[Coronary stenosis in angina pectoris with normal resting electrocardiogram]. The arteriographic abnormalities found in 104 patients with typical angina pectoris and an electrocardiogram at rest which was normal at the time of arteriography were compared with those of 238 cases with typical angina pectoris, but with an abnormal electrocardiogram (127 having ST/T changes, 111 having transmural necrosis). There was no major difference between the two groups as far as the degree of coronary stenosis was concerned, nor in its extent and distribution. However, by comparison with the group with an abnormal electrocardiogram, very tight stenoses of the three trunks or of one trunk alone were slightly less common in the patients with a normal electrocardiogram; also, for each of the three trunks, the index of the lesion was slightly less raised, and the circumflex and right coronary arteries were slightly less commonly, affected, although the difference was not usually great enough to achieve significance. The action of the left ventricle and/or the value of left ventricular end-diastolic pressure were, however, manifestly better conserved in those with a normal electrocardiogram (p less than 0.001). An aorta-coronary bypass graft is more likely to be indicated in this group of patients.


[Pacemakers in children].

[Pacemakers in children]. This is a study of pacemakers in 32 children with permanent pacemakers, 7 of them for congenital block, and 25 for post-operative block, representing a total of 69 pacemaker implantations. After a brief survey of the results, there is a discussion of the problems of the indications, relative for the congenital blocks, and absolute for the surgical blocks after a short period of observation. The choice of type of pacemaker rests upon three essential features: minimum inconvenience, a good length of active life, and the facility of an increased rate. Recent technical progress has allowed these features to be combined. The pacemakers currently available are shown on a table. The results are to a large extent determined by extreme care being taken over the implantation; meticulous asepsis, a low threshold on the electrode test, a pacemaker which is "comfortable" in its site, all these are essential if the serious complications are to be avoided, namely infection and pacemaker failure. The best route for the child, as for the adult, is by way of an epigastric approach with an abdominal pocket. In the very small infant, it seems better to implant by left thoracotomy, and to site the pacemaker intrapleurally.


[Value of hemodynamic surveillance by radiocardiography in human heart transplants]. Eighteen cases of cardiac transplantation have been carried out for 16 recipients since October 1973, there being 8 survivors at present. The importance of screening in such a treatment is vital. It is a simple method, easy to control, can be carried out at the bedside, is reproducible, reliable, and completely harmless, and by allowing the haemodynamic function of the graft to be seen at all times, helps in the marching of the donor and the recipient, in following the function of the graft in the immediate post-operative period, and in discovering rejection crises, and evaluating the long-term fate of the transplant.


[Simultaneous measurement of cardiac output by indium 113 m detected externally and by dye dilution of indocyanine green]. The cardiac output of 11 patients was measured by a method of dilution of a short-life radio-isotope, and compared with measurements obtained simultaneously by a dye dilution technique. After sudden intravenous injection of siderophilin (transferrin) labelled by Indium 113 m, the precoridal radioactivity was measured by a single panel detector probe. In 9 patients these measurements were carried out twice with a 15 minute interval. The correlation coefficient between the two methods was 0.884 for 20 measurements, and 0.939 for the first 11 measurements. The reproducibility of these measurements was comparable for the two techniques. The radio-isotope method of measuring cardiac output, which can be carried out at the bedside, is a simple, reliable and reproducible technique.


[Abnormalities of insulin secretion in coronary patients. Apropos of 67 cases]. The curve of blood insulin levels recorded during the oral provoked hypoglycaemia test (OPHG) was studied in 67 proven coronary patients. None of the curves obtained was normal. The abnormalities found in this way are of two types: either a hypoinsulinaemic response, with a high non-retarded peak (type 1) or a high retarded peak (type 2), or else a hypoinsulinaemic response, with a flat curve (type 3) or a very small late peak (type 4). The possible role of these abnormalities of insulin secretion in the pathogenesis of atheroma is discussed. The correlations between age, sex, obesity, hypertriglyceridaemia, and the OPHG curve are investigated. The preliminary results of a test in which insulin levels are monitored after intravenous provoked hypoglycaemia, followed by tolbutamide, are reported.


[Action of chloro-acetyl-ajmaline on the electrical properties of the human heart]. The electrophysiological changes caused by the intra-atrial injection of 1.5 mg/kg of chloro-acetyl-ajmaline were studied in 23 patients by recording the His potential and by the stimulustest method. The length of the basal cycle being kept constant by atrial stimulation, measurements were made before and after the injection, on the one hand of the -VA node conduction time (A-H interval) and the infra-His conduction time (H-V interval) and on the other of the refractory periods of the right auricle, A-V node, and the His-Purkinje system. The effective refarctory period of the right ventricle was determined under pace-making of the ventricle. Finally, the variability of the sinus rate was measured. The results were as follows: 1. The sinus cycle was significantly shortened after administration of the drug (p 0.001); 2. The conduction time and refractory periods of the A-V node were not influenced by this substance; 3. The H-V interval was increased in 20 patients by an average of 11 ms (p less than 0.001). The relative refractory period of the His-Purkinje system was reduced in 4 cases out of 7 by 21 ms (p less than 0.05); the effective refractory period in one case showed a reduction of more than 45 ms. These findings will serve as a base line for assessing the anti-arrhythmic action of chloro-acetyl-ajmaline.


[Effect of a depressant drug on the recovery time of the sinus. Attempt of application to the diagnosis of sinus dysfunctions]. The authors have studied the effect of a depressant drug, 71247 or piprofurol, on the recovery time of the sinoatrial node after rapid electrical stimulation of the atrium (CSRT). 72 patients, divided into three groups, underwent the test: 14 patients with documentary evidence of sinus dysfunction; 48 patients in whom a sinus disorder was suspected, and 10 controls. As a general rule, the sinus recovery time was found to be significantly prolonged in the patients as compared with the controls. The authors have applied this test to the diagnosis of latent sinus dysfunction, categorising three different degress of RESA values: normal (less than or equal to 550 ms), average (between 550 and 1,000 ms), and prolonged (greater than 1,000 ms). In 6 patients from group one and seven from group two, the post-stimulatory pause was normal or average before the test, and prolonged after the injection of 71247; on the other hand the test did not give evidence of any prolongation of the pause in the controls. In this way a dynamic pharmacological test of depression brings and interesting slant on the diagnosis of disorders of the sinus.


[Contribution of echocardiography to the diagnosis of infradiaphragmatic total anomalous pulmonary venous return]. The authors report the case of a neonate with an abnormal pulmonary venous return which was totally infradiaphragmatic. Multiscan and monoscan echocardiography made the diagnosis, demonstrating an echo-free zone behind the left atrium extended backwards behind the mitral ring and the left ventricle. The child underwent successful surgery, and a follow-up echocardiogram showed that this abnormal space was lessened, responding with the collecting trunk.


[Obstinate diarrhea in infants. A review of 84 cases]. Eighty-four cases of obstinate severe diarrhoea in infants are reported. Criteria for clinical and biological severity are precised. Histological examination of the small bowel was performed in 57 cases; a total atrophy of intestinal villi was found in only 33% of the cases during the first 3 months. Exclusive parenteral feeding, from the beginning or after failure of enteral feeding was given to 71 infants. Later on, enteral renutrition at constant flow, was administered, after simple preparation, in most cases. Seventeen died out of 84 infants, 7 of them within 2 weeks. For the others, the average time for recovery was 4 months. The conditions of prevention of obstinate severe diarrhoea in infancy are emphasized.


[The significance of in-vitro tests with respect to testing of substances for carcinogenic activities (author's transl)]. The actual possibilities to test chemical substances for carcinogenic activities are critically assessed. Short-term-tests are especially discussed. By these tests--now utilized for screening of chemicals--specific biological activities can be determined, which correlate with carcinogenic effects in vivo. The phase of checking and improving the vitro-tests is not yet finished with regard to the rate of correlation of the results from those tests and the results from long-term experiments in animals as well as from clinical and epidemiological human data. Parallel to this investigations, results from long-term-tests should be critically evaluated, because the experimental induction of tumors in animals is up to now the only way to prove carcinogenic activity of a chemical. Short-term-tests should be utilized as screening methods for the selection of suspicious substances, which should or must be further tested in long-term animal experiments. At present results from short-term-tests are not sufficient to classify a substance as a carcinogen or a non-carcinogen. Certain short-term-tests can and will get significance for the evaluation of the carcinogenic risk of chemicals to man when comparing the metabolism of carcinogens in vitro using enzymatic systems of a series of mammalians including man.


[Electroencephalographic parameters in psychomotor attacks (author's transl)]. An investigation of certain electroencephalographic parameters recorded during 19 psychomotor attacks was made. Each attack had been recorded in full. Fourteen of the attacks were preceded by a temporal focus, 13 were provoked by hyperventilation, 18 were initiated focally, 9 were accompanied by seizure potentials, 7 revealed primary or secondary delta rhythms, and 8 were followed by temporal delta focus.


Arteriovenous fistulas for long-term dialysis. Factors that influence fistula survival. We reviewed our total experience with arteriovenous (AV) fistulas for long-term hemodialysis. We are unable to show any significant difference in the survival of AV fistulas based either on the type of material used to create the fistulas or on their location. Complications encountered early in this experience largely were due to technical or judgmental errors. Thrombosis of radiocephalic fistulas resulted from failure to use a vein of adequate caliber. Failure of bovine artery heterograft AV fistulas resulted either from wound infection or from the use of a diseased artery that was incapable of delivering sufficient blood to keep the fistula open. Infection around a heterograft fistula frequently was associated with a lymphocele. The meticulous division, between clips or ligatures, of all tissues deep to the skin prevented lymphocele formation.


Biological characteristics of a stimulatory factor for viral replication detected in egg fluids. Yolk sac and allantoic fluids and albumen from uninfected chicken eggs contain a low-molecular weight factor which, after 90 minutes of contact with cell cultures, significantly enhances viral replication. Of several viruses tested, Semliki Forest virus exhibited the highest (10(5)-fold) responsiveness to this enhancing factor. Maximal enhancement was obtained with cells subjected to low multiplicities of infection. The stimulation of viral replication was linear with the age of the cells in culture. The enhancing factor did not operate through an anti-interferon mechanism. However, it exerted a boosting effect on the low-grade cellular metabolism of ageing cell monolayers. Some of the physico-chemical features of the enhancing factor were determined and conjectures concerning its chemical makeup are discussed.


