appear at infusion tomography, ultrasonography may demonstrate signs of gallbladder disease. Infusion tomography, on the other hand, may be of great value if ultrasonography is not informative.


Enterocylsis: the small bowel enema. How to succeed and how to fail.

Enteroclysis, the infusion of contrast medium directly into the small bowel, is a precise, rapid method for thorough small bowel examination. This technique demonstrates far more pathology than any other method when it is properly executed. However, the examination is sure to fail with poor techniques, thereby discrediting a superb method. Experience has shown that failures are usually due to inadequate technique or poor judgment or both during the examination. This article covers the proper and improper techniques of the examination and gives examples of each. The most common problems that arise during the examination are discussed in the order in which they usually develop.


A clinical study of tuberculous colitis.

During the last 8 years, the diagnosis of tuberculous colitis has been made radiologically in 22 cases. Twelve were confirmed by histological or bacteriological evidences. The X-ray findings are classified into three types as follows: Type A, showing an extensive scarred area in the ileocecum and ascending colon. Type B, showing annular stricture in the ascending colon and dilatation of its oral side. Type C, showing pouchformation (pseudo-diverticulum) and deformity in the cecum. We emphasize that histological examination and culture of the biopsy specimens by endoscopy were useful for the diagnosis of tuberculous colitis. Furthermore, radiologic changes of the colon by administration of antituberculous drugs were observed.


Endoscopic electromyography of the sphincter of Oddi.

Endoscopic electromyography of the human sphincter of ODDI has provided useful information for the patho-physiological studies on the choledocho-duodenal junction. The pattern and rhythm of the electromyogram observed on the spincter of ODDI were different from those of the duodenum recorded simultaneously in basal tracings of our initial four cases. In the half of other ten cases with consecutive tracings, the different pattern and rhythm of electromyograms between the sphincter of ODDI and the duodenum were also confirmed. It was possible, from our results, to speculate that the functional independence of the sphincter of ODDI from the duodenal wall muscles was in existence.


Changes of pancreatic exocrine function after major resection of the pancreas in dogs.

Changes of an exocrine function after major resection of the canine pancreas were observed by pancreozymin-secretin test and the results were compared with an endocrine function examined by glucose tolerance test. The exocrine function of the remnant pancreas revealed characteristic changes according to the resection rate of the pancreas: 1) After removal of 50 to 70 per cent of the entire pancreas, diabetes did not develop and the exocrine function of the remnant pancreas was well maintained. 2) After 70 to 90 per cent pancreatectomy, diabetes developed six weeks or more later and the exocrine function of the remnant pancreas per body weight decreased slightly. The degree of disturbance of the exocrine function in the diabetic dogs was greater than that in the non-diabetic group, but the exocrine function per the remnant pancreas weight increased and it was greater than normal level even in the diabetic dogs. The hypersecretory state of the exocrine pancreas after surgery was verified. 3) After 90 per cent or greater resection of the pancreas, diabetes occurred immediately and disturbance of the exocrine function was remarkable. Hypersecretory state did not appear. 4) Both the endocrine and exocrine functions after major pancreatic resection were found to be related to the resection rate, but there were significant differences in the reserve capacity of the endocrine and exocrine pancreas.


Role of plasma histamine in liver injury--clinical and experimental investigations.

Plasma histamine level (PHL) was evaluated by a modified fluorometric assay (Suzuki) in the patients with various forms of liver disease as well as rabbits with liver injury. And the data obtained were compared with liver function tests in assessing the stage and prognosis of hepatic dysfunction. In acute hepatitis, if its prognosis was "good", as was also shown in the animal group with single dose administration of CCl4, the level of plasma histamine attained a peak before that of serum transaminases, and returned to normal prior to that of the latter. In persistent and chronic hepatitis, although correlation between PHL and other liver function tests was poor and variable, PHL remained high. And the estimation of PHL during the course of this state showed that it was elevated prior to that of serum transaminases, in dicating high level of plasma histamine in this state, even in apparent "steady state", worsening of the disease. In liver cirrhosis PHL correlated with the degree of serum transaminases as well as serum gammaglobulin. In "poor prognosis" group (patients with hepatic coma and rabbits treated with consecutive administration of CCl4) PHL increased extremely high, which was contrasted with the lowered levels of transaminases. These results strikingly suggest that histamine is involved in liver injury and estimation of PHL in the course of hepatic disorder is useful for a prediction of prognosis.


Serum glycoproteins in the liver diseases. VIII. Desialylated glycoproteins in the liver cirrhosis.

