Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra. In the present study dopamine (DA)-containing and other output neurons of the substantia nigra (SN) wer identified by antidromic stimulation from postulated target nuclei, the caudate-putamen, the thalamus, the cortex and the pontine reticular formation. To guide electrode placements, the topography of the nigrostriatal projection system was determined by retrograde tracing methods. Spontaneously active cells present in the SN were then classified in two groups according to the shape of their action potentials and their firing rate. Type I cells were located mainly in the pars compacta and could be antidromically-activated (AD-activated) from various locations along the course of the nigrostriatal pathway (caudate-putamen, globus pallidus, MFB) but not from other brain areas (ventromedial thalamus, motor cortex, pontine reticular formation). These neurons had a slow bursting pattern of firing, a very slow conduction velocity (0.58 m/sec), and a wide action potential. Their firing rate was dramatically reduced following the intravenous administration of apomorphine (ID 50: 9.3 microgram/kg), or the iontophoretic application of DA and GABA. Type II cells were located predominantly in the pars reticulata; most of them could be AD-activated from the ventromedial thalamus and the MFB but not from the motor cortex. A few of these cells could be AD-activated from the pontine reticular formation and the thalamus. A minority of type II cells, located in or near the pars compacta could be AD-activated from the caudate-putamen. In addition, their conduction velocuty was much higher (2.8 m/sec) and their firing rate far in excess of that exhibited by type I neurons. These neurons were inhibited by the iontophoretic application of GABA but not of DA. The microinjection of 6-hydroxydopamine (a neurotoxin relatively specific against catecholamine-containing neurons) in the vicinity of the MFB blocked selectively the propagation of antidromic spikes in type I but not type II cells. It is concluded that type I cells are the DA neurons of the nigrostriatal pathway. Type II cells are mainly oupput neurons that project to the ventromedial thalamus, the pons and the forebrain. This telencephalic projection most likely constitutes a second, non-DA, fast-conducting nigrostriatal pathway.


A simple improved method to stain Thiobacillus. Best stains are obtained by immersion of the fixed smear in 1.5-2% acid fuchsin at pH 3.2-3.6.


Altered polyamine profiles in prostatic hyperplasia and in kidney tumors. Polyamine concentrations were evaluated in normal human prostatic tissue as well as hyperplastic prostate. Normal tissues had high concentrations of putrescine and spermine with intermediate spermidine concentrations, whereas there was a dramatic increase in the spermine concentration in patients with hypertrophy of the prostate. Although not highly significant, spermidine concentrations were elevated slightly in benign hyperplasia, whereas the putrescine content was decreased compared to normal tissue. Polyamine concentrations were measured also in human kidney tumors and corresponding healthy kidney tissue. The concentration of spermidine in renal carcinomas was significantly elevated when compared to histologically normal areas of the same kidney. The spermine concentration of the tumor was generally lower but not highly significant (p less than 0.01). These data suggest that polyamines are accumulated above normal levels in pathological conditions such as benign hyperplasia of the prostate and renal carcinoma. In both cases, spermidine turnover rate may be influenced by carcinogenesis.


Comparative behavior of simian virus 40 T-antigen and of tumor-specific surface and transplantation antigens during partial purification. The simian virus 40-specific T-antigen has been extracted from SV AL/N mouse embryo tissue culture cells by treatment with Triton X-100 detergent. The extracts contained tumor-specific transplantation antigen (TSTA) and tumor-specific surface antigen. These extracts were purified by ammonium sulfate precipitation and diethyl-aminoethyl cellulose and phosphocellulose column chromatography and were assayed for the three antigens. We found that T-antigen, TSTA, and much of the tumor-specific surface antigen copurified through all purification steps. This finding is consistent with previous suggestions of the close degree of homology that must exist between the protein species carrying these three antigenic determinants. The antibody-mediated cytolytic assay appears to detect a new type of antigen on the cell surface, different from T-antigen and TSTA; two antigenic fractions were obtained from the phosphocellulose column that had tumor-specific surface antigen activity, but one of these did not have T-antigen or TSTA activities.


Metabolism and cytotoxicity of 5-azacytidine in cultured Novikoff rat hepatoma and P388 mouse leukemia cells and their enhancement by preincubation with pyrazofurin. 5-Azacytidine transport into cells was measured in the absence of metabolism in adenosine triphosphate-depleted and uridine kinase-deficient Novikoff cells. Azacytidine is transported with about the same efficiency as uridine and cytidine by the facilitated nucleoside transport system of these cells. The phosphorylation of azacytidine in untreated, wild-type cells, however, is much more inhibited by uridine and cytidine than is its transport into the cell. This inhibition seems to be responsible for the specific protection of cells by these nucleosides from azacytidine toxicity. Azacytidine is incorporated by Novikoff and P388 cells into both RNA and DNA, and this incorporation seems to be responsible for its cytotoxicity; an inhibition of de novo pyrimidine nucleotide synthesis is not a major contributory factor. Incorporation of azacytidine into nucleic acids is relatively slow, but it is enhanced 3 to 4 times when cells are preincubated with pyrazofurin. Pyrazofurin inhibits de novo pyrimidine synthesis and thus causes a depletion of cellular pyrimidine nucleotides. Azacytidine is largely cytostatic for Novikoff and P388 cells, but a sequential treatment with pyrazofurin and azacytidine markedly increases the cytotoxicity over that observed with drug alone or when administered together with drug, even at higher concentrations. Increased cytotoxicity correlates with the increased incorporation of azacytidine into nucleic acids.


Observations on cell lines derived from a patient with Hodgkin's disease. Permanent cell lines have been established from a spleen nodule and lymph node of a male Hodgkin's disease (HD) patient whose father has the same disease. Th in vitro growth pattern morphological and cytogenetic characteristics of these lines maintained continuously for over 2 years are described. The cultures contain a population of mixed cell types that grow in suspension. Between 5 and 10% of the cells have surface immunoglobulins M and D. B-cell alloantigens are also detectable. While the cultures are predominantly lymphoid, some of the large cells, by light and electron microscopy, resemble the Reed-Sternberg and Hodgkin's cells of the original biopsies. Although the cells maintain the human diploid karyotype, they are heterotransplantable in nude mice. After 14 months of culture, chromosome rearrangement and losses, commonly seen in leukemic bone marrow, occurred. Close to 100% of the cells are Epstein-Barr nuclear antigen positive, but they lack Epstein-Barr viral (EBV) capsid antigen and EBV-induced early antigen. Nucleic acid hybridization tests indicated that there were no more than two EBV genome equivalents per cell. Tests with HD sera free of anti-EBV were negative. Electron microscope examination of the cells revealed the presence of intracellular as well as extracellular rare pleomorphic particles ranging from 400 to 1200 A. The nature of these particles, which increased in number after the cultures were treated with halogenated pyrimidines but not with dimethyl sulfoxide, remains questionable. The cultures derived from the mouse-passaged HD cells, however, had reverse transcriptase activity and readily identifiable type C particles which were probably of murine origin. These cultures have some unique features that make them useful in studying the perplexing pathological entity of HD.


Lactate--a suppressor of differentiation in embryonic cells. All kinds of visible differentiation in cultured amphibian embryonic cells are suppressed in the presence of lactate. This effect differs in certain respects from that observed with actinomycin, but like the latter lactate inhibits RNA synthesis. In this communication we present some further observations on the effect of lactate.


The three type of human viral hepatitis. Infections with hepatitis A and B viruses are common in all parts of the world and constitute a major public health problem. The identification of specific antigenic markers of these viruses has led to the development of sensitive laboratory tests. These, in turn, have resulted in a better understanding of the epidemiology, pathogenesis, immunology, and the nature of these common infections. In the case of hepatitis type B, laboratory tests revealed a persistent carrier state of the surface antigen in some 120-175 million people and established the significance of hepatitis B virus in the pathogenesis of serious chronic liver disease, including a strong association with primary hepatocellular carcinoma in tropical and some subtropical regions. In addition, the specific diagnosis of hepatitis types A and B has revealed a previously unrecognized form of hepatitis which is clearly unrelated to either type. This new form of infection of the liver is now the most common type of hepatitis after the transfusion of blood and blood products in some areas of the world and it also appears to be an important cause of sporadic hepatitis, particularly among adults.


Influenza surveillance.

Influenza surveillance. THE MAIN OBJECTIVES OF INFLUENZA SURVEILLANCE ARE: to measure the impact of the disease by collection and analysis of epidemiological information on morbidity and mortality, and to anticipate future epidemics and pandemics by the collection and analysis of influenza viruses. The World Health Organization's influenza programme is based on the collaboration of 98 national influenza centres in 70 countries and the 2 WHO Collaborating Centres in Atlanta and London.Epidemiological information may be based on morbidity figures derived from a variety of sources such as returns from physicians or hospitals; mortality statistics or new claims for sickness benefit; school or industrial absenteeism, etc.The laboratory aspects of influenza epidemiology are certainly more uniformly covered than the statistical aspects. Since the advent of the A/Hong Kong/1/68 (H3N2) influenza virus A subtype there have been a number of variants with antigenic "drift" but only three succeeded in causing widespread epidemics: A/England/42/72, A/Port Chalmers/1/73, and A/Victoria/3/75. In 1972, the influenza B virus also showed some antigenic "drift", the new variants being characterized by B/Hong Kong/5/72.Whenever a new variant appears, the degree of protection afforded to the population by the available vaccine is assessed. In the light of these data, WHO publishes annually in the Weekly epidemiological record recommendations formulated by the WHO Collaborating Centres on vaccine composition.


[Evolution of anti-Rh antibodies idiotypy in a blood donor over 9 years]. Anti-idiotypic sera were obtained in Rabbits immunized with Rh antibodies (isolated from the serum sample collected in 1974 from a Blood Donor). The sera agglutinate, at high titers, red cells coated with the immunizing antibodies and, at different titers, cells coated with antibodies from serum samples taken at other periods. Inhibition of hemagglutination of anti-idiotypic sera by different samples from the same Donor was complete with the immunizing serum and partial with other samples. These results show that idiotypes or idiotypic specificities appeared or disappeared during the period studied and represent the first observation on evolution of antibody idiotypy in Man.


