Studies on the possible contribution of a peripheral presynaptic action of clonidine and dopamine to their vascular effects under in vivo conditions. The functional consequences of drug-induced stimulation under in vivo conditions of alpha-adrenoceptors and dopamine receptors at vascular adrenergic nerve endings (presynaptic receptors) was studied in the autoperfused hindquarters or hindlegs of cats anaesthetized with urethane. The changes in perfusion pressure in response to electrical stimulation of the lumbar sympathetic chain were taken as a measure of noradrenaline release from the vascular adrenergic nerves. Presynaptic inhibitory alpha-adrenoceptors and dopamine receptors were activated by clonidine and dopamine, respectively. According to in vitro experiments these two drugs are more potent stimulants of peripheral presynaptic than postsynaptic receptors. The lowest frequency of stimulation of the lumbar sympathetic chain which yielded a reproducible pressor response was 4 HZ for the autoperfused hindquarters and 1 HZ for the hindlegs; Clonidine was tested over a wide dose range (1-100 mug/kg i;v). A reduction of the stimulation-induced pressor response in the autoperfused hindquarters or hindlegs was observed only after the rather high dose of 100 mug/kg of clonidine. The inhibition was marked at low frequencies of stimulation (1-4 HZ) and weak or absent at high frequencies (16 and 32 HZ). The dose of clonidine (100 mug/kg) which proved to be effective at presynaptic receptors produced a transient increase in blood pressure and in perfusion pressure of the hindquarters and hindlegs and virtually abolished spontaneous sympathetic nervous activity. In spinal cats, the clonidine-induced increases in blood pressure and perfusion pressure were very pronounced and of rather long duration. Thus, under in vivo conditions clonidine showed no selectivity for presynaptic alpha-adrenoceptors in a blood-perfused vascular bed, and its presynaptic action was negligible as compared to its powerful central sympatho-inhibitory effect. Dopamine was constantly infused into the auto-perfused hindquarters or hindlegs at increasing rates until a vasoconstriction due to stimulation of vascular (postsynaptic) alpha-adrenoceptors occurred. The monoamine did not inhibit the stimulation-induced increases in perfusion pressure of the autoperfused hindquarters or hindlegs and, thus, an effect on presynaptic receptors was not found. The results underscore the importance of in vivo experiments for assessing the therapeutic significance of drug-induced stimulation of presynaptic receptors.


Scanning electron microscopic studies on the cytolytic effect of phallolysin on isolated rat hepatocytes and AS-30 D hepatoma cells. Rat hepatocytes and AS-30 D hepatoma cells were treated in vitro with phallolysin, the toxic haemolysin from the death cap fungus Amanita phalloides. Scanning electron microscopy revealed dose-dependent formation of bulky protrusions on the cell surface, which later on burst, expelling intracellular material into the surrounding medium, while the cells became stainable with trypan blue. After 1 haemolytic unit (HU)/ml the protrusions burst within 10 min; after 3 HU/ml all cells were destroyed within 3-5 min. Susceptibility of hepatoma cells did not differ from that of hepatocytes.


Ca2+ -uptake into noradrenaline-storing granules of bovine splenic nerves. Noradrenaline-storing granules, a mitochondrial fraction and a microsomal fraction of bovine splenic nerve trunks were prepared by differential centrifugation. These particulate fractions were characterized by their noradrenaline content, succinate dehydrogenase and glucose-6-phosphatase activity. In the presence of ATP-Mg2+ all three fractions accumulated 45Ca2+ during incubation with 0.1 mM 45 CaCl2, buffered with potassium phosphate or glycylglycine (pH 7.5; 28 degrees C). The accumulated 45 Ca2+ was not removable by EGTA, and the uptake was absent at 0 degrees C or after destruction of the particles by sonication. The behaviour of the 45 Ca2+ -uptake into all three fractions against varying ATP-concentrations, metabolic inhibitors (pentachlorophenol, desaspidine, 2,4-dinitrophenol, N-ethylmaleimide, p-chloromercuribenzoate, sodium azide, amobarbital) and drugs (phenoxybenzamine, verapamil, prenylamine, reserpine, bretylium, phentolamine) was studied. Under nearly all conditions there were differences between the 45 Ca2+ -uptake into mitochondria and that into microsomes, which suggests two distinct uptake processes. The 45 Ca2+ -uptake into the granule fraction behaved intermediate between the two other fractions under many conditions, but not under all. Therefore, it is not possible to explain the 45 Ca2+ -uptake into the granule fraction as being due to contamination with mitochondria and microsomes; an inherent ATP-Mg2+ -dependent 45Ca2+ -uptake into the nerve granules must be postulated, which is not directly coupled with the noradrenaline transport into these particles. A particulate fraction (14000-100000 g), containing noradrenaline granules, was prepared from the vas deferens of the rat. Incubation with 5 X 10(-6) M (-)-noradrenaline and 0.1 mM 45Ca2+ showed that the particles of this fraction take up noradrenaline and 45Ca2+. The uptake of both was dependent on ATP-Mg2+. The ATP-Mg2+ -dependent uptake of both noradrenaline and 45Ca2+ was substantially reduced in the corresponding tissue fraction prepared from denervated vasa deferentia.


On the mechanism of the decrease in cerebellar cyclic GMP content elicited by opiate receptor agonists. Morphine, dextromoramide (4 mumol/kg i.p.) and vimonol R2 (17 mumol/kg i.p.) in analgesic doses (28 to 112 mumol/kg i.p.) decreased 3',5'-cyclic guanosine monophosphate (cGMP) in rat cerebellar cortex; morphine also decreased the cGMP content in deep cerebellar nuclei. Intrastriatal but not intracerebellar injections of morphine (20 mug) decreased cerebellar cGMP content. Naltrexone, an opiate receptor antagonist, but only apomorphine, a dopaminergic receptor agonist, blocked the effect of morphine on cerebellar cGMP. Pretreatment with 3-acetylpyridine (3-AP) which destroys the climbing fibers, failed to antagonize the effect of morphine on cerebellar cGMP. These results suggest that activation of opiate receptors in striatum decreases cerebellar cGMP content presumably by reducing activity in the mossy fiber excitatory input to cerebellum.


Glucocorticoids: effects on prostaglandin release, cyclic AMP levels and glycosaminoglycan synthesis in fibroblast tissue cultures. Glucocorticoids (GCs) reduced cyclic AMP levels and inhibited glycosaminoglycan (GAG) synthesis in secondary embryonic mouse fibroblast cultures, when cells were incubated for short periods (30 min). The order of potency was dexamethasone greater than prednisolone greater than hydrocortisone. The effect was more marked, when cyclic AMP levels and GAG synthesis were increased by addition of PGE1. Glucocorticoids exerted no longer an inhibitory effect on cyclic AMP and GAG synthesis in cultures pretreated for 48 h with the steroids. Addition of PGE1 caused a stronger rise in cyclic AMP and GAG synthesis than in controls without GC-preincubation. This enhancement was even more pronounced, when PGE1 was added together with the GCs. The reversal of the inhibitory effect of the GCs into a potentiating effect following preincubation correlated to a reducation of endogenous PGE formation in the cultures. Short-term treatment with GCs did not reduce endogenous PGE levels, but prolonged incubation markedly decreased PGE levels. PGE formation recovered following addition of fresh medium after the 48 h incubation with the steroids, but the amount of PGE formed remained significantly lower than in untreated cultures. Non-glucocorticoid steroid hormones did not decrease PGE levels. The results indicate that the apparent loss of inhibitory activity of GCs on cyclic AMP and GAG synthesis observed after prolonged incubation may result from a reduction of endogenous PGE formation which renders the cells more sensitive to the stimulatory effect of exogenous PGE1.


Further evidence for the involvement of cAMP in central blood pressure regulation. In order to test the hypothesis that the activity of cardiovascular centres is determined by their content of cAMP a number of drugs which influence the activity of either phosphodiestase or adenylcyclase were injected in doses of 100-1000 mug/kg into the lateral cerebral ventricle of cats. The effects on blood pressure and heart rate were studied. The phosphodiesterase inhibitors papaverine, carbocromene, theophylline and caffeine caused hypertension and tachycardia which increased with the dose while the phosphodiesterase activator imidazole exerted opposite effects. Sodium fluoride which activates adenylcyclase increased blood pressure and heart rate substantially. The results confirm the above-mentioned hypothesis.


[Electrographic manifestations of sleep in the neuronally-isolated cat cortex]. Electrographic manifestations of sleep were studied in the neuronally isolated cortex prepared after Khananashvili (1961). Development of electrographic sleep-waking manifestations in the neuronally isolated cortex depended on the time passed after cortex isolation. During the first weeks they were not clear, but after 4-6 months it was possible to record all the sleep-waking stages characteristic of the normal animals. During different sleep-waking stages the electrical manifestations in the neuronally isolated cortex occured simultaneously with the signs of sleep in the other, control hemisphere. Most prominent changes during all sleep-waking stages in neuronally isolated cortex occurred in the theta and delta bands, and the less prominent, in the gamma band. The ways of sleep activity propagation in the neuronally isolated cortex are discussed.


[Influence of sympathetic fiber stimulation on conduction of excitation in the cat pterygopalatine ganglion]. Interaction between excitation passing through parasympathetic and sympathetic pathways was studied by recording of action potentials evoked in postganglionic nerves of the cat pterygopalatine ganglion by both testing stimuli applied to the greater superficial  petrosal nerve and conditioning stimuli applied to cervical sympathetic nerve. Depression of synaptic transmission through the ganglion is shown to take place under stimulation of the cervical sympathetic nerve. The magnitude of such inhibition reached to 13 +/- 3%.


[Advances in gammaencephalography for the study of intercranial lesions]. Simultaneously to the development of new techniques such as the computerized axial tomography, the gamma-angioencephalography is progressing in the field of cerebral investigation in its original way, keeping on non invasing character. In view to analyze this evolution we shall examine first its technical possibilities, then the extractible data of the various techniques. Finally we will consider in which way we must bring most of our effort for the best utilization of the gamma-angioencephalography in the routine work, on one hand, and for progressing in the knowledge of the physiopathology of some lesions, specially vascular accidents, on the other hand. Technical modalities are multiple. Besides the standard technique (pertechnetate angiography with rapid sequential views, regional transit curves, early and late static views) it is possible to replace or to repete the injection: --changing the patient's position, --using another radiopharmaceutical labelled with technetium -or another isotope, or two tracers for two compartments; --carrying out a pharmacodynamic or CO2 test, --using radioxenon, and secondly a pure vascular tracer, to measure relative regional blood pool and relative regional blood flow. a) morphological ones (vascular tracks, regional blood pool, radioactive areas: number, form, homogeneity, outline), b) dynamic and quantitative ones (transit times, blood flow, extravascular diffusion, changes of these parameters when changing the radiopharmaceutic, or when using a test). Progresses can take place in three ways, very closely related to each other: a) In the methodology, to precise --relative merit of the different radiocompounds according to the various cerebral lesions, --methods for examination according to the clinical problems, --computing and date processing techniques. b) In the indications, to choose the best, the simplest, though the surest method for the daily clinical problems, and the best one to assemble special information escaping to the morphological radiological techniques. This choice needs frequent and close discussions between clinicians and nuclear specialists. c) In the signification of the data, to interprate correctly: --preferential uptakes in lesions or in compartments, --changes in the relative volumes of vascular bed and extravascular space in lesions, --vascular reactivity to an hemodynamic test, --accumulation or clearance of a diffusible tracer such as xenon. It is not always easy to reach a non equivocal interpretation of a whole group of data. It can be better to give a descriptive analysis which brings together elements for the diagnosis and physiopathological observations helpful for a therapeutic action and to follow up the disease at short and long term.