[Cellular composition of the lymph nodes of monkeys (rhesus macaque) under normal and experimental conditions]. By means of mathematical methods, quantitative and qualitative changes were studied in different structural components of the mesenteric (ileocecal) lymph nodes in normal monkeys (Macaca rhesus) and under per os administration of Salmonella typhi murium, streptomycin-dependent. Cellular composition was calculated in the cortical plateau, cortical (lymphoid) cords and in follicules. Average percent of every cell type was determined. Vaccine administration, was stated to inhibit cytopoiesis in the cortical plateau and in the follicules with light centers. An inverse correlation was noted between the content of small and medium size lymphocytes. Different reactivity of certain structural components in the lymph nodes was demonstrated. As a response to the vaccine administration, plasmocellular acidophilic and macrophagal reactions were most pronounced in the cortical (lymphoid) cords.


[The autonomic division of oculomotor nerve nuclei in mammals and during human development]. Development of the vegetative component of the oculomotor nerve nuclei was studied in the main mammalia orders and in human ontogenesis. In phylogenesis parasympathetic nuclei of Jakubovitch--Edinger--Westphal and those of Perlia are formed later than somatic nuclei of the oculomotor nerve. The animals studied have, together with well developed somatic components of the oculomotor nerve nuclei, gomologues of parasympathetic nuclei, which are rather well developed in carnivores and monkeys. In human prenatal ontogenesis, somatic nuclei are formed first and then parasympathetic ones. Both parts of the oculomotor nerve nuclei are fully developed in adult man.


Prognostic factors in the survival of 1,484 stroke cases observed for 30 to 48 months. I. Diagnostic types and descriptive variables. Survival and factors affecting survival were studied in 1,484 new cases of acute definite stroke occurring between Jan 1, 1970, and June 30, 1971, in Manitoba. The 962 infarctions, 279 hemorrhages, and 243 unidentified strokes were ascertained from hospital claim reports. Personal, clinical, and laboratory data were collected from hospital medical records, death certificates, and autopsy reports. Cases were followed up until Dec 31, 1973, to determine survival. Survival was significantly better in infarction than in hemorrhage, in subarachnoid hemorrhage than in intracerebral hemorrhage, in men than in women, in the young than in the old, in the married than in the single, in hemorrhage cases from rural areas than from urban areas, and in those discharged home than in those transferred to long-term care hospitals. These data may help in predicting the outcome of stroke and in planning for more efficient care.


Multiple ocular anomalies associated with maternal LSD ingestion. Severe ocular malformations, including microphthalmos, intraocular cartilage, cataract, persistent hyperplastic primary vitreous, and retinal dysplasia, occurred in a premature baby girl. The mother had ingested LSD during the first trimester of pregnancy. To our knowledge, this is the third case reported of ocular teratogenesis associated with maternal LSD ingestion. Further cases must be documented to establish an actual cause and effect relationship between the drug and the induced malformations.


Aicardi's syndrome. Case report, clinical features, and electrophysiologic studies. Aicardi's syndrome consists of abnormalities of the ocular fundus, myoclonic seizures, mental retardation, and congenital malformations of the brain and vertebral column in females. The pathognomonic chorioretinal lesions were noted on ophthalmologic examination of a 22-month-old girl, observed for 19 months with severe myoclonic seizures and profound mental retardation. Computerized tomography confirmed major malformation of the brain. Roentgenograms showed anterior fusion of two thoracic vertebrae. Electroretinography was normal, but visual evoked responses were abnormal. Only 72 children are known to have this syndrome; no affected siblings have been reported. The absolute sex limitation--all cases have been female--suggests that the disorder is produced by a mutation on one of the X chromosomes, and is nonviable in male conceptuses. These genetic considerations dramatically influence counseling of parents regarding likelihood of occurrence of the syndrome in subsequent offspring.


Ocular features of Aicardi's syndrome.

Ocular features of Aicardi's syndrome. Four cases of Aicardi's syndrome are reported. The constant features of this syndrome are infantile spasms, chorioretinopathy, and agenesis of the corpus callosum. The chorioretinopathy appears to be a defect of the pigment epithelium and choroid without significant retinal involvement. Additional ocular features include microphthalmia, colobomas of the optic nerve and choroid, persistent pupillary membrane, and glial tissue extending from the disc. The cause of the syndrome is uncertain. It occurs only in females and is nonfamilial. A male lethal syndrome resulting from a gene on the X chromosome occurring as a spontaneous mutation has been suggested. The possible role of intrauterine infection needs further investigation.


Experimental retinal vascular occlusion. I. Pathogenesis of central retinal vein occlusion. In 45 eyes of rhesus monkeys, five types of central retinal vascular occlusion were produced by lateral orbitotomy: group 1, central retinal vein occlusion (CRVO) alone; group 2, CRVO with simultaneous central retinal artery (CRA) occlusion; group 3, CRVO with transient clamping of the CRA for either 2 to 2 1/2 hours (group 3A) or 6 to 7 1/2 hours (group 3B); and group 4, CRVO with segmental retinal ischemia. The eyes were examined by fundus photography and fluorescein angiography for up to nine months. Group 1 developed venous stasis retinopathy (VSR) and group 3B hemorrhagic retinopathy (HR). In group 4 the ischemic and nonischemic segments of the retina developed segmental HR and VSR, respectively. Groups 2 and 3A developed neither VSR nor HR. Retinal capillary obliteration occurred in groups 2 and 3B and in the ischemic part of group 4, starting one to three weeks after the occlusion and progressing thereafter. These studies indicate that clinically co-called CRVO consists of two distinct entities: VSR and HR, with retinal ischemia playing an important role in the production of HR. On the basis of the present and other available information, the pathogenesis of CRVO was concluded to be multifactorial.


Traumatic corneal endothelial rings.

Traumatic corneal endothelial rings. Nonpenetrating "blast injuries" to the eye in two patients resulted in multiple, small, corneal epithelial foreign bodies that were associated with characteristic ring-shaped opacities of the corneal endothelium. These endothelial lesions were clinically visible immediately after injury and became more pronounced during the next several hours. They disappeared within days and resulted in no permanent loss of visual acuity. This communication describes and illustrates the appearance of these endothelial lesions both clinically and in an animal model. Light and electron microscopic observations of an experimental model, with the use of monkey and rabbit eyes, revealed that the ring-shaped opacities resulted from swelling of the corneal endothelium, as well as accumulation of fibrin and leukocytes on the injured cells. Except for the epithelial impact site and the concussion injury of the endothelium, the cornea was uninvolved, and the stroma remained clear.


Treatment of asthma in children.

Treatment of asthma in children. Children present a special problem, as the morbidity from asthma is high. Deaths occasionally occur. Evaluation of frequency and severity is mandatory in designing therapy. Adequate theophylline dosage is an effective bronchodilator. Nebulized salbutamol is a great advantage in moderate and moderately severe asthma because of its speed, ease of administration and effectiveness. Intravenous salbutamol is a considerable advance in the treatment of severe asthma. The use of nebulized Intal makes this drug available to the younger child for prophylaxis. Effective prophylactic long term management must include an environmental evaluation including detection of allergens and, if possible their removal, and the evaluation of physical pulmonary trigger factors and attention to emotional physical health.


Vaccination for hemorrhagic enteritis of turkeys. Laboratory and field evidence indicates that a safe and effective procedure has been developed for vaccinating turkey poults against hemorrhagic enteritis of turkeys. Vaccination is by drinking-water administration of turkey-spleen-propagated pheasant-origin live avirulent virus to 4 1/2-week-old-poults. The effect of vaccination was studied in a field location having recurrent 10-15% mortality and in a second location having recurrent mortality of 0.1-0.2%. The poults involved totaled 214,554.


Pathology produced by, prevalence, of, and probable life-cycle of a species of Sarcocystis in the domestic fowl. Sarcosporidiosis was found to be the cause of a severe myositis in 3 fowls in Papua New Guinea and 2 in Australia. This represented 3.8% of a series of fowls examined in Papua New Guinea. The overall prevalence of infection in these birds was 45%. Both epidemiological and experimental evidence suggested that the dog was the definitive host for this particular type of sarcocyst.


[Immune hemolytic anemia and thrombocytopenia after peroral therapy with a penicillin derivative (phenoxymethylpenicillin)]. A previously apparently healthy male patient developed Coombs-positive haemolytic anaemia and thrombocytopenia during phenoxymethylpenicilline intake. A drug dependent IgG red cell antibody was demonstrated in patient's serum. In vitro tests with patient's serum suggested formation of complexes involving penicilline which by complement mediated mechanisms were able to agglutinate red cells in saline medium. Platelet agglutinins were demonstrated in patient's serum but their drug dependence has not been fully elucidated. The mechanism of drug mediated autoantibody synthesis might have been involved in the pathogenesis of thrombocytopenia.


[Difficulties in the identification of serum M-component]. The essential criteria for M-component identification , according to precise M-component definition based on literature data, are cited. Problems and difficulties in M-component identification are illustrated on selected cases. It is pointed out that, beside of M-component, IgA/albumin (fig. 3) as well as Ig/anti IgG soluble complexes (fig. 6) may occasionally have the appearence of electrophoretically homogeneous serum protein fraction: if this is suspected the true nature of homogeneous fraction must be further elucidated. In addition, it is stressed that lipoprotein specific staining of electropherogramms, can be very helpfull in the detection of small or abscure serum M-components (fig. 5).


A passive hemagglutination test for detecting bovine serum albumin antibodies. A microtiter passive hemagglutination test is described for detecting and titrating antibodies in chickens. Chicken erythrocytes are coated with antigen (bovine serum albumin = BSA) in the presence of 0.25% glutaraldehyde. Such sensitized erythrocytes are agglutinated in the presence of antibodies against BSA. The sensitivity and specificity of the test are not affected by salt concentrations in the range of 0.9-9%. This test measures the course of antibody response in chickens immunized with BSA.


Regulation of onset of development of UDP-glucuronosyltransferase activity towards o-aminophenol by glucocorticoids in late-foetal rat liver in utero. 1. A precocious development of UDP-glucuronosyltransferase activity (EC 2.4.1.17) towards o-aminophenol is demonstrated in 15-17 day foetal rat liver in utero after dexamethasone administration to the mother. 2. This stimulation of liver transferase activity in utero is directly proportional to the dose of dexamethasone infected. 3. Precocious development of transferase activity in utero can also be effected with the natural glucocorticoid cortisol by multiple injections of large amounts of this hormone into the mother. 4. Transferase activity towards o-aminophenolin foetal lung, kidney and upper alimentary tract can also be precociously stimulated by dexamethasone in 17-day foetuses in utero. 5. Natural development of hepatic transferase activity between days 18 and 20 of gestation is retarded after foetal hypophysectomy by decapitation in utero. 6. Overall glucuronidation of o-aminophenol, as observed in foetal rat liver, is also precociously stimulated by dexamethasone. 7. From this and from evidence previously presented we suggest that glucocorticoids, which are known to increase in rat foetuses between days 17 and 20 of gestation, trigger the normal development in utero of hepatic transferase activity towards o-aminophenol which occurs at that time. We also suggest that these hormones are responsible for the rise in activity of the enzyme in foetal lung, kidney and upper alimentary tract which occurs during the same gestational period.