[Model of the interaction between trypsin and alpha 2-macroglobulin of porcine serum]. A comparative study of the dissociation into subunits of Porcine alpha2 M, either native or bound to trypsin (Tn), has been carried out in order to determine the modifications of the alpha2 M structure due to the formation of the Tn-alpha2 M complex. Analytical ultra-centrifugation at pH 3.5 shows that the dissociation is smaller when alpha 2 M is bound to trypsin. Electrophoresis in 4% polyacrylamide gels, in presence of 0.1% SDS, of alpha2 M and Tn-alpha2 M incubated in 1% SDS leads to the same conclusion; the enzyme must stabilize the quaternay structure of alpha2 M. In presence of SDS + beta-mercaptoethanol, only a molecular weight (M.W.) 200,000 band is revealed in electrophoresis pattern of native alpha2 M. In the case of reduced Tn-alpha2 M, some other bands of M.W. 100,000, 50,000, 30,000 appear. When trypsin is inactivated by TLCK 100,000 M.W. band is present, accompanied by the 200,000 M.W. band whose intensity is function of the alpha2 M concentration. The 100,000 M.W. band appears therefore characteristic of the formation of the complex which must imply a proteolytic cleavage in the middle of the 100,000 polypeptidic chain of alpha2 M. A model of the complex is proposed in which the enzyme forms a proteic bridge between the two halves of the alpha2 M molecule.


[Histofluorescence of catecholamines and visualization of retrograde transported peroxidase in the same tissue section and in the same neuron]. The demonstration of fluorescent catecholamines and horseradish peroxidase (HRP) in the same neuron has been achieved in the Rat in two ways: by submitting vibratome sections to a modified glyoxylic acid fluorescence method followed by the usual procedure to reveal HRP; or by combining the last procedure with the cryostat technique of Chiba et coll. After HRP injection into the striatum or the nucleus accumbens of the Rat, non-fluorescent HRP labelled neurons were observed in the substantia nigra and the ventral tegmental area respectively, in addition to the HRP labelled fluorescent dopaminergic neurons.


[Progressive antithrombin activity in rabbit plasma. Role of alpha macroglobulins]. Immunological methods associated with a kinetic study of blood coagulation allowed us to show the influence of the 2 rabbit alpha macroglobulins on the plasma progressive antithrombin activity. This study allowed the authors to discuss the participation of the alpha macroglobulins during the fibrinoformation and to think that these proteins have an immediate antithrombin activity.


[Detection of antigenic determinants of membranes using an insoluble peanut lectin]. The binding of lectins on insoluble supports may be used to detect the interactions occurring between these molecules and the sites of some receptors of membranes. An example is given, using the "anti-T" lectin extracted from peanut, to show the presence of determinants with terminal free glactose on the surface of erythrocytes and lymphocytes.


Gallium and bleomycin scans in the clinical staging of testis tumor. Twenty-one patients with testicular tumors had gallium scans prior to retroperitoneal lymph node dissection. Eleven of 14 patients found to have nodal involvement had positive scans, and 2 of 7 patients with negative nodes had false positive scans. Bleomycin scans were positive in 4 of 5 patients with nodal metastases. While these scans provide a simple, non-invasive and occasionally useful technique for the clinical staging of testis neoplasms, they do not, in our experience, significantly supplement other staging procedures.


In vitro histamine and serotonin release by radiographic contrast media (RCM). Complement-dependent and -independent release reaction and changes in ultrastructure of human blood cells. Peripheral leucocytes and platelets from twenty healthy volunteers were incubated in vitro with radiographic contrast media (diatrizoate-Hypaque, iothalamate-Conray and iodipamide-Cholografin) under varying conditions. All radiographic contrast media (RCM) were able to induce histamine release from peripheral leucocytes and the release reaction was dose-dependent. There were individual differences in the sensitivity of leucocytes to different RCM. The highest values (up to 80% histamine release) were found with high concentrations (0.07-0.3 M) of diatrizoate. The addition of normal human serum (NHS) to the reaction mixture led to a further increase in histamine release (P is less than 0.01), probably due to complement activation. The mechanism seems to be mediated by proteins of the alternative pathway, because serum depleted of complement components (factor B, factor D, properdin) did not show this synergistic effect. IgG-depleted serum, however, was able to show the augmented release reaction. Washed platelets incubated with RCM released serotonin in a dose- and time-dependent reaction. The most powerful serotonin-releasing RCM was found to be iodipamide, which produced a release reaction in all people investigated at concentrations of 0.04-0.09 M, while diatrizoate and iothalamate were effective only in half of the tested individuals at high concentrations (0.3 and 0.2 M respectively). The addition of plasma proteins to the reaction mixture inhibited the serotonin release quantitatively. There was no difference in inhibitory potency between autologous and heterologous plasma or serum; sera depleted of various complement components showed similar effects as NHS. The serotonin release was not due to platelet lysis, as determined by the concentration of lactic dehydrogenase present in the supernatant during serotonin release. Incubation of the leucocytes with RCM produced ultrastructural changes, including degranulation of basophils, aggregation of platelets and infiltration of the aggregates by polymorphonuclear leucocytes. The most prominent changes were observed when complement was present in the reaction mixture.


Receptors for fluoresceinated human thyroglobulin in peripheral blood lymphocytes. Fluoresceinated human native and desialylated thyroglobulin were incubated with peripheral blood lymphocytes. 1% of the lymphocytes, in twenty samples from normal human blood donors, showed a bright granular fluorescence where neither the number nor pattern of fluorescence differed from lymphocytes from the blood of thyroiditis patients. Fluoresceinated albumin and gamma-globulin did not bind to the lymphocytes, and a 500-fold excess of native non-fluoresceinated thyroglobulin inhibited the binding and pre-incubation with anti-IgM serum abolished it. Binding with desialylated thyroglobulin was negligible, and the pattern of fluorescence was pale and uniform. Analysis by sucrose gradient centrifugation and double diffusion in agar gel showed that fluorescein dissociates thyroglobulin into 12S fragments and reduces its immunoreaction with autoantibodies. It can therefore be concluded that the 12S molecule produced by fluoresceination maintains its determinants for lymphocyte receptors, whereas further dissociation, as in desialylated fluoresceinated thyroglobulin, leads to a marked reduction in the binding with lymphocytes.


Corticosteroid treatment of cutaneous hemangiomas: how effective? A report on 24 children. Twenty-four children with cutaneous hemangiomas were treated with corticosteroids. The indications for therapy included interference with important bodily functions by the hemangioma, thrombocytopenia related to the hemangioma, or serious cosmetic effects secondary to the hemangiomas. Five children had no improvement, twelve had possible improvement, five had probable improvement and two had definite improvement while on corticosteroids. One child had growth retardation as a complication of corticosteroids; this was reversed when the medication wa dicsontinued.


The effect of various drugs on adenosine triphosphate content and histamine release from rat peritoneal cell suspensions rich in mast cells. 1. Iopanoic acid and iophenoxic acid were potent inhibitors of compound 48/80-induced histamine release from rat peritoneal cell suspensions rich in mast cells and caused a parallel dose-related reduction in ATP content of these cells. 2. Lignocaine was less potent and ouabain and probenecid were ineffective in inhibiting histamine release and reducing cellular ATP content. 3. Various drugs can inhibit 48/80-induced histamine release from rat peritoneal cells and this activity may result from depletion of cellular ATP. It is apparent that little structural specificity is required for activity in this cell system.


[Open prostatic surgery in patients over 80 years (author's transl)]. The fact that a patient needing prostatic surgery is over 80 years old need no longer be a reason why open surgery should not be considered in the treatment programme of the general practitioner or internal physician. Out of 45 men aged between 80 and 92 only two died as a result of surgery. Life expectancy is not reduced by the operation.


[Indications and risks of anti-arrhythmia treatment with propafenone (author's transl)]. Propafenone, a new anti-arrhythmia drug, was given at an average dose of 70-140 mg (1-2 mg/kg body-weight) to 124 patients with various types of cardiac arrhythmias. It proved successful in patients with ectopic beats and tachycardias of atrial or ventricular origin. Ectopic beats were suppressed in 40 of 81 patients, while sinus rhythm was restored in 15 of 19 patients with paroxysmal tachycardias. On the other hand, sinus rhythm was restored in only 5 of 22 patients with atrial tachy-arrhythmias, while in most of the others in this group the heart rate decreased markedly during propafenone injection. The effect of propafenone was on atrial and ventricular myocardium and on the conduction system, lowering the discharge rate of sinus node and ectopic pacemakers. ECG signs of pre-excitation disappeared in 4 of 9 patients with WPW syndrome given the drug. Propafenone may prolong atrioventricular and intraventricular conduction, as well as cause a transitory decrease in cardiac function and a fall in systemic arterial blood pressure. It should, therefore, not be given to patients in severe heart failure, hypotension or shock, or with high-degree atrioventricular, intraventricular or sinoatrial block.


[Micro-electrophoresis of unconcentrated cerebrospinal fluid (author's transl)]. 100 divided samples of cerebrospinal fluid were examined by micro-electrophoresis and conventional paper-electrophoresis. Results of the two tests agreed well for gamma-globulin, albumin, alpha1 and beta fractions, but poorly (because of methodological differences) for pre-albumin, alpha2 and tau fractions.


Comparison of the human evoked electrospinogram recorded from the intrathecal, epidural and cutaneous levels. In 30 patients (17 of whom had a clinically normal spinal cord) spinal cord potentials evoked by peripheral nerve stimulation were studied with computer averaging techniques in order to compare the intrathecal, epidural and skin records. In epidural and skin records, segmental spinal cord potentials either recorded from lower cervical or lower thoracic intervertebral levels often had similar shapes and latencies, especially with regard to the first component of the intrathecally recorded responses. The second slow component became less significant and was even absent in some cases. The amplitude of the first component was on average 33% of that recorded intrathecally when recorded epidurally and only 10% when recorded from the skin. In three cases potentials of very prolonged onset latency were recorded epidurally or cutaneously while in the same cases intrathecal records resulted in potentials with normal latencies. Cervical tract responses at the C6--7 intervertebral level after stimulation of the posterior tibial nerve were studied by the 3 recording methods. Epidural and skin records failed to reveal such a response regularly, while intrathecal recording invariably provided the cervical tract response. The 3 recording methods were discussed with respect to clinical applications and research. It can be stated with some reservation that epidural and skin surface recording techniques could be exploited it one could know the time of arrival segmental afferent inputs at the spinal cord.


