Conservation and chromosomal localization of DNA satellites in balenopterid whales. DNA satellites were isolated from three balenopterid species, viz. the minke, sei, and fine whales. In each of them at least two DNA satellites were recognizable with buoyant densities in neutral CsCl of rho = 1.702/1.703 and rho = 1.710/1;711, respectively. cRNAs from each satellite group were used for filter and in situ hybridisations. Homo-and heterologous DNA-cRNA hybrids within each satellite group yielded virtually identical melting curve profiles showing conservation of at least a considerable part of the DNA satellite sequences. There was no evident sequence homology between the rho = 1.702/1.703 and the rho = 1.710/1;711 satellites by filter hybridisation.--The in situ hybridisation showed that in each species the rho = 1.702/1.703 satellite was located in centromeric-paracentromeric C-bands in a few pairs, whereas the rho = 1.710/1.711 satellite was located in terminal C-bands throughout the karyotypes.--The data on the whale DNA satellites indicate that the quantitative evolution of the sateliite DNA sequences preceded species divergence of the balenopterids and that the satellite sequences have remained relatively unaltered since the divergence took place. The function of satellite DNA is considered to imply the introduction of both chromosomal and genic polymorphisms and thus being of great importance in speciation, Based upon these concepts a model is postulated for the function of satellite DNA. According to this model at meiotic pairing euchromatinheterochromatin overlapping between homologous chromosomes is considered to be of a general occurrence. This overlapping is presumed to be accentuated by the size heteromorphism frequently observed between homologous heterochromatic segments (C-bands). In the region of such euchromatinheterochromatin overlapping, cross-over would be excluded. The overlapping is suggested to be rectified progresssively in the chromosome arms, leaving unaffected crossing-over distant to the euchromatin-heterochromatin junctions. The consequence of this will be that genes in the proximity of the junctions are collectively inherited and selected, whereas genes distant to the the heterochromatin will be independently assorted and selected.


The immediate effects of intravenous specific nutrients on EEG sleep. This study examined the immediate influence of intravenous amino acids and glucose on sleep as measured by all-night EEG recording. The study on 9 normal female subjects was of a latin-square design. Slow wave sleep (SWS) was increased by both solutions whilst dream sleep (REM) was decreased by amino acids and increased by glucose. Total sleep time was not affected. Subjective feelings as to restlessness, quality and depth of sleep under the impact of the various solutions were gathered. The work further elucidates the effect of nutrition on sleep and supports certain theories as to the function of the main sleep component.


[Temporal organization of paroxysmal discharges in the child. I. Biotelemetric recordings during wakefulness]. Based on telemetric recordings performed on 6 children, a study of the time distribution of intra-clinical paroxysmal discharges was carried out. It was tested whether  this distribution is stochastic, and if not so, whether is depends upon an internal biological rhythm or upon environmental and behavioural factors. The times of occurrence of paroxysmal discharges, generalized and/or focal or partial, were located by visual inspection, and fed into a computer for statistical evaluation. Discharges and intervals were thus quantified for the overall recording time, for one situation or for groups of situations; the chronological distribution of discharges during successive 300 sec epochs was also computed. In all the cases, the discharge density varied from one moment to the next, but not in random fashion: the hypothesis of an internal modulation of the discharges was verified in some specific cases, more often, the changes in the discharge chronology seemed to be related to modifications of psychophysiological states observed during the successive experimental situations. The factors involved, namely, alertness, specific attention, stress, posture, etc., seemed to play a different role in each case; no simple correlation with the topography of discharges could be established. One explanation does not exclude the other: modulation of the discharges by biological rhythms could at any time be masked by variations due to environmental factors and to the subject's specific reaction to the latter. This type of study presents considerable methodological and interpretative difficulties which tend to emphasize individual differences rather than allowing to draw general laws.


On and off effects in the background EEG activity during one-second photic stimulation. The changes in alpha band power of the background EEG activity during 1-sec light stimulation were investigated in 10 normal human subjects. The EEG data were band-pass filtered, centering on the alpha range, and the time-dependent power changes were evaluated for their significance. The most significant finding was a light-on power decrease (on-effect) occurring in occipital areas 250--500 msec after onset of the stimulus, observed in all subjects, and reaching values of 72.2 +/- 13.2% decrease, with reference to power in the pre-stimulus interval. In 8 subjects there was also a significant light-off power decrease occuring 250--500 msec after offset of the photic stimulus (average across subjects: 41.8 +/- 24.4%) also in the occipital region. Similar on- and off-effects were observed in central regions, with lesser statistical significance. This pattern of light-on and  -off power decreases was consistent and reproducible, with small inter- and intraindividual variability.


Spectral analysis of the electromyogram of the temporal muscle in the rhesus monkey (Macaca mulatta). Spontaneous EMG activity of one mandibular elevator and postural muscle, the anterior temporalis, was recorded from 20 unanesthetized rhesus monkeys subjected to 4 experimental protocols. The EMG activity was analyzed with a spectral analyzer to determine changes in particular frequency bandwidths after (1) administering a dissociative drug, (2) placing weights on the mandible, (3) detaching the muscle, and (4) adaptation of the muscle to oral respiration. The mean distribution of frequency components indicated that ketamine--HCl increased the power of all frequencies below 400 c/sec, particularly those at 20--40 c/sec. A period of hyperactivity and increased recruitment and discharge of motor units occurred within the first 30 min following administration of the drug. Passive and sustained lowering of the jaw with increased weights indicated that increasing the front incisor distance 2--4 cm significantly decreased the frequency components below 400 c/sec accompanying a decrease in active motor units. Comparison of frequency components of the temporalis EMG before and within 40 days after detachment suggested some subtle variations in the mean distributions predominantly around 200 c/sec but without significant changes. Comparison of the mean spectral distribution between 8 nasal-breathing and 8 oral-breathing monkeys indicated a significant loss of power in the normal dominant frequency range of 20--100 c/sec in the oral respiratory group except for enhancement of the 20 c/sec bandwidth. The results suggest that the anterior temporalis alters its EMG activity during both short (i.e., min, h) and long-term (i.e., months, year) adaptations of the muscle.


On-line statistical detection of average evoked potentials: application to evoked response audiometry (ERA). An objective method of EP detection in averaged EEG epochs is described which is based on the statistical properties of the averaged EEG in the absence of time-locked EP activity. The statistical properties of the subject's averaged background EEG are summarized by making a set of comparisons between two consecutive EEG epochs immediately preceding each stimulus presentation. After every stimulus presentation, a second set of comparisons is made between the post-stimulus EEG epoch and the immediately preceding pre-stimulus EEG epoch. These two sets of comparisons are then examined to determine whether the latter differ significantly from the former. The technique has been programmed for on-line use on a 12-bit minicomputer, validated on cooperative adult subjects and used for ERA threshold determinations in young children. Using response detection criteria yielding an empirically determined false positive error rate of between 1 and 4%, threshold estimates averaged about 10 dB higher than psychophysical thresholds. The efficiency with which such ERA thresholds may be obtained with this method is substantially greater than that of conventional ERA procedures employing subjective evaluation of averages. Further, the technique allows variation of detection criteria to suit non-audiometric needs and empirical determination of the false-positive error rate under any set of conditions.


The relationship of head size to alpha frequency with implications to a brain wave model. Analogies between brain waves and waves in physical systems suggest that EEG frequency may be partly determined by cortical surface area. Since a number of other physiological and anatomical parameters probably influence EEG frequency, only a weak correlation is to be expected. A study was made of 159 subjects, some of whom had either very large or very small heads. A single number representing head size was determined as the cube root of three linear measurements. Several characteristic EEG frequencies were determined for each subject by means of Fourier analysis. The data indicate that alpha frequency is significantly correlated with head size: larger heads tend to produce slower alpha rhythms. It was also shown that alpha frequency tends to be lower in all subjects above roughly age 60. Subjects above produced significantly less alpha rhythm than the younger group. It is suggested that analogies between brain waves and physical waves may explain a number of phenomena which are typical of EEG.


Intermittent photic stimulation. Clinical usefulness of non-convulsive responses. The clinical usefulness of non-convulsive responses induced by intermittent photic stimulation (IPS) was studied in 46 patients whose evaluation included both electroencephalography (EEG) and computerized cranial tomography (CT scan). Three patterns of photic responses were identified and related to background EEG activity and type of lesion seen on CT scan. An asymmetry in photic driving manifested only by a consistent amplitude difference greater than 50% was rarely associated with other EEG changes such as focal slowing or significant asymmetry in the alpha rhythm. In contrast, an asymmetry in development of the photic response correlated well with ipsilateral focal slowing and CT scan evidence of parenchymatous brain disease. Bilateral, symmetrical high amplitude single spikes evoked by individual light flashes were seen only in patients with diffuse encephalopathies. In no patient with structural brain disease as judged by CT scan was an abnormality in IPS the only EEG finding. There was also no apparent relationship between the anatomical site of a focal cerebral lesion and the type of response induced by IPS. Photic stimulation is of limited value in non-epileptic patients. Little clinical significance can be attached to nonconculsive responses in the absence of associated EEG changes which by themselves are generally more informative.


The cumulative inhibitory effect of repetitively flashed stimuli on the recovery process of the human visual evoked potential to a test stimulus. Cumulative inhibitory effects produced by visual response to flashed conditioning stimuli were measured by means of the amplitude reduction of the visual evoked potential (VEP) to a test stimulus. Four kinds of conditioning stimuli were used: a single conditioning stimulus and 3 repetitive conditioning stimuli with interstimulus intervals (ISIs) of 100, 200 and 400 msec, respectively. The VEP amplitude for the test stimulus was reduced most when the stimulus was paired with the single conditioning stimulus. It still remained small when the test stimulus was paired with the repetitive conditioning stimulus of 400 msec ISI, increased significantly when the ISI was shortened from 400 to 200 msec. Explanations of the VEP behaviors in terms of the stimulus relevance, task difficulty and the recovery rate of the cortical excitability were discussed.