Carbonic anhydrase activity in mammalian skeletal and cardiac muscle. 1. The presence of extravascular carbonic anhydrase activity in skeletal muscle, and its absence from cardiac muscle, were demonstrated in the rat. 2. The activity in skeletal muscle is approximately correlated with the proportion of dark fibres present in the middle fibre bundles.


A species difference in nucleoside phosphorylase activity and inosine-stimulated insulin secretion in isolated islets of Langerhans. Inosine is a potent simulant of insulin release from rat but not from rabbit islets of Langerhans. Further investigation showed that nucleoside phosphorylase activity is exceptionally low in rabbit islets. The ability of inosine to promote insulin release seems to be related to islet nucleoside phosphorylase activity, which can display marked species differences.


The fractionation of histones isolated from Euglena gracilis. 1. The histones of Euglena gracilis were separated by gel filtration into five fractions. 2. Each fraction was characterized in terms of its electrophoretic, solubility and compositional properties. 3. Euglena gracilis clearly contains histones corresponding to vertebrate H1, H2B, H3 and H4 fractions, although they all differ in containing more lysine. 4. The remaining Euglena histone is considered to be homologous to vertebrate histone H2A, but it differs in having a much higher ratio of lysine to arginine. 5. The Euglena histone H1 appears to be lacking in aspartic acid. 6. Electrophoresis in the presence of sodium dodecyl sulphate indicates that the molecular weights of the Euglena histones are close to those of the homologous vertebrate histones.


Structural requirements in the reaction of morphine uridine diphosphate glucuronyltransferase with opioid substances. The influence of the 3-hydroxyl and N-alkyl groups in the reactivity of narcotic compounds with morphine UDP-glucuronyltransferase was studied. Opioids possessing both, one or none of these groups were tested for inhibition of morphine glucuronidation in rabbit liver microsomal preparations. Compounds with only a 3-hydroxyl group (normorphine) or an N-methyl group (codeine, ethylmorphine) were less potent competitive inhibitors than those containing both groups (dextrorphan). Norcodeine, with neither of these groups, had no inhibitory effect. The synthetic narcotics (+)- and (-)-methadone, (-)-alpha-acetylmethadol and meperidine, with only an N-alkyl group, were effective competitive inhibitors. No stereoselectivity of the morphine glucuronyltransferase for opioid isomers was observed, and [methionine]enkephalin does not react with morphine glucuronyltransferase. Differences of pKa values and water/lipid solubility of narcotics could not explain the effects. Results indicate that the N-alkyl group plays a critical role in the interaction of narcotics with the morphine UDP-glucuronyltransferase.


Reversible inhibitors of penicillinases. Reversible competitive inhibitors of a penicillinase, beta-lactamase 1 from Bacillus cereus, were studied. These represent the first inhibitors of a penicillinase that lack the beta-lactam ring. The products of the enzymic reaction, namely penicilloic acids, are inhibitors; their decarboxylation products, the penilloic acids, are also inhibitors, and have somewhat lower Ki values. Inhibitors have been prepared from benzylpenicillin, phenoxymethyl-penicillin, methicillin (2,6-dimethoxybenzamidopenicillanic acid) and 3-hydroxy-4-nitrobenzamidopenicillanic acid. Decarboxylation of the penicilloic acids from benzyl-penicillin, or from phenoxymethylpenicillin, leads to epimerization (at C-5) of the penilloic acid. Nuclear-magnetic resonance spectroscopy at a frequency of 270 MHz can distinguish the epimers. Other competitive inhibitors studied were boric acid, benzene boronic acid and m-aminobenzeneboronic acid. Boric acid itself was the best inhibitor of beta-lactamase I so far found.


Vitamin A receptors. Retinoic acid binding in ocular tissues. Analysis of the sucrose-density-gradient patterns of the 110 000g supernatant fractions of adult and foetal retina and pigment epithelium showed them to contain a limited number of highly specific binding sites ('receptors') for [3H]retinoic acid that sediment at approx. 2S. Binding in pigment epithelium is higher than in any tissue yet reported. A 5S binding component is also observed and is probably due to serum contamination. Fractionation studies indicate that [3H]retinoic acid binding in the retina is lower in the photoreceptor units than in the retinal inner layers. This is in contrast with previous results that show greater [3H]retinol binding in photoreceptors. Studies with dystrophic human and rat retinas, which lack the photoreceptor layers, confirm that [3H]retinoic acid binding is greater in the non-photoreceptor layers of the retina. No specific [3H]retinoic acid binding is found in corneal epithelium, although endothelium and the conjunctiva demonstrate specific 2S binding. Such differences in retinol and retinoic acid binding may indicate different roles for the two compounds in ocular tissues.


Nature of collagens synthesized by monkey periodontal-ligament fibroblasts in vitro. 1. First subcultures of fibroblast-like cells from adult monkey periodontal ligament were incubated in the presence of 14C-labelled amino acids and produced significant amounts of type-I and type-III collagens. 2. The proportion of type-III collagen produced was calculated on the basis of the recovery of procollagens from DEAE-cellulose chromatography to be approx. 20%, and at least 10% when analysed as collagens on CM-cellulose chromatography. 3. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the procollagens, the collagens and their CNBr peptides was used to confirm the identity of the collagen types. 4. In serum-free media extensive conversion of type-I procollagen, but not of type-III procollagen, into collagen was observed, suggesting that a specific type-I procollagen peptidase was produced. 5. The pattern of collagen synthesis was not significantly different from that obtained with fibroblasts derived from skin corium of the same animals.


[Autoradiographic studies on the distribution of 14C-piracetam in the simian brain]. Autoradiography of the brain of the monkey Callithrix jacchus 2 and 6 h after oral application of 200 mg 14C-piracetam/kg (2-oxo-pyrrolidine-l-acetamide-2-14C) shows that the drug is preferably concentrated in the cortex of cerebrum and cerebellum. This specific affinity of piracetam which was observed earlier in dog and rat is thus confirmed in the primate and seems to be species independent. Beside the dominant cortical concentration there is a characteristic storage of piracetam in many nuclei of other brain areas, for instance, nucleus caudatus, hippocampus, n. anteriores thalami, n. dorsales thalami, corpus geniculatum laterale and mediale, corpora mamillaria, nucleus supraopticus, substantia grisea centralis, colliculi superiores and inferiores. Furthermore piracetam is stored in the blood vessel wall of the brain over 6 h. The hypophysis and pineal body take up radioactivity intensively.


[Insulin and pro-insulin secretion following intravenous administration of tolbutamide, glisoxepide and glibenclamide]. 12 metabolically healthy subjects were i.v. administered equipotent doses (ED30) of tolbutamide (7.5 mg/kg), glisoxepide (0.02 mg/kg) and glibenclamide (0.006 mg/kg). Prior to and 2, 5, 8, 10, 20, 40, 60 and 120 min after the injection the following serum parameters were determined: blood glucose, immunologically measurable insulin (IMI) with the double-antibody method (Hales and Randle) and proinsulin (IMP) enzymatically (ISP-method). The maximum level of insulin follows the injection of tolbutamide with a value of 70.5 micronU/ml after 2 min, of glisoxepide after 5 min (67.0 micronU/ml) and of glibenclamide after 20 min (32.3 micronU/ml). The proinsulin fraction of the total insulin shows a level of 12.5 micronU/ml before the test. After the administration of the three compounds proinsulin increases, too, but reaches only 20-40% of the total immunoreactive insulin. The amount of secreted insulin and proinsulin during the 120-min test is rather the same for the three substances. The average increase of insulin is nearly identical for tolbutamide and glisoxepide, whereas it is less for glibenclamide. Both the mean blood sugar depression and the highest mean increase of proinsulin is reached after glisoxepide. The significance of the one-chain precursor of insulin as a part of the sulfonylurea stimulated total insulin for glucose depression is discussed.


Connective tissue composition of aortas from non-human primates. A comparative study. Connective tissue composition of aortas from several non-human primate species has been studied in an effort to relate collagen, elastin, ang glycosaminoglycan (GAG) content to species susceptibility to atherosclerosis. Among the species studied the baboon contained the highest content of GAG in the aorta. While the distribution of individual GAG varied from species to species, heparan sulfate (HS) was the highest GAG in aortas from most of the species. The ratio of HS to chondroitin sulfates (CS) plus dermatan sulfate (DS) was lowest in the baboon, a species relatively less susceptible to atherosclerosis, and highest in the squirrel monkey, a very susceptible primate. If a relationship exists between HS to CS + DS ratio in the aorta and atherosclerosis, the primates can be arranged in the following decreasing order of susceptibility: squirrel, chimpanzee, stump-tailed, rhesus, African green, patas, baboon. In studies of other connective tissue components, the proportion of total collagen to elastin was found lowest in the baboon. Such observations emphasize the importance of connective tissue in the pathogenesis of atherosclerosis.


Slow virus E malattie croniche del sistema nervoso centrale. The purpose of this report was to detect whether some subacute or chronic human neurological diseases are significantly associated with traditional virus like papovavirus and paramixovirus and non conventional agents (scrapie-like) or non classified (multiple sclerosis associated agent or MSAA). In this connection for M.S. the data concerning the ethiological factors paramixovirus or MSSA are presented and discussed and it is hypothesized the virus mechanism in the pathogenesis of M.S.


Studies of HLA antigens in multiple sclerosis. This review describes the presently available data on HLA typing in patients with multiple sclerosis (MS). Almost 2,000 MS patients and 12,000 normal controls have been studied with HLA typing in 15 different laboratories. The combined data show remarkably homogeneous results, and are as summarized: an increased frequency of HLA-Dw2 of B7, B8, Bw18, A3, and A1. A decreased frequency of A2, A28, B12, Bw15, Bw17, Bw22, and Bw40. Analysis of data seems to indicate that the HLA linked MS susceptibility gene is linked to HLA-Dw2, and the other deviating HLA antigen frequencies, except B8, may be explained as a secondary phenomenon, due to linkage disequilibrium. The presented data do not allow any conclusions as to whether the MS susceptibility gene operates in a dominant or recessive way. The important of HLA as a marker for disease and MS in particular is discussed, and preliminary data on HLA studies of MS patients of other ethnic groups, notably American blacks, seem to indicate that genetically determined ethnic differences, notably those of HLA, may partly be responsible for the unique geographic distribution of the disease.