EEG studies on patients with chronic obsessive-compulsive neurosis before and after psychosurgery (stereotaxic bilateral anterior capsulotomy). In 35 patients with chronic severe obsessive-compulsive neurosis the EEG was studied before, shortly after (10 days) and 1--2 years after a psychosurgical intervention (stereotaxic bilateral anterior capsulotomy). The preoperative EEG was completely normal or borderline in most of the patients (94%). After surgery EEG changes appeared in 90% of the patients. In most of them (75%) these consisted in bilaterally synchronous bursts of rhythmic slow waves with a maximum in the frontal regions. No consistent change of the alpha activity could be found. At the follow-up examinations most of the EEGs (79%) showed the same pattern as at the preoperative control. No focal or epileptiform abnormalities were observed, either at the immediate postoperative or at the follow-up examination.


Sleep respiratory arrhythmias in control subjects, narcoleptics and non-cataplectic hypersomniacs. Normal subjects may present central-type apneas or periodic respiration during sleep (stages I and II and paradoxical sleep). The importance of these respiratory disorders increases with age. Hypersomniac patients can manifest either similar or more significant sleep respiratory disorders than normal subjects. The presence of cataplexy or obesity does not permit the prediction of the existence of respiratory arrhythmias or of their type. Sleep respiratory arrhythmias of central type are not likely to cause hypersomnia; however, an aggravating role may be played by obstructive apneas.


Preparation for movement in the cat. I. Unit activity in the cerebral cortex. Single unit activity was recorded from the 'motor' cortex of cats during performance of a forelimb flexion movement. Two classes of cortical neurons were defined with respect to the onset of electrographic activity associated with this movement. 'Early' unit, first showing changes in firing rates more than 0.5 sec prior to the movement, were found almost exclusively in the medial precruciate cortex. The lateral cortex appears to be made up almost uniformly of 'late' unit, that is, neurons whose activities are more closely related with the actual movement. The medial cortex, on the other hand, contains both 'early' and 'late' units and thus may have the additional function of participating in the neural system which is the substrate for response set.


Preparation for movement in the cat. II. Unit activity in the basal ganglia and thalamus. Of the movement-related units in the globus pallidus and entopeduncular nucleus 30--40% show early (more than 500 msec) onsets of their movement-related activity preceding self-initiated 'elbow'-flexing movements in cats. The medial pericruciate motor cortex and the VL-VA thalamic nuclei display similar distributions of onset times, in contrast to the lateral cruciate cortex where 97% of neurons change their activity much later. The possible significance of the early activity is discussed in relation to the notion of 'response set'. It is suggested that these data support the concept that the basal ganglia participate in the enabling and sequencing of movements rather than in directly causing them to occur.


Differential hemispheric activation during complex visuomotor performance. Bilateral EEGs were recorded from central, temporal and parietal scalp locations from seven male and seven female human subjects (Ss) while they were engaged in verbal and non-verbal tasks. Alpha power was higher in the right hemisphere when Ss listened to verbal material being read to them; the reverse was true when Ss performed in an imaginative block rotation task. Compared with intergame rest periods, alpha power was suppressed in the right hemisphere when Ss either watched or played Pong (TV tennis). Watching Pong was as effective in producing in producing alpha asymmetry as playing the game in the parietal region, but motor involvement enhanced asymmetry at central and temporal leads. Performance was non-linearly related to asymmetry, first increasing and then decreasing as asymmetry increased.


A spectral method for removing eye movement artifacts from the EEG. A frequency-domain technique for compensating for eye artifacts in mid-line scalp EEG when power spectra are to be calculated is reported. It has been tested in 12 subjects during voluntary and random eye movements. The method which involves calculating the ratio of EEG and EOG spectra adequately controls for low-frequency components in the EEG due to eye artifacts and allows recovery of the dominant peaks in the scalp EEG spectrum.


Electrophysiological localization of central somatosensory lesions in patients with multiple sclerosis. Somatosensory evoked potentials (SEPs) and selected indices of peripheral nerve function were compared in 30 multiple sclerosis (MS) patients and 15 normal controls. A high incidence of delayed SEP onset was observed in the MS patients, correlating with sensory loss--particularly of joint position and vibration sense. Using a method for deriving an indirect estimate of spinal cord conduction velocity, the longitudinal level of the sensory disturbance could in many cases be localized either to the spinal or to the supraspinal segment (or both) of the somatosensory pathway. Abnormally low spinal conduction velocity correlated with clinical judgements of spinal cord malfunction, but abnormalities were encountered also in some cases with no clinical evidence of myelopathy. Electrophysiological studies can contribute to the assessment of patients with suspected MS by demonstrating conduction abnormalities in specific segments of the somatosensory pathway.


[Effects of optic nerve section in baboons on the geniculate and cortical spike activity during various states of vigilance]. Eye movement potentials during wakefulness (EMPs) and so-called spike (PGO) activities were studied in 4 adult baboons before and after optic nerve (ON) section. The latter was performed either in two stages at a 23-day interval or simultaneously. During wakefulness in the intact animal, triphasic EMPs were observed in darkness with smaller amplitude and longer duration than in the light. After section of one ON, the 3 EMP components persisted, but with a smaller amplitude of the first wave. After section of the second ON morphological changes appeared: the amplitude and duration of the potentials were intermediate between those noted in darkness and light but with an intermingled sharp spike. Geniculate EMPs reappeared 11 days after simultaneous ON section, with the same evolution as previously described. During slow wave and REM sleep, intact animals presented lateral geniculate (LG) monophasic and biphasic spikes, called spikes I and II. At the cortex, they occurred either generalized or limited to one area (anterior or posterior) and were called pontogeniculocortical spikes (PGC). After section of one ON, the pattern of occurrence of phasic activities remained identical in LG. Sharp spikes (spike III) appeared; then their occurrence increased. At the end of the second month after the second section, only spikes II and III remained, spike I disappearing, while PGC amplitude diminished. When both ONs were cut simultaneously, spike III was observed from the first day and PGC activity tended to disappear partially for 11 days. Their later evolution was similar to that noted previously. However, changes were seen earlier (the highest rate of spike III occurring at day 35). In both cases, PGC spikes at the cortex increased in amplitude and frequency of occurrence.


[Effects of optic nerve section in baboons on the EEG activity and sleep-waking cycles]. EEG rhythms recorded during the various states of alertness and sleep--waking cycles were studied in 4 baboons before and after optic nerve section. Visual deafferentation induced a general increase in amplitude of all the cortical rhythms, with general accentuation of pre-existing activities such as occipital eye movement potentials (EMPs), the fronto-rolandic rhythm and the alpha rhythm, spindles, REM ponto-geniculo-cortical (PGC) spikes; an increase in amplitude of the geniculate rhythmic activity, its frequency and occurrence was also noticed. When the blind baboons were placed in a monotonous environment, sleep--waking cycles occurred at any time of the 24 h. Total sleep time and total REM duration were not changed; however, deep sleep (stages 3 and 4) duration decreased (by around 50%) whereas stages 1 and 2 increased. The light factor thus plays a role in the sleep--waking cycle organization. However, its influence does to seem to be essential since its loss can be compensated by auditory stimulation. Finally, light possibly influences the systems involved in slow wave sleep regulation.


Human hippocampal formation EEG desynchronizes during attentiveness and movement. The relation of the hippocampal EEG to behavior and to the neocortical EEG is being studied in psychomotor epileptics. Hippocampal recordings displaying only rare epileptiform spikes and slow waves are found to follow grossly the simultaneously recorded neocortical EEG, becoming desynchronized during wakefulness and paradoxical sleep (PS), and displaying large irregular slow waves during slow-wave sleep. In the one patient reported in this clinical note, strong rhythmic 5--6 c/sec waves dominated the neocortical and hippocampal EEG during quiet wakefulness. These slow waves were replaced by desynchronized activity during PS and during difficult tasks, suggesting a further desynchronizing influence. The findings in all patients suggest that the rhythmic slow activity ('theta') found in rats and cats during specific behaviors is not observed in the human hippocampal formation during the homologous behaviors.


Occipital spikes and eye movement activity during paradoxical sleep in visually defective children. In visually defective children occipital spikes were analysed in periods with and without eye movements during paradoxical sleep. A decrease was shown in correspondence with eye movements, mainly when the spike rate was low.


VEP latency and RT as power functions of luminance in the peripheral visual field. Behavioral correlates of P1 latency of visual evoked potentials (VEPs) were investigated using visual reaction time (RT) as a measure at the fovea, 20 degrees and 40 degrees nasal retinal eccentricities along the horizontal meridian of the right eye. Three luminances of the target in steps of 1 log units were used: 26, 260 and 2600 cd/m2. As luminance increased VEP latency and RT decreased. Further, as eccentricity increased VEP latency and RT increased. The highest product-moment coefficient of correlation (r = 0.998) was found between RT and P1 latency in the fovea, whereas the coefficient of correlation was found to be slightly small in the peripheral loci. The data (both VEPs and RTs) were fitted by the power function of the form: T = kLB + T0 where T, k, L T0 and B indicate VEP latency (or RT, scaling constant, luminance, asymptotic latency and exponent of the power function, respectively. This shows how the VEP latency and the RT can be related to luminance with exponent B. It was found that psychophysical power law governs VEP latency as well as RT with an exponent of about -0.32. It was suggested that both RT AND P1 latencies of VEP originate in the similar nonlinear visual system.


Update: chronic sphenoidal electrodes.

Update: chronic sphenoidal electrodes. A technical modification in the type of material used in the chronic sphenoidal electrode previously described (Ives and Gloor 1977) has further improved their clinical use and benefit of the EEG work-up of epileptic patients. This procedure has become a routine investigation for all patients with suspected temporal lobe epilepsy at the Montreal Neurological Hospital.