The effects of cerebellectomy on a penicillin epileptogenic focus in the cerebral cortex of the rat. (1) Total removal of the cerebellum from the rat anaesthetised with urethane was found to increase the duration of epileptiform foci produced by injection of 25 U of Penicillin into the cerebral cortex. (2) This was not due to reduction in blood pressure nor to non-specific brain damage resulting from the cerebellectomy. (3) The effects of total cerebellectomy are not due to the removal of the inhibitory influence of the Purkinje cells on the intracerebellar nuclei, which from part of an excitatory cortico-cortical circuit. (4) The underlying mechanism is obscure, but it is possible that the cerebellum produces some inhibitory tone, which decreases the lifetime of penicillin foci.


'Limbic spindles': a re-appraisal.

'Limbic spindles': a re-appraisal. Respiration-linked spindles are frequently recorded from nasopharyngeal electrodes and these have been reported to represent neuronally generated limbic activity. Evidence is presented from sphenoidal and nasopharyngeal recordings suggesting that these spindles are artifactual, due to unstable electrode contacts that record palatal vibration during partial airway obstruction.


A gated, high voltage iontophoresis system with accurate current monitoring. A circuit description for a multichannel constant current source for microiontophoresis is presented. The circuitry allows a high voltage compliance, accurate monitoring of ionotophoretic current without use of batteries, and automatic current neutralization. Drugs may be applied either manually or with an external digital gate signal. A monitor to detect current unbalance greater than a preselected level is also included.


A self-powered, preprogrammable, constant current, electronic stimulator for implantation in conscious and unrestrained, small animals. A completely implantable electronic brain stimulator was designed and constructed using commercially available Complementary Metal Oxide Semiconductor digital, integrated circuits. All stimulation parameters were preprogrammed prior to implantation. They included bipolar pulse width (0.5 msec), constant current intensity (120 muA) and frequency (125 pulses/sec) as well as pulse train length (33 sec) and the interval between pulse trains (70 min). After complete encapsulation, the unit weighed 6.2 g and measured 30 mm X 15 mm X 8 mm. The units were easily implanted under the skin in the flank areas of 300 g rats. The 5 muW power consumption allowed implanted lifetimes of over 6 months. A miniature magnetic switch was included inside the package to allow testing of the unit after implantation. Stimulators were implanted in 17 rats for periods of 4--62 days in a study exploring the relationship between long term electrical stimulation of the lateral hypothalamus and the development of arterial pathology.


Auditory evoked potential development in early childhood: a longitudinal study. Serial recordings of auditory evoked potentials (AEPs) to clicks were obtained using a vertex-mastoid derivation from 16 normal children during sleep over an age span from near birth to age 3. The AEP components studied were: N0 (38 +/- 10 msec), P1 (79 +/- 24 msec), N1 (109 +/- 39 msec), P2 (186 +/- 35 msec), N2 (409 +/- 97 msec), P3A (554 +/- 116 msec), P3B (757 +/- 121 msec) and P3 (728 +/- 128 msec). Amplitudes and latencies of the components were calculated and regressions of the measures on age were computed for the group as a whole, for each subject and for subsets of the data based on sleep stage, sex, order of stimulus presentation and a rearing/race factor. For the group as a whole the latencies of P1, P2, P3, and P3B decreased with age. The amplitudes of P1N1 and the N2P3 waves increased with age. Most change occurred during the first year of life. In general, the changes with age were also found to hold across all of the factors examined, although individuals varied widely in the degree to which they conformed to the trends found for the data as a whole. The amount contributed by each of the factors mentioned above to the total variance was estimated. The proportions varied for different EP components but, in general, age, sleep state, and subject factors other than rearing/race and sex accounted for most variance. One half to 5/6 of the unexplained variance in AEP latencies and amplitudes (i.e., that not due to age, sleep state, etc.) occurred across rather than within subjects. For both the group as a whole and for individual children, P2 and N2 latencies were found to exhibit the greatest stability across time. The results of the longitudinal study reported here were in good agreement with those of a previous study from this laboratory which utilized a cross-sectional design.


On how P300 amplitude varies with the utility of the eliciting stimuli. The bulk of the relevant evidence indicates that stimuli which elicit the P300 component of the human event-related potential (ERP) tend to be unexpected and task relevant. Yet, contradictory evidence has been presented which implied that P300 amplitude is modulated by the intensity difference between two equally relevant, equally probable feedback stimuli (Adams and Benson, 1973). The two experiments reported here were designed to clarify this contradiction. Subjects were instructed to press a button one second after a cue light. A tone at one of two intensities was presented 200 msec later indicating whether the time estimate was 'correct' or 'incorrect'. The magnitude of P300 varied as a function of the difference in intensity between S+ and S-; the smaller the difference, the smaller was P300, regardless of stimulus meaning (S+ or S-). We attribute this effect to the degree to which the subject chooses to utilize the tones in the performance of the time estimation task. In support of this hypothesis, we found that performance of the subjects as time estimators degraded as the difference between S+ and S- decreased. Moreover, a study of choice reaction times taken for the different pairings of S+ and S- showed that the stimulus pairs were not equally discriminable. It appears that as the S+/S- pairs become increasingly difficult to discriminate, their feedback value decreased and this decrease is positively correlated with a decrease in P300 amplitude. This interpretation received support from Exp. 2 in which the stimulus conditions were the same as in Exp. 1, but the subject's task was to count the "s+ stimuli. Here, when subject had no option but to process each individual stimulus, the P300 amplitude remained constant despite variations in S- intensity. Thus, it appears that task relevance must be defined in terms of the subject's behavior rather than by the experimenter's instructions to the subject.


Components of the frequency-following potential in man. The scalp recorded frequency-following potentials (FFP) are a composite of several FFP's which may be distinguished by comparing simultaneously recorded waveforms from vertical and horizontal derivations in response to tones of very low frequently (below 350 Hz). The two most prominent FFP's were designated FFP1 and FFP2. FFP1 was recorded equally well in vertical and horizontal derivations and at a high stimulus intensities tended to be the predominant FFP. FFP2 followed FFP1 usually by about 1.7 msec and was optimally recorded in the vertical derivation. FFP2 threshold was about 10 dB lower than threshold for FFP1 and in several subjects, FFP2 was observed at 25 dB SL. Two other FFP's, a far-field recorded cochlear microphonic potential and a low-amplitude FFP, the latter presumably of neural origin, were also studied.


Age-related variations in evoked potentials to auditory stimuli in normal human subjects. Auditory evoked potentials were recorded from 47 subjects ranging in age from 6 to 76 years in order to assess the effects of maturation and aging on the evoked (N1 and P2) and event-related (N2 and P3) components. Because of clear differences in the effects of age on the event-related components between children (less than 15 years of age) and adults the subjects were divided into two populations for analysis. For adults there was a systematic increase in the latency and decrease in amplitude of each component with age. Also the rate of the age-related increase in latency was proportional to the latency of the component. The scalp distributions of both the stimulus-evoked and event-related components were found to vary with age yielding a more nearly equipotential distribution for older subjects. For children the latencies of the event-related components decreased with age. The stimulus-evoked components had latencies which were not significantly different from those predicted from the adult data. In contrast to the adult data, age affected the scalp distributions of the stimulus-evoked components differently than the event-related components. These results suggest an aging process is relfected in the auditory evoked potential which is not the simple inverse of maturational processes.


Normal variability of the brain-stem auditory evoked response in young and old adult subjects. The brain-stem auditory evoked response was studied under three combinations of intensity and rate of click stimulation in 25 young and 25 old adult subjects. The responses show a great intra and inter subject variability. Waves 1, 3 and 5 are constant and reproducible markers of the response while waves 2, 4, 6, and 7 are variable and frequently asymmetrical or absent. Wave peak latencies increase with an increase in stimulation rate, a decrease in stimulus intensity and an increase in age. Interpeak conduction times, except those involving wave 2, are unaffected by a change in stimulus intensity. Wave 1-3 time increases with an increase in stimulus rate and an increase in age while wave 3-5 time is not affected by any change in stimulus parameters or age. Wave amplitude alone is not a reliable measure of normality. Normal values for peak latencies, interpeak conduction times and interear symmetry are presented. One tailed 95 and 99% confidence intervals for normal interpeak conduction times are presented with appropriate corrections for stimulus rate used and patient age. No corrections need to be made for changes in stimulus intensity. This suggests that no correction is necessary when studying patients with conductive type hearing deficits. Laboratories using the same stimulation technique appear to produce equivalent normative conduction time values.


Electroencephalographic studies in multiple sclerosis. Specific changes in benign multiple sclerosis. EEG changes were analysed in a group of 260 patients with definite multiple sclerosis, 156 women and 104 men, average age 38.8, at different stages of the disease. Among 103 patients with an evolution up to 5 years, 34% had significantly abnormal EEG'S while in 157 patients with an evolution from 5 to 45 years abnormal records were obtained in 47.8%. The larger group showed EEG differences between benign (66 patients), malignant (23 patients) and moderate courses (68 patients) patients. The frequency of abnormal and doubtful EEGs was highest in the benign group (80.4%) and largest in the malignant group (24.1%). The main characteristic in malignant multiple sclerosis in the steadily progressive stage was a flat EEG. There was also a significant correlation between a flat EEG and intellectual deficit. In benign multiple sclerosis the dominant activities were slow (6-10 c/sec) and high voltage (80-180 muV) alpha-theta rhythms spreading all over the cortex, usually associated with "centrencephalic" discharges. A self-limiting effect of lesions around the 3rd ventricle on auto-agressive immunological processes is proposed.


Interhemispheric relationships of reponses to sine wave modulated light in normal subjects and patients. (1) The interhemispheric amplitude correlations of the fundamental (A1) and second harmonic (A2) components of responses to sine wave modulated light were determined in the occipital, parietal and temporal scalp areas of a group of normal subjects and a group of patients with unilateral irritative EEG phenomena. The interhemispheric amplitude correlation was computed at 10- and 16-c/sec stimulation frequencies and under 3 conditions: no modulation and no attention (M-, A-), modulation 30%, and no attention (M+, A-) and modulation 30% and attention (M+, A+). The correlations wre expressed in the rank correlation coefficient of Kendall (rK). (2) Analysis of variance revealed that the interhemispheric amplitude correlation of A1 in the normal group was significantly larger than that in the patient group at a stimulation frequency of 10 c/sec and under the conditions (M-, A-) and (M+, A-). (3) Both groups presented the largest correlation coefficients in the occipital scalp area. (4) In the normal group a significant increase of rK occurred under the influence of modulation. Attention caused a decrease of the correlation coefficient of A1. In the group of patients this influence was not clear. (5) The standard deviation of the mean interhemispheric phase differences was considered as a measure of synchrony of the response components between the two hemispheres. The smallest values of standard deviation were found in the occipital scalp area of the normal group at 10 c/sec stimulation frequency. Considerable variations between individuals were observed in both groups. (6) The correlation between the interhemispheric amplitude correlation (rK) and the interhemispheric synchrony was influenced by changing modulation depth from 0 to 30% and by introduction of attention, mostly in the group of normal subjects. This phenomenon was considered to support the theory that in patients with unilateral EEG disturbances the interhemispheric relations are different from those in normal subjects. (7) The findings as to amplitude correlation (rK) were the same under the condition (M-, A-) as under the condition (M+, A-).


