[In-vitro studies with human transfer factor]. Human transfer factor was prepared from "buffy coat" of human donors by ultra filtration. These batches of transfer factor were tested for their ability to increase DNA-synthesis of antigen(mitogen) incubated lymphocytes. An increase of DNA-synthesis was measured by the ratio of appr. 2. Column chromatographic separation of transfer factor on sephadex G-10 or DEAE cellulose columns showed an elution pattern with many peaks. In the lymphoblastogenese assay some peaks were found to be stimulatory, others in contrast inhibitory. It seems likely from our results that transfer factor represents a mixture of different chemical compounds with activating or inhibitory action on lymphoblastogenesis.


Accumulation and elimination of dieldrin in muscle tissue of channel catfish. Dieldrin accumulation and elimination in muscle tissue of channel catfish (Ictalurus punctatus) from water and food was determined in the laboratory. Twenty-eight-day exposure of fish 150-225 mm and 350-400 mm long to 75 parts per trillion (ng/liter) dieldrin resulted in the larger catfish consistently accumulating more dieldrin than the smaller fish. After 28 days of elimination, dieldrin levels in both size groups were nearly equal. Catfish exposed to 2 ppm (mg/kg) dieldrin through their diets accumulated significantly more dieldrin in muscle than did fish exposed to 75 pptr in water. When fish were exposed to dieldrin both in food and water, dieldrin from both sources contributed to the total dieldrin load. Large catfish accumulated more dieldrin from food and water than did smaller catfish. After 28 days of elimination, levels of dieldrin were not significantly different in muscles of 150-225 mm and 350-440 mm catfish exposed via both food and water.


Liver cadmium levels in North Carolina residents who died of heart disease. Using data from an autopsy series, we found a strong positive correlation between liver concentration of cadmium and death from heart disease. In view of recent experiments reported in the literature, the possibility that a low level of cadmium has a toxic effect on the cardiac conduction system is supported.


Further toxicologic studies with commercial and candidate flame retardant chemicals. Part II. A number of commercial and candidate flame retardants were studied with regard to their toxicity to goldfish, inhibition of cholinesterase, inhibition of acetyl choline binding to its receptor and insecticidal properties. Several of the flame retardants were notably toxic to fish. Some of the compounds showed modest inhibition of cholinesterase and/or microsomal oxidases, but none inhibited acetyl choline receptor binding. Whereas several of the flame retardants showed little or no insecticidal properties when added alone to a housefly diet, piperonyl butoxide greatly synergised their toxicity to houseflies.


[Ventilatory and cardio-respiratory responses during exercise in chronic pulmonary restrictive disease (author's transl)]. Cardio-respiratory changes were studied during light exercise (20 or 40 W) in 45 patients with diminished vital total lung capacity. Diagnosis was : fibrosis (8 subjects, group I), lobectomy (7 subjects, group II), pachypleuritis (11 subjects, group III), thoracoplasty (7 subjects, group IV) and kyphoscoliosis (12 subjects, group V). Changes during exercise were characterized by : an increase in breathing rate much more marked than normally, with a lesser increase in tidal volume, so that ventilatory equivalent was steady, and below 30 except in group I; an increase in PaCO2, even in group I which was hypocapnic at rest, very marked in groups III and V, with worsening of hypoxemia in most cases; and enhancement of pulmonary artery hypertension, severe at rest already in group I.


Central haemodynamics during exercise in patients with restrictive pulmonary disease. Pulmonary precapillary hypertension present only during exercise is the first stage of corpulmonale. Examination of the reaction of central haemodynamics to exercise is the only way to detect it. In a model situation like unilateral pulmonary artery occlusion (UPAO) in healthy subjects, an increase in pulmonary artery pressure (Ppa) during exercise is a linear function of restriction of the pulmonary vascular bed and blood flow increase. Central haemodynamics during exercise in younger subjects after pneumonectomy (PNE) resemble the situation with UPAO provided the remaining lung is intact. In older patients after PNE the same rise of blood flow is associated with a considerably greater rise of Ppa. PNE patients compared to healthy individuals increase their cardiac output during exercise more by increasing stroke volume. Patients with pulmonary fibrosis show a disproportionate rise in Ppa in relation to flow. This is due to reduced distensibility of the pulmonary system. Hypoxia also seems to be involved in pulmonary hypertension during exercise. Pulmonary wedge pressure rises at work but remains within the normal range, even in patients having marked hypoxaemia at rest and during exercise. In idiopathic intersitial pulmonary fibrosis (IIPF), pulmonary hypertension during exercise is greater than in other forms of pulmonary fibrosis. Inhalation of oxygen during exercise in patients IIPF leads to a reversal of hypoxaemia but the decrease of Ppa is small and due to a passive decrease of cardiac output. Finally right ventricular function in restrictive pneumopathies is discussed.