[Characteristics of brain scintigraphy in pediatric age group and its diagnostic value in brain tumors (author's transl)]. The diagnostic value of brain scintigraphy in intracranial diseases has been well recognized. Numerous reports have appeared in the literature concerning its use in adult cases. The reports dealing with pediatrics cases, however, are quite limited in number. The major factors limiting such studies in children may be considered as follows; (1) infratentorial tumors are common in this age group, in which its diagnostic accuracy has been believed to be quite low, (2) problems of exlosing children to radiation and (3) difficulty in keeping children in one position for a considerable length of time. These difficulties were almost overcome by the use of 99m Tc with a very short half life and a gamma camera, resulting in increased application of this procedure to children. The purpose of this report is to analyse and discuss the scintigraphical characteristics in children and evaluate the diagnostic value in brain tumors. The subjects consist of 199 non-tumoral cases and 53 cases of verified brain tumors. Following conclusions were obtained: (1) Aging changes are noted in normal brain scintigrams of children. One of them is related to the mode of visualization of the basal structures in lateral views. The cranial base appears to be flat before the age of 4 years. A triangular process then appears at the cranial base, approaching that of adult over the age of 10 years. Another change is related to appearance of the temporal and occipital muscles over the cranial vault and the posterior fossa. This becomes apparent about the age of 7 years and produces such masking effects as to interfere with diagnosis in this region over the age of 10 years. (2) The choroid plexus are visualized in about 10% of cases. (3) In brain tumor cases, the detecting rate is 93% in gliomas, and 73% in non-gliomatous tumors. It is particularly low in congenital tumors.


ACTH and brain RNA: changes in content and labelling of RNA in rat brain stem. The influence of synthetic ACTH1-24 and ACTH1-10 on rat brain RNA was studied. ACTH1-24 (5 IU/100 g s.c.) treatment resulted in a small decrease in labelling of brain stem RNA (-12%), measured 30 min after the injection of [5-3H] uridine (100 muCi; s.c.), without affecting the distribution of radioactivity of the acid-soluble precursor pool. Furthermore, a small and transitional reduction of total brain stem RNA was found. Similar treatment of adrenalectomized rats (36 h after surgery) resulted in a marked increase (+ 40%) in labelling of brain stem RNA, without affecting the distribution of radioactivity in the acid-soluble pool. In both intact and adrenalectomized rats, treatment with ACTH1-24 did not affect RNA of cortex cerebrum and cerebellum. ACTH1-10, a fragment of ACTH without corticotropic activity in vivo, exhibited no effect on brain stem RNA in either intact or adrenalectomized rats, nor did corticosterone (1 mg/100 g) affect adrenalectomized rats.


[Value of angiography in the diagnosis of peripheral nerve tumors]. In current practice, arteriograpy is already acknowledged, at the present time, as a method of primary importance which cannot be dispensed withfor diagnosis, prognosis and treatment. By opposition, considering pathology of the peripheric nerves, arteriography is often overlooked before chirurgical exploration though it affords the same advantages as in the remaining fields of pathology. Technically our preference goes to selective angiography by direct puncture of humeral or femoral artery. Arteriography will permit:-Visualisation of the location of the tumor close to the major vessels;-Evidence of the exact site of the efferent and afferent pedicles;-Discovery of other localisation. Mostly arteriography helps preoperatively to histological diagnosis. It must be recalled that benign neurinomas often assume a misleading aspect on the tumorography with stagnation of the contrast medium which might suggest malignancy. These benign tumors have three peculiar features: 1. Arteries are observed to stretch out around the lesion but never to narrow. 2. There is no explosive vascularisation ; hypervascularisation appears progressively, is located on the periphery of the lesion, and occupies but a part of the whole area. 3. Veins are not invaded but pushed apart and duly appear in normal timing. This peculiar aspect is quite the opposite of what can be observed in malignant tumors, which are, by far, less frequent.


Cyclic AMP levels in cerebrospinal fluid in manic-melancholic patients. The concentrations of adenosine 3'5'-cyclic monophosphate (cyclic AMP) in cerebrospinal fluid (CSF) in manic-melancholic patients were studied. As control groups served patients suffering from other psychiatric disorders as well as neruological and orthopedic patients. The results showed no difference between the various diagnostic groups, including melancholic versus manic patients, unipolar versus bipolar types. The severity of the affective states measured by rating scales showed no correlation to cyclic AMP levels in CSF. The cyclic AMP levels were apparently not influenced by electroconvulsive therapy or treatment with lithium, neuroleptica, or tricyclic antidepressants.


Juvenile dystonic lipidosis: an unusual form of neurovisceral storage disease. An unusual neurovisceral lipid storage disorder in two unrelated juvenile patients manifested itself by dystonia and involuntary movements, with facial grimacing, dysarthria, gait difficulty, and impaired manual dexterity. Supranuclear paresis of vertical gaze and splenomegaly were present. Absent were seizures, major intellectual deterioration, spasticity, or blindness. Histiocytes showed lysosomal storage of various phospholipids, cholesterol, neutral lipids, and autofluorescent material. Appendiceal neurons showed only an increse of phospholipids by histochemistry. Neuronal deposits differed ultrastructurally from these in histiocytes. Leukocyte sphingomyelinase activity was normal. The nosology of this disease and its relationship to so-called juvenile types of Niemann-Pick disease is discussed. The primary metabolic defect in these patients remains unknown.


Skeletal muscle pseudohypertrophy in primary amyloidosis. Macroglossia and skeletal muscle enlargement with weakness appeared in a 38-year-old male who was shown to have amyloidosis and light chain multiple myeloma. Free lambda light chains were present in serum and urine. Skeletal muscle contained large amounts of amyloid and other amorphous material infiltrating blood vessel walls and connective tissue. Muscle fibers, particularly the type II variety, were diminished in size. Amyloid and similar amorphous material also were present in skin. This patient represents an unusual, but somewhat uniform, type of involvement of the neuromuscular apparatus in nonfamilial primary amyloidosis.


Schistosomiasis of the spinal cord.

Schistosomiasis of the spinal cord. Four cases of spinal cord schistosomiasis were characterized by paraparesis, sensory loss, and sphincter disturbances progressing over hours to days. One patient showed deterioration over months and remission after laminectomy, followed by the typical, rapidly progressive deficits. Biopsies on two patients showed granulomatous and necrotizing myelitis. Spontaneous improvement and unremitting deterioration, despite chemotherapy, make evaluation of treatment difficult. A survey of all previously reported cases provided no consistent pattern of response to any treatment modalities. Laminectomy for decompression and diagnosis, administration of antischistosomal medications, and high-dose oral prednisone early in the illness are recommended.


Alloxan diabetic neuropathy: electron microscopic studies. Peripheral nerves of diabetic rats were studied 2 years after alloxan injection. We observed demyelination and remyelination, axonal degeneration and regeneration, reduplication of basal laminae around vessels and Schwann's cells, as well as onion bulb formation by proliferated Schwann's cells. Crystalline deposits composed of aggregates of fibrillary electron dense material often occurred in vessel walls and endoneurium of diabetic animals but rarely were seen in nerves from age-matched control animals. Glycogen accumulated in myelinated and unmyelinated axons within mitochondria. Axoplasmic inclusions resembling Lafora's bodies and the inclusions of glycogenosis type IV were frequent and often were accompanied by deposits of particulate glycogen. The findings suggest that the neuropathy in alloxan diabetes is caused by metabolic impairment of anxons, Schwann's cells, and vessels, leading to segmental demyelination and axonal degeneration.


Effects of triiodothyronine on oxidative phosphorylation in immature rat brain mitochondria. Oxidative phosphorylation was measured polarographically in brain mitochondria isolated from 1 to 3-week-old normal and triiodothyronine-treated rat pups. Adenosine diphosphate (ADP)/oxygen ratios with nicotinamide-adenine dinucleotide (NAD)-linked substrates, but not with succinate, were increased in brain mitochondria from experimental animals at each age. Control ratios and respiratory rates were not affected. Thus, the normal maturational increase in ADP/oxygen ratios with NAD-linked substrates is accelerated in brain mitochondria from rats treated with triiodothyronnie from birth. This effect on efficiency of oxidative phosphorylation is similar to that of throid hormones on other properties of the maturing brain.


A neuromuscular transmission block produced by a cancer tissue extract derived from a patient with the myasthenic syndrome. The myasthenic syndrome occasionally is associated with bronchogenic carcinoma. The neuromuscular transmission defect in this syndrome is characterized by a reduction of acetylcholine release from motor nerve endings. This paper reports that an acetone extract of cancer tissue from a patient with the syndrome reduces the acetylcholine release from motor nerve endings and produces a neuromuscular transmission defect in the frog nerve-muscle preparation. This suggests that the pathogenic substance(s) contained in the extract may be produced by certain types of bronchogenic carcinoma and may cause the myasthenic syndrome.


Effect of corticosteroids on sciatic nerve-tibialis anterior muscle of rats treated with hemicholinium-3. An experimental approach to a possible mechanism of action of corticosteroids in myasthenia gravis. We studied the effect of intraperitoneally administered corticosteroids on the neuromuscular transmission in the sciatic nerve-tibialis anterior muscle preparation of the anesthetized rat stimulated at a rate of 10 Hz. Administered simultaneously with hemicholinium-3 (HC-3), 80 mug per kilogram (that is, half the lethal dose for 50 percent survival), prednisolone and dexamethasone cause a marked reversal of the block of the neuromuscular transmission caused by HC-3. The effect of aldosterone is very small. The blocking action of d-tubocurarine is not antagonized by either prednisolone or dexamethasone. Choline provides total protection against the HC-3 blockade, whereas physostigmine, in a just sublethal dose, is ineffective. We tentatively conclude that in myasthenia gravis the carrier-mediated transport of choline into the nerve endings may be deficient and that the beneficial effect of corticosteroids in this condition is based on their ability to ameliorate the deficient choline transport.