Excitatory and inhibitory components of the eyeblink responses to startle evoking stimuli, studied in the human subject. Integrated EMG recordings have been used to study the eyeblink component of the human startle reflex. They have shown that the response, to either an auditory or a painful stimulus, consists of an initial excitation followed by a more prolonged period during which a second stimulus, of the same or different sensory modality, fails to evoke a response, or evokes one which is reduced in amplitude. The period of reduced responsiveness does not follow voluntary or spontaneous eyeblinks. Increasing the duration of the startle evoking stimulus has little effect on the excitatory component of the response, but prolongs the subsequent period of reduced responsiveness. When stimuli of one modality are presented repetitively to the subject, the eyeblink response is habituated; the response to a subsequent testing stimulus, of a different sensory modality, is then smaller than that evoked by the testing stimulus alone, but greater than that evoked by the testing stimulus when it follows a single conditioning stimulus. It is concluded that the excitatory and inhibitory components of the startle reflex are at least partially separable and that stimulus novelty has some significance in eliciting a response.


[Sleep in children with episodic sleep phenomena: a comparison with the normal child]. (1) The sleep pattern of 23 children, aged 5-12 years, with episodic nocturnal phenomena (night-terrors, somnambulism, rhythmic movements) was recorded during two successive nights. It was compared with that of a group of 21 normal children of the same age. (2) In the pathological group, slow wave sleep (SLP, stages 3 and 4) was significantly shortened during the 2 nights. This deficit mainly involved the first 3h of sleep. (3) As for the slow wave sleep, REM sleep (SP) modifications prevailed during the first hours of sleep. The first REM period was delayed and preceded by more numerous and atypical partial REM periods. The duration of the first REM period increased faster as a function of its latency than in the normal child. (4) In contrast with this difficulty for REM sleep to occur during the first part of the night, the subsequent REM sleep pattern was similar in the 2 groups (total REM sleep duration, mean REM period duration, mean REM cycle duration). For equal latencies, REM periods had similar duration. Finally, the total REM sleep amount was a linear function of the total sleep time, with more or less identical coefficients for the two groups. (5) The part played by these modifications during the first hours of sleep in the occurrence of night terrors and somnambulism is discussed.


REM sleep in primary depression: a computerized analysis. REM sleep in 35 inpatients with primary depression was automatically analyzed for 7 consecutive nights during placebo administration. For the total night of sleep, as well as each individual REM period, the number of REMs, their total voltage integral over time, the sum of their durations and the average REM size were automatically calculated. Validity of these automated REM measures was established by significant correlations with manually scored REM measures. Changes in REM sleep across the night were also investigated. Similar to findings in normal subjects, REM time did not change from REM period to REM period. Average REM size increased significantly from REM period 2-3 and 3-4. Contrary to what is seen in normal subjects, REM frequency was high during the first REM period, significantly decreased from the first to second REM period and then remained constant. Finally, a significant inverse correlation between REM frequency for the first REM period and REM latency was noted. This pattern of REM sleep is interpreted as indicating a high pressure for phasic REM at the beginning of the night which is dissipated by the first REM period.


'Alpha-pattern coma' and survival after cardiac arrest. A case of survival despite on EEG in the alpha range during coma after cardiac arrest in connection with acute myocardial infarction is reported. The other 5 published cases are referred to. On the basis of the available literature it is concluded that it is impossible to determine the few patients who will survive despite 'alph-pattern coma'.


Sleep patterns in cat induced by gammahydroxybutyric acid. Intravenous injections of gammahydroxybutyric acid (GHBA) (150-200 mg/kg) induce desynchronized sleep (DS) in the cat. This was shown by recording the EEG, eye-movements, the neck EMG, heart-rate and arterial pressure. The decreases in arterial pressure were not different from those recorded during naturally occurring DS. GHBA, given at doses above 200 mg/kg induced anaesthesia, during which arterial pressure was elevated. At the end of GHBA-induced sleep or anaesthesia there was a stage during which the animals were ataxic. The EEG showed a hypersynchronous spike pattern and arterial pressure was markedly elevated.


A sample and hold amplifier system for stimulus artifact suppression. A sample and hold amplifier system has been described which is capable of eliminating stimulus artifacts from a variety of biological recordings which would otherwise be impossible to interpret during electrical stimulation. Factors contributing to the prolongation of stimulus artifact are discussed in relation to the design requirements of this system. The application of this artifact suppression circuit to monitoring EEG seizures during electrical stimulation is demonstrated.


Antigenic activity and mobility of bovine pituitary hormones. The antigenic activity and mobility of bovine pituitary hormones; follicle stimulating hormone (FSH), growth hormone (GH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and melanophore stimulating hormone (MSH) were studied with the aid of agar gel diffusion and electrophoresis. MSH and ACTH were the only hormones not demonstrating antigenicity. Tests by electrophoresis showed "gamma" mobility of the pituitary hormones exhibiting antigenic activity. The observation of antigenic determinants exhibiting identity with immunoglobulins suggests that the bovine pituitary gland houses immunoglobulin molecule and the various pituitary hormones.


Sequential interaction of macrophages, initiator T lymphocytes and recruited T lymphocytes in a cell-mediated immune response to soluble antigen. We have investigated the sequential interaction of macrophages, initiator T lymphocytes (ITL) and recruited T lymphocytes (RTL) in the development of a T cell-mediated response to soluble antigens. Macrophages were pulsed with soluble antigens and used to sensitize ITL in vitro. The ITL were irradiated to prevent their proliferation and then injected into the footpads of syngeneic mice. Sensitized ITL were found to recruit immunospecific RTL in the draining lymph nodes, as determined by a thymidine uptake assay of the lymph node cells in vitro. The richest source of lymphocytes with ITL activity was the thymus, and progressively less activity was detectable among spleen or lymph node lymphocytes. The magnitude of the subsequent RTL response could be modified by genetic differences between the ITL and the antigen-pulsed macrophages that were used to sensitize them. Thus, ITL conveyed an immunogenic signal to RTL whose magnitude reflected the genotype of the macrophages, but whose specificity was directed by determinants of the soluble antigen.


Specificity of helper T cells for different antigens. BALB/c nude mice have been injected with 10(6) congenic thymus cells, a number which allows some, but not all mice to respond to any particular T-dependent antigen. These mice have been tested for their ability to respond to three bacteriophages, T4, T7 and phiX, sheep and horse erythrocytes, and alloantigens of C3H and C57BL/6 mice. The number of mice able to respond to each of these antigens was of the same order of magnitude. Sheep and horse erythrocytes showed cross-reactivity at the T cell level, i.e. the responses to these two antigens were not independent. The same was observed for C3H and C57BL/6. Otherwise, the responses were independent showing that the antigens are recognize by different populations of specific helper T cells.


Effects of hydralazine on canine muscarinic ganglion stimulation. The effects of hydralazine upon the caudal pressor responses during occlusion of the abdominal aorta and vena cava evoked by: (1) preganglionic electrical stimulation of the lumbar sympathetic chain, (2) neostigmine and (3) McN-A-343 were investigated in the anesthetized dog. Hydralazine (10 microgram/kg, i.v.) produced a small but significant reduction of the pressor response to lumbar electrical stimulation prior and following blockade of nicotinic transmission with chlorisondamine (1.0 mg/kg). However, hydralazine was not effective in blocking the pressor responses elicited by neostigmine and McN-A-343. On the other hand, small doses of atropine (20 microgram/kg) produced a blockade of residual pressor responses evoked by all three stimuli. On the basis of these findings, the site of action of hydralazine appears to be different from that of atropine. It is proposed that hydralazine affects ganglionic transmission by acting at sites other than muscarinic in nature.


Cerebellar afferent projections from the perihypoglossal nuclei: an experimental study with the method of retrograde axonal transport of horseradish peroxidase. Details of cerebellar afferent projections from the perihypoglossal nuclei were studied in the cat by means of retrograde axonal transport of horseradish peroxidase (HRP). Labeled cells were observed bilaterally (with a preponderance ipsilaterally) in nuclei intercalatus and praepositus hypoglossi following injections in various folia of the entire vermis, paraflocculus, flocculus, fastigial nucleus, and the nucleus interpositus anterior and posterior. Relatively high densities of labeled cells were found in nucleus intercalatus following injections in the anterior part of the vermis, whereas labeled cells in nucleus praepositus hypoglossi were found more frequently following injections in the posterior part of the vermis. Labeled cells in the nucleus of Roller were found only following injections in the anterior lobe vermis, posterior vermal lobules VI and VII, in the flocculus and in the nucleus interpositus anterior. No labeled cells could be detected in the three subdivisions of the perihypoglossal nuclei following HRP injections in crus I, crus II, paramedian lobule, and lateral cerebellar nucleus. The distribution of the HRP positive cells indicated the presence of a topographically organized projection from certain regions of the perihypoglossal nuclei to different parts of the cerebellum. The afferent and efferent connections of the perihypoglossal nuclei in relation to a functional role in eye and head movements are discussed.


Specific reaction of aloe extract with serum proteins of various animals. We found that aloe extract contains a lectin-like substance which reacts with serum proteins of various animals. Furthermore, in human serum 2 proteins, alpha2-macroglobulin and alpha1-antitrypsin, were shown to be reactive with aloe extract.


Effect of aging on immune and tolerant states. A model has been described for studying the effect of aging on the cellular events involved in the induction, maintenance, and termination of a central tolerant state representative of the natural tolerant state to self. This model may permit an approach to the examination of the immune status of subpopulations of T and B cells to self antigens during aging. Prelminary data with NBZ mice, which show signs of accelerated autoimmune disease, suggest a possible defect detected by changes in polyclonal activation of B cells. This defect appears to be at the B cell level and not to involve suppressor T cells.