Peripheral limiting factors during exercise in chronic lung diseases. In normal subjects the sensation of general fatigue subjectively limits the physical performance, whereas in patients with reduced respiratory function the sensation of breathlessness is the common limiting symptom. Patients with chronic obstructive lung disease may adopt an intermittent exercise pattern (e.g. when climibing stairs), in which the work periods are brief in duration but relatively high in intensity. The immediate ventilatory demand can in that way be reduced. The local metabolism of the working muscles can meet the increased demand, which demonstrates that peripheral factors are unlikely to limit the physical performance in these patients. For evaluating the importance of peripheral factors limiting the exercise tolerance of daily activities, such as stair-climbing or walking uphill, such activities should specifically be studied considerating also the exercise pattern shown by the patient. Even in bronchitic patients with reduced arterial oxygen tension there are no evidence that the skeletal muscles are working under more anaerobic conditions than in normal persons at the same relative work load. The blood lactate as related to the heart rate usually lies within normal limits. In patients with respiratory failure, however, lack of energy supply from the energy rich compounds may develop. Thus, only in extreme situations can the exercise performance of the respiratory patients be expected to be specifically limited by peripheral factors. Physical inactivity leads to changes in the muscle metabolism as in normal persons with reduced aerobic capacity in the muscles. The specific effects of steroid treatment on the muscle function in patients with chronic obstructive disease have not been studied, but may be an important factor limiting muscular performance at certain types of exercises.


[Adaptation of body plethysmography to the study of respiratory mechanics during muscular exercise (author's transl)]. A pressure-corrected integrated flow plethysmograph allowing the study of mechanical characteristics of the ventilatory system during muscular exercise is described. In order to limit the increase in temperature inside the body box during exercise, a forced convective flow passes through the box. Thermal exchanges induced by this flow have been studied. They are sufficient to allow muscular exercise during 15 minutes at a constant power of 100 W. It has been verified that this type of box allows measurement of the usual parameters of ventilatory mechanics: pulmonary volumes, compliance, resistance using the panting method. The measurement of resistance during spontaneous breathing inside the box is not possible.


Oxygen breathing during exercise in patients with diffuse interstitial fibrosis. 100% oxygen breathing during submaximal exercise in patients with diffuse interstitial lung disease diminishes cardiac output and pulmonary artery hypertension. The pressure drop in the pulmonary artery is most marked in patients with concomitant bronchial obstruction. At rest hyperoxia produced only minimal cardiopulmonary changes. The ventilatory and hemodynamic responses are discussed to find out if differences in these variables during oxygen breathing could be a reliable index for functional classification.


[Metabolic and respiratory parameters during muscular exercise in man (author's transl)]. Muscle can use ATP exclusively as the direct source of energy for contraction. The muscle ATP stores cannot provide more than 1 or 2 kcal of muscular work. tthe energy for resynthetizing ATP is supplied by three processes : the breakdown of creatine phosphate, anaerobic glycolysis and aerobic processes. These three mechanisms are characterized by different inertia, maximal output and capacity. Taking into account the part of aerobic processes in energy production, the physical fitness of an individual is usually expressed by its maximal oxygen uptake (VO2 max.). When the energy requirements cannot be met by aerobic reactions, the subject contracts an oxygen deficit which is compensated for during the recovery period by an oxygen uptake exceeding the rest requirements. During exercise tidal volume and ventilatory frequency are increased. The increase in ventilatory output is directly related to the workload until 75% of the maximal aerobic power is reached. For higher relative workloads the increase in ventilatory output is steeper. This increased ventilation allows the organism to limit the decreases in PaO2 and pH during exercises of high intensity.