Alteration in pattern of EEG activities and convulsant effect of cocaine following chronic adminsitration in the rhesus monkey. The effects of chronic administration of high doses of cocaine were studied in monkeys (Ss) with electrodes implanted in the brain. The Ss were injected daily with cocaine at a minimal convulsant dose (MCD) during polygraphic recording of EEGs, eye movement, respiratory and heart rates. The initial cocaine MCDs ranged from 3.2 to 6.5 mg/kg i.v. in ten Ss and markedly increased on each successive day following repeated daily injection (75--100% increase within 5--12 days). The elevated daily cocaine MCD was maintained for 1.5--2 months, and thereafter it gradually decreased and stabilized at levels between 20 and 30% above baseline within 2 months. During this period, the duration of daily convulsions evoked by cocaine MCD markedly decreased and stabilized at a constant level (30--35 sec) along with the latency of convulsions. The pattern of daily convulsions evoked by cocaine MCD changed from multiple episodes of intermittent tonic-clonic convulsions, which occurred during the earlier stage (1--2 months) of chronic treatment, to a single episode of sustained tonic-clonic convulsion. The Ss became extremely placid and tame or were profoundly depressed in their overall behavior most of the time. Simultaneously, the Ss continuously showed persistent rhythmic slow waves (5--6 c/sec) predominantly in the neocortex and limbic system structures. The results strongly suggested that chronic cocaine administration at high doses caused relatively permanent alteration of EEGs and behavior in the Ss, and the limbic system structures played an important role in the effect.


Visual evoked potentials during hypothermia and prolonged circulatory arrest. Visual evoked potentials were recorded in eight children during hypothermia and circulatory arrest. The potentials were lost in all children recorded in late arrest. The evoked potential is a more sensitive indicator of CNS stress as provoked by combined hypothermia and hypoxia than is the EEG. EEG activity persisted in six of the eight children in this series even during circulatory arrest. The EEG had been seen to do the same in more than half of a larger series of children recorded at that stage. The results suggest that evoked potentials may be a sensitive indicator of early impairment of cerebral function and may demonstrate useful change sooner than the EEG. The examination may be useful in following children with illnesses producing hypoxia or anoxia. The N1 component was as easily and as frequently identifiable as the P2 component. Under the stress of this procedure, the latency of the P2 component became more variable than the N1 peak. The results suggest the N1 component may be as useful and perhaps more useful than the P2 wave in following the effect of some CNS stresses in children.


Continuous bipolar recording of the EEG in patients with fulminant hepatic failure. The experience gained from continuous bipolar recordings of the EEG in 20 patients with fulminant hepatic failure is described. In most cases the recordings obtained were of good quality and allowed the progression of the disease to be more accurately followed. In six patients, a dramatic change in the EEG as associated with a sudden deterioration in the patients' clinical condition and in four of these patients treatment was instituted more promptly than would have been possible had no EEG monitor been available. In addition to its use as a non-invasive patient monitor, continuous EEG monitoring may be useful in establishing the relation between EEG appearance, raised intracranial pressure, and sudden changes in neurological signs in patients with fulminant hepatic failure.


Sawtooth waves: concomitants of rapid eye movement sleep in monkeys. Sawtooth waves, 2--3 c/sec activity of at least 40 micro V, occurred primarily during clusters of REMs in stump-tailed macaques. On the average the activity began well after the onset of REMs but occasionally occurred soon before or immediately after a cluster of REMs. The activity was clearly defined but occupied less than 0.6% of an 8-h sleep record. A sawtooth burst was, on the average, 7.5 sec in duration.


Human magnetic auditory evoked fields.

Human magnetic auditory evoked fields. Magnetoencephalographic (MEG) averaged auditory evoked fields to click stimuli (N = 512) were recorded from four human subjects. The MEG was recorded with an asymmetric second derivative SQUID gradiometer located in an aluminum shielded room. Unlike conventional EEG auditory evoked potentials, which have a widespread distribution, evoked magnetic fields appear to be localized to the general area of the primary auditory cortex and diminish rapidly in amplitude as the gradiometer is moved away in any direction.


Time shift evoked potentials (TSEPs): method and basic results. A simple technique for generating averaged evoked potentials to auditory signals that appear to move in space is described. Shifts in the apparent location of the signal were created by digitally delaying the output of a white noise generator with a minicomputer. The two channels were reconverted to two analog signals and presented binaurally through headphones. Shifts inthe apparent location of the signal produced a time shifted evoked potential (TSEP) that was not present during monaural control runs. TSEP amplitudes were largest near the vertex and varied as a function of the presentation format.


A film projecting system as a diagnostic and training technique for eye movements of cerebral palsied children. Films are presented for tracking on a translucent screen after reflection from a galvanometer driven mirror. A wave function generator produces picture displacements of amplitude and velocity capable of stimulating selectively (or simultaneously) the saccadic and smooth pursuit systems. This audiovisual signal permits prolonged eye movement recording and training sessions because of increased motivation and alertness. Optokinetic and vestibulo-ocular reflexes can also be tested. An infra-red photoelectric device monitors the horizontal component of eye movement. Records provide the necessary information for syndrome definition and training progress evaluation. Preliminary results show the technique to be perfectly suitable for the diagnosis of functional disorders and sensory-motor training of the cerebral palsied child's oculomotor system.


A single channel method for recording vertical and lateral eye movements. A method is described for single channel bipolar recording of EOG which allows the detection of both vertical and lateral eye movements as small as 1 degree of visual angle.


The initial positive component of the scalp-recorded somatosensory evoked potential in normal subjects and in patients with neurological disorders. The initial positive component of the scalp-recorded somatosensory evoked potential to median nerve stimulation was studied in 12 patients with sensory impairment for all modalities of the unilateral extremities due to lesions at or above or below the thalamic level, taking the potentials obtained from eight normal subjects as control. In normal subjects, this potential could be easily obtained in ear reference recordings with a peak latency of 12--15 msec. This finding and positive polarity of this potential indicate that the earlobe could be active for this potential. The wide distribution of this potential was different from the subsequent negative-positive diphasic components. In patients with lesions at or above the thalamic level the p15 potential was of normal configuration and latency to stimulation of the affected side, whilst in patients with lesions in the brain stem or in the cervical cord it could not be obtained to stimualtion of the affected side. These findings and short latency of the p15 potential suggest that it may be the result of activity of the medial lemniscal systems from the medulla to the thalamus.


The effects of interaction between large and small diameter fiber systems on the somatosensory evoked potential. The effect of interaction between large and small diameter fiber systems on the somatosensory evoked potential (SEP) was studied in anesthetized cats. Activation of large diameter fibers of the peroneal or radial nerves eliminates the late components of the SEP produced by stimulation of all fibers in the contralateral median or radial nerves. The inhibitory effects of a selective conditioning stimulus to the large diameter fibers of the peroneal nerve on the radial nerve evoked SEP was eliminated by bilateral transection of the dorsal column and spino-cervical tracts. However, interaction could still be obtained following transection when both large and small diameter fibers in the peroneal nerve were stimulated. The results of this study support the hypothesis that a correlation exists between activity in different fiber groups in afferent nerves, their conduction pathways through the cord, and the components of the cortical evoked potential.


Auditory brain stem potentials in monkey (M. mulatta) and man. Auditory brain stem potentials were mapped over the head of the rhesus monkey following monaural clicks. Latency and amplitude were dependent upon the recording site. No electrically indifferent point could be found on the head or neck. The results are interpreted as showing that waves I and V originate from single generators, whereas waves, II, III and IV originate from bilateral structures. Latency varied in a linear fashion with changes in intensity and click rate. In contrast there were variations in amplitude of the potentials independent of stimulus change. A comparison was made of auditory brain stem potentials in man, monkey, cat and rat to demonstrate the similarity of the responses across species.


Single motor unit activity in extraocular muscles in man during fixation and saccades. Extraocular motor unit activity was recorded electromyographically from the lateral and medial rectus muscles in eight normal subjects, together with their EOGs. Twelve motor units showed a discharge pattern characterized by regular firing during positions of fixation, a burst of saccadic "on" activity and complete silence during saccades in the "off" direction. Two other units seemed to be phasic or predominantly phasic. Interval analysis in 7 of the above 12 units during positions of fixation showed a linear rate position relationship of the units together with an extreme regularity of consecutive discharge intervals. The peak frequency of saccadic motor unit activity occurred at the onset of the burst and increased with increasing size of the saccade up to 15--20 degrees. The motor units stopped firing a few milliseconds before the onset of a saccade in the "off" direction but resumed their activity before the end of the eye movement, with an instantaneous discharge rate which was greater than the post-saccadic discharge rate. It was shown that the antagonist muscle plays an active part to end the saccade by serving as a brake.


Myoclonus developing after vermisectomy in photosensitive Papio papio. Two vermisectomized photosensitive baboons exhibited two different types of myoclonus, one induced by intermittent light stimulation (ILS) and the other occuring "spontaneously". The characteristics of these two types of myoclonus are described from a clinical and from an ECoG point of view. Myoclonus induced by ILS (ML) started at the eyelids and secondarily invaded the face and body; it was always preceded by frontorolandic spike-waves or polyspike-waves. The "spontaneous" myoclonus which followed vermisectomy (MV) was "massive", but involved firstly the trunk and secondarily the face and limbs; no ECoG paraoxysm accompanied this myoclonus, but we observed a parietal evoked potential of small amplitude, 10--15 msec after its onset. If MLs can be considered as consequences of the fronto-rolandic paroxysmal discharges, MVs seem to originate in the brain stem but appear similar to action myoclonus. This experimental situation showing two types of myoclonus resembles human hereditary degenerative syndromes (dyssynergic cerebellar myoclonus, progressive myoclonic epilepsy), without being exactly comparable. The conditions in which MVs were seen and their modifications during sleep and by different drugs are described. The relationships between MVs and MLs and myoclonic epilepsy are discussed.


Muscle reaction to passive shortening in normal man. We have studied in 32 healthy subjects the EMG activity of biceps and triceps brachii, wrist flexors and wrist extensors, triceps surae and tibialis anterior, sterno-cleido-mastoideus (SCM) and splenius, during their passive shortening. A shortening reaction was observed more frequently in wrist extensors, SCM and tibialis anterior than in biceps and triceps brachii. The response appeared only when the joint reached a specific angle regardless of the starting point or the speed used to reach this position. During a muscle ischaemia which abolished the tendon reflex the reaction was not modified. During a joint ischaemia produced distal to the examined muscle its amplitude was strongly reduced. Our results support the hypothesis that joint receptors could play a role in its origin, perhaps through a long-loop reflex.