In vitro correlate of tranplantation immunity: spleen cell migration inhibition in the lizard, Calotes Versicolor. Sensitization to skin allografts in the lizard, Calotes versicolor, was assessed using the in vitro capillary migration inhibition (MI) assay. In the presence of the respective donor antigen, an appreciable degree of MI of sensitized spleen cells was observed as early as 4 days after grafting. A maximum level was attained on day 7 and this response was maintained as long as one month after grafting with only slight fluctuations in the level of MI. When the clinical manifestations of graft rejection culminated on day 35, the degree of MI was still at the maximum level. MI of allograft-sensitized spleen cells is an antigen specific event, and the same level of inhibition is observed whether the specific antigen is provided in the form of intact spleen cells or spleen extract.


Formation of free radicals from carcinogenic benz[c]acridines in the presence of proteins. Formation of a free radical from carcinogenic and noncarcinogenic benz[c]acridine derivatives in the presence of proteins was examined. When aqueous mixture of benz[c]acridine and protein was stirred for a long period, shielded from light, benz[c]acridines were converted into free radicals. Albumin had the greatest effect in accelerating the free radical formation, and the effect was smaller in globulin, histone, and deoxyribonuclease. The g-value of the free radicals thus obtained was 2.005. Intensity of the electron spin resonance (ESR) signals of the free radical from carcinogenic derivatives was higher than those of the free radical from noncarcinogenic derivatives. There was a corresponding correlation among the ESR signal intensity of the free radical formed from the mixed system of benz[c]acridine and protein, charge of the K-region or ring nitrogen of the compound, and carcinogenicity of benz[c]acridines.


Effect of chemotherapeutic agents on the growth of rat bladder cancer, BC-47. Effect of clinically available chemotherapeutic agents on transplantable and tissue culture bladder carcinoma cell line, BC-47, which were syngeneic to host animals, was confirmed. Adriamycin, vincristine, and bleomycin possessed predominant antitumor activity. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) also reduced the tumor load of the host after which the tumor began to grow at the site of inoculation. Alkylating agents such as nitrogen mustard N-oxide (Nitromin), cyclophosphamide, 3,3'-dimesyloxydipropylamine tosylate (864T), and mitomycin-C possessed a weak activity, while antimetabolites such as 5-fluorouracil, 1-(1'=furyl)-5-fluorouracil (FT-207), cytosine arabinoside, and behenoylcytosine arabinoside possessed no activity.


Enzyme-immunoassay of human alpha-fetoprotein. An enzyme-immunoassay for the quantitation of human alpha-fetoprotein was developed employing the so-called sandwich method using filter paper discs as a solid-phase. Filter paper discs were activated with cyanogen bromide and the specific antibody to alpha-fetoprotein was covalently bound to the discs. The enzyme-labeled antibody was prepared by coupling the antibody to alkaline phosphatase with the aid of glutaraldehyde. The antibody-coated filter paper discs were incubated with the samples containing alpha-fetoprotein, which was bound to the discs, then the discs were incubated with the enzyme-labeled antibody solution. The enzyme activity bound on the discs was then measured, and was found to be proportional to the amount of alpha-fetoprotein in the sample. The present method provided an accurate measurement for human alpha-fetoprotein in test serum in a range of 40 approximately 1,000 ng/ml. The sensitivity was almost comparable to that of radioimmunoassay. alpha-Fetoprotein levels in the normal and patient sera tested with this method were in good agreement with the values obtained by the radioimmunoassay technique.


Alpha-fetoprotein (AFP) in benign liver disease. Evidence that normal liver regeneration does not induce AFP synthesis. One hundred sera samples, obtained during the early postoperative period from 11 patients after a partial hepatectomy, were assayed for alpha-fetoprotein (AFP). None were AFP-positive by radioimmunoassay, despite clinical and biochemical recovery associated with normal liver regeneration. AFP was elevated in 29% of patients with acute hepatitis, 34% of patients with chronic active hepatitis, and in 75% of patients with massive hepatic necrosis. The mechanism and significance of AFP elevations in some patients with acute and chronic hepatitis is uncertain but probably does not reflect normal liver regeneration.


Hyperviscosity syndrome attributable to hyperglobulinemia in chronic active hepatitis. A young women with clinical and histological features of chronic active hepatitis was noted to have extremely high levels of immunoglobulin (14.6 g per dl). This was associated with the hyperviscosity syndrome, diffuse coagulation abnormalities, and renal insufficiency in the absence of severe liver disease. Correction of these features occurred with plasmapheresis before corticosteroid therapy was begun. A similar group of persons with very high gamma-globulin levels, described previously under the heading of "plasma cell hepatitis," may form a distinct and rare subgroup of chronic active hepatitis patients.


[Selection for fertility under gestagen synchronization of estrus in mice]. The results of selection of mice for the selection index, with the use of gestagenic synchronization of oestrus for 12 generations, allows to affirm that: The synchronization effect decreases with successive generations, which is connected with the existence of a negative correlation between the synchronizability and fertility. The selection effect in the control population was higher than that in experimental one, subjected to oestrus synchronization. It can be supposed that gestagen dimishes the correlation between the genotype and the phenotype, thus decreasing the selection efficiency in the experimental population. A similar tendency was found for the number of implantations and litter size at the age of 1, 10 and 21 days after birth.


A new rapid method for selective extraction of RNA from fixed mammalian tissues. Treatment of formalin-fixed mammalian tissues with concentrated or 50% phosphoric acid at 5 degrees C for 20 and 50 min. respectively reveals complete extraction of RNA as judged by methyl green followed by staining with pyronin. This procedure also causes depolymerisation of DNA as indicated by the red staining of the nuclei. Sections treated with concentrated phosphoric acid at 5 degrees C for 30 min. causes disruption of the double helical structure of DNA what results in the depression of the pyronin staining. Similarly treated sections show Feulgen positive nuclei. Treatment of sections in 25 % phosphoric acid at 60 degrees C for 15 min. followed by staining with methyl green and pyronin show red nuclei, nucleoli and the cytoplasm. This indicates that extraction of RNA is only possible in cold and not at elevated temperature.


Effect of tepa, shikonin and ecdysone on the alkaline phosphatase in the larvae Aedes aegypti (L.). Effect of shikonin, tapa and ecdysone was studied on the activity of alkaline phosphatase by biochemical and histochemical methods. Tepa and shikonin (sterilants) inhibited the enzyme activity while ecdysone slightly increased the activity. This behaviour has been discussed in the present paper.


[Rapid cytological staining in gynecology]. It is reported on a new method of rapid cytological staining permitting valid assessment of pathological changes in the genital area, cytohormonal findings, and criteria of malignancy. The staining technique is simple, inexpensive and quick (2 minutes) and can be performed during daily routine work. The smear can immediately be evaluated and discussed with the patient. For documentation of the results the same criteria apply as in normal cytological diagnosis. Another advantage is the durability of the smears thus permitting later comparison.


The elimination in dogs of trypsin-alpha-macroglobulin complexes inactivated by the Kazal or the Kunitz inhibitor. The elimination of trypsin-alpha-macroglobulin complexes and similar complexes with the trypsin inactivated by low-molecular weight inhibitor was studied in anesthetized dogs. The complex was inactivated either by the Kazal (pancreatic secretory trypsin inhibitor, PSTI) or the Kunitz inhibitor (Trasylol BE). The inhibitors were labelled with 125I and in the case of the trypsin-alpha-macroglobulin complex the trypsin was labelled with 125I. All of the inactivated complexes exhibited a half-life of about 5 min in the dog. The elimination in plasma was exponential until 80 - 85% of the initial dose was cleared in 30 min and nearly negligible thereafter as seen by radioactivity measurements. Simultaneously increasing amounts of dialyzable radioactive substances with a lower molecular weight than the inhibitors were recovered in the urine. No significant differences in the elimination of trypsin-alpha-macroglobulin complexes were detected in plasma or in the urine before and after inactivation with the Kazal inhibitor (PSTI) or the Kunitz inhibitor (Trasylol BE).


Synergistic cytotoxic effects of antibodies directed against different cell surface determinants. Three antibody populations were raised in rabbits against surface antigens on guinea-pig L2C leukaemic lymphocytes: against idiotypic determinants on the lambda chain of the surface immunoglobulin, against C region determinants on the lambda chain, and against the surface antigens recognized by conventional anti-lymphocyte sera. Complement and K-cell cytotoxicities effected by the antibodies on L2C cells were studied in vitro. In both cytotoxic systems mixtures of the antibodies revealed synergy, in that the titres of the mixtures exceeded predicted additive titres of their components. The synergy was greater when the mixed antibodies were directed to determinants on the same molecule rather than to determinants on different molecules.


Immunodiffusion method for identification of group A streptococci. The development of a method suitable for identification of group A streptococci by microprecipitation in gels is described. The method is based on preparation of specific sera containing high antibody levels agains the antigenic determinant characteristic of group A streptococcal polysaccharide. In a comparative study with a counterimmunoelectrophoresis method, the proposed test proved to be specific, easily read, and less complicated. Results were obtained in 2 h.


Existence of multiple immunodeterminants in the type-specific capsular substance of group B type Ia streptococci. Rabbits immunized with group B, type Ia streptococci produce two distinct populations of protective antibodies. Evidence is presented indicating that these antibodies are directed against two major immunodeterminants which coexist in the specific type Ia antigen. Immunochemical data, using purified antibody preparations, indicate that the type substance, a sialic acid polymer consisting of galactose, glucose, glucosamine, and sialic acid, possesses two distinct immunodominant determinants, terminal sialic acid residues and a galactosyl oligosaccharide. Antibodies directed against either of these determinants were shown to possess in vivo and in vitro opsonic capabilities.


Heterologous radioimmunossay of monkey alpha-fetoprotein. Immunoelectrophoresis showed that rabbit anti-human alpha-fetoprotein (AFP) cross-reacts with monkey AFP which was not detectable in the serum from an adult non-pregnant monkey. A heterologous radioimmunoassay of monkey AFP was developed using this antiserum which circumvented the need for purified monkey AFP. The radioimmunoassay is of sufficient sensitivity to measure AFP in maternal and fetal serum and amniotic fluid in the rhesus monkey.