The significance of a low amniotic fluid creatinine and a mature lecithin/sphingomyelin ratio. Creatinine levels were measured in 546 specimens of amniotic fluid with a lecithin/sphingomyelin ratio of 2.5 or more. With amniotic fluid creatinine levels below the normal range, 3 of 6 infants had major congenital abnormalities and two had severe rhesus isoimmunization; 3 of the infants died. Of 514 cases with amniotic fluid creatinine levels within the normal range (mean +/- 2 SD), 13 babies (2.5%) had major congenital abnormalities but only one of the babies died, giving a perinatal mortality rate of 0.2%. The significance of these findings is discussed.


Maternal anticonvulsants and optic nerve hypoplasia. Seven patients with optic nerve hypoplasia, born of epileptic mothers, are presented. All the mothers took anticonvulsants during pregnancy. The possibility that maternal anticonvulsant therapy may play a role in the genesis of optic nerve hypoplasia is discussed in the light of what is known about the teratogenicity of these agents.


Effect of age, weight and adequacy of zinc intake on the balance between alkaline ribonuclease and ribonuclease inhibitor in various tissues of the rat. 1. Deficiency of zinc inhibits growth and also increases the activity of alkaline ribonuclease in certain tissues of the rat (Prasad & Oberleas, 1973). Zn could influence ribonuclease activity by direct effects on the enzyme or its natural inhibitor, or non-specifically as occurs when growth rate is affected by various other factors. These possibilities were studied. 2. Alkaline ribonuclease was shown to be inhibited by Zn in vitro, but the concentrations of Zn required were so high that the enzyme was probably not directly affected by changes in tissue Zn concentration caused by dietary deficiency. 3. At lower concentrations, Zn added in vitro increased the activity of alkaline ribonuclease in tissue homogenates probably by inactivating the inhibitor of the enzyme. 4. Age, weight and particularly food restriction caused tissue-specific alterations of ribonuclease and ribonuclease inhibitor concentrations in liver, kidney, oesophagus, testis and thymus. 5. The ribonuclease activities in liver, kidney and testis of Zn-deficient rats were unaltered in comparison with those of pair-fed rats. In thymus, which decreased in weight in the Zn-deficient animals, there was a concomitant increase in ribonuclease activity, but in oesophagus, the deficiency reduced the activity of ribonuclease. 6. The effects of Zn deficiency upon alkaline ribonuclease and its inhibitor are probably secondary consequences of reductions in food intake or growth.


Further studies on the enzymatic conversion of prostaglandin endoperoxide into prostacyclin by porcine aorta microsomes. A simple, rapid radiochemical assay for prostacyclin synthesis has been used to characterize the enzyme in arterial walls which converts prostaglandin endoperoxides to prostacyclin. The enzyme displays a broad pH optimum, and catalyses a rapid conversion of saturating concentrations of the endoperoxide at 37 degrees C. Hydroperoxides of several unsaturated fatty acids are potent inhibitors of the enzyme, and act in a time dependent manner. The isomerase which converts prostaglandin endoperoxides to prostaglandin E2 or D2 was not detected in the arterial wall.


Immobilized bovine lactose synthase. A method of topographical analysis of the active site. Bovine galactosyltransferase (UDPgalactose: D-glucose 4beta-galactosyltransferase, EC 2.4.1.22) was covalently coupled to Sepharose 4B by reaction at pH 5.0 with the activated mixed disulfide Sepharose-glutathione-2(5-nitropyridyl)-disulfide. The Sepharose-protein conjugate was presumably coupled via the unique highly reactive cysteine of those thiols on the bovine enzyme. The gel-bound N-acetyllactosamine and lactose synthase activity of about 0.4% was consistent with the affects of diffusion and the 90% activity reduction noted upon thiol modification of the dissolved enzyme. The residual lactose biosynthetic activity of the bound enzyme appeared possible only if the reactive thiol were physically distinct from the active site since the bulky Sepharose-glutathione group must not obscure the alpha-lactalbumin binding region.


Demonstration of 5'-methylthioadenosine phosphorylase activity in various rat tissues. Some properties of the enzyme from rat lung. An enzyme (5'-methylthioadenosine phosphorylase) that catalyzes the phosphorolytic cleavage of 5'-methylthioadenosine to 5-methylthioadenosine to 5-methylthioribose-1-phosphate and adenine was found in various rat tissues. Liver and lung had the highest enzyme activities and heart the lowest, most of the activity (greater than 90%) was recovered in soluble tissue fractions. The enzyme from rat lung was purified about 30-fold by pH treatment (NH4)2SO4 fractionation, and gel filtration. The enzyme did not require an added metal-ion for activity, and was not inhibited by EDTA. Many compounds were tested for their inhibitory effects; of these, ribose 1-phosphate, 2-deoxyribose 1-phosphate, fructose 1-phosphate, adenine and guanine were shown to inhibit. Kinetic patterns on reciprocal plots were linear as a function of the concentration of either 5'-methylthioadenosine or phosphate. More detailed kinetic studies suggested that the rat lung 5'-methylioadenosine phosphorylase catalyzes an equilibrium-ordered reaction, and that 5'-methylthioadenosine is the first substrate to bind and 5-methylthioribose-1-phosphate is the first product to be released.


Effects of staphylococcin 1580 on cells and membrane vesicles of Bacillus subtilis W23. 1. Uptake of L-glutamic acid is inhibited, and preaccumulated L-glutamic acid is released from Bacillus subtilis cells treated with staphylococcin 1580. Uptake of alpha-methylglycoside is enhanced at low bacteriocin concentrations and inhibited by excess bacteriocin. 2. Inhibition of amino acid uptake into membrane vesicles is somewhat less sensitive to staphylococcin 1580 than uptake into whole cells under similar conditions, when the bacteriocin concentration is expressed per weight unit of membrane protein. Inhibition of uptake into vesicles is independent of the electron donor system used, but varies with different substrates. 3. Influx of L-glutamic acid into vesicles under anaerobic conditions is severely hampered by staphylococcin 1580. The L-glutamic acid carrier functions are slightly affected only. 4. Staphylococcin 1580 abolished the membrane potential induced by respiration or by a potassium diffusion potential in the presence of valinomycin, as measured with the fluorescent dye 3,3'-dipropylthiadicarbocyanine. 5. The effects of staphylococcin 1580 on cells and membrane vesicles allowed the classification into three groups with different sensitivity to the staphylococcin concentration.


Plasma phencyclidine pharmacokinetics in dog and monkey using a gas chromatography selected ion monitoring assay. Phencyclidine was determined by gas chromatography selected ion monitoring in six dogs and seven monkeys. Aliquots of venous blood were taken over 4 h in the monkey after 1.1 mg kg-1 and over 24 h in the dog after 1.0 mg kg-1 of phencyclidine i.v. Pentadeuterated phencyclidine was used as the internal standard. In the electron impact mode the most abundant fragments in the mass spectrum of phencyclidine were m/e 91 and 200, and 96 and 205 in the [2H5]phencyclidine spectrum. These fragments were used to quantitate the amount of phencyclidine present. In both species, a complex exponential decline of plasma phencyclidine was found in most animals that fit a two compartment open model. In monkeys, the mean half-life (beta phase) was 2.36 h and in the dog it was 2.86 h. Compared with the monkey, the dog considerable emergence delirium. The two species had rather different pharmacokinetics which may be relevant to the observed differences in degree of anesthesia and recovery.


Mass spectrometry of acylated sugars as trimethylsilyl ether derivatives. A way for location of long chain fatty acyl groups. The mass spectra of the trimethylsilyl ethers of the four positional isomers of methyl-O-palmitoyl-alpha-D-glucopyranoside have been studied, and the structures of the principal ions assigned by the use of exact mass measurements and deuterium labelling on the aliphatic chain, the trimethylsilyl group and the glucosidic methyl group. The origin of some fragments has been elucidated by analysis of reactions of metastable ions. The mass spectra of the different isomers exhibit major differences, which depend upon the presence or absence of the aliphatic chain. These results indicate that this is a useful method for determining the position of an acyl group in a methyl glucoside. The applicability of this mass spectrometric method in structural determination of unknown acylated sugars is discussed. The structure of a corynomycoloyl-alpha-D-trehalose, isolated from Corynebacterium diphtheriae, has been determined by mass spectrometry as an application of the method. The molecular weight of this compound has been determined by field desorption mass spectrometry (cationization method), and the study of the electron impact spectrum of the trimethylsilyl derivatives clearly demonstrates that the corynomycolic acid is linked by an ester group to position 6 of the trehalose molecule.


Centrifugal method of determining red cell deformability. A recently developed technique for deforming red blood cells (RBC) in which they are centrifuged through buffer and into a glutaraldehyde solution was evaluated as a method of assessing cellular deformability (i.e., the ability of the entire RBC to form a new configuration). To accomplish this, RBC populations of differing cellular deformability were tested, using three generally accepted techniques to obtain these differences: partial fixation with low concentrations of glutaraldehyde, density fractionation, and suspension of RBC in nonisotonic media. Our results indicate that at a constant deforming force the mean deformed length of the RBC decreased under conditions where cellular deformability is known to decrease, thus suggesting the usefulness of this centrifugal method for the estimation of this cellular property.


Probes of transmembrane potentials in platelets: changes in cyanine dye fluorescence in response to aggregation stimuli. A noncovalent fluorescent probe that responded to changes in transmembrane potential was used to study the response of washed human platelets to aggregating agents. Concentration-dependent changes in the fluorescence were observed in response to ADP and to thrombin. No such changes were observed in response to collagen fibrils. Thus there was an indication that platelet membrane potential changed in response to aggregating stimuli, supporting the hypothesis that the mechanisms of platelet aggregation resembled the mechanisms of other systems that show stimulus-response coupling (e.g., muscle, adrenal chromaffin cells). The different responses to specific agents indicate that the agents may trigger platelet aggregation through different mechanisms.


Trout hepatic enzyme activation of aflatoxin B1 in a mutagen assay system and the inhibitory effect of PCBs1. In summary, it was demonstrated that the trout PMF may be successfully employed in the Ames mutagen assay method by utilization of proper salts solution and a metabolic preincubation period at 25 degrees C. It has also been observed that, unlike the rat, pretreatment of rainbow trout with various PCBs decrease the mutagen assay response to AFB.