Myoelectric frequency changes in children during static force production. Neuromuscular adaptations to a submaximal static contraction for a period of 2 min were investigated using children as subjects to detect changes in the contributing frequency components of the electromyogram (EMG) recorded from surface electrodes. The purpose of this study was to determine the similarity between EMG response patterns of children and published data for adult subjects under similar conditions. Spectral analysis of the EMG signal revealed a shift to lower frequency components and a concurrent increase in total variance of the signal as a response to fatigue. The frequency shift and increase amplitude for the EMG signal were discussed in light of evidence for recruitment and synchronization of motor units and changes in muscle fiber conduction velocity as possible mechanisms.


Rapid eye movement sleep cycle, clock time and sleep onset. The phase of the REM sleep rhythm was studied in 10 normal subjects each of whom was sleep studied for 4 consecutive nights. For analysis, each night of sleep was aligned according to clock time and each minute was scored as REM or non-REM. With these data, REM probability was found as a function of clock time. Fractional harmonic analysis indicates a 90 min periodicity. The REM probability curve shows peaks occurring at 1:30 a.m., 3:15 a.m., 4:30 a.m., 5:45 a.m. and 7:00 a.m. Statistical measures comparing the time of REM sleep across subjects suggests that subjects tend to have REM sleep at the same time of the night as each other. The influence of elapsed time after sleep onset on REM sleep is also reestablished. Results indicate that the time of REM sleep is determined by both clock time and time of sleep onset, suggesting two clocks, one sleep dependent and the other related to the basic rest activity cycle (BRAC), which are responsible for driving REM sleep. Furthermore, the similarity of REM times across subjects indicates the possible existence of an extra-personae REM driving force linked to clock time and possibly the BRAC.


Human auditory sustained potentials. I. The nature of the response. In response to a sustained toneburst a negative baseline shift can be recorded from the human fronto-central scalp regions with an onset latency of approximately 150 msec. This auditory sustained potential is distinct both in its scalp distribution and in its stimulus relationships from the transient response occurring at the onset or offset of the toneburst. It differs from the contingent negative variation in that it can occur in the absence of attention or during sleep. Attention to the auditory stimulus can increase the amplitude of the sustained potential, possibly through the addition of an extra negative potential related to auditory expectancy or uncertainty.


Human auditory sustained potentials. II. Stimulus relationships. The auditory sustained potential recorded from the human scalp increases in amplitude with increasing stimulus intensity. At rapid rates of stimulus presentation its amplitude decreases but proportionately less so than the amplitude of the transient onset auditory evoked potential. The frequency specificity of this rate effect is complex, suggesting that there may be two underlying components of the scalp-recorded auditory sustained potential. The amplitude of the auditory sustained potential is smaller when the tonal frequency of the stimulus is higher. With prolonged stimulus durations there is some adaptation of the amplitude of the auditory sustained potential. This potential is larger in amplitude when sounds are presented binaurally than monaurally, and has a symmetrical coronal scalp distribution that is unaffected by the ear of stimulation.


Clinical application of compressed spectral array in long-term EEG monitoring of comatose patients. To obtain continuous information about the cerebral electrical activity in the early course of coma, an apparatus was designed which included a small fast computer capable of calculating the Fourier transform. The practical application of this system of CSA to 123 comatose patients in a neurosurgical intensive care unit overcame the technical difficulties connected both with the patient's and environmental conditions. The advantages of such a technique are mainly due to its capacity of synthetising EEG signals and to its clarity of presentation, which is easily grasped even by people not specifically trained in electroencephalography. Hours of EEG activity are compressed into a pictorial and synoptic representation that shows in real time the distribution and temporal behaviour of frequencies as well as the intensity of total electrical activity. The immediate detection of these parameters permits evaluation of any worsening or improvement of cerebral electrogenesis, as well as of the inter-hemispheric asymmetries at their onset. EEG monitoring thus provides useful elements for assessing the comatose state in individual cases and for adjusting treatment. Finally, the spectrographic aspect of the first 48 h, as a whole, carries a great prognostic significance. The most striking finding from this study was the confirmation that the comatose states that, in their early course, show only a fixed slow-wave EEG activity are far more rare than those that display an electrical activity changing in time.


Occipital rhythmic activity within the alpha band during conditioned externally paced movement. The time-dependent behaviour of the power within the alpha band during conditioned movement was studied from the scalp EEG of 9 normal humans. Two tasks were used: (1) button pressing at imperative signal S1 and release at signal S2; (2) button pressing at imperative signal S2, preceded by warning signal S1. Together with a complex correlate of the CNV and EPs, the components of power decrease related to initiation of movement were not clearly identifiable in the central areas. They were sharply isolated in the occipital areas, using tone as the imperative signal. During initiation of movement a significant short-lasting decrease in power of the occipital alpha activities was observed in all 9 subjects. However, 'mu activity', tested in the classical manner and with help of power spectra, was not present in some of these subjects.


Averaged evoked potentials and frequency modulation. Frequency modulated (FM) auditory stimuli result in average vertex potentials similar to the usual auditory average evoked potential (AEP). For stepwise increase or decrease in tone frequency the AEPs are similar. For FM stimuli modulated by pulses of different durations 'on' responses are evoked by the transition of the stimulus from the longer duration to the shorter duration frequency tone while 'off' responses result when the frequency transition is from the shorter to the longer duration tone. Ramp modulation of the stimulus frequency results in average evoked responses; the amplitude of these responses is proportional to the slope of the ramp as well as the frequency of the tone that precedes the ramp. Thus, if the tone preceding the ramp is also a ramp but of smaller slope the AEP is attenuated and with sufficiently large slope the AEP can be completely extinguished. No AEPs were obtained at the offset of ramp modulated stimuli. The standard deviation (S.D.) of the reaction time (RT) distributions to stimulus onset indicate that the AEP amplitude is inversely proportional to the S.D. values. Thus, the attenuation phenomena appeared to be related to the uncertainty of the subject as to the exact time the stimulus occurred, both of which seem to be the result of sensory difficulty to the type of stimuli used. AEPs to negative ramps were smaller than AEPs to positive ramps; this may be on account of the psychological inequality between the stimuli.


Latency of luminance and contrast evoked potentials in multiple sclerosis patients. Luminance and contrast visual evoked potentials (VEPs), were studied in 18 multiple sclerosis (MS) patients and 11 healthy subjects. Luminance EPs were recorded to stimulation with noise modulated light (0--60 Hz); contrast EPs were obtained to appearance-disappearance or reversal of a checkerboard pattern with various check sizes and repetition periods. Our results indicate that the apparent latency of luminance EPs to noise modulated light can hardly be used for diagnosis of MS, since the range of normal values scatters widely and greatly overlaps the range of latency values in MS patients (detection rate of 3/13). Our data confirm, on the other hand, that the latency of contrast EPs can be used to discriminate between MS patients and healthy subjects (detection rate of 12/18). We recommend for diagnostic purposes to determine the apparent latency from the phase spectrum of the responses to checkerboard reversal at repetition rates between 5 and 20 Hz, since in this frequency range the failure rate was found to be minimal. The specificity of the apparent latency data can be improved if the wave form of the transient reversal EP at a lower repetition rate (around 2 Hz) is also inspected. We suggest that an increased latency can be ascribed to several causes, only one of these being an increased conduction time due to demyelination. Indirectly this confirms that an increased EP latency is not specific for MS.


Recovery function of short latency components of surface and depth recorded somatosensory evoked potentials in the cat. Recovery functions of early components of surface and depth recorded somatosensory evoked potentials were studied in the cat. At interstimulus intervals of 50 msec or less differentiation of surface components was optimal. Component I showed less decrement at all ISI's than did component II and recovery curves of both were distinctly different from those of components III (anterior) and IV and the cortical SEP. The latter three potentials had similar recovery curves. Comparisons of latencies and recovery curves of surface recorded potentials with those of depth recorded potentials indicate that component I principally reflects activity in posterior column, that potentials in medial lemniscus, cuneate nucleus, and lateral cuneate nucleus contribute to component II, that the major generator for the contralateral component III is the ventral postero-lateral nucleus of the thalamus, and that component IV is largely due to activity in the sensory radiation. The results of this study support previous observations and conclusions about the origin of short latency, surface recorded somatosensory evoked potentials preceding the cortical SEP.


The effects of chiasmal compression on the pattern visual evoked potential. The visual evoked potentials (VEPs) to pattern reversal stimulation (26' individual check subtense, 11 degrees total field) have been examined in 10 patients with proven chiasmal compression. Bipolar occipital-sylvian and occipital-parietal recordings were taken with electrodes placed according to the Modified Maudsley system. In all patients abnormalities, taking the form of latency delays or amplitude reductions, were found in response to monocular stimulation which, without exception, were maximal in the traces corresponding to the hemisphere contralateral to the field defect. In seven patients responses to a 13' pattern were also examined. In six of these the lateralisation of abnormality was enhanced. The discrepancy between these and previous findings is discussed, the importance of stimulus and recording parameters being stressed.


A CNV study in a group of patients with traumatic head injuries. CNVs were studied in a group of 27 subjects with traumatic head injuries followed by protracted coma. Before CNV recording, all patients were subjected to Wechsler-Bellevue Intelligence Scale and to Benton's visual retention test. The findings were compared with those obtained from 80 normal subjects. A statistically significant decrease was observed in the CNV area in the group with traumatic lesions. No correlation could be found between CNV parameters and the results of the mental tests. In 7 of the subjects who presented the highest percentage of errors in Benton's test, a large post-imperative negative variation was observed.


Alpha and the eye.

Alpha and the eye. It has been suggested by Lippold that the alpha rhythm is the result of a modulation of the corneo-retinal potential by translational eye tremor. We have attempted to replicate a critical test of the ocular origin of the alpha rhythm, altering the magnitude of the corneo-retinal potential while concomitantly measuring alpha amplitude. No changes in alpha amplitude related to changes in corneo-retinal potential could be seen. We are thus unable to confirm Lippold's hypothesis.


EEG feedback training: enhancement of somatosensory cortical activity. The mu rhythm is a spontaneous electroencephalographic pattern which can be recorded over human somatosensory cortex in the absence of movement. Power spectral analysis across 50 sessions of EEG feedback training showed that mu activity could be systematically enhanced, whereas the 12--14 c/sec component of low voltage fast activity could not be modified. Results indicate that long-term modification of at least one normal cortical rhythm, initially present in the human EEG, is possible with feedback training but that training cannot produce such a rhythm.