Early postoperative bleedings after prostatectomy in the light of statistical figures. A statistical analysis of intraoperative and early postoperative bleedings in cases of surgery for prostatic adenoma is presented, consideration being given to the surgical technique and to lethality. It has emerged that all patients having had intraoperative or early postoperative bleedings had been operated on by the Hryntschak method and all were over 60 years of age (average age 68 years). Age-matched patients operated on by the Freyer method had no major bleedings.


Characterization of changes observed in the corneal endothelium with the specular microscope. The specular microscope reveals little of the internal features of the corneal endothelium, but in certain experimental and clinical situations vague markings of four different appearances occur and indicate intracellular disturbances. Comparison of the specular microscopical appearances of the affected cells in vitro with stained flat-mount preparations of the same cells shows that three of the markings are due to intracellular vacuoles and the fourth to cell rupture. The differing specular microscopical appearances of the vacuoles are discussed.


Demonstration of a progestin receptor in human benign prostatic hyperplasia and prostatic carcinoma. Cytosol from human benign hyperplastic and carcinomatous prostatic tissue has been shown to contain a progestin receptor with a dissociation constant of approximately 10(-9) M. The receptor was measured using 3H-labeled R 5020 (17 alpha, 21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. Progesterone, cyproterone acetate, and R 1881 (methyltrienolone) were efficient competitors to R 5020 for binding sites on the receptor whereas testosterone, 5 alpha--dihydrotestosterone, estradiol, cortisol, and several hydroxylated and saturated derivatives of progesterone did not compete. The [3H]R 2020-receptor-complex had a sedimentation coefficient of approximately 4 S, an isoelectric point of approximately 5, was heat-labile, and was destroyed by treatment with trypsin but not with deoxyribonuclease or ribonuclease. Seventeen of 21 patients with benign prostatic hyperplasia and three patients with prostatic carcinoma had 1 to 40 fmoles of specific R 5020-binding sites per mg of cytosol protein. One sample of normal prostatic tissue did not contain significant amounts of progesting receptor. Tissue specimens removed by transvesical adenoma enucleation displayed a larger number of specific R 5020-binding sites than electroresected specimens. The progestin receptor in hyperplastic prostate may be involved in the mechanism of the action of progestins used in the medical treatment of benign prostatic hyperplasia. Quantitation of progestin receptor in cancer of the prostate may form part of the basis of a predictive test program for endocrine therapy of prostatic malignancy.


An improved Timm sulphide silver method for light and electron microscopic localization of heavy metals in biological tissues. Modifications of the Timm sulphide silver method for the demonstration of heavy metals are described. To improve the structural preservation of the tissues perfusion with a glutaraldehyde fixature is employed before perfusion with the sodium sulphide solution. For the subsequent staining for light and electron microscopy, procedures for plastic embedding, paraffin embedding and cryostat sectioning are presented. Examples from several tissues are shown, including the pituitary, pancreas, intestine, tongue, kidney, testis and brain. The staining of autolytic, postmortal human brain tissue is demonstrated.


Adaptation of the Naphthol Yellow S staining for objects with high protein content. In measuring isolated rat liver cells stained with Naphthol Yellow S (NYS) at optimal conditions of pH (2.8), the absorbances measured at the absorption peak of 430 nm appeared to be far too high locally to enable accurate cytophotometric measurements. In order to bring down these absorbances, different techniques for flattening the cells, off-peak measurement and NYS staining at non-optimal pH levels have been applied respectively. Using albumin incorporated in polyacrylamide model films, the reliability of off-peak measurements and the quantitative aspects of the modified protein staining procedures have been investigated. It was found that the NYS procedure can be used as a quantitative protein staining not only at pH 2.8, but also at pH 2.0, 3.5 and 4.0 respectively. The problem with regard to the cytophotometric measuring of isolated liver cells could only be solved, however, by combining a specially developed flattening procedure (by centrifuging small drops of suspension) with staining at non-optimal pH levels. In contrast to the model film results, off-peak measurements applied in situ appeared to give rather unreliable results. In cases of a combined Feulgen-NYS staining, the Fuelgen-DNA values were not significantly influenced by any of the modifications of the original NYS staining procedure.


[Artificial mesh in the reconstruction of the posterior auditory canal wall (author's transl)]. Mersilene mesh was used in the reconstruction of the posterior wall of the auditory canal in 12 radical mastoidectomy and attico-antrotomy cavities. Reestablishment of a stable metal wall occurred in 7 patients. In 2 the mesh had to be covered with soft tissue in a second procedure. 3 implants required removal. This technique because of the 25% failure rate can only be recommended reservedly.


Inhibition of Escherichia coli division by protein X. We propose that protein X provides the connection between damage to Escherichia coli DNA and inhibition of septation and cell division. This connection is needed to guarantee that each new bacterium receives a complete DNA copy. We present several new experiments here which demonstrate that the degree to which septation is inhibited following damage to DNA is correlated with the amount of protein X that is produced. Rifampin selectively blocks protein X production. This drug was shown to allow cells whose DNA had been damaged by nalidixic acid to resume septation. Several mutants formed septa-less filaments and also produced protein X at 42 degrees C; rifampin both inhibited their production of protein X and permitted them to form septa and divide. Essentially complementary results were obtained with a dnaA mutant which at 42 degrees C stopped making DNA, did not produce protein X, and continued to divide; added bleomycin degraded DNA, induced protein X, and inhibited septation. These results, as well as previous observations, are all consistent with the proposal that protein X is produced as a consequence of DNA damage and is an inhibitor of septation. We suggest that septation could require binding of a single-stranded region of DNA to a septum site in the membrane. Protein X could block this binding by combining with the DNA. This control could provide an emergency mechanism in addition to the usually proposed coordination in which completion of DNA synthesis creates a positive effector for a terminal step of septation. Or it could be the sole coordinating mechanism, even under unperturbed growth conditions.


Patient education in the community hospital. Recent events have led to a favorable climate for the development of hospital-based patient education. A pilot model program in a community hospital is utilized to illustrate the variety of settings in which patient education is conducted, and includes: group classes, patient clubs, volunteer visits, individual instruction, community outreach, screening and detection programs, and behavior modification workshops. The use of television for inpatient education is highlighted in a discussion of media approaches and needs.


Comparison of two aqueous biphasic systems used for the partition of biological material. Two biphasic systems, both consisting of water, dextran and poly(ethylene glycol) but differing in the molecular weight of the latter polymer, Mr = 35 000 (systems A) and 6000 (systems B), have been studied. The phase diagrams for the two systems at 20 degrees are compared. The partition of proteins influenced by salts and the viscosity of the phases are direct functions of the difference in composition between the upper and the lower phase as measured by the lengths of the tie-lines found for the systems in the phase diagram. The solubility of gamma-globulin is 1.5-2 times larger in an A system than in a B system with corresponding tie-line. In both systems, poly(ethylene glycol) palmitate has less effect on the partition of serum albumin than would be predicted from the distribution of poly(ethylene glycol) and reflects the non-ideality of simple equilibrium models.


Androgen receptor content of the normal and hyperplastic canine prostate. A procedure was developed for measurement of androgen receptors in cytoplasmic extracts of prostates from intact dogs. The protocol utilized exchange saturation analysis at 15 degrees C employing the synthetic androgen R1881 (17beta-hydroxy-17alpha-methylestra-4,9,11-trien-3-one) as the ligand probe and quantitatively detected total cytoplasmic androgen receptor (R(c), androgen-free receptor, and R(c)A, androgen-occupied receptor) present at the initiation of the assay. This protocol was employed in conjunction with a tissue mince saturation analysis procedure (for quantitation of nuclear androgen receptor) to quantitate total androgen receptor content of normal and hyperplastic prostates obtained from young (2.5- or 4.6-yr old) and aged (12.5-yr old) purebred dogs of known birth date. The total cytoplasmic androgen receptor content (picomoles per prostate) of hyperplastic prostates was 4.6-fold greater than that of normal prostates. The total nuclear androgen receptor content of hyperplastic prostates (picomoles per prostate measured in crude nuclear preparations) was either 5.0- (4.6-yr-old dogs) or 7.8-fold (2.5-yr-old dogs) greater than that of normal prostates. However, androgen receptor content per cell was identical for hyperplastic and normal canine prostates, with the exception that nuclear androgen receptor was diminished in prostates from 2.5-yr-old dogs. The cell content per gram dry weight was identical for hyperplastic and normal canine prostates. We conclude that canine prostate hyperplasia is characterized by coordinate proliferation of androgen receptor-positive and androgen receptor-negative cells and is not a consequence of increased accumulation of 5alpha-dihydrotestosterone due to proliferation of androgen receptors per prostate cell.


Induction of allogeneic unresponsiveness in adult dogs. Role of non-DLA histocompatibility variables in conditioning the outcome of bone marrow, kidney, and skin transplantation in radiation chimeras. Exposure to supralethal total body irradiation and transplantation of bone marrow from a DLA- and pedigree-identical donor have regularly produced successful engraftment and the establishment of stable long-term chimerism in beagles of the Cooperstown colony. Bone marrow allografts performed in pairs of dogs bearing identical DLA haplotypes derived from different pedigree origins (i.e., different classes of the same haplotype) yielded two different results. Depending upon the particular haplotype pedigree combination used, such transplants either led to long-term chimerism or to failures of engraftment, secondary disease, and death of the recipients (i.e., pedigree-incompatible combinations). Radiation chimeras given bone marrow from a DLA-and pedigree-identical donor were challenged within 8-12 h after marrow transplantation with a renal allograft obtained from another DLA- and pedigree-identical donor. The recipients have remained unresponsive to such renal allografts and have survived indefinitely with normal renal function. In contrast, renal allografts obtained from donors bearing the same DLA haplotypes derived from pedigree-incompatible sources were rejected within 25-50 days after transplantation. The long-term surviving recipients have also been unresponsive to skin allografts obtained from their donor of marrow and the kidney donor. Skin grafts obtained from other DLA- and pedigree-identical dogs were rejected within 13-41 days, and grafts from DLA-incompatible donors survived for 10-25 days. These results highlight the potential importance of genetically controlled histocompatibility determinants other than DLA in conditioning allograft reactivity. The determinants uncovered in the present study appear to be linked to the DLA complex, as demonstrated by the ability of the pedigree origins of DLA haplotypes present in individual dogs to serve as an effective marker system for such non-DLA antigen(s). The results also point to the potential usefulness of the early postirradiation period for the induction of allogeneic unresponsiveness in large adult mammals.