The value of computer axial tomography (CAT) in cranio-cerebral malformations. Cranio-cerebral malformations commonly present in three ways: (1) with a visible structural defect; (2) with symptoms of neurological abnormalities but without evidence of raised intracranial pressure; (3) with macrocephaly or signs of raised intracranial pressure. The large contribution made by computed axial tomography to the diagnosis and management of these cases is discussed in relation to a series of 217 patients. Invasive studies were performed in only 55 cases mainly to obtain further anatomical information prior to surgery.


The pilo-Ruffini complex: a non-sinus hair and associated slowly-adapting mechanoreceptor in primate facial skin. A spray-type of nerve ending identified as a Ruffini corpuscle closely associated with a non-sinus hair has been defined in terms of its histologic, ultrastructural and physiologic parameters. The hair and its associated mechanoreceptor, termed a pilo-Ruffini complex, responds as a slowly adapting (SA) mechanoreceptor, whereas most non-sinus hair-associated mechanoreceptors are rapidly adapting. Morphologically, the terminal nerve fibers branch repeatedly within a unique connective tissue matrix, and the neurite and associated connective tissue matrix forms a collar around the hair follicle. This receptor, on the basis of its organization, is interpreted as corresponding to the corpuscle or end organ of Ruffini.


Fine structure of meganeurites and secondary growth processes in feline GM1-gangliosidosis. Electron microscope studies were carried out on neurons of the hippocampal formation in a feline mutant with beta-galactosidase deficiency and GMI-gangliosidosis. Fusiform processes with characteristics similar to meganeurites of Golgi studies were identified between cell bodies and axons of pyramidal and granule cells. The presence of dense material subjacent to the plasma membrane at the meganeurite-axon junction provides evidence that meganeurites form at the axon-hillock region and displace the initial axonal segment distally. Meganeurites of hippocampal neurons exhibited pleomorphic secondary processes with fine structural features of growth cones. Spines and spine-synapses were abundant on perikarya and meganeurites. Numerous membranous cytoplasmic bodies (MCBs) were encountered amongst otherwise normally appearing organelles of the cell body. MCBs were densely packed in meganeurites except near their peripheral area. They were less common in dendrites and rare in synapses of the neuropil. The observations provide further support for the view that meganeurites of mature cortical neurons in ganglioside storage diseases have embryonic growth characteristics.


Meganeurites and other aberrant processes of neurons in feline GM1-gangliosidosis: a Golgi study. Golgi studies were carried out on neurons in several forebrain structures of young adult mutant cats with inherited beta-galactosidase deficiency and neurobehavioral deterioration due to GM1-ganglioside storage disease. Meganeurites similar to those observed in several human gangliosidoses were present on small and medium pyramidal neurons, granule cells of the fascia dentata and spiny neurons of the caudate nucleus. Large and giant pyramidal cells of the motor cortex exhibited prominent somatic spines but lacked meganeurites. Cortical non-pyramidal neurons and aspiny caudate cells were relatively normal in appearance although they showed variable increases in cell body diameter. The range of morphological alterations in different types of cortical neurons in feline GM1-gangliosidosis was identical to that found in human ganglioside storage diseases. Neurite outgrowth from meganeurites was particularly prominent in the feline mutant. The extensive proliferation of neurites confined to meganeurites indicates that the latter have growth properties typical of embryonic neuronal elements. The demonstration of neurite outgrowth from meganeurites of mature cortical neurons in feline GM1-gangliosidosis suggests a possible role for gangliosides in neurite formation during neuronal differentiation and synaptogenesis.


Functional development of the dorsolateral prefrontal cortex: an analysis utlizing reversible cryogenic depression. The dorsolateral prefrontal cortex of rhesus monkeys was functionally inactivated by local hypothermia as the monkeys performed spatial delayed-response and spatial delayed-alternation tasks at different stages of postnatal development. Cryogenic depression of prefrontal cortex at a temperature sufficient to induce 21--25% decrements in delayed-response performance in 34--36-month-old-monkeys, produced deficits of only 7--8% in 19--31-month-old and no detectable loss in younger monkeys, 9--16 months of age. Delayed-alternation performance was impaired by local hypothermia as early as 8.5 months of age, but maximal cooling-induced deficits on this task were not observed before 33 months of age. Thermal gradients mapped in representative monkeys at different stages of development were remarkable similar, indicating that the age-dependent differences in behavior were not attributable to technical factors. The results obtained in the present study on normal developing monkeys confirm the interpretation of previous research on brain-damaged infants that functional maturation of the dorsolateral prefrontal cortex is protracted over several years of postnatal life, and extends the earlier studies by indicating that the lower limit for maturity of dorsolateral function is close to puberty in this species. Further, the present study revealed that delayed-response and delayed-alternation performance are dissociable dorsolateral functions which achieve maturity at different rates. The convergence of evidence from reversible neural depression and permanent lesion methods provides strong validation for neurobehavioral analysis as a general approach to the study of regional maturation of the brain.


Non-spatial memory after selective prefrontal lesions in monkeys. Separate groups of monkeys were trained on delayed object alternation, delayed object matching, and delayed color matching, after which half the animals in each group received lesions of the cortex in the principal sulcus, and the other half, lesions of the inferior frontal convexity. The inferior convexity lesions produced severe and lasting impairments on all three tasks, perhaps as a result of the perseverative disorder that has been associated with damage to this region. By contrast, the principal sulcus lesions, which yield such severe deficits on spatial memory tasks, led to only small, transient disruptions on each of the three non-spatial tasks. According to these results, the non-spatial memory deficits that have been found after unrestricted lateral prefrontal lesions are due mainly to damage below the principal sulcus in the inferior prefrontal cortex. The function of the tissue in the principal sulcus itself, on the other hand, appears so far to be limited largely to the spatial modality.


Discharge patterns of basal ganglia neurons during active maintenance of postural stability and adjustment to chair tilt. Neurons in the putamen and globus pallidus were studied in awake monkeys making active postural adjustments during static and dynamic chair tilt. When the chair was held horizontal and the monkey actively maintained a restricted head position, neurons had tonic firing rats similar to those described previously, with low frequency patterns in the putamen and low frequency-burst or intermediate (IFD) to high frequency (HFD) tonic patterns in neurons in the pallidal segments. Over half of the neurons with IFD or HFD discharge rates and a smaller proportion of those with slow discharge rates showed changes in firing that were temporally correlated with chair tilt. Phase shifts of firing frequency relative to sinusoidally vaired chair position varied in units with different tonic discharge frequencies. Maximum and minimum discharge rates in IFD neurons occurred near maximum chair velocities, whereas the phase shift decreased in HFD neurons, which had higher discharge rates during the horizontal chair position. Neurons with changes in discharge during chair tilt were found in all portions of the putamen and globus pallidus studied.


Apparent absence of symmetrical transcription in Tetrahymena mitochondria. Transcription in Tetrahymena pyriformis mitochondria has been examined for whether or not symmetrical transcription occurs. A ribonuclease A digestion in high-ionic strength was used as a test for the presence of double-stranded RNA (dsRNA) either before or after self-annealing. This test was applied to RNA prepared using pulse lengths of from 1 to 30 min. If symmetrical transcription occurred, then the amount of dsRNA should have varied inversely with pulse length. There was no evidence for the presence of dsRNA other than a ribonuclease-resistant core. A search was also made among the largest transcripts present (greater than 26S) since this region of a sucrose gradient is enriched in symmetrical transcripts in HeLa cells. Again none were found. In order to allow for possible rapid processing as the reason for the failure to find dsRNA, total cellular RNA was extracted as quickly as possible, and the ribonuclease digest analyzed by Sephadex chromatography. No large pieces of dsRNA were found.


Recommendations for screening programs for congenital hypothyroidism: Newborn Committee of the American Thyroid Association. The newborn committee of the American Thyroid Association recommends establishment and expansion of screening programs for congenital hypothyroidism because of the high frequency of the disease (1/5000 to 1/6000 births), the difficulty in making a clinical diagnosis and the fact that the disease is easily curable. The regional approach for such a program is recommended, and the Quebec experience with measurement of thyronine and thyrotropin concentrations by means of filter-paper blood spots can serve as a model.


Plasma thyroid-stimulating hormone and thyroxine concentrations in breast cancer. Plasma TSH and thyroxine levels were measured in 74 early breast cancer patients and 53 with advanced disease, 77 patients with cancer arising in other organs and 67 healthy women of similar age. The mean plasma TSH levels were higher in the breast cancer cases than the other two groups; the difference was statistically significant only in those with advanced disease. Twelve percent of the early breast cancer and 15% of the advanced breast cancer patients had elevated plasma TSH concentrations, compared with only 1% of the other cancer patients and 3% of the controls. Four breast cancer patients with plasma TSH levels above 85 microIU/ml had subnormal plasma thyroxine levels. Five of 29 (17%) early breast cancer patients had excessive plasma TSH responses to TRH.


Plasmacytoma of the stomach: diagnosis with the aid of immunoperoxidase technique. A gastric tumor, originally diagnosed as a plamacytoma in 1953, but in which the diagnosis was disputed, has been re-examined by the immunoperoxidase staining technique. The demonstration of a single type of immunoglobulin in the tumor cells is considered conclusive evidence of its neoplastic nature. Two further cases of gastrict plasmacytoma encountered in recent months have also been examined by this technique and similar results obtained. The pathology of plasma cell tumors is discussed and a brief review of the literature is added with regard to the management and the overall poor prognosis.


Primary osteosarcoma of the kidney.

Primary osteosarcoma of the kidney. Osteosarcoma arising in the kidney is a bona fide entity. A case is reported and described in clinical and pathological detail. Characteristic changes include a palpable stony hard renal mass associated with radiographic demonstration of sunburst calcification in the kidney. The case presented is unique in that virtually the entire specimen was composed of bone.


Diagnosis and treatment of obstructive jaundice secondary to liver metastases. Metastatic disease to the liver and adjacent lymph nodes and may cause jaundice by compression upon the major biliary ducts. Small field relatively high dose radiotherapy after accurate localization can result in effective palliation of jaundice in selected patients.