EEG signs of cerebrovascular disorder, using physical exercise as a provocative method. A group of patients suffering from cerebrovascular insufficiency was submitted to a pilot EEG investigation using physical exercise as a provocative method. Two control groups, one of young (20--30 years) and another of older (more than 50 years) subjects, were also investigated. Quantitative EEG spectral data, determined at rest and during a period after physical exercise, showed that deviations of the frequency distribution of the alpha band were related to cerebrovascular insufficiency.


Electronic circuit breaker for recording and stimulation from same electrode. An electronic circuit breaker is described which allows stimulation and recording through the same electrode and automatically shifts modes with a minimal delay. This circuit has been used efficiently in the experimental study of convulsive activity (Kindling).


Cumulative sum technique and its application to the analysis of peristimulus time histograms. The cumulative sum procedure introduced by Hurst (1950) involves subtraction of a control reference level from a series of datum points and adding the differences consecutively. The resultant curve shows trends indicating changed levels of points. The technique has been applied to peristimulus time histograms in order to reveal small changes in the probability of spike occurrences normally obscured by random fluctuations. The combined process of cumulative sum and PSTH cuts the overall number of trials needed in real time and reduces the uncertainty of decision making during the experiment.


Closer correlation between serum triiodothyronine and basal metabolic rate during antithyroid drug treatment in patients with Graves' disease. The correlations between serum triidothyronine (T3), thyroxine (T4), 131I-triiodothyronine resin sponge uptake (RT3U) or free thyroxine index (T7) and the basal metabolic rate (BMR) during antithyroid drug treatment in 86 patients with Graves' disease were investigated. Although serum T3, T4, RT3U and T7 during therapy with MMI showed significant positive correlations with BMR, the coefficient of correlation (r = 0.6088, P less than 0.001) between T3 and BMR was the highest of all. While the normal range of BMR in control subjects was between -1.9 and +14.9 (the range of mean +/- SD), the corresponding values of T3, T4, RT3U and T7 calculated from the regression lines, ranged from 94.2 to 184.0 ng/dl, from 5.32 to 8.75 microgram/dl, from 26.5 to 28.9% and from 1.57 to 2.47 respectively. On the other hand, when the corresponding values of BMR to normal values of T3 (100-170 ng/dl), T4 (7.6-12.2 microgram/dl), RT3U (26.7-36.5% and T7 (2.29-3.49) in control subjects were calculated from the regression lines, the range of value obtained from the regression line of T3 coincided better with normal value of BMR in control subjects that those calculated from other regression lines (T4, RT3U and T7). These results suggest that serum T3 level would be a better index of evaluation of the thyroid function that T4 or RT3U in patients with Graves' disease under antithyroid drug treatment.


Complementation in vitro of mutant and wild-type ATPase of Escherichia coli using isolated subunits. 1. The inactive ATPases of four different mutant strains of Escherichia coli have been purified to homogeneity. 2. Molecular weights, subunit patterns in sodium dodecylsulfate electrophoresis and immunological properties of mutant and wild-type proteins are identical. The mutant enzymes compete with the wild-type enzyme for the binding sites on the membrane. 3. On freezing and thawing in salt solutions, the ATPase is split into subunits IA (alpha, gamma, epsilon), IB (delta; alpha, gamma, epsilon), and II (beta). By complementation in vitro of the isolated subunits, it is shown that subcomplex IA (alpha, gamma, epsilon) is altered in the mutant strains described here.


Quantitative determination of single serum proteins during acute hepatitis in childhood. Fifteen serum proteins were estimated by linear immunodiffusion in blood samples from children with acute hepatitis. Blood was drawn at the beginning of the disease and three weeks later. The results were compared with results obtained from a group of age-matched normal children. At the beginning of the disease prealbumin and beta-2-glycoprotein I were depressed, whereas alpha-1-acid-glycoprotein, alpha-1-antitrypsin, cerloplasmin and alpha-2-HS-glycoprotein were found to be elevated. Alpha-2-macroglobulin, transferrin and beta-lipoprotein showed a significant elevation after three weeks. Beta-1-A/C, IgM and IgG remain elevated during time of observation. Albumin, haptoglobin and IgA were similar in patients and controls and did not change during the period of observation.


Postextrasystolic relaxation in the dog heart. Left ventricular relaxation was studied in 8 dogs using parameters derived from the left ventricular pressure: the fastest pressure fall and the time constant of pressure decline. Effects of extrasystolic rhythm interventions were examined on the relaxation parameters of the post-relative to the preextrasystolic beat. Postextrasystolic potentiation of these parameters could not be demonstrated. Possible influences of physiologic variables as peak left ventricular pressure, endiastolic aortic and enddiastolic left ventricular pressure on relaxation mechanism were evaluated. The nonselective description of myocardial relaxation by pressure derived parameters is discussed.


Cytofluorometric analysis of macrophages activated in vivo or in vitro. The relative RNA content of single macrophages was measured by cytofluorometry after differential staining of cellular DNA and RNA with the metachromatic fluorescent dye acridine orange. This method allowed the differentiation of two major groups in the adherent macrophage population differing in their RNA content. After in vivo stimulation of mice (by injection of thioglycollate medium) or guinea pigs (by injection of oil), an increasing percentage of macrophages possessing a high RNA content is recovered. In vitro stimulation of macrophage cultures with lipopolysaccharide had the same enhancing effect on cellular RNA content. Cytofluorometric measurement of RNA content may possibly become an efficient and rapid method of measuring macrophage activation.


Induction of immunological tolerance to the penicilloyl antigenic determinant. I. Evaluation of penicilloylated amino acid polymers and copolymers in mice. Antibody responses to the penicilloyl (BPO) group, the major antigenic determinant of penicillin allergy induced in C3H mice by penicilloylated bovine gamma globulin in complete Freund's adjuvant, were reduced or abolished by various amino acid polymers and copolymers of different composition and size carrying BPO groups. Tolerogenic treatment was effective before or after primary immunization and also during anamnestic responses. The unresponsive state was of long duration and persisted even after several booster injections when efficient tolerogens were used. Among the most promising tolerogens are fully penicilloylated oligolysines with a molecular weight below 10 000.


Induction of immunological tolerance to the penicilloyl antigenic determinant. II. Evaluation of stable and unstable penicilloyl dextrans. A specific tolerant state to the major antigenic determinant of penicillin allergy, the penicilloyl group, was induced in C3H mice primarily immunized with penicilloylated bovine gamma globulin in complete Freund's adjuvant. Tolerance was obtained by intraperitoneal administration of either of two penicilloyl-bearing dextrans of molecular weight 2 X 10(6). One conjugate contained penicilloyl groups stably bound via a 1,6-diaminohexane spacer, the other bore the penicilloyl groups directly bound to the hydroxyl groups of the carrier. These directly bound penicilloyl groups undergo hydrolytic cleavage within 3 days under physiological conditions in neutral aqueous solution. Model experiments showed that the rapid cleavage into carrier and haptenic derivatives also applies to penicilloylated dextran in receptor-bound and particulate form, as may be expected from the highly hydrophilic character of the conjugate. The stable conjugate at 1 mg and the cleavable conjugate at 4 mg doses induced comparable tolerance lasting for at least 8-12 weeks.


The relationship of membrane antigens on 141 (NZB) and EL4 (C57BL) lymphoma cells as demonstrated by antibody-induced resistance to complement-mediated cytotoxicity. We have studied the ability of various antisera to induce resistance to complement-dependent lysis (CdL) (lysostripping) of surface antigens of B and T lymphoma cells. Alloantisera, xenoantisera, as well as anti-Rauscher-leukemia virus (RLV) antisera, were used. Whereas all antisera could induce resistance to CdL mediated by the same serum that served for lysostripping (autolysostrip), only some of the tested antisera could induce resistance to CdL by other antisera (co-lysostrip). In some combinations co-lysostrip was unidirectional, i.e., in a pair of antisera, one induced autolysostrip as well as co-lysostrip, whereas the other antiserum induced autolysostrip only. In other combinations co-lysostrip was reciprocal. These investigations do not support the possibility that viral components and alloantigenic determinants are associated on mouse lymphoma cells.


Selection of antigen-specific cells by adherence to allogeneic cell monolayers: cytolytic activity, graft-vs.-host activity and numbers of adherent and nonadherent cells. Rat lymph node cells taken at the peak of cytolytic activity following a skin allograft were separated into adherent and nonadherent fractions by incubation on monolayers of thoracic duct lymphocytes either of the same strain as the graft donor or of an Ag-B different strain. In the face of a 3-fold enrichment of cytolytic activity in the adherent cells and a 3-fold depletion in the nonadherent cells there was no detectable partition of graft-vs-host (GVH) activity. Supplementary experiments supported the simplest interpretation of this finding, namely that the antigen receptors on GVH-reactive cells did not influence their adherence in this system. Similarly, there was no partition of the GVH activity of nonimmune lymph node cells by adherence. Labeling lymph node cells with either radioactive uridine or thymidine in vitro, suggested that about 20% of DNA-synthesizing cells in the immune population adhered because of antigen recognition.


Acquired heterophile antigens on the surface of human cell lines. Chicken IgM antibodies raised against sheep erythrocytes (SE) reacted with a heterophile carbohydrate antigen designated as "HC". This antigen was visualized by SE rosette formation with antibody-sensitized and formaldehyde-fixed target cells. Cells from eight lymphoblastoid lines and ten lines of diverse histogenetic origin all expressed HC on their surface to a greater or lesser degree when grown in fetal calf serum (FCS). Lymphoblastoid cell lines, HSB2 and Namalva, lost most of their HC antigen after three cell divisions when grown in medium which contained normal human serum (NHS) instead of FCS. The acquired origin of HC was demonstrated by the conversion of HSB2-HC- into HSB2-HC+ cells after incubation in the presence of FCS or fetuin for 18 h at 37 degrees C. The acquisition of HC antigen depended on the concentration of fetuin as well as the time and temperature of incubation. The presence of NHS in the culture medium reduced the degree of HC incorporation. The level of HC expressed on the cell surface was reduced by treating HSB2 cells with sodium periodate but not by proteolytic enzymes. Competitive inhibition with hog blood group substance and sheep IgG suggested similar specificity of HC on target cells which had been sensitized with either fetuin or sheep IgM (Eur. J. Immunol. 1977.7:204). The avidity of chicken antibodies to HC in either of these systems was several orders of magnitude lower than the binding to SE.


alpha-globulin follicular fluid proteins within small and large bovine follicles. Fluids from small (FF-S) and large (FF-L) bovine ovarian follicles were observed electrophoretically for differences in the alpha-globulin protein profile. FF-L possessed a fast migrating alpha-globulin 3 and a greater percentage of FF-L samples contained a higher number of alpha-globulin bands.