The place of exercise testing in the investigation of patients with respiratory disorders. Exercise testing may yield important information in the clinical assessment of patients with a wide variety of conditions. An objective measure of exercise capacity is obtained; limiting factors are identified; the adaptive capacity of the heart and lungs is measured; diagnoses are confirmed or excluded. This paper argues the case for a series of exercise testing procedures which vary from simple ("stages I and II") to complex ("stages III and IV"), which allows exercise testing to be widely applied to clinical investigation and which reserves complex and invasive procedures for the clinical situations in which the information is necessary. Examples are presented to illustrate the relative value of the procedures and the information obtained from each.


Value of simple parameters during exercise in chronic obstructive lung disease. The value of simple physiological parameters as heart rate and peak expiratory flow rate, and bicycle ergometer, together with electrocardiogram is emphasized. Exercise capacity, exercise induced bronchoconstriction and/or electrocardiographic abnormalities are the conditions most important to look for. Recording tidal volume and respiratory air low might give additional information about disproportion between ventilatory "drive" and "performance".


[Therapeutic effects of physical training in patients with chronic respiratory insufficiency]. The therapeutic benefits of physical training for patients with chronic respiratory insufficiency must be assessed on the clinical, physiopathological and sociopsychological planes. As far as the clinical state is concerned, one observes a reduction of dyspnea and of the frequency of hospitalizations and an increase in the level of daily activity. On the physiopathological point of view, one observes an increase in the maximal capacity of exercise ranging from 1 to 33% resulting mostly from a better peripheral oxygen extraction. Pulmonary function is little modified on the spirographic level; however, one observes an improvement of blood gases at rest which seems to result from better alveolar ventilation. No systematic change in the circulatory variables is reported, except for a reduction of the PPA at rest. About the psychological factors, one observes a reduction of anxiety and an increase in motivation to perform muscular exercise. These results are difficult to obtain and often require a long rehabilitation. Socially, numerous obstacles are encountered to a social reinstatement : a relatively advanced age, a disadvantaged social environment, a low cultural level and an affectively weak surrounding. The solution to these different problems must be sought for each individual and the rehabilitation must be pursued continually; this often necessitates the hospitalization of the patient in a rehabilitation institute. On the basis of these studies, it seems certain that physical training is beneficial to patients with chronic respiratory insufficiency. However different programmes should be proposed for patients in an advanced or intial stage of their illness.


On the design and effectiveness of training regimes in chronic obstructive lung disease. Most patients with chronic obstructive lung disease (COLD) show a favourable response to progressive endurance training. Symptomatology is reduced and effort tolerance is extended. However, there is little change of pulmonary function scores. Possible explanations of the clinical gains include 1) psychological encouragement, 2) improvements of mechanical efficiency, 3) restoration of cardiovascular fitness, thus breaking a vicous circle of dyspnoea, inactivity and worsening dyspnoea, 4) strengthening of the body musculature, thus reducing the proportion of anaerobic work, 5) biochemical adaptations reducing glycolysis in the active tissues, and 6) indirect responses to such factors as group support, with advice on smoking habits, breathing patterns and bronchial hygiene. tdespite immediate gains of performance, there is no reason to believe exercise can restore destroyed pulmonary tissue. Further study is thus needed to test whether training can influence long-term prognosis in COLD.


Neurosyphilis.

Neurosyphilis. In the future it seems probable that cases of neurosyphilis will be seen sporadically by physicians and neurologists. As a result of the almost universal ingestion of antibiotics for trivial conditions, many cases of syphilis will be modified or arrested and some patients will be cured of the disease without ever knowing that they have acquired it. In others, developing neurosyphilis may be attenuated by inadequate chance treatment and the clinical and laboratory manifestations may become more subtle and difficult to recognize, leading to errors in diagnosis. Clinical experience of the varied manifestations of neurosyphilis has become less widespread among physicians and consequently greater care should be taken to ensure that the diagnosis is not missed.