Effects of systemic administration of 6-hydroxydopamine on the circumventricular organs in nonhuman primates. I. Area postrema. 6-Hydroxydopamine (6-OH-DA) has been shown to produce degenerative changes in noradrenergic nerve terminals and preterminals in the CNS following intracisternal, intraventricular or direct injection into the brain parenchyma. Systemic injection of 6-OH-DA is known to result in degenerative changes in noradrenergic terminals in the peripheral nervous system. However, only a few studies have been carried out on the effects of systemic injections of 6-OH-DA on noradrenergic terminals in the CNS. In the present study cynomolgus and squirrel monkeys were injected intravenously on two successive days with total doses of 350 mg/kg and 150 mg/kg of 6-OH-DA, respectively, and sacrificed at 2 and 24 h following the second injection. Degenerative changes in the area postrema (AP) neurons in all injected animals were characterized by a generalized increase in electron density of cytoplasmic elements in axonal terminals and preterminals. Multilamellar bodies, clusters of clear and dense core vesicles, increased numbers of secondary lysosomes, and an increase in the number of glycogen increased markedly in injected animals, but no other glial alterations were observed. The number of mast cells in the AP was greater in injected than in noninjected animals, both in the perivascular spaces (PVS) and in parenchymal locations. Cell processes in the PVS were occasionally observed to contain electron dense bodies, and degenerative changes were seen in supraependymal processes in some injected animals.


Cell surface microvilli and cell agglutinability. Detached cells of some transformed mouse fibroblast lines have a villous surface whereas similarly treated cells of other lines are relatively smooth. These differences in surface morphology of detached cells are not reflected in their agglutinability with ConA and they cannot unambigously be explained from their morphology in situ. Treatments of normal and transformed Swiss mouse fibroblasts that induce marked changes in agglutinability with ConA do not cause equivalent changes in surface morphology. It is, therefore, unlikely that agglutinability of mouse fibroblasts by ConA is determined by the number of microvilli on the cell surface.


Asymmetric distribution of anionic sites on rat liver nuclear membranes. The labelling characteristics of isolated rat liver cell nuclei was studied using polycationized ferritin as an ultrastructural probe for anionic sites. At low concentrations of the marker the nuclear surface was partly labelled eg. at sites of nuclear annuli. At high probe concentrations the entire cytoplasmic surface of the outer nuclear membrane bound ferritin particles. On the other hand, the cisternal surfaces of nuclear membranes could not be labelled although in parallel experiments Concanavalin A-ferritin bound to the cisternal surface of both nuclear membranes indicating free access of ferritin particles to the perinuclear space. The results indicate that nuclear membranes show a distinct vectorial asymmetry in respect to the presence of anionic surface sites.


Preservation of cytoskeletal elements for electron microscopy. Attached murine fibroblasts were subjected to different fixation and dehydration procedures in order to study the preservation of cytoskeletal elements. The organization of the microtubular and microfilamentous system was identical whether or not post-fixed with osmic acid after glutaraldehyde fixation. Critical point drying did not preserve structures absent in conventionally dehydrated and embedded cells.


Evidence for the involvement of a diol-epoxide in the binding of 7,12-dimethylbenz(a)anthracene to DNA in cells in culture. 1,1,1-Trichloropropene 2,3-oxide (TCPO), a known inhibitor of the enzyme epoxide hydrase, inhibits binding of the carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), to the DNA of secondary mouse embryo cell cultures under conditions which do not appreciably decrease the overall metabolism of this carcinogen. This suggests that the formation of a transdihydrodiol is a necessary step in the metabolic pathway leading to DNA binding and that binding probably occurs through the generation of a reactive diol-epoxide. In concert with this, the major DMBA-DNA product  isolated by chromatography on Sephadex LH-20 eluted with a methanol-water gradient is resolved into two separate components in a methanol-sodium borate solution gradient suggesting that, as is known for benzo(a)pyrene, two stereoisomeric diol-epoxides are involved in the binding of DMBA to DNA.


Neutralization effect of some agents on the antimicrobial activity of ammoniacal silver nitrate. The effect of some agents on the antimicrobial activity of ammoniacal silver nitrate, an endodontic medicament, was tested with Streptococcus faecalis by the serial tube dilution method. Its results indicated that sodium hypochlorite, hydrogen peroxide, and blood had a marked inhibitory effect. However, the presence of dentin, necrotic tissue, saliva, and hydrogen sulfide gas liberated from protein decomposition showed no or little effect on the antibacterial properties of the chemical. Since antiseptics or antibiotics generally may be decomposed by necrotic tissues, these findings suggested that the use of ammoniacal silver nitrate not only may resolve the problem of recalcitrant cases in endodontic treatment but also may simplify the disinfecting procedure for root canals.


Effect of nitroprusside on regional myocardial blood flow in coronary artery disease. Results in 25 patients and comparison with nitroglycerin. The effect of nitroprusside on regional myocardial specific blood flow (RMBF) was evaluated in 25 patients with the xenon-133 washout technique. Six patients were normal (group 1), six patients had coronary artery disease without collateral vessels (group 2), and thirteen patients had coronary artery disease with collateral vessels (group 3). In group 1, RMBF was unchanged following nitroprusside. RMBF decreased significantly in both group 2 and group 3, including seven patients in group 3 with high-grade collateral vessels. The results were compared to the effect of nitroglycerin in 31 patients previously studied using the same technique. Mean arterial pressure and pressure-rate product were comparably reduced by both drugs. In contrast to the findings with nitroprusside, after sublingual nitroglycerin RMBF decreased markedly in normals and increased in patients with coronary artery disease and high-grade collaterals. The data suggest that nitroprusside may primarily affect resistance vessels within the coronary circulation, as opposed to the effect of nitroglycerin on conductance vessels. Thus, nitroprusside could result in redistribution of blood flow away from ischemic areas and potentially increase ischemic injury in some patients with coronary artery disease.


Etiology of the negative chronotropic responses to transient coronary artery occlusion in the anesthetized rhesus monkey. Etiology of the negative chronotropic response to coronary artery occlusion was studied in chloralose-anesthetized monkeys. One-minute occlusion of the circumflex (CIRC) coronary artery resulted in marked negative chronotropic responses and consistent alterations in atrial electrograms. These responses were dependent on interruption of flow to a small proximal CIRC branch, and postmortem examination revealed that it perfused the sinus node region. The negative chronotropic response was not dependent on any apparent neural reflexes because it was not affected by autonomic blockade. Coronary artery occlusion in anesthetized monkeys can result in significant decreases in heart rate and changes in atrial electrical activity when flow to the pacemaker region is interrupted. We suggest that (1) rhesus monkeys may be suitable for study of the sick sinus syndrome, and (2) atropine-resistant bradycardia and atrial arrhythmias observed in postinfarction patients may be due to sinus node artery blockade.


Evaluation of a Behring laser-nephelometer prototype in the measurement of IgG, IgA and IgM. A helium-neon laser nephelometer prototype manufactured by Hoechst Behring Institut was evaluated and used in our laboratory during a two-month period for the measurement of IgG, IgA and IgM. Two methods of dilution were usedto prepare standard curves. The best results were obtained when the patient serum was diluted one hundred fold (10-100 microliter) and incubated for 15 min at room temperature in a disposable plastic cuvette with the specific antiserum diluted five fold (100-300 microliter). The intensity of the light scattered by the antigen-antibody complexes was then immediately read on the digital voltmeter. The working ranges were 186-5944 mg/dl for IgG, 33-1066 mg/dl for IgA and 17-545 mg/dl for IgM. Standard curves obtained for the three immunoglobulins on six different days could be superimposed perfectly demonstrating an excellen reproducibility. The coefficient of variation for IgG (n = 8) was 4.1% at 5800 mg/dl. The results (n = 37) produced by the laser nephelometer (y) correlated very well with those obtained by radial immunodiffusion (x) for: IgG y = 8.07 + 1.00 X, r = 0.997, IgA y = - 6.51 + 1.05 X, r = 0.996, IgM y = 3.35 + 0.98 X, r = 0.998.


Direct assays of lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate with a centrifugal analyzer. Methods are described for direct assays of lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate in plasma with the GEMSAEC centrifugal analyzer. The methods for lactate, beta-hydroxybutyrate, and acetoacetate are kinetic and ratiometric, eliminating the need for specimen-blank assays. The pyruvate method is an end-point assay, because endogenous lactate dehydrogenase interferes in a kinetic pyruvate assay. The methods are precise and accurate and 1-min of analysis time is adequate for each assay. Rapid assessment and monitoring of metabolic acidosis is possible with these methods, as is illustrated by examples.


Sporadic non-toxic goitre: an investigation of the hypothalamic-pituitary-thyroid axis. Thyrotrophin releasing hormone (TRH) tests have been carried out on sixty-two patients with sporadic non-toxic nodular goitre. 61% gave a subnormal thyroid stimulating hormone (TSH) response but had normal plasma thyroxine (T4) and triiodothyronine (T3) levels. T3 administration suppressed 131I uptake by the thyroid adequately in 74% of these and there was normal stimulation of thyroid uptake by exogenous TSH. Prolactin (PRL) rose normally after TRH in all the TRH non-responders. Normal TSH response to TRH was restored by partial thyroidectomy and in some cases by propyl thiouracil administration. Possible reasons for these findings are discussed. It is concluded that these cases were truly euthyroid.


The inter-relationship of thyroid hormones, vitamin A and their binding proteins following acute stress. The effects of surgical stress on the metabolism of the retinol-binding-protein-thyroxine-binding-prealbumin complex were investigated. The immediate postsurgical period was characterized by a rapid decline in the serum concentration of retinol, retinol binding protein and triiodothyronine and an increase in the 24 h urinary excretion of retinol, retinol-binding-protein and thyroxine. Similar, but less pronounced, changes were seen in other subjects suffering acute myocardial infarction but were not observed in normal healthy euthyroid males or in pre-operative euthyroid patients. The preparation of specific anti-retinol binding protein anti-serum and the use of this in 'monorocket' immunoelectrophoresis are also described.


Effect of selective goitre resection on absent thyrotrophin response to thyrotrophin releasing hormone in idiopathic euthyroid goitres. Absent thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH) was found in ten of fifty consecutive nodular goitrous patients who were clinically and biochemically euthyroid. These ten patients together with a reference group engaging fifty-eight healthy individuals matched for sex, age, and geographic region form the basis of the present study. Patients with autonomously functioning single adenomata were excluded from the investigation. In the patient group, values of serum thyroxine (T4), free T4-index, and serum TSH did not differ significantly from those recorded in the reference group, whereas serum triiodothyronine was found to be significantly higher in the patients, although within the normal range. After selective resection of the goitre, the TSH responsiveness to TRH recovered completely. Routine indices of thyroid function, however, demonstrated no major deviation from pre-operative levels. During a follow-up period of 1 year, no systematic alterations were recorded in TSH response to TRH nor in the thyroid function tests, indicating maintenance of euthyroidism with restored normality within the pituitary-thyroid axis. The present study lends support to the view that increasing functional autonomy apparently is a common trend in goitre evolution in a non-endemic area.