[Cancer of the gastric stump after resection for ulcer]. Fourteen cases of primary cancer of the gastric stump as a long-term sequel to resection for ulcer are presented. Surgery was undertaken in all cases, though radical intervention was only possible in 6. Questions of diagnosis and surgical tactics associated with this type of neoplasia are discussed. It is felt that early ascertainment could be aided by fibrogastroscopic controls carried out on a large scale at the time of the symptomatological overture. The possibility of preventive examination is also mooted.


[Wilms' tumor. Our clinical experience]. The survival of children with Wilms' tumour is evaluated in 11 males and 12 females treated between 1967 and 1975 in the light of the clinical stage, age at diagnosis, and sex. The subjects were aged from 4 months to 6 years. Six were in stage I, 4 in stage II, 4 in stage III, 7 in stage IV, and 2 in stage V. Survival in stage I was 100% at 36 months and gradually decreased with the stage. Patients aged less than 2 years presented a survival of 50% two years after diagnosis, compared to 24% in those over 2 years old. Sex appears to be irrelevant to prognosis.


Amniotic fluid adenosine 3',5' - monophosphate in prostaglandin-induced midtrimester abortions. Cyclic adenosine 3'5-monophosphate (cAMP) was serially measured in the amniotic fluid (AF) of 9 patients undergoing midtrimester abortions induced by intraamniotic prostaglandins. The results demonstrate an increase in AF cAMP ranging from 2- to 7-fold within the 6 hours of observation. The fetal heart tones were closely monitored by a Doppler instrument and the time from injection of abortifacient to fetal demise (IDT) and to fetal expulsion (IAT) was accurately recorded. No correlation between the rate of AF cAMP increase and IDT or IAT could be demonstrated. The concentration of cAMP in amniotic fluid obtained from patients with fetal demise in utero was lower than that found in AF of fetuses of corresponding gestational age where the fetus was alive. The significance of AF cAMP as a potential indicator of fetal distress is discussed.


Hodgkin's disease in siblings: a family study. Hodgkin's disease may sporadically occur in more than one member of a family. A family in which two siblings were documented to have the nodular sclerosing form of the disease was studied for immunological competency, distribution of HL-A antigens, and Epstein-Barr virus (EBV) antibody titers. All family members examined, except the living individual with HD, had no significant abnormality in humoral and cellular immunity. HL-A antigens previously reported to appear in Hodgkin's disease with increased frequency were not found. Antibody titers to the viral capsid antigen of EBV were normal. Therefore, none of the genetically associated laboratory tests related to cancer (particularly Hodgkin's disease) were found in this family. The evidence from this family thus supports the probable importance of environmental factors in the etiology of Hodgkin's disease, particularly in the nodular sclerosis group.


Bluetongue virus as a cause of hydranencephaly in cattle. Hydranencephaly was produced in a foetus and a calf by intra-uterine infection with an attenuated Type 10 bluetongue virus. Laparotomy was performed on the respective dams and the foetuses, respectively 126 days and 138 days old, were inoculated intramuscularly through the uterine wall with 1 ml of a virus suspension containing 5 x 103 tissue culture infective doese. The younger feotus was aborted on Day 262, while the other one was born alive on Day 273. Both foetuses showed marked hydranencephaly.


Oral-facial manifestations of Klippel-Trenaunay-Weber syndrome. Report of two cases. Two cases of the Klippel-Trenaunay-Weber syndrome are presented. In one of the cases postsurgical complications arose in association with the vascular component of the syndrome complex. Oral surgeons and dentists must remain aware of the potentially serious complications of dental and/or surgical procedures in such cases. Other stigmata of the syndrome are discussed and related to similar conditions.


Formation of amino acids by cobalt-60 irradiation of hydrogen cyanide solutions. Aqueous solutions of hydrogen cyanide (0.004-0.1 M) were exposed to cobalt-60 gamma rays. Among the products formed on hydrolysis of the irradiated solution; glycine, alanine, valine, serine, threonine, aspartic acid, and glutamic acid have been identified.


[Antibodies against the Epstein-Barr Virus nuclear-antigen in children with malignant disease (author's transl)]. Sera of 25 patients and 50 health children were tested for the presence of antibodies against the Epstein-Barr Virus Nuclear-Antigen (EBNA). We examined 15 children with acute lymphocytic leukemia, who showed a mean arithmatic titer of 1 : 5.33, 1 child with acute myeloblastic leukemia and 1 child with the chronic myeloblastic form showing no reactivity. Two children with lymphogranuloma had titers 1 : 16 and 1 : 32, respectively. 1 patient with lymphoepithelial carcinoma and 5 with lymphosarcoma showed a mean arithmetic titer of 1 : 170.66. Control persons had antibodies against EBNA in the amount of 1 : 2.56. We think that the humoral reactivity against this regularly viral-genome-associated antigen is an additional indicator for the causative role of the Epstein-Barr Virus.


Action of human hyperlipemic sera on the biosynthesis of intercellular matrix macromolecules in aorta organ cultures. Explants from rabbit aortic media were incubated in MEM medium supplemented with 14C-lysine and with 10 p. 100 hyperlipemic (type IV and V) or normal human serum respectively. The incubated fragments were extracted at increasing ionic strength. The insoluble collagen and elastin were hydrolysed with collagenase and alcoholic potassium hydroxyde respectively. The radioactivity was determined in the extracts and the radioactive labelling profile of proteins was investigated on polyacrylamide gel electrophoresis in SDS. With the exception of the collagenase extract (polymeric collagen) the incorporation of the radioactivity into insoluble collagen is not altered or increases. These the incubation was carried out in the presence of hyperlipemic serum. Incorporation of the radioactivity into insoluble collagen seems not to be altered. These results show a decreased protein synthesis with a relative increase in the biosynthesis of polymeric insoluble collagen in the aortic media incubated in the presence of hyperlipemic serum.


[Immunologic study of human low density lipoproteins]. The human serum Low Density Lipoproteins (d : 1,020 - 1,055 g/ml) is composed of lipoproteins B and small amount components which can be precipited during an immunological reaction specifically with lipoproteins C antibodies. Moreover the ethyl-ether treatment induces a dissociation of the LDL into several subunits which have different immunological specificities.


Radiologic recognition of adriamycin cardiotoxicity. A case of congestive heart failure in a child with Wilms' tumor treated Adriamycin is presented and discussed. The role of Adriamycin in the production of cardiotoxicity is reviewed.


Feuerstein and Mims syndrome with resistant rickets. A case of Feuerstein-Mims syndrome (naevus sebaceous, convulsions and mental retardation) is described in association with vitamin D resistant reckets.


The sleep state characteristics of apnea during infancy. The sleep state characteristics of infant sleep apnea were studied in 36 twins examined by polygraphy at 40, 44, and 52 weeks after conception. The definition of sleep apnea is dependent upon the length of apnea, sleep state, and post-conceptional age. None of the infants had apnea longer than 20 seconds and apnea of 10 seconds or longer was uncommon. The attack rates for apneas 2 to 4.9 seconds long were highest in REM and lowest in qliet sleep. The attack rates for apneas 5 to 9.9 seconds long were equal in REM and indeterminate and lowest in quiet sleep. The percentage of infants with apnea of 10 seconds or longer at 40 weeks was highest in REM (27%) and indeterminate sleep (42%) and lowest in quiet sleep (12%). At 52 weeks, apnea 10 seconds or longer during REM decreased to 0%. The effect of maturation on apnea varies with sleep state. Over the period from 40 to 52 weeks, quiet sleep apnea was unchanged and indeterminate sleep apnea decreased only between 40 and 44 weeks. Although REM apnea 2 to 4.9 seconds long was unchanged, REM apnea 5 to 9.9 seconds long decreased between 40 and 44 weeks, and REM apnea of 10 seconds or longer decreased from 27% at 40 weeks to 0% at 52 weeks. This suggests that semi-independent apnea turn-on and turn-off mechanism operate during REM sleep. A correlation between brief apneas and the longer apneas was seen only during REM sleep. For all sleep states, there was no correlation between the levels of apnea of 5 seconds or longer at 40, 44, and 52 weeks.


Herpes simplex: a possible cause of brain-stem encephalitis. Herpes simplex virus was isolated from the tracheal aspirate of a 10-year-old boy presenting with acute onset of multiple cranial nerve palsies and a mild right hemiparesis. There was also an elevated herpes complement-fixation titer with decrease in the following weeks infection by herpes virus have been debated, we propose that this represents a case of brain-stem encephalitis due to herpes simplex infection. The importance of early diagnosis and evaluation of therapy are emphasized by this case in which the patient recovered completely.


Compartmentation of cardiac adenine nucleotides and formation of adenosine. After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either 14C-adenine or 14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3'5'-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substances. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart. Our findings provide evidence that at least two different adenine nucleotide compartments of the heart severe as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.


The effect of an inhibitor of adenylate cyclase on the development of pyrogen, prostaglandin and cyclic AMP fevers in the rabbit. An exotoxin of Bacillus thuringiensis known to inhibit adenylate cyclase in vitro has been used to investigate the role of cyclic AMP in the pathogenesis of fever in the rabbit. Intra-hypothalamic microinjections of the exotoxin are non-pyrogenic and significantly attenuate the hyperthermia caused by intrahypothalamic microinjections of both bacterial pyrogen (endotoxin) and prostaglandin E1. The hyperthermia produced by dibutyrl cyclic AMP is not affected by the exotoxin. These results support the idea that adenylate cyclase is activated during the development of fever in the rabbit.


[Intranuclear inclusions in giant cell bone tumor. Demonstration by electron microscopy]. In a case of giant cell tumour of bone, electron microscopy revealed filamentous inclusions within the nuclei of all the giant cells. Although not invariably present in such tumours, their similarity with the nucleocytoplasmic inclusions seen in osteoclasts in Paget's disease is underlined. This raises interesting questions as to their nature and the histogenesis of these disorders.


The missed menstrual period.

The missed menstrual period. The most likely cause of a missed menstrual period in a woman of childbearing age is pregnancy, stress, or the effects of the pill. If fear of pregnancy is the basis of the problem, simply reassuring the patient that menstrual extraction is available may bring spontaneous resolution.


Effect of drugs stimulating dopaminergic system on phosphodiesterase activity in rat striatum. Two forms of phosphodiesterase exist in the rat striatum, one with high (PDE -- I), and one with low (PDE -- II) affinity to substrate (cyclic 3',5'-AMP). The results obtained suggest that inhibition of PDE -- I activity by apomorphine or amantadine is partially related to their stimulating effect on dopaminergic system in the striatum.