Electron microscopy in the early diagnosis of genetic disorders of the skin. Electron microscopy is shown to represent an effective tool in the early diagnosis of genetic disorders. On the basis of ultrastructural findings in various dominant and recessive types of ichthyoses and epidermolyses, defects of structural proteins of the skin proved to form the main intrinsic pathogenetic feature of some dominantly inherited types whereas quantitative impairments characterize their closely resembling recessive counterparts. Most of the diseases concerned severely disable the involved patients. Early diagnosis is therefore of high importance. In those cases where an exact diagnosis in newborn children is difficult or impossible with respect to their clinical features, electron microscopy provides the clinician with reliable and significant criteria to differentiate between closely resembling entities.


Antitumor immunity after surgical removal of 3-methylcholanthrene-induced murine tumors: correlation between resistance and delayed hypersensitivity reaction. The relationship between tumor resistance and the antitumor delayed hypersensitivity reaction (TDHR) after resection of the tumor was studied by using the syngeneic 3-methylcholanthrene-induced murine tumor, MCA-DDD. MCA-DDD was inoculated subcutaneously into the tail of DDD mice and 4 weeks later the tumor-bearing tail was resected. The tumor resistances of the mice were then determined from the diameters of the tumor that developed 14 days after subcutaneous challenge of the mice with tumor cells in the flank. It was found that the mice showed a specific resistance to the tumor until 30 days after tumor resection. In parallel with tests on tumor resistance, TDHR of the mice after tumor resection was examined by the footpad test. The cell-free fraction of sonicated MCA-DDD tumor cells was used as the preparation of tumor antigens. TDHR of the mice appeared soon after tumor resection, reached a maximum on day 7, and then decreased slowly until day 29. Mice that acquired tumor resistance showed rapid increase of TDHR after challenge with fresh tumor cells. TDHR was high on day 4 after the challenge and its level was well correlated with tumor resistance of the mice.


Effect of alpha-benzene hexachloride on 2-fluorenylacetamide carcinogenesis in rats. Studies were made on the effect of 0.06% alpha-benzene hexachloride (alpha-BHC) on hepatic changes, including development of hepatomas, in rats treated with 0.025% 2-fluorenylacetamide (2-FAA) at the same time. alpha-BHC inhibited the induction of hepatocellular carcinomas and oval cells infiltration in rats treated with 2-FAA for 5 months. However, it did not inhibit induction of hyperplastic nodules, it induced liver adenocarcinomas in 4 of 11 rats, and it caused remarkable cyst formation in the liver of rats treated with 2-FAA.


Tumor-specific skin-reactive antigen solubilized from a syngeneic guinea pig liposarcoma by 3M potassium chloride. Tumor-specific and skin-reactive antigen of a syngeneic liposarcoma (H-10) of Hartley/F guinea pig was solubilized with 3M potassium chloride and purified by precipitation with 2M ammonium sulfate, followed by Sephadex G-200 gel filtration. The antigenic activity of 7 fractions obtained was estimated by the delayed-type skin reaction elicited in syngeneic animals immunized with H-10 cells admixed with BCG. Accurate relative activity of the fractions comparable to the skin reaction elicited by living H-10 cells was calculated by the parallel line assay method in which the dose-response curves of the fractions are compared with that of living cells. About 30 approximately 50 microgram protein of the 3 fractions eluted slowly from the Sephadex column elicited the skin reaction equivalent to that elicited with 1 X 10(6) of living H-10 cells. Tumor-specific skin reactivity per microgram protein of these 3 fractions was roughly 20 approximately 40 times higher than that of lyophilized cells.


Percutaneous transhepatic intubation of bile ducts for combined internal-external drainage in preoperative and palliative treatment of obstructive jaundice. Percutaneous transhepatic intubation and combined internal-external drainage of the biliary system was performed in 15 patients with occlusion of the extrahepatic bile ducts due mainly to cholangiocarcinoma, metastases of the hepatoduodenal ligament, and tumors of the periampullary region. The technique is described and the value of the procedure in temporary decompression and combined internal-external bile drainage prior to radical surgery is demonstrated. Its advantages as a palliative method are evident in far-advanced malignancy when extensive and complicated surgical procedures are ill-advised.


Whipple's disease: case report with immunological studies. A patient with Whipple's disease is described whose small bowel biopsy demonstrated antigenicity to rabbit antisera to groups A, B, C, and G streptococci and Shigella flexneri, but not to antisera to pneumococcus or Shigella sonnei by immunofluorescent techniques. In addition, the patient's lymphocytes responded normally to phytohemagglutinin and to concanavalin A. These studies support the idea what Whipple's disease is mediated by a bacteria-like agent which shares certain antigenic similarities with groups A, B, C, and G streptococci and S. flexneri, and that T cell dysfunction does not appear to be an essential prerequisite for the disease.


[Alpha-fetoprotein, HPL, ostriol and SP1 concentrations in prostaglandin-induced mid-trimester abortions (author's transl)]. Maternal serum concentrations of AFP, HPL, SP1 and Estriol were measured in the course of prostaglandin-induced abortions. Termination of pregnancy between the 13th and 25th week of pregnancy was done for medical reasons. Patients were treated with PGE2, PGF2alpha and with 16-phenoxy-PGE2-methansulfonamid, respectively. Prostaglandins were administered systemically, i. e. intravenously. Current measurement of HPL and AFP-concentrations showed a contrary sense. These changes of concentrations were related to fetal death and membrane rupture in some cases as is demonstrated in four diagrams. Typical and sharply decreasing values of Estriol followed fetal death in patients with intact pregnancies before. As for an anencephalic fetus, AFP-concentrations increased slightly too, HPL values decreased like in other abortions. Only minimal changes of SP1 concentrations were found generally in all patients and during abortion time.


[Serum concentrations of prolactin, growth hormone, and alpha-fetoprotein under long-term administration of an oral contraceptive containing cyproterone acetate (author's transl)]. Serum prolactin, growth hormone, and alpha-fetoprotein were determined in women taking a new oral contraceptive, consisting of 2 mg cyproterone acetate and 50 microgram of ethinylestradiol. Because these women were suffering from acne vulgaris they were taking this contraceptive containing a gestagen with antiandrogenic activity. Prolatin and growth hormone were determined because both may favour the development and the growth of mammary tumors and because their secretion may be stimulated by estrogenic compounds. Alpha-fetoprotein is a marker of hepatocellular carcinoma, which may be associated with long-term use of oral contraceptives. During one year of treatment with cyproterone acetate and ethinylestradiol there was a continuous rise of serum concentrations of prolactin. However, this rise did not exceed the normal range. In contrast, serum concentrations of growth hormone did not change significantly. Serum alpha-fetoprotein levels remained below the detection limit of the method.


[Polymorphism of immunoglobulin Gm- and Km-allotypes in northern Altaians (western Sibiria)]. In two small adjacent groups-kumandinias and chelkanians-the distribution of G1m(a), G1m(x), G1m(f), G3m(b1), G3m(b5) and Km(1) serum allotypic markers was studied. Gmf;b haplotype frequency in kumandinians was found to be 0.310; in chelkanians living eastward it was 0.212. Gma and Gmax frequencies were observed to be 0.606 and 0.084 in the former and 0.687 and 0.101 in the latter. Km1 frequency was found to be 0.074 in kumandinians and 0.087 in chelkanians. Unusual Gm(a, f) henotype was observed in both groups with a frequency lesser than 5%.


[Endorphins--endogenous peptides with morphine-like effects. 2. Biological importance, clinical apsects]. Since 1974 peptides with opiate-like action both in vivo and in vitro have been isolated from the nervous system of various vertebrates and man. The localization of these peptides (endorphins) within the central and peripheral nervous system reflects the possible biological functions in which they may participate: the response of the CNS to painful stimuli (dorsal horn of the spinal cord, central grey matter, thalamus); the control of emotions (limbic system); the regulation of vegetative functions (medulla oblongata); the response of the body to stress the control of endocrine function (hypothalamus, infundibulum, hypophysis); the control of extrapyramidal motor activity (brain stem) or the control of intestinal motility (intramural nervous plexus). Up-to-date knowledge suggests that the endorphins may function as neurotransmitters, neuromodulators or hormones and that such functions vary according to the special sites of synthesis, storage and action of these various peptides within the body.


The hyaline cell: a distinctive feature of "mixed" salivary tumours. We have identified and described a distinctive type of cell which is characteristic of the "mixed" salivary tumour. This "hyaline cell" or plasmacytoid cell is particularly common and conspicuous in "mixed" tumours of the palate and other sites in the mouth. It occurs also in tumours of the major glands, but with much lesser frequency. The hyaline cell is found in "mixed" salivary-type tumours in other sites, e.g. the skin. It is not present in the other types of salivary tumour, notably adenoid cystic carcinoma, adenolymphoma, mucoepidermoid and acinic tumour. Ultrastructural study suggests that the hyaline cell is an indicator of myoepithelial differentiation. Current concepts of the acceptable pathways of myoepithelial differentiation in "mixed" tumours are discussed briefly. The specificity of the hyaline cell will probably prove valuable in separating "mixed" tumours from monomorphic adenomas, thus retaining the identity of the latter. The hyaline cell is almost as distinctive a feature of "mixed" tumours as is myxochondroid tissue and its specificity is of practical value in the diagnosis and classification of salivary tumours.


A combined stain for elastin and acid mucopolysaccharides in large blood vessels. A reliable, reproducible combined stain for elastin and acid mucopolysaccharides has been developed and is particularly suitable for the study of large blood vessels as muscle and collagen are also stained. The technique is described.


Health center streamlines use of audiovisual aids. Audiovisual aids and programs can be used to help provide effective and efficient in-hospital continuing education programs. The cost of audiovisual equipment can be minimized and use can be maximized by implementing standardization policies that identify and simplify the number and types of equipment to be purchased.