Nephrotoxicity of cis-platinum (II) dichlorodiammine. The renal function of 15 patients receiving cis-platinum (II) dichlorodiammine (CPDD) was examined prospectively in detail to elucidate early evidence of nephrotoxicity. Patients were given a total of 49 couses of CPDD at 20 mg/m2/day for 5 days with 1,000 ml of saline prehydration. Renal function was monitored by serial determinations of serum creatinine and glomerular filtration rate (measured as 125I-iothalamate clearance) and by measurement of parameters of tubular function, including tubular reabsorption of phosphorus, urine-to-serum glucose ratio, total protein, and total free immunoglobulin light chain excretion, serum electrolytes, and urine pH and specific gravity. There was no significant change in mean serum creatinine within a course of treatment, nor was there a cumulative increase in the serum creatinine. In 9 of 19 evaluable courses there was a small transient fall in glomerular filtration rate with prompt recovery. There was no cumulative decrease in glomerular filtration rate through 3 courses of treatment. Four of the patients with preexisting renal insufficiency suffered no significant additional nephrotoxicity. There was no tubular dysfunction demonstrable in any of the patients. This study represents the first prospective detailed examination of multiple parameters of renal function in patients treated with CPDD and reveals that the only parameter to show any change with this schedule of drug administration was the glomerular filtration rate.


The effect of berberine on bilirubin excretion in the rat. Berberine-containing herbs have been used in folk medicine to relieve neonatal jaundice. In the present investigation, the acute and chronic effects of berberine on bilirubin excretion were studied in rats. Acute doses of berberine were found to increase the secretion of bilirubin in experimental hyperbilrubinemia without affecting the UDP-glucuronyltransferase activity and BSP clearance. Continuous treatment abolished this effect. This apparent tolerance could be attributed to the inhibitory action of chronic berberine treatment on UDP-glucuronyltransferase activity, but the mechanism of this inhibition was not elucidated. Liver microsomal protein concentration, ethylmorphine N-demethylation, and BSP clearance were unchanged.


Canine brucellosis. Current status of methods for diagnosis. A critical review of the performance of several methods used for the serodiagnosis of canine brucellosis is presented. It is concluded that none of the procedures commonly used is, in itself, adequate to permit a definitive diagnosis in all cases. The diagnosis is simplified when several animals in a kennel are infected; however individual cases pose a variety of problems, especially when complete clinical histories are not submitted or opportunities for infection have not been disclosed. Blood cultures are an essential part of the laboratory diagnosis of B. canis infection, but bacteremia is frequently absent in chronically infected dogs. Judgements must therefore be made on the basis of bacteriologic results in concert with a variety of serologic tests, and an evaluation of clinical signs. In some instances, laboratory diagnosis is not possible without repeated samplings. The minimal diagnostic effort should include the screening of sera by the slide agglutination test (SAT). Negative results, in the absence of clinical signs, strongly suggest absence of infection. Positive SAT results indicate that further laboratory study is required. A two-stage testing procedure of all SAT-positive serums is therefore recommended. The tube agglutination test (TAT) or the 2-mercaptoethanol-TAT (ME-TAT) are valuable complementary methods; however either of these latter procedures, in conjunction with immunodiffusion analysis, appears to provide the best chances for accurate judgements of serologic results in difficult cases.


Pulmonary and endocrine function before and after therapy with cromolyn sodium in asthma. Studies in steroid-dependent and nonsteroid-dependent asthmatic children and adolescents. This study evaluated growth, chest radiographic manifestations, pulmonary function, and function of the pituitary-adrenal axis before and after therapy with cromolyn sodium in two groups of asthmatic youngsters, ie, 18 steroid-dependent patients and ten nonsteroid-dependent patients. The following three groups evolved: (1) steroid-dependent patients; (2) patients weaned from therapy with steroids; and (3) nonsteroid-dependent patients. Growth failure and cataracts were limited to the steroid-dependent group, while abnormalities of the lungs and pituitary-adrenal axis occurred in all three groups. Symptomatic benefits from therapy with cromolyn were striking for all groups. Chest x-ray films and the distribution of alveolar ventilation were more likely to reflect this clinical improvement than tests of pulmonary function and analyses of blood gas levels. Endocrine abnormalities in the steroid-dependent group were significant and were not quickly reversed by withdrawal of therapy with steroids. Even nonsteroid-dependent patients had abnormalities which may be related to having chronic asthma. Therapy with cromolyn seemed to promote some restoration of the function of the pituitary-adrenal axis, as indicated by better responsiveness to administration of metyrapone, which correlated with improved symptomatic control of asthma.


Influence of the use of a surgical isolator on the rate of infection in the treatment of hydrocephalus. Two series of patients treated for hydrocephalus (101 original shunt insertions, 81 revisions and 35 reinsertions after infections) have been operated on in the same location, 146 with a surgical isolator (SI), 71 without a SI. Due to temporary poor technical conditions, the use of a SI was decided because, the overall rate of acute postoperative infections had suddenly increased from 9 to 19.7%. Then, although these technical conditions remained unchanged, the use of the SI immediately reduced the overall rate of acute postoperative infections from 19.7 to 7.4%. In original shunt insertions, this rate decreased from 24.9 to 5.8% and in revisions from 10.7 to 5.5%. In reinsertions after infection, it only fell from 27.2 to 16.6%. With the SI, the rate of peroperative contamination is almost nil. If postoperative contaminations due to wound disruption or scalp necrosis, and shunt reinsertions after infection are not taken into account, the rate of acute postoperative infection is 0.8%. The data presented indicate the efficiency of the SI. This results from elimination by the SI of airborne contamination and errors in aseptic technique. These two factors are probably the main sources of infection in shunt insertions for hydrocephalus.


Adult male--infant interactions among monkeys living in nuclear families. Adult male rhesus monkeys were housed in nuclear families containing adult female mates, offspring, and other infants and adults. Behaviors exhibited by the adult males were recorded 4 days per week over a 37-month period; in interactions involving other monkeys, the identity and the responses of those participants were also recorded. The results indicated that, although adult males were less active and more stable in their behavioral levels than mates or offspring, they clearly distributed both initiates and responses differently to male offspring, female offspring, mates, and both infant and adult monkeys from other families. These results suggest that adult males have the potential to play more important roles in the social development of infants than had been previously suspected on the basis of field data. Implications for human father-infant interactions are discussed.


Pyocyanine production by Pseudomonas aeruginosa. Dextrose enhanced the growth of P. aeruginosa but suppressed the biosynthesis of pyocyanine. The preformed pigment could be released from dead cells. Pigmentation was not correlated directly with number of viable organisms in the culture. High concentration of maltose likewise inhibited pyocyanine production. Maltose contained in medium used for pyocyanine production by P. aeruginosa should be kept in low concentration or omitted.


Drug resistance among Mycobacterium tuberculosis strains isolated in Taiwan during 1975. 455 strains of Mycobacterium tuberculosis were isolated from patients with history of treatment in Taiwan Provincial Tuberculosis Control Bureau and tested for resistance against various antituberculosis agents including streptomycin (SM), paraaminosalicylic acid (PAS), isoniazid (INH), cycloserine (CS), prothionamide (1321TH), kanamycin (KM), ethambutol (EMB), and rifampicin (RFP). In vitro resistance to SM and INH was more frequently found than others and the resistance to a single drug was more common than multiple resistance.


The role of de novo purine synthesis in lymphocyte transformation. Genetic defects in purine metabolism are associated with severe immunodeficiency. Adenosine deaminase deficiency impairs the function of both B- and T-lymphocytes whereas in purine nucleoside (inosine) phosphorylase deficiency there is more severe impairment of T-lymphocyte functions than of B-lymphocyte functions. The relative unimportance of the salvage pathway catalysed by hypoxanthine-guanine phosphoribosyltransferase is shown by the normal responses of T-lymphocytes from patients with the Lesch-Nyhan syndrome to antigenic and mitogenic stimulation. A mild deficiency of B-lymphocyte function is found in these patients. Agents inhibiting the de novo pathway of purine synthesis, including azaserine, 6-mercaptopurine and azathioprine in low doses, block the responses of normal human lymphocytes to mitogenic stimulation. These observations emphasize the importance of the de novo pathway of purine synthesis in lymphocyte responses to antigenic and mitogenic stimulation. There is considerable heterogeneity in the amount of labelled uridine incorporated into human and rat lymphocytes. This does not appear to reflect only a difference between T- and B-lymphocytes


[Results of treating the acute stage of Crohn's disease by a dietary regimen (author's transl)]. 23 consecutive patients (13 women, 10 men; mean age 31 years) with acute exacerbation of Crohn's disease were treated by a dietary regimen based on "resting" the bowel by parenteral nutrition or a balanced synthetic diet (Vivasorb), followed by stepwide introduction of a low-residue diet. Cardinal symptoms such as severe abdominal pain, diarrhoea, incomplete ileus or weight loss responded favourably to treatment in each case. Postoperative fistulae closed in two of three patients. Enterocutaneous fistulae, however, remained open in all five patients, although the volume of secretion decreased distinctly in four. During the follow-up period (averaging nine months after discharge from hospital) symptoms recurred in five patients, necessitating operative treatment in three.


Conservation of active ribosomes in acetone-treated cells of Tetrahymena pyriformis. The preparation of an acetone powder of cells of Tetrahymena pyriformis GL is described. A comparison of ribosomal particles isolated from acetone-treated and untreated cells shows that structurally and functionally intact ribosomes can be isolated from acetone-treated cells. Fully active ribosomes have been isolated from acetone powder of Tetrahymena that had been stored for more than 6 months at 4 degrees C. Thus, this procedure allows easy storage of large quantities of cells for the bulk preparation of active ribosomes.


Phosphorylation in vivo of Ribosomes in Tetrahymena pyriformis. Phosphorylation of ribosomal proteins in vivo was studied in exponentially growing and starved cells of the ciliated protozoan, Tetrahymena pyriformis. No phosphorylation of ribosomal proteins could be demonstrated in cells growing exponentially in complex nutrient media. However, when Tetrahymena cells were transferred into a non-nutrient medium, pronounced phosphorylation of a single ribosomal protein was observed. During two-dimensional polyacrylamide gel electrophoresis the phosphorylated ribosomal protein migrated in a manner virtually identical to that of the phosphorylated ribosomal protein S6 of rat liver. The phosphorylated ribosomal protein has a molecular weight of 38000 as estimated by dodecylsulfate polyacrylamide gel electrophoresis. Thus, the phosphorylated ribosomal protein found in starved Tetrahymena is apparently homologous with the ribosomal protein which is predominantly phosphorylated in higher eukaryotes. When phosphorylated ribosomes were dissociated by treatment with high concentration of KCl, the phosphorylated protein was found only on the small subunit. If dissociation was achieved by dialysis against a buffer low in MgCl2, the phosphorylated protein was distributed almost equally between the two subunits. This indicates that the phosphorylated ribosomal protein is located at the interface between the two subunits.