Central action of nomifensine.

Central action of nomifensine. Nomifensine, a new antidepressant drug, affects the central noradrenergic neurons in the rat. Nomifensine does not affect the noradrenaline level in the brain, but retards the depletion of noradrenaline after inhibition of its synthesis. Apomorphine and dimethylaminoadamantane accelerate the depletion of noradrenaline and amphetamine does not affect it. Nomifensine potentiates the flexor reflex of the hind paw of a spinal rat and depresses the body temperature.


The role of peptides in the central nervous system function. The role of peptides such as fibrinogen degradation products (FDP), albumin degradation products (ADP), globulin degradation products (GDP), Bradykinin (BRS) and Angiotensin II (A) in CNS function is presented. Peptides change the activity of the CNS, of the centrally acting drugs and of some neuromediators. The mechanism of the phenomena observed is discussed.


[Hyperlipoproteinemia in children. Correlation between changes in the parents and newborn infant]. The families of 13 children who had presented hyperlipoproteinemia at birth were studied. Total cholesterol, LDL cholesterol, triglycerides and electrophoresis of LP were performed. The parameters studied were divided in three groups: a) Inespecific indicators (alpha-LP, betas/alphas relation). b) Indicators of the beta-LP group (total and LDL cholesterol and beta-LP). c) Indicators of the prebeta-LP group (TG, prebeta-LP and prebeta-1). In all cases at least one of the parents had hyperlipoproteinemia. All the parents, but one, showed alterations in the same group of indicators as their children. Obesity, diabetes mellitus, arterial hypertension, coronary insufficiency, myocardial infarction and cerebrovascular accident where observed in the families of the hiperlipidemic parents, but not on those of the normolipemic parents.


Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase. The spectra of the ferric form of most heme proteins [metmyoglobin, methemoglobin, horse radish peroxidase (EC 1.11.1.7), and ferricytochrome c at pH 1.5] are converted from high-spin (open crevice) structure to low-spin (closed crevice) form under pressure. Pressures up to 8000 kg/cm2 (780 MPa) have no effect on the spectra of high-spin ferro- and ferricytochrome c, which have a closed crevice structure at pH 7.0. Spectra of deoxy-ferromyoglobin and deoxy-ferrohemoglobin are reduced in intensity, but pressure does not change the positions of the absorption maxima. Cyanide ion prevents pressure-induced spectral changes in metmyoglobin and methemoglobin up to 8000 kg/cm2. Carbon monoxide (with a high affinity for the ferro heme iron) has a similar effect on ferromyoglobin and ferrohemoglobin. The pressure required to cause spectral changes in the heme proteins falls in the order, cytochrome c (pH 7.0) greater than horse radish peroxidase greater than myoglobin greater than hemoglobin. We have calculated a volume change of --50 cm3/mol associated with the configurational change accompanying the reformation of the iron-methionine bond in cytochrome c at low pH.


Effect of phosphorylation of smooth muscle myosin on actin activation and Ca2+ regulation. A 35--70% ammonium sulfate fraction of smooth muscle actomyosin was prepared from guinea pig vas deferens. This fraction also contains a smooth muscle myosin kinase and a phosphatase that phosphorylates and dephosphorylates, respectively, the 20,000-dalton light chain of smooth muscle myosin. Phosphorylated and dephosphorylated smooth muscle myosin. Phosphorylated and dephosphorylated smooth muscle myosin were purified from this ammonium sulfate fraction by gel filtration, which also separated the kinase and the phosphatase from the myosin. Purified phosphorylated and dephosphorylated myosin have identical stained patterns after sodium dodecyl sulfate/polyacrylamide gel electrophoresis. They also have similar ATPase activities measured in 0.5 M KCl in the presence of K+-EDTA and Ca2+. However, the actin-activated myosin ATPase activity is markedly increased after phosphorylation. Moreover, the actin-activated ATPase activity of phosphorylated myosin is inhibited by the removal of Ca2+ in the absence of any added regulatory proteins. Dephosphorylation of myosin results in a decrease in the actin-activated ATPase activity. Skeletal muscle tropomyosin markedly increased the actin-activated ATPase activity of phosphorylated but not dephosphorylated myosin in the presence, but not in the absence, of Ca2+.


Isolation from normal and Rous sarcoma virus-transformed chicken fibroblasts of a factor that binds glucose and stimulates its transport. A glucose binding fraction was obtained by sucrose gradient centrifugation and Sephadex G-200 chromatopgraphy from confluent normal cells and Rous sarcoma virus-transformed fibroblasts. It was more or less loosely bound to the membrane fraction, most strongly in sarcoma cells, and most loosely in slowly growing confluent fibroblasts. In an average of three determinations, the content of binding factor was increased 2.5-fold in transformed cells, and compared reasonably well to a nearly 4-fold increase in glucose uptake. The addition of 5 mug/ml of purified glucose binding factor to the overlaying fluid in the 100-mm plates increased 7-flod the low glucose uptake of starved fibroblasts. The stimulation was an additive increment to the known stimulation by calf serum.


Synthesis and characterization of "face-to-face" porphyrins. The syntheses of four binary porphyrins, two of which are constrained to a "face-to-face" conformation, and their Co2+ and Cu2+ derivatives are described. Electron spin resonance indicates that the intermetallic separation in the binuclear "face-to-face" porphyrins is about 6.5-6.8 A. Electronic spectra and proton magnetic resonance spectra support the postulated "face-to-face" conformations. A hypothesis that related compounds may serve as multielectron redox catalysts for O2 and N2 is presented.


Nuclear coupling of 33S and the nature of free radicals in irradiated crystals of N-acetyl-L-cysteine. Hyperfine structure due to 33S in its natural abundance of 0.76% has been measured in the electron spin resonance of free radicals produced by x-irradiation of single crystals of N-acetyl-L-cysteine at 77 K. These measurements proved that the radicals produced at 77 K with principal g values of 1.990, 2.006, and 2.214 are monosulfide radicals with the 3p unpaired electron density of 0.70 on the S. They are believed to be negatively charged molecules RCH2S-H or neutral RCH2SH2 radicals in which 90% of the spin density of the captured electron is concentrated in a d-p hybrid orbital on the S. As the temperature is raised to 300 K, these, as well as the carbon-centered radicals produced at the lower temperature, are mostly converted to neutral disulfide radicals RCH2SS like those observed in irradiated cystine.


Electronic properties of the casein-methylglyoxal complex. Measurements of the electron spin resonance, direct current conductivity, microwave permittivity, and electronic transference number are reported for the brown casein-methylglyoxal complex. Compared with normal white casein, the colored casein complex exhibits an increased electronic activity. This is considered to arise from the electron-accepting action of the methylglyoxal in separating electronic charge from an otherwise completely occupied electronic ground state of the casein macromolecule.


Experimental test of the vibronically coupled tunneling description of biological electron transfer. Evidence for the constructs central to vibronically coupled electron transfer has been obtained. Our experiments show the existence of a weak (f congruent to 10(-6)) charge-transfer absorption band in the near infrared for the bound donor-acceptor complex, cytochrome c-Fe(CN)6. Such a charge-transfer band had been predicted from the theory of such transfers. The experimental method, using a form of excitation modulation spectroscopy, measures only the optical absorption that induces charge transfer between the donor and the acceptor (and does not detect other absorptions) and allows the study of charge-transfer bands whose absorbances are small compared to the sample absorbance. The energy position and oscillator strength of the band agree with the general predictions of this vibronically coupled tunneling theory. We suggest that, in this system at room temperature, the electron transfer can be described by this tunneling theory. This model system result gives credence to the short electron transfer distances the theory has predicted for biological electron transfers.


Rates of aggregation, loss of anchorage dependence, and tumorigenicity of cultured cells. The net rate of spontaneous aggregation of cells suspended with EDTA was measured for various cell types including spontaneous transformants and cells transformed with DNA and RNA viruses. The anchorage dependence as determined by growth in methyl cellulose and the tumorigenicity in vivo were also determined. All cells that had lost their anchorage dependency and were tumorigenic showed a high net rate of spontaneous adhesion. A31 was the only nontransformed cell line to have a high net rate of adhesion. The net rate of spontaneous aggregation of cells is a quick and reliable index of tumorigenicity and offers a new approach to understanding the mechanisms of cell surface changes associated with transformation.


Infectious DNA of spleen necrosis virus is integrated at a single site in the DNA of chronically infected chicken fibroblasts. The infectious DNAs of a number of avian leukosis-sarcoma and reticuloendotheliosis viruses were digested with six nucleotide-specific restriction endonucleases, and the digests were tested for infectivity. All of the enzymes inactivated the viral infectivities except for EcoRI, which did not inactivate the infectivity of the DNA of two of the reticuloendotheliosis viruses, spleen necrosis and chick syncytial viruses. The infectious DNA of spleen necrosis virus after digestion with EcoRI had a buoyant density in CsCl solution greater than the density of the high-molecular-weight infectious viral DNA. The infectious EcoRI-digested spleen necrosis virus DNA from chronically infected chicken cells was uniform in size, 10 megadaltons, which indicated a single site of integration. The infectious EcoRI-digested spleen necrosis virus DNA from acutely infected cells was heterogeneous in size, ranging from 8-14 megadaltons, which indicated multiple sites of integration. These results are consistent with the hypothesis that cells that integrate infectious spleen necrosis virus DNA at a single site survive and multiply, whereas cells that integrate infectious viral DNA at additional sites either die or selectively lose or inactivate the DNA in the additional sites.


Assignment of the integration site for simian virus 40 to chromosome 17 in GM54VA, a human cell line transformed by simian virus 40. GM54VA human cells transformed by simian virus 40 (SV40) were fused with peritoneal macrophages obtained from three different mouse strains. All 27 hybrid clones studied were positive for SV40 tumor antigen in 100% of their cells and contained human chromosome 17. Human chromosome 17 was the only human chromosome present in five of the hybrid clones. Fusion of GM54VA cells and either thymidine kinase (EC 2.7.1.75)-deficient mouse or Chinese hamster fibroblasts resulted in the growth in hypoxanthine-aminopterin-thymidine medium of hybrid clones positive and negative for SV40 tumor antigen. Counterselection of the hybrid clones positive for tumor antigen in medium containing 5-bromodeoxyuridine resulted in the growth of hybrid cells that were negative for tumor antigen. These experiments indicate that negative for tumor antigen. These experiments indicate that SV40 is integrated in only one of the two parental human chromosomes 17. Because the genome of SV40 has been assigned to human chromosome 7 in two other SV40-transformed human cell lines, at least two different integration sites for SV40 would seem to be present in human cells: one located in human chromosome 7 and the other located in human chromosome 17.