The assessment of developmentally disabled children with the WISC-R, Binet and other tests. Administered the WISC-R, Revised Stanford-Binet, Bender, VMI, and WRAT to 50 children referred for a multidisciplinary evaluation of developmental disabilities. The correlations among the various WISC-R measures (Standard Scores and IQs) and Binet IQ were significant, with relatively strong relationships among the Binet IQ and those WISC-R subtests that require concentration, short-term auditory memory, visual-motor integration, and the acquisition of new learning. Data showed that the Binet MA correlated as well or better with the other tests than did the various scores from the WISC-R.


Staining properties and stability of a standardised Romanowsky stain. An evaluation of the standardised Romanowsky stain of Marshall et al. has been made in a routine haematology laboratory. It was noted that this stain had several advantages over the May-Grünwald Giemsa stain used in most British laboratories. These advantages include ease and speed of preparation, a shorter staining time, and reproducibility of results. These results are described in detail. The stability of the stock stain solution and of the 'working' stain (stock + buffer) has been studied by, respectively, thin-layer chromatography and visible spectroscopy. No change was detected in the composition of the stock solution at ambient temperature over a period of six months. Stability was unaffected by the composition of the container (polyethylene, PyrexTM, or soda-glass) or by daylight. The 'working' solution was stable for 3 hours. Thereafter a precipitate is formed, consisting of thiazine dyes and eosin in a molar ratio of approximately 2:1.


Retinal ganglion cells in the crucian carp (Carassius carassius). I. Size and number of somata in eyes of different size. Ganglion cell somata were drawn, measured and counted in flat-mounted crucian carp and goldfish retinas stained with cresyl violet or methylene blue. Some diameter histograms suggest that the ganglion cells can be divided into two populations with overlapping soma sizes: a large group of small cells and a small group of large cells, the latter constituting 2.5-5% of all ganglion cells. With increasing distance from the optic disc the mean soma diameter increases while the ganglion cell density decreases. In a peripheral growth zone close to the margin the ganglion cells become smaller again. The total number of ganglion cells in retinas of different size was calculated from the areas of the flat-mounted preparations and the cell densities in two representative regions. In the crucian carp population used in this work the total number of ganglion cells per retina was found to increase from roughly 140,000 (mean of 8 scattered value) to a full 200,000 between eye diameters 4 and 10 mm, this increase taking place mainly between eye diameters of 4 and 6.5 mm. Thus, due to a drastically decreasing cell density, the total number of ganglion cells increases only by a factor of about 1.5 while the retinal area becomes sixfold. During the same growth period the mean soma diameter increases by a factor of about 1.3 and the soma volume more than doubles. The optic nerve of a small crunated and myelinated axons were found. The axons in the optic nerve are, on an average, considerably thicker than the axons on the retinal surface.


Laminar differentiation of the hippocampus, fascia dentata and subiculum in developing rats, observed with the Timm sulphide silver method. The laminar staining of the rat hippocampal region with the Timm sulphide silver method is from studies on adult rats known to depend on the various fibersystems terminating in these laminae. In order to illustrate the development of these fibersystems the laminar differentiation of the Timm staining of fascia dentata, hippocampus and subiculum is presented for rats between 1 and 31 days old. Corresponding changes in cytoarchitectonics as revealed by thionin staining are briefly demonstrated. Even on the first postnatal day there are indications of the mature, laminar staining pattern, and between three and nine days all the laminae corresponding to the terminal fields of the major afferent and intrinsic systems appear. After 12 days only minor additions to the laminar pattern develop, but there are adjustments of absolute and relative dimensions of layers and fields, and also the staining densities of individual laminae change. These observations are in good correlation with the available information on both hippocampal neurogenesis and cytodifferentiation, and the few fiber tracing studies performed on the developing hippocampal region. Compared to the latter, which ideally marks only one system or one lamina per animal, the Timm method provides an excellent means for getting an overview of the general developmental situation at the different ages. Thus developmental gradients along septotemporal, medio-lateral and basal-apical axes are found; which should be heeded in future studies on hippocampal synaptogenesis. The observations are discussed in relation to current models for neuronal growth and formation of nervous connections.


A new concept of triggering mechanisms of IgE-mediated histamine release. It is generally accepted that an initial step of reaginic hypersensitivity reactions is a bridging of mast cell--bound IgE antibody molecules by antigen. Since IgE molecules are firmly bound to receptors on mast cells, bridging of cell-bound IgE molecules probably brings receptor molecules into close proximity. A hypothesis was therefore presented that such a local change in membrane structure and/or possible interaction between adjacent receptor molecules may be triggering mechanisms of IgE-mediated histamine release. The hypothesis was tested by use of antibodies against "exposed portion" of receptor molecules on rat basophilic leukemia cells. It was found that antireceptor antibodies and its F(ab')2fragments induced noncytotoxic histamine release from normal rat mast cells without participation of IgE, while the monovalent Fab' fragments of the antibody failed to do so. However, sensitization of normal rat skin with the Fab' fragments followed by an intravenous injection of antirabbit IgG induced skin reactions. These findings support the concept that bridging of receptors rather than polymerization of IgE molecules is responsible for the activation of membrane-associated enzymes which in turn leads to histamine release.


Potential genetic risks from stationary magnetic field. Cytogenetic analysis of Dede cell lines (Chinese hamster) was used to study the mutagenic effect of stationary magnetic field (SMF) and the combined effect of SMF and TEPA. Cytogenetic analysis showed a moderate mutagenic effect after exposure to SMF. In combination with TEPA, only the additive effect of the two mutagens was observed.


Dissociated and reconstituted subcellular alloantigen capable of stimulating mouse cytotoxic T lymphocytes in vitro. Reconstituted subcellular membrane fragments were prepared from sonicated murine lymphoid tissue membrane fragments by detergent solubilization and dialysis. The reconstituted subcellular antigen was compared with sonicated cell membranes and x-irradiated cells for the ability to stimulate the formation of allogeneic cytotoxic thymus-dependent lymphocytes in vitro. The results showed that the reconstituted subcellular antigen had properties similar to those reported for the sonicated antigen. Both types of antigen could stimulate immune spleen cells but not normal spleen cells. Furthermore, soluble H-2 antigens, even of membrane origin, were incapable of the stimulation unless reconstituted into membrane fragments large enough to be centrifuged at 48,000 X G for 30 min.


The induction of cytolytic T lymphocytes with purified plasma membranes. Subcellular fractions were demonstrated to be effective in stimulating primary and secondary allogeneic CTL responses. 5' nucleotidase activity was used to assess purification of plasma membranes and stimulating activity was found to co-purify with the plasma membrane fraction of the cell. Electron micrographs of these purified plasma membranes showed the majority of the material to be in the form of vesicles of relatively heterogeneous size. The cytolytic T lymphocytes generated by incubation with purified plasma membranes demonstrated immunologic specificity.


Virus-induced immune complex disease: identification of specific viral antigens and antibodies deposited in complexes during chronic lymphocytic choriomeningitis virus infection. Structural proteins of LCMV were identified and their role in the immune complex glomerulonephritis of LCMV carrier mice was examined. Purified LCMV contained three major polypeptides, a single nonglycosylated nucleoprotein with an estimated m.w. of 63,000, and two surface glycoproteins of 54,000 and 35,000. Deposition of nucleoprotein antigen in the glomeruli of LCMV carrier mice of several strains was demonstrated by immunofluorescent staining with a monospecific antibody. In addition, Ig eluted from kidneys of three strains of LCMV carrier mice was shown by immune precipitation to react against all of major viral polypeptides of LCMV. Antibody from normal mice, and from mice with immune complex disease unrelated to LCMV did not show deposition of LCMV antigen in glomeruli, and Ig eluted from the kidneys of these mice did not react against LCMV antigens. Hence, mice infected at birth with LCMV and persistently infected throughout their life make antibodies to all the known structural polypeptides of the virus.


The role of H-2 and H-2-like determinants in syngeneic and allogeneic cytostasis. Specific sensitization against H-2 determinants was affected by immunizing allogeneic mice with spleen and lymph node cells in H-2 congenic combinations. Lymph nodes from the sensitized and non-sensitized mice were respectively cultured together with H-2 syngeneic tumour cell lines. The growth and viability of the tumour cells was subsequently measured by the amount of radiothymidine incorporation. If the tumour cells incorporated less isotope when cultured with the immune cells than with the normal cells this was termed 'cytostasis'. To identify the H-2 genes controlling the sensitization phase in the cytostasis assay, we studied the effect on different transplantable tumour target cells of lymphoid cells from mice sensitized against different congenic spleen cells. The results suggest that the cytostasis assay can can measure an in vitro specific response to H-2-incompatible sensitizing antigens, and that I--B incompatibility, together with K and/or D, is essential to produce effectors. Furthermore, H-2 allogeneic sensitization could induce cytostasis even against tumour cells syngeneic for the H-2 halotype of the responder strain. The implications of these findings are discussed.


Human alpha-fetoprotein in the epidermal cells of Bowen's disease. Human alpha-fetoprotein (HAFP) was demonstrated in clusters of atypical cells of an extensive Bowen's disease involving the pubic area. Frozen sections were studied by indirect immunofluorescence using monospecific rabbit anti-HAFP antiserum or purified rabbit anti-HAFP antibody followed by staining with fluorescein isothiocyanate (FITC)-labeled goat anti-rabbit gamma-globulin and by a direct technique using FITC-labeled rabbit anti-HAFP Fab2 fragments. Sections of fetal liver served as positive controls and sections of adult human skin and liver were used as negative controls. Preabsorption of the anti-HAFP antibodies with purified HAFP blocked the fluorescence. This finding adds Bowen's disease to the list of premalignant disorders which possess HAFP as an oncofetal marker of their malignant potential. HAFP might possibly enhance malignant behavior through interference with cellular immunosurveillance mechanisms.