Serum desialylated glycoprotein livel of cirrhotic patients was determined and a diagnostically significant elevation of these proteins was observed. The level of these patients was usually 2--10 times of that seen in normal subjects and the elevation was signifi-ant (p less than 0.001) when compared to the level in patients with chronic aggressive hepatitis, severe (2B). Serial determinations of these proteins in the cirrhotic patients showed no correlation between them and SGPT as a whole but in several cases in which SGPT fluctuated the former associated with the latter. In patients with decompensated cirrhotic liver these proteins returned nearly to the level of compensated patients when it was improved. The level of these proteins in cirrhotic patients correlated, not always, with serum albumin (r = -0.46, p less than 0.02) and indocyanine green clearance rate (r = -0.73, p less than 0.05), but not with SGPT as well as the other liver function tests.


Crohn's disease in Japan: The Japanese Research Committee for Crohn's Disease.

Sixty four cases of Crohn's disease were diagnosed. From our resluts reported here, the following conclusions were confirmed: 1) Crohn's disease as reported in Western countries certainly occurs among Japanese, too. 2) The most characteristic feature of Crohn's disease in Japanese patients was a long longitudinal ulcer along the mesenteric attachment of the small intestine, in addition to a cobblestone appearance. 3) In establishing the diagnosis of Crohn's disease, it was most important to distinguish Crohn's disease from intestinal tuberculosis.


Congenital multiple cystic dilatation of the intrahepatic biliary ducts (two cases with simple type of Caroli's disease).

Two cases of Caroli's diseases (simple type) precisely diagnosed prior to the operation by the direct cholangiography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography, were reported. They both had a long cystic duct, and association of cystic lesions of bilateral kidneys was revealed in one of them. Excessive biliary output had been observed postoperatively in both of them. A cholecystectomy and choledochodrainage successfully gave rise to favourable results in both cases reported.


Reduction of twenty-four-hour gastric acidity with combination drug therapy in patients with duodenal ulcer.

Four "extra-effort" drug regimens were tested to determine which most nearly eliminated 24-hr gastric acidity in 8 patients with duodenal ulcer. The regimens included two 300 mg cimetidine tablets with meals and at bedtime; one 300 mg cimetidine tablet plus an anticholinergic drug with meals and at bedtime; 300 mg cimetidine with meals and at bedtime plus liquid antacid 1 and 3 hr after meals and at bedtime; and 300 mg cimetidine, an anticholinergic drug, and antacid, taken simultaneously as each meal was finished and at bedtime. No regimen completely eliminated gastric acidity. However, compared to standard cimetidine therapy (300 mg four times daily) which led to a median 24-hr pH of 2.6, each "extra-effort" regimen except cimetidine plus an anticholinergic was significantly better in reducing gastric acidity. During the daytime hours, cimetidine with meals plus antacid 1 and 3 hr after meals was most effective (median pH 5.0). However, the more convenient regimen of cimetidine, an anticholinergic drug, and antacid was almost as effective (median pH 4.3). None of the "extra-effort" regimens was significantly more effective than standard cimetidine therapy during the hours of sleep.


Electrical and mechanical activity in the ex vivo perfused total canine colon.

Electrical and mechanical activity were studied in the ex vivo total canine colon, supported in a perfusion chamber by a supporting dog. Regular electrical activity could be recognized visually in 50--70% of the records. The frequency of this activity was in the range of 7--10/min. Fourier analysis also revealed dominant frequencies in this range. Two types of mechanical activity were observed. The first consisted of small amplitude repetitive contractions, which appeared both during quiescent periods and during vigorous contractions. The frequency of this rippling, when periodic, usually approximated that of the electrical activity. The second type consisted of large amplitude prolonged (30--135 sec) contractions. Without stimulation, the large amplitude contractions were asynchronous and not propagated. Following neostigmine, however, the large amplitude contractions were always propagated aborally and were usually associated with evacuation of the colon. The rippling contractions had a frequency similar to the regular electrical activity and are probably under their control. The large amplitude, prolonged duration contractions are unlikely, however, to be solely under myogenic control.


Enterogastric reflux in normal subjects and patients with Bilroth II gastroenterostomy. Measurement of enterogastric reflux.

Initially, scintigraphy was established as a valid method for detecting and quantitating enterogastric reflux. A new, tubeless technique for the measurement of enterogastric reflux was developed. 99mTc bound to [(2,6 dimethylphenylcarbamoylmethyl) iminodiacetic acid] (5 mCi) was administered intravenously to visualize the liver and biliary tract. One hour later, a standard liquid meal labeled with 111In bound to diethylene-triamine penta-acetic acid (250 microCi) was given. The 99mTc and 111In activities were recorded simultaneously for 1-min periods at 15-min intervals for 2 hr over liver, gallbladder, and gastric areas of interest. Enterogastric reflux indices were determined. Ten normal subjects and 13 patients with vagotomy, hemigastrectomy, and Bilroth II gastrojejunostomy were evaluated. The enterogastric reflux index in asymptomatic postsurgical patients was increased significantly to 24.6 +/- 4.7 compared with 8.2 +/- 6.0 (P less than 0.01) in normal subjects. In postsurgical patients with the syndrome of alkaline gastritis, the enterogastric reflux index was increased significantly to 86.3 +/- 7.1 (P less than 0.01) compared with asymptomatic postsurgical patients.