The humoral immune response of NIH Swiss and SWR/J mice to vaccination with formalinized AKR or Gross murine leukemia virus. The humoral immune responses of NIH Swiss and SWR/J mice immunized with formalin-inactivated AKR or Gross murine leukemia virus, respectively, were examined. Both immune sera had high titers of antibodies detectable in radioimmune precipitation assays using [3H]leucine-labeled AKR virus and in radioimmunoassays using purified virion components. The predominant antibody titers were directed against gp71 and pl15(E). The immune response against gp71 was predominantly type-specific, whereas the reactivity with pl15(E) was predominantly group-specific. A weak immune response against p15 was also detected. Both sera were cytotoxic against cells replicating the AKR-Gross virus type but not against cells replicating Friend murine leukemia virus. This cytotoxicity could be specifically blocked with purified gp71 of AKR murine leukemia virus. Sera from immune NIH Swiss mice neutralized AKR virus, but did not neutralize Rauscher, Scripps, or wild mouse leukemia virus.


Rauscher-leukemia-virus-related sequences in human DNA: presence in some tissues of some patients with hemotopoietic neoplasias and absence in DNA from other tissues. A [3H[cDNA probe synthesized from the RNA genome of Rauscher murine leukemia virus (MuLVR) and purified by hybridization to MuLVR70S RNA was hybridized to DNA from human normal and hemotopoietic neoplasia tissues. This cDNA hybridized completely to its homologous 70S RNA and was free of self-complementary sequences. Sequences complementary to MuLVR cDNA were found in DNA from tissues of some patients with leukemia (2 of 8), Hodgkin's disease (3 of 10), and one patient with multiple myeloma. DNA from spleen and kidney of a patient with nonneoplastic disease did not contain detectable MuLVR-related sequences. These virus-related sequences in the DNA from these neoplastic tissues were related but not identical to MuLVR sequences because differences of approximately 6 degrees in the midpoints of thermal elution profiles were found between the heterologous and homologous duplexes. These nucleotide sequences are not the same as the proviral sequences of baboon type-C virus previously found from some other patients with leukemia [Reitz et al. (1976) Proc. Natl. Acad. Sci. USA 73,2113-2117; Wong-Staal et al. (1976) Nature 262, 190-195], because there is no sequence homology between nucleic acids from MuLVR and baboon virus. The absence of these nucleic acid sequences in many tissues of patients with neoplasia and from the few tissues examined from people with nonneoplastic disease suggests that they are not endogenous elements but are acquired after fertilization. Taken together with the previous detection of baboon and woolly monkey type-C viral related components in some human tumors, the results suggest acquisition of at least three types of type-C viral sequences in the human population.


Transient induction of a nuclear antigen unrelated to Epstein-Barr nuclear antigen in cells of two human B-lymphoma lines converted by Epstein-Barr virus. Infection of cells of the Epstein-Barr virus (EBV)-negative human B-lymphoma lines BJAB and Ramos with EBV preparations from P3HR-1 or B 95-8 cells converted these cells to EBV genome carriers expressing Epstein-Barr nuclear antigen (EBNA) in almost 100% of these cells. Induction of these cells as well as of clones from P3HR-1 EBV-converted BJAB cells with iododeoxyuridine, aminopterin, and hypoxanthine resulted in the appearance of a nuclear antigen in about 1-6% of the cells 1-4 days after induction. The antigen is different from known EBV-induced antigens like EBNA, viral capsid antigen (VCA) or the D- and R-subspecificities of the early antigen (EA) complex. It is demonstrated by indirect immunofluorescence and inactivated after acetone fixation. The antigen was not detectable after induction of uninfected BJAB and Ramos cells nor has it been found in noninduced or induced P3HR-1 and Raji cells. Thus, it appears that EBV-infection mediates the expression of this antigen, for which the name TINA (transiently induced nuclear antigen) is suggested. Sera reacting against TINA generally contained high antibody titers against EBV-induced EA. Only a limited number of highly EA-reactive sera, however, were also positive for TINA. Among 200 sera tested thus far, TINA reactivity was most frequently observed in sera of patients with nasopharyngeal carcinoma (7 out of 28), in sera of the only two patients with immunoblastoma tested and occasionally in sera from patients with Hodgkin's disease and chronic lymphatic leukemia. Among 70 sera from nontumor patients, TINA reactivity was observed three times: two patients suffered from "chronic" infectious mononucleosis, the other revealed persistent splenomegaly.


Identification of virion polypeptides in hamster cells transformed by herpes simplex virus type 1. Ten polypeptides were detected on the surface of the virion of herpes simplex virus type 1. Of these ten polypeptides, three were detected in hamster cells transformed by herpes simplex type 1.


Nucleotide sequence of the 5' end of araBAD operon messenger RNA in Escherichia coli B/r. The transcription reaction in vitro provides a means of analyzing the nucleotide sequence of the mRNA of the araBAD operon. By controlling the time of synthesis, we obtained araBAD mRNA of varying lengths beginning from the 5' end. These 5' fragments were freed of lambda RNA transcripts by successive hybridizations to the sense strands of a pair of lambda ara transducing phages that carry ara genes in opposite orientations. The purified 5' fragments were ordered by their times of appearance during synchronized RNA elongation and by nearest neighbor analyses. The results, when combined with the knowledge of the NH2-terminal sequence of the product of the first cistron (L-ribulokinase gene araB), establish the nucleotide sequence of the first 69 bases at the 5' end of the araBAD operon mRNA. The AUG starter codon for L-ribulokinase is located at positions 29-31. The sequence is: 5' A-C-C-C-G-U-U-U-U-U-U-U-U-G-G-A-U-G-G-A-G-U-G-A-A-A-C-G-A-U-G-G-C-G-A-U-U-G-C-A-A-U-U-G-G-C-C-U-C-G-A-U-U-U-U-G-C-A-G-U-G-A-U-U-C-U-G-(U)-. . .3'.


A protein covalently linked to poliovirus genome RNA. Poliovirion [32P]RNA, after digestion with RNase T2, yields mononucleotides and a labeled compound "X," which is not negatively charged at pH 5. X contains, relative to the label in virion RNA, one to two phosphates and is partially acid insoluble. It can be labeled with tritiated amino acids 3 hr after infection, is insoluble in chloroform/methanol, and can be digested with Pronase. These observations suggest that X is a protein. The protein cannot be removed from the polio genome when the RNA is (i) sedimented through a sucrose gradient in 0.5 M NaCl, (ii) heated to 100 degrees in the presence of sodium dodecyl sulfate followed by sedimentation through a sucrose gradient in 80% dimethylsulfoxide, or (iii) banded in 4 M cesium trichloroacetate. Digestion of the 32P-labeled protein with Pronase yields one major 32P-labeled product, which contains pUp. The protein migrates faster than capsid protein VP4 in a polyacrylamide gel. Our data show that the genome of poliovirus, but not poliovirus mRNA [A. Nomoto, Y. F. Lee, and E. Wimmer (1976) Proc. Natl. Acad. Sci. USA 73, 375-380], is covalently attached to a small virus-coded protein (molecular weight less than 7000), which we call VPg. VPg is probably linked to the 5' end of the polio genome. Possible functions of VPg in viral replication are discussed.


Enzymatic synthesis of oligonucleotides of defined sequence: synthesis of a segment of yeast iso-1-cytochrome c gene. The deoxyribooligonucleotide, d(pT-T-A-G-C-A-G-A-A-C-C-G-G), constituting a segment of yeast iso-1-cytochrome c gene, has been synthesized by a combination of chemical and primarily enzymatic methods. The starting primer, d(pT-T-A-G1, was chemically synthesized by the phosphodiester method and was extended stepwise, by reactions catalyzed by polynucleotide phosphorylase.


Regulation of behavioral events by thyrotropin releasing factor and cyclic AMP. Like dibutyryl cyclic AMP, thyrotropin releasing factor (TRF) has potent antianesthetic properties, but only dibutyryl cyclic AMP shortens narcosis dose-relatedly. In contrast, only TRF reverses amobarbital-induced hypothermia (dose-relatedly). In naive rats, dibutyryl cyclic AMP (25-200 mug) induces convulsions while TRF (5-100 mug) produces intermittent hyperactivity and sedation but never convulsions. To determine whether behavioral events may be regulated in the central nervous system through an interaction of the two naturally occurring compounds, TRF (5-100 mug) and dibutyryl cyclic AMP (25-200 mug) were injected simultaneously into the lateral ventricle of the brain of naive rats or rats anesthetized with amobarbital (80 mg/kg). TRF (12.5-50 mug) and dibutyryl cyclic AMP (100-200 MUG) DID NOT SHORTEN NARCOSIS FURTHER THAN DIBUTYRYL CYCLIC AMP alone. Amobarbital protected against the lethal effects of the two compounds injected simultaneously. Long-lasting locomotor disorders and mortality rate increased with increasing doses of TRF (12.5-25 mug) and dibutyryl cyclic AMP (100-200 MUG) GIVEN TO NAIVE RATS. Results did not support the postulate that cyclic AMP is the second messenger of TRF.


Comparison of the analeptic potency of TRH, ACTH 4-10, LHRH, and related peptides. Various peptide hormones appear to exert behavioral and pharmacologic effects apart from their classical endocrine actions. Thytrotopin-releasing hormone (TRH), for example, antagonizes the sedation and hypothermia produced by barbiturate and other depressant drugs and de Wied has shown that ACTH 4-10, TRH, LHRH and certain related substances show some activity in inhibition of extinction of a pole-jumping avoidance response in the rat. These data provided the impetus for screening ACTH 4-10, LHRH, and related peptides for analeptic activity. ACTH 4-10 and ACTH 4-7 were inactive in antagonizing pentobarbital whether administered peripherally or centrally. ACTH 4-7 amide and 4-Met(O2), 8-D-Lys,9-Phe-ACTH 4-9 were active regardless of route of administration LHRH and two tripeptide fragments (pGlu-His-Trp-NH, and pGlu-His-Phe-NH2) showed analeptic activity only after intracisternal administration. Thus, some peptide fragments related to ACTH 4-10 and LHRH were shown to share to some degree the analeptic properties previously demonstrated for TRH.


An endogenous inhibitor of N-methyltransferase activity and opiate receptor binding in rabbit tissue. We have characterized and purified a peptide extracted from newborn rabbit brain, lung and liver. This peptide has a molecular weight of 1500 and has the ability to inhibit adult rabbit lung N-methyltransferase activity in vitro and can also bind to opiate receptor in rat brain homogenate.