The effects of non-steroidal anti-inflammatory drugs on cholinergic and histamine-induced contractions of guinea-pig isolated ileum. 1 Eleven non-steroidal anti-inflammatory drugs (NSAID) reversibly inhibited contractions of the longitudinal muscle of the guinea pig isolated ileum induced by acetylcholine, histamine, electrical transmural stimulation and nicotine in this order of increasing potency. 2. After the addition of prostaglandins E1, E2 or F2alpha, with partially effective concentrations of NSAID (but not with higher concentrations which almost totally prevented the responses) the inhibitory effects of NSAID were reversibly lost, except for electrically induced contractions and prostaglandin F2alpha. 3 The effects of NSAID may be due to actions on biological membranes or on distribution of ions in addition to their inhibitory effect on prostaglandin synthesis. Prostaglandins may reverse the inhibition by non-selective sensitization of smooth muscle to various agonists.


Tissue blood flow and distribution of cardiac output in cats: changes caused by intravenous infusions of histamine and histamine receptor agonists. 1 The effects of infusions of histamine on blood pressure, cardiac output, heart rate, total peripheral resistance, stroke volume and tissue blood flow have been determined in anaesthetized cats using radio-active microspheres to measure cardiac output and tissue blood flow.2 Histamine caused dose-dependent falls in blood pressure and total peripheral resistance over the dose-range 1 x 10(-8) to 3.3 x 10(-7) mol kg(-1) min(-1). Histamine had no effect on cardiac output, heart rate or stroke volume.3 Histamine caused vasodilatation in the heart and stomach, with increased blood flow through these organs, and in the small and large intestine where blood flow was maintained despite the falls in arterial blood pressure. Blood flow to the brain, kidneys, liver, adrenal glands, skeletal muscle, spleen and skin was reduced when arterial blood pressure fell. Vascular resistance increased in the skin and spleen, presumably due to reflex vasoconstriction when blood pressure fell.4 The selective H(1)-receptor agonist 2-(2-aminoethyl)pyridine lowered blood pressure and decreased total peripheral resistance but did not change cardiac output, heart rate or stroke volume. 2-(2-Aminoethyl)pyridine caused vasodilatation in the heart, small and large intestine and kidneys. Vascular resistance was increased in the spleen and skin.5 The selective H(2)-receptor agonist 4-methylhistamine also lowered blood pressure and decreased total peripheral resistance but did not change cardiac output, heart rate or stroke volume. 4-Methylhistamine caused vasodilatation in the heart, stomach, small and large intestines and skeletal muscle. Vascular resistance was increased in the skin.


The effect of sulphamethoxypyridazine on liver and plasma levels of vitamin A in rats. 1 Long-acting sulphonamides are highly bound to plasma proteins; the present study deals with the effects of this binding property upon a vitamin A compound also transported by plasma proteins. 2 Sulphamethoxypyridazine was administered in rats either orally or by intraperitoneal injection. 3 A significant fall in plasma vitamin A level and an increase in hepatic vitamin A concentration were observed. 4 These results suggest an interference by sulphamethoxypyridazine with the transport of vitamin A, either through competition between the drug and vitamin A for binding sites of plasma proteins, or through altered secretion of the vitamin from the liver.


An excitatory action of iontophoretically administered lithium on mammalian central neurones. 1 The action of iontophoretically administered lithium was studied on spinal Renshaw cells an interneurones and on supraspinal neurones in cerebral cortex, thalamus, hypothalamus and brain stem in anaesthetized cats and rats. 2 There was a correlation between the effects of Li+ and those of acetylcholine (ACh), although rather more cells were unaffected by Li+ than by ACh. 3 The usual effect was an excitation of rather slow onset, but occasionally effects were produced with time courses similar to those of ACh. The excitation was blocked by ACh antagonists and was best demonstrated with dihydro-beta-erythroidine on Renshaw cells. 4 The postsynaptic excitant action of ACh on Renshaw cells was reduced by Li+. 5 Depressant actions of Li+ were encountered on cells also depressed by ACh. 6 It is concluded that Li+ may facilitate cholinergic transmission at some sites in the CNS by increasing the release of ACh by an unknown mechanism. Similar effects at non-cholinergic synapses might also occur but would appear to be of less importance. Since facilitation of neuronal firing with Li+ was usually observed, the depressant effects on postsynaptic responses to ACh may be of little consequence.