The chemistry of the reaction of 2-hydroxy-5-nitrobenzyl bromide with his-32 of alpha-lactalbumin. His-32 of bovine or human alpha-lactalbumin reacts with the tryptophan reagent 2-hydroxy-5-nitrobenzyl bromide at pH 7. The reaction depends on the native conformation of the alpha-lactalbumin molecule and it is restricted to position 1 of the imidazole nucleus. The synthesis and characterization of 1-(2-hydroxy-5-nitrobenzyl)-histidine, 3-(2-hydroxy-5-nitrobenzyl)-histidine and 1,3-bis(2-hydroxy-5-nitrobenzyl)-histidine are described.


Non-ribosomal nucleotide sequences in 7-S RNA, the immediate precursor of 5.8-S ribosomal RNA in yeast. The topography and the length of the non-ribosomal sequences present in 7-S RNA, the immediate precursor of 5.8-S ribosomal RNA, from the yeast Saccharomyces carlsbergensis were determined by analyzing the nucleotide sequences of the products obtained after complete digestion of 7-S RNA with RNase T1. The results show that 7-S RNA contains approximately 150 non-ribosomal nucleotides. The majority (90%) of the 7-S RNA molecules was found to have the same 5'-terminal pentadecanucleotide sequence as mature 5.8-S rRNA. The remaining 10% exhibited 5'-terminal sequences identical to those of 5.9-S RNA, which has the same primary structure as 5.8-S rRNA except for a slight extension at the 5' end [Rubin, G.M. (1974) Eur. J. Biochem. 41, 197--202]. These data show that the non-ribosomal nucleotides present in 7-S RNA are all located 3'-distal to the mature 5.8-S rRNA sequence. Moreover, it can be concluded that 5.9-S RNA is a stable rRNA rather than a precursor of 5.8-S rRNA. The 3'-terminal sequence of 5.8-S rRNA (U-C-A-U-U-UOH) is recovered in a much longer oligonucleotide in the T1 RNase digest of 7-S RNA having the sequence U-C-A-U-U-U-(C-C-U-U-C-U-C)-A-A-A-C-A-(U-U-C-U)-Gp. The sequences enclosed in brackets are likely to be correct but could not be established with absolute certainty. The arrow indicates the bond cleaved during processing. The octanucleotide sequence -A-A-A-C-A-U-U-C- located near the cleavage site shows a remarkable similarity to the 5'-terminal octanucleotide sequence of 7-S RNA (-A-A-A-C-U-U-U-C-). We suggest that these sequences may be involved in determining the specificity of the cleavages resulting in the formation of the two termini of 5.8-S rRNA.


Anger camera imaging of perfused and nonperfused brain tissue with intra-arterial 133Xenon technique. The regional cerebral blood flow, the regional blood flow distribution, and the regional distribution of perfused (= vital) brain tissue been imaged with a digitalized conventional Anger camer. An analog scaler was placed behind the PM-tubes to reduce dead-time loss. The input pulse rate was doubled to counteract the effect of scaling on counting statistics, and the gamma emission was filtered through 1 mm of brass to increase the fraction of the integral count rate within the 40% window. In this way the 31 keV peak disappears, and Compton scatter and disturbing coincidences are markedly reduced. This improves spatial resolution. The flow parameters are imaged regionally in 3 X 3 mm2 matrix elements after flat field correction and smoothing. The matrix is 64 X 64 interpolated to 128 X 128. Patient studies emphasized the importance of imaging the distribution of perfused and nonperfused tissue in cases of infarctions, dilacerations, etc., where angiography and conventional brain scanning may often be negative.


Absent kidney sign associated with symmetrical and uniformly increased uptake of radiopharmaceutical by the skeleton. In 11 patients 99mTc-stannous H.E.D.P. bone scans showed absent renal images associated with symmetrical and uniformly increased uptake of radiopharmaceutical by the skeleton. These appearances are frequently seen in renal osteodystrophy but are uncommon in malignant disease. Their significance in hypervitaminosis D requires further evaluation.


Serum and cerebrospinal fluid IGM in 203 neurological patients. Simultaneous serum and CSF IgM determinations were made by electroimmunodiffusion in 5 normals and 203 patients. Absent from normal CSF, IgM was found in 56 patients (27%): (1) A blood-CSF transudation was present in 25 patients (12%). IgM seems of no diagnostic value in these cases. (2) A purely local synthesis was demonstrated in 17 patients (8%), concerning proved (bacterial, viral, parasitic) or supposed (multiple sclerosis) persistent infectious aggressions. (3) In the last 14 patients with IgM in CSF, a transudation was associated with a local synthesis of IgG (meningitis pattern). (4) A ratio IgM .10(3)/albumin above 10 seems an argument for multiple sclerosis.


Effects of the angiotensin II antagonist 1-sar-8-ala-angiotensin II in hypertension in man. The angiotensin II antagonist 1-sar-8-ala-angiotensin II (saralasin) was infused in forty-six patients with hypertension of various aetiology (essential, renal arterial or parenchymal disease, primary hyperaldosteronism), before and/or during sodium volume depletion obtained by chlorthalidone and low sodium diet. When saralasin was infused in twenty-five patients ingesting 130 mmol of sodium per day, including patients with proven renovascular hypertension, the changes in mean arterial pressure and ranged from +10 to -7 mmHg (mean: +0.20 mmHg) and were not related to the plasma renin concentration (PRC) (r = -0.11). During sodium volume depletion, saralasin induced changes in mean arterial pressure, ranging from +21 to -76 mmHg, which were closely related to log PRC (n = 32; r = -0.87). Combined sodium depletion and antagonism of angiotensin II 'normalized' mean arterial pressure (less than or equal to 100 mmHg) in twenty-one of the thirty-two patients, while pressure remained between 106 and 147 mmHg in eleven 'poor' responders, so that pressor mechanisms other than sodium volume and angiotensin must be responsible for the remaining elevation of pressure in these patients. The study indicates that arterial pressure is not dependent on the immediate pressor effects of angiotensin II in sodium replete patients, and in sodium deplete subjects whose PRC remains low, while it is at least partly angiotensin II dependent during sodium volume depletion in the others. The results cast doubts on the clinical usefulness of saralasin in the investigation of patients with hypertension, when studied in the conditions of the present study.


The role of adrenaline and of the vagus in gastrin release and acid secretion in dogs. Serum gastrin, gastric acid secretion and plasma adrenaline in response to intravenous injection of 2-deoxy-D-glucose and to insulin were measured in six dogs with gastric fistulae before and after denervation of the antrum and the intestine (antral-intestinal vagotomy). Serum gastrin and gastric acid secretion were also measured in the same dogs during intravenous infusion of adrenaline in doses which produced an elevation of plasma adrenaline to levels occurring during hypoglycaemia and after the injection of 2-deoxy-D-glucose. Antral-intestinal vagotomy reduced basal gastrin concentration slightly and basal gastric acid secretion considerably. The rise in serum gastrin in response to 2-deoxy-D-glucose and hypoglycaemia was abolished while the increase in gastric acid secretion was reduced after antral-intestinal vagotomy. Beef meal-stimulated gastrin secretion was the same before and after vagotomy. Intravenous infusion of adrenaline had no effect on either serum gastrin or gastric acid secretion. It is concluded that in the dog, in contradistinction to man, gastrin release after insulin is dependent on an intact vagus. Release of gastrin by adrenaline in the dog does not appear to be physiological since it is not achieved by the amount of adrenaline released in response to hypoglycaemia.


Ethanol-induced hypoglycaemia in man: its suppression by the alcohol dehydrogenase inhibitor 4-methylpyrazole. Infusion of ethanol (0.6 g/kg body wt) caused marked hypoglycaemia in subjects fasted for 36 h. Previous administration of the alcohol dehydrogenase (ADH) inhibitor 4-methylpyrazole (4-MP, 7 mg/kg body wt i.v.) strongly suppressed the ethanol-induced hypoglycaemia. The rate of ethanol elimination was 84.6 mg/kg per hour. 4-MP at the dose used caused a 21% reduction of ethanol elimination, but had no significant effect on blood acetaldehyde levels. 4-MP also significantly suppressed the ethanol-induced elevation of blood lactate and almost completely prevented the increase in the 3-hydroxybutyrate/acetoacetate ratio, but had only a slight effect on the lactate/pyruvate ratio of venous blood. The results demonstrate that the hypoglycaemia and lactacidaemia produced by the oxidation of alcohol can be prevented by a dose of 4-MP that diminishes or prevents the ethanol-induced shift in the NAD-coupled redox state of the liver.


A radioimmunoassay for human thyroglobulin: methodology and clinical applications. A specific double-antibody radioimmunoassay with a sensitivity of 2.5 ng/ml has been developed for measuring thyroglobulin (Tg) in human serum. As endogenous anti-Tg antibodies in serum interfere in the assay, only sera with a negative tanned red cell (TRC) test are suitable for analysis. Tg was detectable in 84.7% of the euthyroid subjects, with a mean value of 6.1 (values ranging from nondetectable to 43.0 ng/ml). Values were significantly higher in women than in men. Tg release by the thyroid appears to be under pituitary control, as suggested by TSH stimulation and T3 suppression tests. Elevated Tg levels were found in hyperthyroidism, simple goitre, and differentiated thyroid carcinoma. The significance of circulating Tg and the possible application of the Tg RIA are discussed.


Secondary hypertriglyceridaemia in patients with parenchymal liver disease. Hypertriglyceridaemia occurring in patients with liver disease has been studied by measuring hepatic triglyceride lipase (H-TGL) and plasma lipoprotein lipase (LPL) by selective precipitation of H-TGL with specific antibodies. Lipid analysis, determination of lecithin-cholesterol-acyltransferase (LCAT) activity, and liver function tests were performed in parallel in fifty patients with acute hepatitis, twenty patients with chronic active or persistent hepatitis and fifty with cirrhosis of the liver. Total post-heparin lipolytic activity (PHLA) decreased with the severity of liver dysfunction. This decrease was due to low H-TGL and only to some degree to low LPL activity. With improvement over several weeks of hospitalization, hypertriglyceridaemia disappeared with a concomitant increase of H-TGL and LPL. It is concluded that impaired triglyceride metabolism in liver disease is at least partly caused by diminished plasma hepatic TGL activity.