Neuroheptapeptide influence on attention and memory in man. Twenty normal, male volunteers were administered a subcutaneous injection of either ACTH/MSH 4-10 or diluent and two weeks later received the alternate injection in a complete crossover, double-blind design with order balanced. Subjects were given a battery of psychological tests, including a continuous performance task (CPT), following each injection. Visual evoked responses were recorded during the CPT. Resting, eyes-closed EEGs were also obtained. ACTH/MSH 4-10 improved attention and in so doing improved visual-motor learning and visual, but not verbal, memory, EEG data were consistant with activation of the diffuse thalamic projection system.


Peptide enhancement of neuromuscular function: animal and clinical studies. Evidence is presented for an extra-adrenal effect of ACTH and ACTH analogs on muscle action potentials (APs), contractions and fatigue in in situ experiments. ACTH, alphaMSH, betaMSH and ACTH 4-10 increase the amplitude of APs and contractions and decrease fatigue in intact, hypophysectomized and in adrenalectomized rats, subjected to repetitive indirect stimulation (supermaximal strength, 5/sec or 10/sec for 30 min). Elevation of endogenous ACTH resulting from adrenalectomy or cold stress, or both, has the same effect as ACTH administration. ACTH peptides are most effective in depressed physiological conditions e.g. following hypophysectomy. As the effect of ACTH 4-10 is abolished after section of the motor nerve, it is inferred that this peptide may affect central motor neurons. Preliminary observations from clinical studies with ACTH 4-10 in patients with muscle disease, in whom a pathological decline in amplitude of a short series of evoked muscle APs was prevented by peptide administration, also indicate a possible action of this peptide on central nervous system neurons.


Neuropeptide MSH/ACTH 4-10 enhances attention in the mentally retarded. Twenty adult mentally retarded men were randomly assigned to receive MSH/ACTH 4-10 or a vehicle control solution in a double blind procedure. After an intravenous injection the subjects were presented with an orienting sequence and a series of behavioral tests. Treatment with the peptide resulted in a significant decelerative heart rate response during the test stimulus of the orienting sequence. Improved performance of the intradimensional and extradimensional shift of a visual discrimination procedure was significant for subjects receiving MSH/ACTH 4-10. The pattern of response on the subproblem analysis of the extradimensional shift reflected greater dimensional attention in the subjects treated with the peptide. Attentive subjects given MSH/ACTH 4-10 evidenced significant improvement on a rhythm matching test, a test of spatial localization and a visual retention test. The data were interpreted as indicating that the peptide resulted in improved attention of stimulus processing. It was speculated that MSH/ACTH 4-10 may be unquely coded for perceptor/attentional functioning and may be useful as a treatment for disorders of attention.


Dorsal hippocampus: a site of action of neuropeptides on avoidance behavior? Vasopressin and ACTH 4-10 induce a dose dependent long-term, respectively short-term inhibition of extinction of a pole jumping avoidance response in animals with sham lesions in the antero-dorsal hippocampus. Small lesions, causing a restricted damage in this area of the brain, partly inhibit the behavioral effect of vasopressin. Extensive lesions in the antero-dorsal hippocampus completely prevent the inhibitory effects of vasopressin and of ACTH 4-10 on extinction of the avoidance response. The extensive lesions in the dorsal hippocampus complex do not interfere with the rate of extinction, but acquisition of the response is retarded. These observations do not allow the conclusion that the hippocampal complex is the locus of action of neuropeptides in relation to avoidance behavior; it is more likely that this brain region is but one site of behavioral action of these hormones, and that the limbic system needs to be intact to permit the neuropeptides to exert their behavioral effects.


Effects of neonatal cerebral ventricular injection of ACTH 4-9 and subsequent adult injections on learning in male and female albino rats. An investigation of permanent developmental effects of a potent, long acting ACTH/MSH 4-10 analogue (Organon 2766) on adult passive avoidance performance and of subsequent peripheral adult injections of the same substance on visual (black and white) discrimination learning and reversal in a Thompson-Bryant box was conducted. A subproblem analysis of visual and position preferences during reversal was performed. No differences in passive avoidance performance or in original discrimination learning were obtained. Both infant and adult treatments enhanced reversal learning and visual orientation (proportion of responese to the previously positive stimulus). Infant treatment suppressed position orientation in males and enhanced position orientation in females. These effects were interpreted as indicating that ACTH-like peptides enhance attention to the relevant stimulus by a direct effect on the brain.


Effects of ACTH peptide fragments on memory formation. The effects of peptides derived from ACTH on the formation of long-term memory have been investigated in male mice. Post-training administration of ACTH 4-10-L-Phe-7 (ACTH-L) improved retention for both passive and active avoidance tasks. Administration of ACTH 4-10-D-Phe-7 (ACTH-D) impaired retention for both tasks. The optimum dose for ACTH-L was about 0.3 mg/kg; the optimum dose for ACTH-D was in the range of 1.0-3.0 mg/kg. Using the passive avoidance task, it was shown that either drug had to be administered within 60 min of training to be highly effective. Amnesia produced by anisomycin (Ani), an inhibitor of protein synthesis, was lessened by ACTH-L and increased by ACTH-D, ACTH-D opposed the memory facilitating effects of ACTH-L. Using intact mice, ACTH-L or ACTH-D did not significantly change the incorporation of valine into protein, nor did these peptides influence the inhibition of protein synthesis caused by anisomycin. The results show that ACTH may play a major role in memory processing, perhaps by facilitating essential protein synthesis at sites specific for the memory being established.


Reversal of amnesia by an orally active ACTH 4-9 analog (Org 2766). The ACTH 4-9 analog, H-Met((O2)-Glu-His-Ph-D-Lys-Phe-OH (Or 2766), attenuates in rats CO2-induced amnesia for a one-trial passive avoidance step-through response when administered prior to the retrieval test but not when given prior to acquisition. Even a dose of 0.001 mug/rat Org 2766 yields an anti-amnesic effect. In this respect Org 2766 is more active than the ACTH fragment ACTH 4-10. An anti-amnesic effect was also obtained when Org 2766 was administered orally. ACTH 4-10 (100 mug/rat) has to be given SC within 8 hr of the retrieval test in order to be effective. A similar time span of effectiveness was observed when Org 2766 was SC injected in a dose of 0.1 mug/rat. The anti-amnesic effect of ACTH 4-10 remains when the time interval between acquisition and retrieval is extended beyond the usual 24 hr. The same appeared to be true for SC ADMINISTERED Org 2766. It is suggested that ACTH-like peptides, and particularly the orally active Org 2766, may be helpful in the treatment of deficient mental performance.


ACTH 4-10 and short-term memory.

ACTH 4-10 and short-term memory. ACTH 4-10 is a polypeptide which is a fragment of pituitary ACTH and was synthesized by Greven. Studies suggest that it does not have the endocrine or metabolic effects characteristic of ACTH but may have a specific enhancing effect on memory or possibly on attention. Several tasks which emphasized the storage phase of the memory process were presented to young adult (mean age: 23.6 yr) male volunteers. Subjects received 30 mg ACTH 4-10 subcutaneously and their performance on these tasks was compared against placebo. ACTH 4-10 had no effect on unisensory short-term memory. It did, however, impair performance of a bisensory short-term memory task. The bisensory task is complex and requires considerable focussing of attention. It is suggested that ACTH 4-10 may act on the arousal processes which energize behavior unselectively rather than result in focussing of attention.


Cognitive effects of ACTH 4-10 in the elderly. The polypeptide ACTH 4-10 has been shown to facilitate learning in animals, and possibly to improve attention and memory in normal human subjects. The purpose of this study was to assess the effects of ACTH 4-10 in cognitively impaired elderly subjects. In a double blind, cross over design, 24 cognitively impaired geriatric outpatients (mean age=71.4, 12 with mild and 12 with severe impairment) received injections of 30 mg or 15 mg ACTH 4-10 or matched placebo on 3 successive days. A cognitive test battery of memory and nonmemory tests was administered each day both before and after treatment. The 30 mg dosage produced a slowing of simple visual RT, a nonsignificant improvement trend in verbal associative memory, and significant, severity dependent facilitation or impairment in day later visual memory. The results suggest that the ACTH 4-10 effects on cognitively impaired elderly are dependent on the dosage and on the baseline cognitive level of the subjects.


Pigmented villonodular synovitis of the temporomandibular joint. Case Report. Pigmented villonodular synovitis is a lesion containing giant cells and, because of its tendency to recur, it is easily confused with a malignant process. However, careful review of the histological material will reveal that there is no nuclear atypism or mitotic figures. Also, there have been no reports attributing metastases or death to thid disease. The clinical course of our case was definitely benign.


Propranolol and morphine.

Propranolol and morphine. The morphine blocking and anticonvulsant effects of propranolol were investigated in mice. Three different convulsant procedures (electroshock, pentylenetetrazol and thebaine) were used. In addition, LD50's of morphine after different doses of propranolol were done. Sotalol was used as a control drug to check which of the effects of propranolol could be regarded as due to beta blockade. Morphine LD50 in mice is not altered by pre-treatment with propranolol. The anticonvulsant characteristics of propranolol are different from those of sotalol, the former acting mainly on the tonic phase of the seizures. This study does not support the hypothesis that propranolol is a morphine antagonist but reinforces the idea that propranolol has definite central nervous system effects.


Inhibition of catecholamine biosynthesis and memory processes. Rats injected with 60 mg/kg of alpha-methyl tyrosine (alpha-MT) immediately after a training in a shuttle box impaired retention of conditioned avoidance response (CAR). DL-Dopa (200 mg/kg) administered 5, 30, 60, and 120 min after alpha-MT treatment counteracted the depressive effect of this drug during the retention test; at longer times it was ineffective. Post-trial injections of 600 mg/kg of diethyldithiocarbamate (DDC) impaired retention of CAR; at a lower dose (300 mg/kg) it had no effect. Administration of alpha-MT (60 mg/kg) immediately after passive avoidance training lowered memory in females but not in males. These results suggest that noradrenaline (NA) is required for memory consolidation processes for about 2 h after training.


Determination of the mass of viruses by quantitative electron microscopy. The photometric method of quantitative determination of dry mass by electron microscopy has been applied to the study of various types of viruses: animal, plant, insect, and bacterial. The method is applicable to all viruses having a mass of 1 x 10-18g or greater. The molecular weight of viruses can be calculated from the mass value by multiplying it by Avogadro's number. In comparison to other methods of determining the molecular weight of viruses, sedimentation and diffusion, sedimentation equilibrium, light scattering, and electron microscopy counting, the method of quantitative electron microscopy is competitive. In some ways quantitative electron microscopy is superior to other methods for the determination of molecular weight: There is no limitation to the size of the virus, no experimental time involved and no concentration and purity of virus preparations required, and finally it is independent of the geometry of the virion. In one important aspect it is unique when compared to other methods; namely, it affords one the capacity to analyse individual virus particles.