Evidence for subtypic determinants in the HLA-DW3 cluster. This study was undertaken to get more insight into the previously suggested heterogeneity of the HLA--DW3 cluster. Preliminary evidence of DW3 heterogeneity was derived from results of intrafamilial mixed lymphocyte culture tests (MLC) where cells of apparently homozygous offspring revealed unexpected stimulations of one of the parents' cells. Therefore, 15 different homozygous typing cells (HTCs) of DW3 specificity were tested against 43 HLA-DW3 heterozygous individuals. The response patterns of the 43 HLA-DW3 heterozygous cells toward 13 HTCs leads to the definition of at least three groups of DW3 stimulating cells. According to these patterns, four groups of responding cells could be classified. These results were confirmed by a MLC checkerboard experiment running all DW3-HTCs against each other. Discussing all possible explanations for these observations, the authors conclude that the existence of DW3 subtypes having some properties in common is the most likely interpretation of the results obtained. Family segregation studies will be needed to define the genotypic situation of the DW3 cluster.


Comparative large-scale propagation of retroviruses from Old World (Mason-Pfizer monkey virus) and New World (squirrel monkey virus) primates. A cell culture method is described for the large-scale (50 to 150 1) production of Mason-Pfizer monkey virus and squirrel monkey virus, two primate retroviruses. Virus production was achieved with suspension cultures of chronically infected A204 human rhabdomyosarcoma cells harvested and clarified in the logarithmic stages of cell culture growth. Methods for the subsequent purification and concentration of virus material utilizing zonal centrifugation also are described. Applications of these methodologies resulted in products that afforded biochemical comparisons of these agents in a manner such that host cell-derived variations were minimized. These data indicated that high levels of production and efficient recovery and purification of virus material were achieved.


Demonstration of components of serum-free culture medium effecting maximum in vitro expression of mouse mammary tumor virus. By using a chemically defined serum-free (SF) medium for propagation of Mm5mtc1 mouse adenocarcinoma cell cultures and clonal derivatives, medium components including hormones, glucose and individual amino acids were evaluated as to modulation of mouse mammary tumor virus (MMTV) porduction. Insulin, hydrocortisone and dexamethasone each increased MMTV production on a per cell basis over constitutive expression that occurs in SF medium devoid of hormones. Maximum production occurred when all three hormones were present. Hormone-stimulated virus expression also was influenced by glucose concentration. Cell growth and maximum MMTV expression increased when thyroxine, asparagine, proline and serine were omitted from the medium formulation. The resulting modified SF medium provides and ideal system for the propagation of high MMTV-producer clones and for the study of the biochemical regulation of MMTV expression.


Cyclic appearance of antibody-producing cells in the peripheral blood in response to a chemically-defiend polyglycerophosphate antigen. Cyclic production of serum antibody and of plaque-forming cells (PFC) of polyglycerophosphate (PGP) specificity was observed in the peripheral blood of rabbits following a single injection of antigen. Individual animals were examined at 4-day intervals up to 28 days post-injection. Direct and indirect PFC displayed initial peaks at 4 days post-injection with an 8-day lag between the first and second peaks and a 12-day lag between the second and third peaks. Serum IgM rose to a peak 4 days after the initial PFC peak and gradually dropped to baseline levels. Serum IgG rose sharply to a peak at 4 days following the initial PFC peak and generally remained at elevated levels for the duration of the experiment. Cycling of background sheep erythrocyte PFC was also observed, but cycles were out of phase with the PGP cycles and with each other.


Purification and characterisation of two proteins from Ascaris suum extract, antigenically different but bearing common allergenic epitopes. Two proteins, FI and FVII, have been purified from a whole worm extract of adult Ascaris suum, using ammonium sulfate precipitation, Sephadex gel filtration and DEAE cellulose chromatography. Both of them provoke reagin formation in mice as tested in presensitized animals with an original immediate hypersensitivity reaction test. They are two chemically and physically different protein molecules showing no cross reaction with a rabbit serum anti-crude extract but bearing common allergenic epitopes as proved when tested in mice.


[Blood volume replacement and hemodilution with hydroxyethyl starch]. For high molecular hydroxyethylstarch (MW 450000, DS 0.7-0.8) an adequate volume effect has been demonstrated in numerous experimental and clinical studies; this colloid is, therefore, suitable for primary volume replacement as well as for preoperative normovolemic hemodilution. In contrast to colloids hitherto known HES infusion results in hyperamylasemia of probably non-pathogenic importance but significance for differential diagnosis in the post-operative period. Anaphylactoid reactions to HES are infrequent (0.08%). With regard to the manifestation and the degree of severity these reactions are not different from those observed after infusion of other colloids. Since the pathomechanism of anaphylactoid reactions to HES is still unknown prophylactic measures are not available. The elimination of HES from the circulation follows a protracted course, therefore accumulation of HES in tissues may occur after repeated infusions presenting a clear disadvantage of HES. There is, however, evidence that starch-preparations will be available in the future presenting an adequate volume effect while the elimination from the organism occurs rapidly. Low molecular hydroxyethylstarch (HES 450000, DS 0.5-0.55) yields inadequate volume effects; for this, low molecular HES can neither be recommended for long-lasting volume replacement nor for preoperative hemodilution.


Degradation of the polysaccharide component of gonococcal lipopolysaccharide by gonococcal and meningococcal sonic extracts. An extract made from the supernatant of Neisseria gonorrhoeae Gc2 strain 1291 degraded the Gc2 polysaccharide antigen. Chemical analysis of this polysaccharide indicated it contains glucose, galactose, glucosamine, galactosamine, glucosamine-6-phosphate, heptose, 2-keto-3-deoxyotonate, and ethanolamine and is the polysaccharide component of gonococcal lipopolysaccharide. Degradation of the polysaccharide by sonic extracts resulted either in complete loss of antigenicity and immunogenicity or in partial degradation to subunits that could inhibit the Gc2-specific hemagglutination inhibition. The factors responsible for degradation were destroyed by heating at 100 degrees C for 5 min or by Pronase digestion, but were unaffected by ribonuclease, deoxyribonuclease, Mg2+, Ca2+, or ethylenediaminetetraacetic acid. The process was pH dependent, with optimal activity occurring at pH 7. Sonic extract supernatants from group B and C meningococcal strains contained degrading properties, whereas similar extracts produced from Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae type II failed to degrade the Gc2 polysaccharide.


Neisseria gonorrhoeae acquire a new principal outer-membrane protein when transformed to resistance to serum bactericidal activity. Resistance to the complement-dependent bactericidal activity of normal human serum is found in nearly all Neisseria gonorrhoeae strains causing disseminated gonococcal infection. Transformation of serum-sensitive gonococcal strain NRL 7189 to serum resistance using deoxyribonucleic acid from three separate disseminated-infection gonococci was accompanied by simultaneous structural and antigenic changes in the principal outer-membrane protein (POMP) of the transformants. In each of 10 separate transformations, there was a reduction in subunit molecular weight of the POMP from that in the recipient (39,000) to that in the deoxyribonucleic acid donors (36,500). Also, in each instance the POMP antigenic type, as measured by enzyme-linked immunosorbent assay, converted from that of the recipient to an antigenic type common to each DGI donor strain. This conversion of POMP antigen was reflected in part by changes in the surface fluorescence of the transformed gonococci to the microimmunofluorescence pattern of the donor strains. These results suggested that serum resistance of gonococci is related to the possession of a POMP of characteristic subunit molecular weight and antigenicity.


Influence of the antigenicity of Brucella preparations on modulation of the immune response to sheep erythrocytes. The relationship between the expression of surface antigenicity of inactivated Brucella and the immunostimulant properties on the sheep erythrocyte response was studied in mice. The agglutinogenic Brucella abortus B19S preparation was compared to two non-agglutinogenic preparations (B19R and PB), using the plaque-forming and rosette-forming cell tests. When Brucella and antigen were injected together, only non-agglutinogenic preparations, even used at low doses, were able to increase the plaque-forming and rosette-forming cell responses measured 4 days after immunization. When the interval between the previous injection of non-agglutinogenic preparations and that of the antigen increased or when they were injected 24 h after the antigen, the modification of those two responses was no longer observed. After day 4, for the simultaneous injection of Brucella and antigen, B19S and PB preparations induced the best responses; this effect was dose dependent. Thus, in the present experimental situation, the modification of the day 4 response appeared independent of those of the ensuing days.


Antigenic relationship of human foamy virus to the simian foamy viruses. A foamy virus isolated by Achong et al. from a human nasopharyngeal carcinoma was studied to determine its antigenic relationship to the eight known simiam foamy viruses (SFV). Using reciprocal cross-immunofluorescent and cross-neutralization techniques, we found the human isolate to be closely related to SFV type 6. In a seroepidemiological survey, neutralizing antibody to the human foamy virus was not detected in the sera of animal caretakers or laboratory personnel who routinely handled a wide variety of nonhuman primates. We conclude that the human isolate most probably represents a variant strain of SFV type 6.


Strain-specific local and systemic cell-mediated immune responses to cytomegalovirus in humans. Employing the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation assay, the antibody and cell-mediated immunity to cytomegalovirus (CMV) were studied in the serum, peripheral blood lymphocytes, tonsillar lymphocytes, and cord blood lymphocytes. The study population consisted of 32 children undergoing tonsillectomy and adenoidectomy. In the lymphocyte transformation assay, three strains of CMV (AD-169, ADH-1-41, and Davis), herpes simplex type 1, and phytohemagglutinin were employed as antigens. Sixty-five percent of the subjects were found to have CMV-specific antibody activity. The lymphocyte transformation response to phytohemagglutinin was similar in all subjects. No CMV-specific lymphocyte transformation activity was detected in cultures of cord blood lymphocytes. Significant cell-mediated immunity was observed in the tonsillar lymphocytes of 30% (3/10) of the seronegative individuals and in the peripheral blood lymphocytes obtained from one such subject. Over 75% (16/21) of the seropositive subjects demonstrated cell-mediated immunity against one or more strains of CMV in the peripheral blood lymphocytes and tonsillar lymphocytes. In the lymphocyte transformation assay, no cross-reactivity was apparent between CMV and herpes simplex type 1. These studies demonstrate the presence of strain-specific systemic and mucosal cell-mediated immune response to CMV in humans. The frequency and distribution of lymphocyte transformation responses to the three CMV strains suggest antigenic heterogeneity of CMV.