Catechol-substituted phenoxypropanolamines: adrenoceptor activity in the anaesthetized cat. 1 The pharmacological actions of racemic noradrenaline, adrenaline, isoprenaline and N-t-butylnoradrenaline have been compared with those of their corresponding derivatives containing an oxymethylene (OXY) link between the ring and ethanolamine side chain. 2 The compounds were tested in the anaesthetized cat for their ability to produce positive chronotropic effects, bronchodilator actions, changes in perfusion pressure in the perfused hind limb and decreases in soleus muscle contractions. 3 All the OXY-derivatives were potent beta-adrenoceptor agonists. The inclusion of the oxymethylene link promotes selectivity for beta1-as opposed to beta2-adrenoceptor activity. 4 In comparison with the parent compounds, the OXY-derivatives of adrenaline and noradrenaline had very weak alpha-adrenoceptor stimulant effects.


Dissimilarity between the responses to adenosine triphosphate or its related compounds and non-adrenergic inhibitory nerve stimulation in the longitudinal smooth muscle of pig stomach. 1 Transmural electrical stimulation (TMS) of longitudinal smooth muscle strips taken from the cardiac portion of the pig stomach produced biphasic responses consisting of initial contractions followed by relaxations. The excitatory component was enhanced by neostigmine and abolished by atropine. After atropine treatment, TMS and nicotine or 1,1-dimethyl-4-phenyl-piperazinium, caused a relaxation or a relaxation followed by an after-contraction. All of these responses were abolished or reduced reversibly with tetrodotoxin and cocaine, while hexamethonium only abolished the response to ganglion-stimulating agents.2 The relaxation caused by TMS reached a maximum amplitude at 5-10 Hz, and was entirely resistant to the effects of alpha- and beta-adrenoceptor blocking agents, or a combination of them, and also to guanethidine. These results strongly suggested that the relaxation was elicited by stimulation of intramural non-adrenergic inhibitory neurones.3 In the presence of atropine and guanethidine, adenosine triphosphate (ATP, 5-20 muM) caused only a tonic contraction, and ATP (25-200 muM) or adenosine diphosphate (25-200 muM) produced a contractile response or a biphasic one (tonic contraction preceded by a slight relaxation). Adenosine monophosphate and adenosine caused only the tonic contraction over the range of concentrations (25-200 muM).4 Stimulation of the intramural inhibitory neurones of the tissue consistently evoked an inhibitory junction potential, which showed a summation during repetitive stimulation. One the other hand, ATP elicited mainly a small depolarization of a few mV.5 When the desensitization to ATP of the muscle was achieved in the presence of atropine and guanethidine, the relaxation induced by stimulation of the non-adrenergic inhibitory neurones could be evoked without any modification.6 Dipyridamole neither potentiated the inhibitory responses due to stimulation of the intramural inhibitory neurones nor showed any consistent effect on the ATP-induced response.7 From these results, it is unlikely that ATP, or any related compound, is the transmitter substance of the intramural inhibitory neurones in the longitudinal smooth muscle of the pig stomach.


An electrophysiological study of the action of crude Enhydrina schistosa venom. 1 Electrophysiological studies on the rat diaphragm revealed that crude Enhydrina schistosa venom has a blocking action on postjunctional acetylcholine (ach) receptors. 2 This venom in concentrations of 0.125-1.0 microgram/ml abolished the extracellular endplate potential (e.e.p.p.) without altering the presynaptic spike. When the phrenic nerve was stimulated at a frequency of 1 Hz the degree of depression of successive e.e.p.ps was approximately the same in records made before and after treatment with venom. 3 In concentrations of 0.25 and 0.5 microgram/ml the venom reduced significantly the amplitude of miniature endplate potentials (m.e.p.ps). The frequency of m.e.p.ps did not increase but was decreased when the amplitue of the m.e.p.ps was much reduced. 4 The crude venom did not alter the resting membrane potential (RMP) of the muscle cell. 5 The venom inhibited the depolarization of the muscle membrane caused by carbachol. 6 It is concluded that an active component in the crude venom is responsible for a blocking action on postjunctional receptors.