A possible mechanism for the action of some myxoviruses. The redox properties of some myxoviruses [Fowl plaque virus strain Rostock (FPV), New Castle Disease virus strain Italy (NDV), B/Hong Kong, A/Port Chalmers, A/Victoria, A/Scotland, and A/Fort Dir) and electron microscopic studies as well as by the determination of the hemagglutination (HA) titer (antigen efficiency). The results have shown that viruses decrease the spin concentration of Cu2+ by acting as a reducing species (electron donor) which will result in the inactivation (oxidation) of the virus. Addition of an oxidizing substance, such as H2O2, to a virus suspension also leads to an oxidation of the viruses, and, thus, to their inability to reduce Cu2+. This result is confirmed by the decrease of the HA titer of viruses with increasing Cu2+ concentrations. H2O2 could not be applied for the HA titer test since it interacts with the erythrocytes of the chicken blood used for this determination. Therefore, another oxidizing substance (oxidized glutathione, GSS) was selected which exhibited a slightly less pronounced effect than Cu2+. Since reduced glutathione (GSH) exerts a similar but less pronounced effect than GSS, it might be concluded that viruses have a redox system of their own and act as reducing or oxidizing substance depending on the biological receptor system. Electron microscopic studies confirm this hypothesis. As can be seen by the electron micrographs, increasing concentrations of either Cu2+, GSS, H2O2, KMnO4, or GSH will, finally, result in a complete destruction of the virus. Because of structural similarities it might be assumed that other types of viruses behave very similarly.


ESR and optical absorption studies on the copper (II) interaction with aromatic amino acids. Electron spin resonance and optical absorption studies have been done in order to investigate the interaction between Cu2+ and aromatic amino acids in aqueous solution at 77 K and at room temperature as well. Depending on the concentration each aromatic amino acid can form two different kinds of complexes with Cu2+ which can be characterized by its ESR pattern. Additional information was obtained from optical d-d and CT transitions.


Effect of economic barriers to medical care on patients' noncompliance. The post-hospital care of 290 patients with selected chronic conditions of a specific severity who were discharged over a 3-month period from a general hospital in Halifax, Canada, was studied. The majority of the patients were married. The average age of the men was 59.2 years and of the women 58.1. More than half of the patients belonged to the low socioeconomic group earning between $1,000 and $6,999 a year. Their average period of education was 8.4 years. Interviews with the patients about their compliance with physicians' orders revealed that 40.4 percent had not complied with one or more of their physician's recommendations. Lack of compliance was related to age, marital status, education, income, and severity of disease. It was also associated with high dosages of medicine and multiple prescriptions. Cost barriers constituted a significant factor in noncompliance.


Pancreatic calcifications in malignant islet cell tumors. Of 623 cases of malignant pancreatic tumor seen at University of Chicago hospitals over the last 30 years, 23 cases of malignant islet cell tumor were found (8 additional cases were found in the literature). Calcification, found in 2 of these cases, was characteristically discrete and nodular (calcifications found in chronic pancreatitis are typically diffuse, multiple, and punctuate). At least 7 of the 10 cases of islet cell tumor with calcification were malignant. Slow growth of the tumor, with calcified metastases, strongly suggests the diagnosis of malignancy; this combination of findings has been established in 3 cases. In 73 cases of benign islet cell tumor, no calcifications were found.


Cytologic and cytochemical behavior of primary malignant bone tumors. Cytologic and cytochemical examination of eighteen cases of round-cell sarcoma of bone allowed classification of these tumors into four cytologic groups. Additional cytochemical examinations based on the PAS and D-PAS reactions, and the demonstration of the activity of peroxidase, naphtol-ASD-Chloracetate esterase, alpha-naphthylacetate esterase, naphthol-AS-acetate esterase with and without sodium fluoride inhibition, acid and alkaline phosphatases yielded no evidence of uniform behavior among the individual groups or within any single group. The studies showed that a positive glycogen reaction cannot be used as a basic criterion for the classification of such tumors as Ewing's sarcoma and for regarding them as a uniform tumor group. It is possible that a pool of tumors is involved, including tumors of monocytic and probably of lymphocytic origin, reticulum-cell sarcoma, tumors of myelocytic and erythroplastic origin, stem-cell tumors, and endothelial-cell tumors. Histologic examination alone is not sufficient for the classification of round-cell sarcomas of bone, and it should be supplemented by cytologic and cytochemical or histochemical methods. Osteosarcomas (23 cases) and chondrosarcomas (8 cases) display cells which are characteristic for these tumors and which could be correlated with their benign counterparts, osteoblasts and chondroid cells. The histologically recognizable degree of malignancy of chondrosarcoma can be evaluated better with the cytologic than with the histologic technic. Indications of the possibilities of differential diagnosis based on the cytologic pictures of benign and malignant osteoplastic and chondroplastic tumors, giant-cell tumors and chordoma are discussed.


Morphological, biological, immunological and biochemical studies on bone tumors of animals and man. Biological studies on FBJ osteosarcoma virus in tissue cultures have led to the isolation of murine sarcoma virus. Characteristic type C-MuLV particles were observed in bone tumors induced by the SD-MSV-M-virus in vitro and in vivo. The SD-MSV-M virus also induced bone tumors in rats of all strains tested, and it has a similar tumor-inducing property in hamsters. Immunoelectronmicroscopic studies showed that envelope antigens of MSV-SD virus in rat bone tumors can be distinguished from those found in hamster bone tumor cells. In tissue cultures of MSV-SD rat bone tumors, two separate cell lines have been established: one of them releases both MSV and MuLV and the other produces MuL virus only. The MuLV in this cell line acts as helper. The different interactions appear to support the concept of control mechanisms for the partial expression of genes which are responsible for neoplastic properties, virus replication, and synthesis of gs-antigens. Biochemical studies on structural rearrangement and subunit composition of RNA released from MSV-SD virus, have shown that there are two forms of the native genome RNA differing in their sedimentation coeffiiecients and in subunit composition. In human osteosarcoma tissue culture, type-C viruslike particles are found. In cocultures derived from human osteosarcoma with cells taken from the bone marrow or peripheral blood of patients with different types of leukemia, certain morphological changes are observed which resemble those induced in  animal cells by RNA tumor viruses. In osteosarcomas where no cytoplasmic antigen could be proved by an immunofluorescence test, the antigen could be produced by cocultivation with antigen-positive leukemic bone marrow cells. Whole human embryo cells treated with fluid from leukemia bone marrow cultures showed the presence of the cytoplasmic antigen when tested with positive sera, but they showed no morphologic changes. In high molecular weight RNA species, sedimentation coefficients ranging from 62S to 68S are demonstrated by molecular hybridization techniques. In cross-hybridization experiments, annealing values were observed only with complementary DNA products synthesized from sarcoma viruses. Three particularly high molecular weight RNA species released from human sarcoma cell cultures showed no cross-hybridization with either the DNA product of Rauscher leukemia virus or that of Gross leukemia virus.


The endogenous origin and transmission of RNA viral genomes that code for cancer. In certain experimental animals, type-C virus genomes are universally prevalent. They are mostly but not exclusively transmitted genetically and produce tumors naturally as well as when transmitted experimentally. The spontaneous virus and tumor expressions are regulated and modified by genetic factors; and virus-specific virogenes used as vaccines prior to high-level natural expressions can suppress natural expressions of the virogenes. Application of this significant information to the prevention of cancer in mice now seems quite feasible; however its application to the control of human cancer is still dependent on the isolation of specific human type-C virus(es).


Pathogenesis of radiation and virus-induced bone tumors. Bone cancer can be induced by radionuclides that localize in the skeleton. Histologically, these experimentally induced tumors resemble those found naturally in man; they range from densely ossified osteogenic sarcomas to osteolytic tumors with giant cells and only a small osteoid component. Fibrosarcomas and hemangiosarcomas also can occur in some species. It has not been possible to determine the dose in terms of absorbed energy necessary for bone-tumor induction because radionuclides are not deposited uniformly, and they diminish in amount with time. Also, the precise time when irreversible noeplastic change occurs is not known. With X-rays, however, 500 rads delivered to the endosteal surface of a mouse femur has been shown to cause osteogenic sarcoma. Bone tumors can be induced in mice by viruses. FBJ osteosarcoma virus and RFB osteoma virus were obtained from spontaneous tumors; FBR osteosarcoma virus came from a radiation-induced tumor. All three are RNA viruses with C-type particle morphology, and they are propagated by injecting cell-free extracts of virus-induced tumor. All three are RNA viruses with C-type particle morphology, and they are propagated by injecting cell-free extracts of virus-induced tumor into newborn mice. Interaction studies with bone-seeking radionuclides and these viruses have led to the hypothesis that radiation produces cancer by inactivating a viral inhibitor. There is also evidence of a bone tumor virus in the human disease. The injection of cell-free extracts of human bone cancer into newborn Syrian hamsters has induced a variety of mesenchymal tumors at a rate significantly higher than in the control hamsters. Sixty tumors of this type, including 20 osteosarcomas, 11 fibrosarcomas, and 9 osteomas, have been diagnosed so far in experimental animals; in control hamsters there has been only one, a fibrosarcoma. Immunofluorescence assays and cytotoxicity studies indicated that these hamster tumors carried a human antigen.


Inhibition by somatostatin of secretin-stimulated pancreatic secretion in man: a study with pure pancreatic juice. The action of somatostatin on compostition and flow rate of pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct was evaluated in 5 healthy volunteers. Synthetic secretin (0.06 CU/kg-h) was intravenously infused throughout the 80-min study. Bicarbonate concentrations in pancreatic juice achieved constant levels (117 +/- 3 muEq/ml) after 10 min, whereas a steady state of juice flow (7.3 +/- 1.4 ml/5 min) was attained after 15 min of secretin infusion. In the third 20-min period, cyclic somatostatic (5 mug/kg-h i.v.) was given, leading to a decrease in pancreatic flow rate by 47% after 10 min, and by 67% after 15 min of somatostatin administration. Alrady 5 min after the infusion of somatostatin had been discontinued, pancreatic flow rate gradually recovered; presomatostatin levels, however, were not reached within 20 min. Cyclic AMP varied roughly in accordance with bicarbonate concentrations, whereas the chloride concentrations were reciprocally related. Bicarbonate, sodium, potassium, protein, and cyclic GMP concentrations did not change substantially due to somatostatin.


Virus antibody levels in IgA deficiency. IgA-deficient blood donors and their age- and sex-matched controls were compared for the occurrence of complement-fixing antibodies in serum against several viruses. The level in the IgA-deficient persons was slightly higher against several respiratory pathogens (adenoviruses, type B influenza virus, parainfluenza virus, and respiratory syncytial virus) that give rise to localized infections, and against coxsackie B group of viruses. No corresponding difference was observed in mumps, varicella, and cytomegalovirus infections, where viraemia is a characteristic feature, or in Mycoplasma pneumoniae infection.