Effect of corticosteroids on the human immune response: comparison of one and three daily 1 gm intravenous pulses of methylprednisolone. In spite of the increasing use of  single and multiple pharmacologic intravenous pulses of MPS for immunosuppression in various diseases, their immunosuppressive effects have not been documented. We treated two groups of six patients with classic RA unresponsive to conventional therapy with either one or three daily 1 gm intravenous doses of MPS and measured the immune response and clinical activity over 16 weeks. Lymphocytopenia with selective T lymphocyte suppression was noted 2 hr following each infusion, which was maximal at 6 hr with complete recovery 24 hr after each dose beyond which no lymphocytopenia or T lymphocyte depletion was seen. Preservation of skin test positivity to recall antigens such as PPD and histoplasmin, rise in antibody titers to the secondary antigens tetanus and typhoid, and primary antibody response to KLH were found in both groups after treatment. Serum gamma globulin concentrations were unchanged. Five of six patients receiving 3 doses and three of six receiving 1 dose had satisfactory improvement in clinical parameters, with maximal benefit seen within the first 4 days. Six patients still felt better at 4 weeks, and one patient in each group entered a clinical remission greater than 16 weeks. We conclude that higher and repeated doses of MPS caused neither greater lymphocytopenia nor more prolonged suppression of recirculating lymphocytes than the conventional oral doses. The clinical benefits stem from reduction of inflammation, and it is doubtful that pulse therapy by itself induced significant generalized immunosuppression.


Androgen binding in cytosols and nuclei of human benign hyperplastic prostatic tissue. Androgen binding sites have been detected in cytosols and nuclear extracts from human benign hyperplastic prostatic (BPH) tissue with exchange assays using [3H]methyltrienolone and [3H]5alpha-dihydrotestosterone respectively. The concentrations of binding sites and the equilibrium dissociation constants for the [3H]steroid-receptor interactions have been determined and the specificity of the binding has been examined. The observed properties of the binding sites are consistent with those characteristic of androgen receptors. The binding sites are present in nuclear extracts from all BPH tissue samples examined to date. The amount of binding detected in the nuclear fraction is higher than that found in the cytosol.


Some properties of hepatitis B core antigen isolated from serum of infected humans. The nucleocapsid of Dane particles (= hepatitis B core antigen; HBcAg) was isolated from human sera either positive or negative for e-antigen (HBeAg)--an apparent marker for the level of infectious hepatitis B virus in serum. HBcAg from the HBeAg-positive serum pool consisted of two distinct populations of particles, one with a buoyant density (d) of 1.358 g/ml and a sedimentation coefficient (S20, w) of approximately 110, and another with d = 1.25 to 1.30 g/ml and S20, w approximately 70. Only the latter type of particles was isolated from an HBeAg-negative serum pool. HBcAg was labelled with 125I-p-hydroxyphenylpropionic acid N-hydroxysuccinimide ester, dissociated and analysed by polyacrylamide gel electrophoresis. One major and one minor polypeptide with apparent mol. wt. of 16000 +/- 500 and 68000, respectively, were detected. Another component have the properties of a glycolipid with a mol. wt. in the order of 10(3) was observed. After isoelectric focusing, HBcAg was recovered in fractions with a pH between 4.0 and 5.8, suggesting heterogeneity in isoelectric points.


Comparative pharmacokinetics of coumarin anticoagulants XXXIII: frequency distribution of dicumarol total clearance in rats. The total clearance of dicumarol was determined in 172 adult male Sprague-Dawley rats. Clearance values ranged from 1.46 to 27.0 ml/hr/kg. Statistical analysis of a histogram of the total clearance values indicated a trimodal distribution, with modes at 6.28, 14.8, and 23.7 ml/hr/kg. The percentage of animals in each of these components was 60.5, 33.7, and 5.8. A previous study had shown that the total clearance of dicumarol was proportional to the fraction of nonprotein-bound drug in serum (serum free fraction) and that interindividual differences in total clearance of dicumarol in rats were due almost entirely to corresponding differences in the serum free fraction. Therefore, it is likely that the observed trimodal frequency distribution of total clearance values reflects a similar distribution of serum free fraction values of dicumarol. The frequency distribution curve for dicumarol total clearance is very similar to the trimodal frequency distribution curve for warfarin serum free fraction values in rats. This observation is consistent with the previously demonstrated strong correlation of serum free fraction values of dicumarol and warfarin in individual animals.


Relationship between functional castration and alpha-fetoprotein produced by hepatoma-bearing female rats. In rats bearing Morris hepatoma No. 7777, serum levels of alpha fetoprotein (AFP) increased as tumour size increased. Hepatoma-bearing females remained in dioestrus once the tumour exceeded a cross-sectional area of 12 cm2. The following changes were seen in tumour-bearing rats compared to control animals: uterine wet weight was significantly decreased, the uterine epithelial mucosa was lower, castration cells developed in the anterior pituitary, and there was a 3- to 23-fold elevation in serum oestrogen levels. We conclude that circulating oestrogen is bound to AFP in hepatoma-bearing female rats and that in this bound state it is unable to exert its normal physiological actions.


Whipple's disease and ankylosing spondylitis simultaneous occurrence in HLA-B27 positive male. A 57 year old male had recurrent arthritis and uveitis for 34 years, spinal symptoms for 10 years, and malabsorption for four months leading to the diagnosis of ankylosing spondylitis and Whipple's disease. HLA-B27 was positive. Out of the four cases of Whipple's and ankylosing spondylitis in the literature, only one had been tested for HLA-B27 and was found to be negative.


Cellular content of amniotic fluid as predictor of central nervous system malformations. Prospective observations on 442 consecutive samples have confirmed that pregnancies with CNS malformations are regularly associated with an abnormal cellular content of amniotic fluid. A crude semiquantitative test of the cell content can give valuable clinical information in relation to borderline amniotic fluid alpha-fetoprotein values, and help to detect false positive AFP's.


Topographical studies on intestinal microvillous leucine beta-naphthylamidase on the outer membrane surface. The location of leucine beta-naphthylamidase on the outer surface of the microvillous membrane of rabbit small intestine was examined by analyzing the interaction of antibodies against leucine beta-naphthylamidase or another microvillous enzyme, sucrase-isomaltase complex, with microvillous vesicles having different relative amounts of these enzymes, in respect to vesicle agglutination, inhibition of enzyme activity, and electron-microscopic morphology. The results obtained indicate that leucine beta-naphthylamidase, or at least its antigenic sites, protrude about 10 nm from the outer surface of the microvillous membrane.


Localization of protein in the rabbit yolk sac splanchnopleur by two methods of autoradiography. The distribution of protein labelled with radioactive iodine or tritium within cells of the yolk sac, after it was injected into the uterine lumen of pregnant rabbits, was studied by means of two autoradiographic techniques, one using the classical loop method of Caro & vanTubergen (1962), and the other using Normandin's direct deposition method (Normandin, 1973). The resolution of the latter method was found to be approximately 10 times more sensitive than that of the former (Hemmings & Williams, 1976); thus rendering the site of labelled protein easier to locate. Both techniques are reproducible, but the direct deposition method is easier to handle. Location of protein was detected within vacuoles, and sometimes free in the cytoplasm.


Characterization of an apparently nononcogenic Marek's disease virus. A new isolate of Marek's disease virus (MDV) was described. This virus, SB, and a clone, SB-1, differed from pathogenic isolates in in vitro growth characteristics as described for other apathogenic isolates. Serologically, as with other apathogenic isolates, SB could be distinguished from pathogenic MDV and the avirulent turkey herpesvirus. SB failed to induce lesions characteristic of Marek's disease (MD) during a 6- to 11-week experimental period. Also, SB was nononcogenic in immunosuppressed chickens or in chickens inoculated with this virus in ovo. However, under those conditions, SB caused a cytolytic infection. The term "nononcogenic" rather than "apopathogenic" was therefore proposed to classify this and similar isolates. SB-1 protected chickens against challenge with either virulent MDV or the non-virus-producing MD tumor transplant, JMV. Possible mechanisms of protection are discussed.


A phosphonoacetate-resistant mutant of herpesvirus of turkeys. A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant of HVT resistant to PA (HVTpa) replicated in duck embryo fibroblast (DEF) culture in media containing 300 microgram PA/ml, whereas the replication of the wild type of HVT (HVTwt) was completely inhibited in DEF culture in media containing 100 microgram PA/ml. The HVTpa was distinct from the HVTwt in plaque morphology, but was indistinguishable antigenically and showed in vitro temperature sensitivity at 41 degrees C (3741 degrees C efficiency of replication was about 5). It replicated poorly in chickens and failed to provide complete protection against challenge with Marek's disease virus (MDV). The HVTpa-induced DNA polymerase had an apparent inhibition constant for PA, an apparent inhibition constant for pyrophosphate, and an apparent Michaells constant for dCTP about 10, 2, and 2.5 times, respectively, greater than the constants for the HVTwt-induced enzyme and was also more thermolabile.


Use of the leukocyte migration inhibition assay to evaluate antigenic differences in human breast cancers and melanomas. The leukocyte migration inhibition assay was used to compare the antigenic reactivity of 3 M KCl extracts of human tumors. Many extracts demonstrated strong reactivity with patient leukocytes, whereas others demonstrated weak or no reactivity, Extracts prepared from primary tumors or local recurrent tumors were more antigenic than extracts from involved lymph nodes or pleural effusions. The least reactive preparations were extracts made from specimens of liver metastases obtained at autopsy. A large standard extract tested at a standard concentration was useful for the evaluation of antigenic reactivity of human tumor extracts. It served as a point of reference in simultaneous tests with one blood sample from each individual, thus eliminating the influence of patient variation on extract reactivity.


Transformation of human embryo cells with the use of cell-free extracts of a human rhabdomyosarcoma cell line (HUS-2): brief communication. Cell-free extracts of the human rhabdomyosarcoma cell line HUS-2 caused the transformation of human embryo fibroblasts. This transformation included morphologic alteration, karyotypic change, and an increase in culture longevity. With the use of sex markers, multiple karyotypes confirmed that the human embryo fibroblasts were transformed, and the use of cell-free material further suggested the presence of a transforming virus. RNA-dependent DNA polymerase activity in a particle with a specific gravity of 1.16 g/cm3 indicated the presence of an RNA type C virus. Evidence also suggested that the known mammalian type C viruses, routine cytopathic effect-inducing viruses, or mycoplasma were not the agents responsible for the transformation. That both the donor (HUS-2) and converted (HUE-T) cell lines cross-reacted with antisera prepared against HUE-T indicated a common antigen arising in the process of conversion of HUS-2 cells to HUE-T cells.