Intestinal uptake of macromolecules. VI. Uptake of protein antigen in vivo in normal rats and in rats infected with Nippostrongylus brasiliensis or subjected to mild systemic anaphylaxis.

Adult Sprague-Dawley rats weighing approximately g were fed bovine serum albumin and sodium bicarbonate by gavage. Serum was obtained at intervals after feeding and tested for immunoreactive bovine serum albumin by radioimmunoassay. Nanogram amounts of immunoreactive bovine serum albumin were detected in serum; peak values were obtained after 4 and 6 hr. The influence of intestinal inflammation on protein uptake was examined in two model systems. Infection of rats with Nippostrongylus brasiliensis was accompanied by partial villous atrophy in the intestinal segments harboring adult worms and mild systemic anaphylaxis in the rat was accompanied by increased intestinal vascular and mucosal permeability. Enhanced uptake of BSA was observed before and shortly after self-cure of infection and during mild systemic anaphylaxis. The molecular size of immunoreactive bovine serum albumin approximated that of the administered bovine serum albumin; no small fragments of bovine serum albumin bearing antigenic determinants were detected.


Transformation of chenodeoxycholic acid and ursodeoxycholic acid by human intestinal bacteria.

Feces from normal subjects and patients with cerebrotendinous xanthomatosis were incubated anaerobically with labeled chenodeoxycholic acid and ursodeoxycholine acid for known periods, and the bile acids formed were analyzed by TLC and scintillation counting. In the normal subjects, 80% of the chenodeoxycholic acid and 41% of the ursodeoxycholic acid were 7-dehydroxylated to lithocholic acid during 2 hr of incubation. In contrast, the fecal flora of the CTX patients transformed only 5% of chenodeoxycholic acid and less than 1% of ursodeoxycholic acid to lithocholic acid during the same time period. In several subjects (normals and CTX), the intestinal flora converted chenodeoxycholic acid to ursodeoxycholic acid without the accumulation of the hypothetical intermediate 7-ketolithocholic acid (3 alpha-hydroxy-7-keto-5 beta-cholanoic acid). These results indicate that the fecal bacterial flora is capable of 7-dehydroxylating chenodeoxycholic acid and ursodeoxycholic acid to yield lithocholic acid. Apparently the enzymes involved are relatively stereospecific since the 7 beta-hydroxy group of ursodeoxycholic acid was removed more slowly than the 7 alpha-hydroxy group of chenodeoxycholic acid.


Griseofulvin-induced cholestasis in Swiss albino mice.

Griseofulvin was fed to male Swiss albino mice, which were sacrificed at varying times after the initiation of the feeding. The following were compared with mice fed a control diet: hepatic histology, hepatic weight, plasma glycocholate, glycolithocholate, cholesterol, bilirubin, and alkaline phosphatase. Concurrent with the development of hepatic protoporphyria, a progressive cholestatic lesion was produced with marked bile canalicular dilatation and elevation of the plasma bile salts, alkaline phosphatase, and cholesterol without a rise in bilirubin. Adaptation to the cholestatic injury occurred in about 60 days despite continued griseofulvin feeding. This was evidenced by decreased values in the biochemical profile with concomitant improvement in the bile canalicular morphology. Following this event of adaptation, Mallory bodies began to appear in the livers, often in the periphery of the hepatic lobule. This model may be useful in studying mechanisms of cholestasis, Mallory body formation, and their relationship to altered microtubular systems in the hepatocyte.


Percutaneous pancreatography: case report and presentation of technique.

A case of traumatic pancreatitis with a radiopaque calculus producing pain by obstructing the distal pancreatic duct is presented. Preoperative ductal anatomy was defined by a percutaneous pancreatogram that established the presence of mechanical duct obstruction as the cause of pain, and the potential for operative relief of duct obstruction. A remission from pain resulted from pancreatic duct decompression by a lateral pancreaticojejunostomy. The potential value of percutaneous pancreatography is discussed.


99mTechnetium pyridoxylidene glutamate imaging in visceral heterotaxy (Ivemark's syndrome).