A trial of an alpha-adrenoreceptor blocking drug (indoramin) in exercise-induced bronchoconstriction. In 10 patients with exercise-induced asthma oral indoramin, an alpha adrenoreceptor blocking drug, was ineffective in preventing the post-exercise fall in peak expiratory flow rate (PEFR). The values of PEFR at rest increased after administration of indoramin, providing indirect evidence for the existence of alpha receptors in the bronchial smooth muscle of asthmatic subjects.


Tracheobronchial clearance and beta-adrenoceptor stimulation in patients with chronic bronchitis. The effect of a beta-adrenoceptor stimulating agent, terbutaline, on mucociliary transport in the lungs was studied in 10 patients with chronic bronchitis. Mucociliary transport was studied by having the patients inhale 6mum teflon particles tagged with 99mTc and by external measurement of the radioactivity in the lungs in the supine position. Terbutaline 0.25 mg and vehicle respectively were given subcutaneously in a cross-over double-blind study. On the average, clearance was slow in the examinations where the patients were given vehicle. Terbutaline produced a marked increase in mucociliary transport in four patients, a smaller increase in one and no effect in the others. Three out of the four patients who showed a marked inrease in clearance had less ventilatory impairment than the other seven patients. This may indicate that the mucociliary transport mechanism is less severely damaged in relatively early stages of the disease than in later stages. On the average FEV1.0 deteriorated significantly during the clearance measurements when vehicle was given, but did not change significantly when terbutaline was given.


Viral, mycoplasma and bacterial infections in nurses with symptoms of respiratory diseases. A consecutive series of 282 nurses of the University Hospital, Groningen, with complaints of the nose and/or throat associated with coughing and/or hoarseness were examined between April 1965 and February 1968. The intent was to obtain information on the incidence of viral, mycoplasma and bacterial infections, and on the relationship of these infections in nurses with chronic nonspecific lung disease (CNSLD). The following results were obtained: 1. Virus infections caused by influenza virus (A, B, and C), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus and/or Mycoplasma pneumoniae were confirmed in 30% of the nurses examined; if influenza was excluded, this figure was 20%. 2. Rhinovirus infections were found more often than all the other virus infections together (if influenza was excluded). 3. Approximately 25% of the nurses had signs of CNSLD. 4. In the course of the virus infections, nine out of 14 nurses with a history of chronic obstructive lung disease showed symptoms of exacerbation or recurrence of a generalized bronchial obstruction. 5. There was no difference in the incidence of virus infections in the group of nurses with and without CNSLD. 6. There were more bacterial infections (without a confirmed virus infection) in the subjects with CNSLD than in those without CNSLD. 7. There were more combined viral/bacterial infections in the patients with CNSLD than in those without CNSLD. 8. Patients with influenza did not have more bacterial infections than patients with other virus infections. This is also true for patients with CNSLD and influenza when regarded separately. The patients without CNSLD tended to have more bacterial infections with influenza than with other viral infections, but the difference was not statistically significant.


[Dynamics of plasma catecholamines and beta-adrenoreceptor functions. Use of a new radio-enzymatic micro-method]. The new method for simultaneous determination of noradrenaline (NA), adrenaline (A) and dopamine in 50 mul plasma has proved specific, sensitive and readily reproducible. In 6 healthy volunteers NA was 190 pg/ml and A 63 pg/ml in the supine position and rose during graded upright exercise to NA 819 pg/ml and A 161 pg/ml (150 watts; p less than 0.001 and less than 0.05 respectively). NA and A paralleled exercise tachycardia (r = 0.894; p less than 0.001) and renin stimulation (r = 0.620; p less than 0.001). 21 patients with essential hypertension exhibited relatively higher NA concentrations both at rest and during graded exercise (p less than 0.05 for both). Exercise-stimulated NA and A further rose following 0.15 mg/kg propranolol i.v. (p less than 0.01 and p less than 0.05 respectively). With increasing age and blood pressure, plasma catecholamine concentrations rise while the reactivity of heart rate and renin secretion decreases. Acute pharmacological blockade of beta-adrenoreceptors increases catecholamine overflow in similar fashion to the physiological dissociation of plasma catecholamines and adrenoceptor responsiveness.


[Lung changes after organ transplantation]. The morphological pulmonary alterations in renal transplant recipients have been investigated in the light of 62 autopsies. Apart from the predominant pulmonary edema of septic, uremic or circulatory origin, pneumonic opportunistic infections were prominent. The most important agents proved to be bacteria, cytomegalovirus and fungi. In most cases, mixed infections were observed. At autopsy, pneumocystis carinii infections appeared to be of little importance. The pathology of the pulmonary changes reflects the reduced defense inevitably following on immunosuppressive medication, which in turn is indispensable for successful transplantation.


Presynaptic electrical coupling in Aplysia: effects on postsynaptic chemical transmission. The large cholinergic interneuron L10 in the abdominal ganglion of Aplysia mediates both chemical and electrical synaptic transmission. The amplitudes of postsynaptic potentials produced by different branches of L10 are differentially affected when the electrically coupled neuron L20 is depolarized or hyperpolarized. Polarizations applied to L20 are transmitted to L10 branches by the "presynaptic"electrical synapse. Depolarization increases the amplitude of the postsynaptic potential, while hyperpolarization has the opposite effect. The differential effects occur because current supplied through the electrical synapse undergoes more electrotonic decrement for the distant branches than for branches closer to the electrical synapse. These findings indicate that the presynaptic electrically coupled neuron may have an integrative role in the modulation of chemical synaptic efficacy mediated by L10.


[Colonic Crohn's disease: diagnostic and therapeutic problems. Apropos of 11 cases]. The authors report a few unusual cases of Crohn's disease of the colon and discuss the diagnostic problems which are raised in such cases. They then review the various colonic diseases liable to be considered in a differential diagnosis, and which may be linked to colonic Crohn's disease, e.g. ulcerative colitis, intestinal tuberculosis, carcinoma of the colon, colonic diverticulosis and sarcoidosis. In a chapter on treatment, they emphasize the favourable effect of acexamic acid and the necessity for very wide colonic resection, and they note a complication which they encountered during surgery for Crohn's disease: lymphatic peritonitis on the 8th day after right colectomy.


[Lymphatic peritonitis occurring 8 days after right colectomy for Crohn's disease]. The authors have observed on two occasions, a diffuse peritoneal syndrome in the post-operative period after right hemi-colectomy for Crohn's disease, and interpret, in the absence of complications at the level of the anastomosis, as peritonitis due to septic lymphorrhea. According to them, it does not seem that this syndrome has the same significance as that described following appendicectomy in children.


[Bone-marrow biopsy in Hodgkin's disease]. In 349 subjects with Hodgkin's disease 520 bone marrow biopsies were carried out: 454 did not lead to the discovery of any tumour (87.5%), 66 permitted us to discover a tumour (12.5%). Among the bone marrows without Hodgkin tissue, the hematopoietic tissue was normal in 233 bone marrows (51.2%), hyperplastic in 157 bone marrows (34.7%), hypoplastic or aplastic in 64 bone marrows (14%). Eosinophilia was noted in 13% of cases, marked plasmacytosis was noted in 24%. Among the cases with a tumour, 89.2% showed a massive lesion; 10.7% showed partial lesions. The frequency of involvement was 5.4% for clinical stages I. 6.2% for stage II. 17.1% for stage III. 47.6% for stageIV. Bone marrow involvement at the start of the disease was found in 3% of cases, even in stages I and II. The involvements were especially frequent in the histological forms, stage III (19.4%) and IV (30.4%). In splenectomised patients, bone marrow involvement was 5 times more common when the spleen was also involved. 50 times more common when the liver was involved. The bone marrow which may be used to detect hematogenic spread of Hodgkin's disease is an investigation which should be carried out as a routine in the early stages of the disease and whenever a relapse is suspected.


[Morphological aspects of the bone marrow in hairy-cell leukemia]. Bone marrow plays a considerable role in the diagnosis of hairy cell leukemia. The morphological aspects should be well known. One should emphasize the existence of aplastic or hypoplastic forms requiring one to repeat biopsy on the slightest clinical suscpicon. Routine histological techniques are sufficient for the diagnosis. The ultrastructural study also provides valuable histological and cytological evidence.


[Bone-marrow biopsy in chronic myeloid leukemia. Value of the initial examination]. In 31 patients with chronic myeloid leukemia, the initial bone marrow biopsy constantly showed considerable cell richness. The maturation of the granulocytes was harmonious in 52% of cases, with a predominance of myelocytes in 32% of cases, and groups of myeloblasts in 13% of cases. Eosinophilia was frequent and fairly intense. Fairly numerous loaded cells and Charcot-Leyden crystals were signs of granulocyte failure in the bone marrow. The erythroblasts were reduced, the megakaryocytes increased. Myelofibrosis was present in 45% of cases. This gave a very characteristic histological appearance. It was not possible to draw up correlations between the type of granulocyte maturation and/or the presence of myelofibrosis and, on the other hand, the clinical course of the disease, but the small number of case studied both in our series and in the literature do not permit one to carry out a proper statistical study.


[Bone-marrow biopsy in chronic myeloid leukemia. Significance during development]. In 29 patients bone marrow biopsy carried out during the course of chronic myeloid luekemia, permitted the authors to divide up the patients into 5 histologically different groups according to the association of 3 parameters: the richness in granulocytes, the state of the matrix, the degree of leukoblastosis. There was, in most cases, correspondence between the histological appearance and the clinical and laboratory symptoms. This was particularly clear when the patient entered the terminal phase of the disease. 4 of the 5 histological groups had an unfavourable short-term prognosis, i.e., granulocyte hyperplasia with myelofibrosis, aplasia with normal matrix or with myelofibrosis and massive leukoblast invasion.


[Extrinsic compression of the celiac trunk by the arcuate ligament of the diaphragm. Apropos of 5 cases]. The authors report 5 cases (3 women and 2 men) of extrinsic stenosis of the coeliac axis by the arcuate ligament of the diaphragm. In one of the latter, the stenosis of the coeliac axis was associated with chronic calcific pancreatitis. These 5 patients were operated on. Division of the arcuate ligament gave on the whole very favourable results. (3 excellent results, one good and one average result). The authors then recall the clinical, angiographic and pathogenic data in this disease which remains exceptional. The diagnosis should be made and operation decided only after a fairly long period of observation during which one has elimiatned the diagnoses of gastro-intestinal, gall bladder, pancreatic and above all psychiatric disease by endoscopy, radiography and symptomatic medical treatment.