Endogenous mink (Mustela vison) type C virus isolated from sarcoma virus-transformed mink cells. A previously described type  virus stock (designated PP-1R), isolated by cocultivating baboon cells with mink cells transformed by Kirsten sarcoma virus (64J1), has been further cloned and characterized. End point-diluted stocks of PP-1R have been obtained that are free of focus-forming activity and lack both Kirsten sarcoma and primate type C viral sequences. Nucleic acid hybridization experiments show that the cloned virus (MiLV) is an endogenous, genetically transmitted virus of the mink (Mustela vison). MiLV replicates in canine, feline, and 64J1 mink cells but not in an untransformed mink cell line. Multiple viral gene copies can be detected in the DNA of normal mink cells in culture and in normal mink tissues; related endogenous viral genes are also detected in several related Mustela species. The virus codes for a p30 protein very closely related antigenically to that of feline leukemia virus but contains p15 and p12 proteins that are antigenically distinct. The mink cell line, Mv1Lu, and its Kirsten sarcoma-transformed derivatives, 64J1, express relatively low levels of type C viral RNA related to MiLV and normally do not produce detectable levels of MiLV p30 protein or complete, infectious viral particles. Infection of sarcoma virus-transformed mink cells with baboon type C virus, however, can augment the level of expression of endogenous mink viral RNA and can result in the synthesis and packaging of mink viral RNA and p30 antigen in extracellular virions. Since the Mv1Lu cell line and its tranformed derivatives have become widely used in studies of retroviruses, the possibility of activating endogenous mink viral genes should be considered by investigators working with these cells.


Marker rescue of endogenous cellular genetic information related to the avian leukosis virus gene encoding RNA-directed DNA polymerase. Endogenous cellular genetic information related to the avian leukosis virus gene encoding RNA-directed DNA polymerase was studied, using a marker rescue assay to detect biological activity of subgenomic fragments of virus-related DNAs of uninfected avian cells. Recipient cultures of chicken embryo fibroblasts were treated with sonicated DNA fragments and were infected with a temperature-sensitive mutant of Rous sarcoma virus that encoded a thermolabile DNA polymerase. Wild-type progeny viruses were isolated by marker rescue with fragments of DNA of uninfected chicken, pheasant, quail, and turkey cells. The DNAs of these uninfected avian cells, therefore, appeared to contain endogenous genetic information related to the avian leukosis virus DNA polymerase gene.


Primate retroviruses: immunological cross-reactivity between major structural proteins of new and old world primate virus isolates. The major 35,000-molecular-weight internal antigen (p35) of the squirrel monkey retrovirus (SMRV) was isolated and partially characterized. Immunological analysis of SMRV p35 led to the demonstration of antigenic determinants common to SMRV and the Mason-Pfizer monkey virus (MPMV). A broadly reactive competition immunoassay was developed utilizing antiserum to MPMV to precipitate 125I-labeled SMRV p35. Although the major structural proteins of MPMV and SMRV competed with equal efficiency in this assay, type B and type C oncornavirus proteins lacked detectable reactivity. Antibodies reactive with the major structural proteins of both MPMV and SMRV were observed in sera of several normal rhesus monkeys with known prior exposure to MPMV-infected animals. These findings demonstrate the ability of sera from naturally immunized primates to recognize broadly reactive interspecies antigenic determinants shared by the major structural proteins of type D oncornaviruses, and they suggest possible horizontal transmission of MPMV among rhesus monkeys. Although sera from a number of squirrel monkeys contained antibody to SMRV p35, the possibility that this latter reactivity was due to endogenous virus activation rather than horizontal transmission cannot be ruled out.


Radioimmunochemical measurement of bone marrow prostatic acid phosphatase. Human acid phosphatases are ubiquitous phosphohydrolases that are present in most respiring tissues and cells. Specifically, human prostatic acid phosphatase is a unique enzyme within a vast family of acid phosphatases concerned with catabolic processes in cellular metabolism. The majority of serum and bone marrow acid phosphatases are of non-prostatic origin and are present chiefly in erythrocytes, leukocytes, platelets and other maturing cells in the bone marrow. The specific concentration of prostatic acid phosphatase in serum and bone marrow is normally relatively low compared to non-prostatic acid phosphatases. Many falsely positive assays for total serum acid phosphatases and bone marrow acid phosphatases have been reported, particularly after traumatic marrow biopsy procedures and mishandling of blood samples in the clinical laboratory and in hematologic disease states. The disruption and lysis of whole blood and marrow cells can liberate non-specific acid phosphatases into the serum. Since standard enzymatic assays do not discriminate accurately prostatic acid phosphatase from non-prostatic acid phosphatase present in the serum spurious results can be realized. A preliminary experience with a promising radioimmunoassay for the specific measurement of prostatic acid phosphatase in bone marrow and serum is presented.


Reversibility of severe bleomycin-induced pneumonitis. The use of bleomycin sulfate as an antineoplastic agent has been limited by its substantial pulmonary toxic effects. The exact incidence and prognosis of bleomycin-pneumonitis is unresolved. Although bleomycin pulmonary toxicity is thought to be dose-related, recent reports have emphasized severe reactions at low doses. Furthermore, severe pulmonary toxicity has been suggested to be progressive, irreversible, and ultimately, fatal. We report clinical, roentgenographic, and pathophysiologic recovery after severe, bleomycin-induced pneumonitis.


[The significance of beta2-microglobulin and carcinoembryonic antigen in the diagnosis of the carcinoma of the pancreas (author's transl)]. The concentration of beta2-microglobulin (beta2m) and carcinoembryonic antigen (CEA) was measured radioimmunologically in the sera of 79 patients with malignant disorders and 15 patients with chronic pancreatitis. Elevated levels of beta2m and CEA were found in 11 out of 22 patients with carcinoma of the pancreas, which sets off this malignancy from chronic pancreatitis and other malignant tumors. Only 3 patients with carcinoma of the pancreas exhibited serum levels within the normal range for both parameters and none of the patients with chronic pancreatitis was shown to have elevated levels of beta2m. The simultaneous determination of beta2m and CEA suggests itself for the diagnosis of pancreatic malignancy especially in the case of a tentative diagnosis of a pancreatic tumor.


Morphometric and morphologic evaluation of pulmonary lesions in beagle dogs chronically exposed to high ambient levels of air pollutants. Beagle dogs (104) comprising one control and seven treatment groups were exposed 16 hours daily for 68 months to filtered air, raw or photochemically reacted auto exhaust, oxides of sulfur or nitrogen, or their combinations. After a further 32 to 36 months in clean air, morphologic examination of lungs by light microscopy, scanning electron microscopy, and transmission electron microscopy revealed two important exposure-related lesions. They were enlargement of air spaces in proximal acinar regions, with and without increases in the number and size of interalveolar pores, and hyperplasia of nonciliated bronchiolar cells. Proximal enlargment of air spaces was most severe, both subjectively and morphometrically, in those dogs exposed to oxides of nitrogen, oxides of sulfur, or oxides of sulfur with photochemically reacted auto exhause. In contrast, hyperplasia of nonciliated bronchiolar cells was most severe in dogs exposed to raw auto exhaust alone or with oxides of sulfur. The air space enlargement and hyperplasia of bronchiolar epithelium correlated with functional impairment reported as occurring in these dogs. Foci of ciliary loss with and without squamous metaplasia were occasionally observed in trachea and bronchi. The observations indicate that enlargement of proximal acinar air spaces with some loss of interalveolar septa can develop in the absence of alveolar fenestrations. The persistnt nature of bronchiolar cell proliferations in such circumstances was also demonstrated. Two major toxicologic implications are (1) the production of permanent lung damage by much lower concentrations of pollutants than previously reported and (2) the apparent lack of additive or synergistic effects between oxidant gases and sulfur oxides.


Home monitoring of blood-glucose. Method for improving diabetic control. 64 diabetic patients measured their own blood-glucose concentration with "Dextrostix' (Ames) and an 'Eyetone' (Ames) meter. The records made at home by 53 of these patients have shown that this led to a significant improvement in blood-glucose control. A majority (64%) were able to maintain "good" control (80% of blood-glucose recordings equal to or less than 10 mmol/l for periods as long as 478 days). This hitherto unobtainable degree of control of blood-glucose was achieved mostly with conventional insulin regimens of twice-daily 'Actrapid' (Novo Laboratories Ltd.) and 'Leo-Retard' (Leo Laboratories Ltd.). Adjustments of insulin dosage and type were found to be much easier and more predictable than with urine-glucose analysis. No significant complications were encountered. Hypoglycaemic episodes were less frequent. 70% of patients preferred blood-tests to urine tests and 92% would like to buy their own meter "if the price was right." The results suggest that self-monitoring of blood-glucose by diabetics makes possible, for the first time, the achievement of near normoglycaemia. This may reduce the incidence of long-term diabetic complications.


Self-monitoring of blood-glucose. Improvement of diabetic control. An accurate pattern of blood-glucose changes in everyday life is the basis for treatment in insulin-dependent diabetes. 69 patients were taught to obtain their own blood-glucose profiles with a 'Reflomat' Boehringer Mannheim) reflectance meter on one working and one rest day, and to repeat these where necessary after adjustment of treatment. 2 did not complete the study satisfactorily. The other 67 produced profiles on 241 dyas. Even patients with a limited education could use the technique accurately and their readings correlated closely with simultaneous laboratory values (r = 0.96). Self-monitoring was especially useful in elucidating problems in diabetic control, preventing hypoglycaemia, and managing diabetic pregnancy. Unlike the measurement of HbA1c which only detects poor diabetic control, self-monitoring also shows how to improve it. Patients found self-monitoring more informative than urine tests; their active involvement in management of their disease resulted in better motivation, greater understanding of diabetes, and a sustained improvement in control. By the end of the study 32 of the 67 patients ahd profiles in which no more than one blood-glucose value exceeded 10 mmol/l. Smaller and more portable machines will make the technique more widely applicable.