A two and one-half year old boy with complex congenital heart disease had Howell-Jolly bodies in his blood raising the possibility of the asplenia syndrome. A 99mTc-sulfur colloid liver-spleen scan was reported normal, but the right lobe of the abnormally reversed liver was mistaken for the spleen. The diagnosis of visceral heterotaxy (Ivemark's syndrome) was established after scanning the patient with a new radiopharmaceutical, 99mTechnetium pyridoxylidene glutamate. The agent clearly demonstrated a left-sided gall bladder, and on comparison with the sulfur colloid scan it was established that asplenia was present. Radionuclide imaging with the new generation of hepatobiliary agents is a reliable method to document asplenia and is useful in studying patients with visceral heterotaxy.


Diagnosis of annular pancreas with endoscopic retrograde cholangiopancreatography.

Two patients with annular pancreas are described. The diagnosis was established unequivocally with endoscopic retrograde cholangiopancreatography before operation. In both patients there was pancreatitis of the annular pancreas. The first patient also had congenital absence of the ventral pancreas and pancreatic insufficiency. The second patient subsequently developed gastric outlet obstruction. The literature is reviewed.


Effect of water and fat on gastric emptying of solid meals.

Gastric emptying of solid egg meals tagged with 99mtechnetium sulfur colloid was studied in 10 normal subjects and in 6 patients after truncal vagotomy, antrectomy, and gastrojejunostomy (Billroth II) for peptic ulcer disease. Technetium sulfur colloid was found to bind more firmly to cooked egg whites than did the water soluble marker DTPA. Water accelerated gastric emptying in Billroth II patients to a greater degree than in normal subjects, in whom the effect of water was minimal and transient. Fat inhibited solid emptying both in normals and in Billroth II patients. These findings suggest that in humans there are jejunal receptors for fat that may inhibit gastric emptying even following truncal vagotomy.


Infant visual habituation as a function of exposure time and stimulus similarity.

The course of visual response integration was examined in four-month-old infants (N = 32 boys and girls) by presenting a bull's eye pattern pair and a striped pattern pair on a single display board. On the basis of Jeffrey's serial habituation hypothesis it was predicted that in the early period of exposure the infant's scanning behavior would be limited to two like pairs, but that as attention waned to the similar pairs one or more of the less preferred stimuli would be integrated into the attending response. A measure of three consecutive looks indicated that attention confined to one similar pair decreased significantly over time, whereas the initially lower three-look sequences to two similar and one dissimilar stimuli increased significantly.


Detecting mutations expressed during early development of cultured mammalian embryos.

Mammalian embryo culture systems can be used to study dominant lethal, recessive lethal, and visible mutations that are expressed between fertilization and early stages of organogenesis. The incidence of dominant lethal mutations has been determined for cultured mouse embryos by morphological observations during pre-implantation and early post-implantation growth in vitro, and the mechanisms of dominant lethal mutations have been studied cytogenetically. Recessive lethal mutations have been studied with cultured embryos, although they can be initially detected only with appropriate breeding protocols. Visible mutations that are due to deletions or single-site base alterations in the DNA can be detected in embryos by isoelectric focusing and gel-electrophoresis techniques.--The principal advantage of cultured embryos for detecting mutations and studying the mechanism of action of particular mutagens is that embryos are accessible for analysis before death with a minimum of indirect maternal effects. The primary disadvantages, which may be alleviated with improved culture conditions, are that only a limited amount of tissue is available, attrition and retardation occur, and offspring are not recovered for further breeding studies.


Minor viability mutants in Drosophila.

Drosophila experiments have demonstrated that spontaneous mutants causing minor decreases in viability occur much more often than those causing drastic effects. They also have a much greater relative effect in heterozygotes, enough that the absolute heterozygous viability decrease is roughly the same for mild as for lethal mutants. On the other hand, with EMS treatment and especially with radiation, the mild mutants are less frequent relative to lethals.--I suggest that the failure to detect heterozygous effects on fitness components from multi-generation radiation experiments on mice due to the relative infrequency of mild effects and the relatively small heterozygous effect of drastic mutants. Chemicals that produce effects more like spontaneous mutations might produce quite different results in such experiments.


Comments on mutagenesis risk estimation.

Several hypotheses and concepts have tended to oversimplify the problem of mutagenesis and can be misleading when used for genetic risk estimation. These include: (1) the hypothesis that radiation-induced mutation frequency depends primarily on the DNA content per haploid genome, (2) the extension of this concept to chemical mutagenesis, (3) the view that, since "DNA is DNA," mutational effects can be expected to be qualitatively similar in all organisms, (4) the REC unit, and (5) the view that mutation rates from chronic irradiation can be theoretically and accurately predicted from acute irradiation data. Therefore, direct determination of frequencies of transmitted mutations in mammals continues to be important for risk estimation, and the specific-locus method in mice is shown to be not as expensive as is commonly supposed for many of the chemical testing requirements.