The effects of prostaglandin E1, bradykinin and histamine on canine synovial vascular permeability. 1 The relative effects of prostaglandin E1, bradykinin and histamine on canine synovial vascular permeability were investigated by a method based on the measurement of the amounts of radiolabelled dextran (molecular weight 20,000) leaking from the circulation into the synovial cavity. 2 Bradykinin, prostaglandin E1 and histamine in that order of potency all increased synovial vascular permeability. Threshold concentrations were 0.3 micrometer, 3 micrometer and 30 micrometer respectively. 3 The effects of infusion of prostaglandin E1 combined with either bradykinin or histamine were greater than mere summation.


A study of light-initiated currents in Limulus lateral eye retinular cells. Light-initiated currents in Limulus lateral eye retinular cells were studied using the voltage clamp technique. To assess the validity of such current measurements, the isopotentiality of retinular cells was determined on triply impaled cells and the effect of voltage clamping one retinular cell on adjacent retinular cells and on the eccentric cell in the same ommatidium was determined. The results of the experiments are: (1) retinular cells are isopotential at loci 100 micron apart; (2) appreciable steady state current during the clamping episodes leaks into neighboring retinular cells and the eccentric cell; (3) light-initiated currents exhibit two components; (4) there is a dynamic change in the resistance of the photoreceptor membrane during development of the receptor potential; (5) suppression of the rising phase (C1) of the receptor potential does not affect subsequent voltage changes; (6) suppression of the sodium influx which normally produces C1 has only minor effects on subsequent voltage changes; (7) reduced [KC1]out increases and increased [CK1]out decreases the reversal potential of light-initiated currents; and (8) reduced [NaC1]out reduces the magnitude and the reversal potential of light-initiated currents.


In vivo neurochemical analysis, by push-pull perfusion, of the mesocortical dopaminergic system of the rat during self-stimulation. The region immediately adjacent to a self-stimulation site in the medial prefrontal cortex of the unanesthetized rat was prelabeled with 0.5 mu Ci 14C-dopamine (DA) injected through an indwelling guide cannula. Then successive 5 min push-pull perfusions of the site with an artificial CSF were carried out at a rate of 25 microliter/min so that a washout curve of declining radioactivity was generated under control conditions. When square wave 100 Hz pulses were delivered to the contiguous self-stimulation site, the release of 14C-DA was enhanced either during the actual interval of electrical stimulation or in the perfusion sample collected immediately thereafter. In parallel experiments, however, self-stimulation by the rat of its ventral tegmental area failed to alter the kinetics of 14C-DA release from the cortex when homologous loci were perfused. Analyses by thin-layer chromatography of the perfusates for their content of catechol metabolities revealed that the homovanillic acid fraction declined during stimulation, whereas the level of DOPAC remained relatively elevated. Evidence was also obtained for the new synthesis and subsequent release of norepinephrine during the stimulation of the cortex of the rat. These results suggest that endogenous dopamine, because of the notable alterations in its release and metabolism, plays an important synaptic role in the mediation of self-stimulation behavior at the level of the cerebral cortex.


Behavioral effects of lesions of precommissural and postcommissural fornix. Lesions which sever different parts of precommissural or postcommissural fornix were compared to the effects of control lesions in several behavioral tasks. Spatial learning and avoidance was impaired by lesions of the descending columns, or by lesions which sever the precommissural communications passing to and from medial septum. Damage to precommissural fibers through lateral septum produced a measurable change only on the avoidance task. This pattern of deficits, considered together with the anatomical relationship of the system, suggests a model in which the medial septum relays kinesthetic information to dorsal hippocampus, which in turn serves as a memory system in the performance of spatial habits. It is less clear what kind of information is relayed by lateral septum, but it may communicate with ventral hippocampus regarding the consequences of punishment, and thus serve as part of a system for defensive suppression of behavior.


Effects of maternal dietary protein restriction on growth of the brain and body in the rat. We studied the growth of the brain and body in rats born of dams fed a low-protein (8% casein) diet ad lib beginning 5 weeks prior to mating and continuing throughout gestation and lactation. Control dams were fed an isocaloric 25% casein diet. Litters were culled at birth to 8 pups. At birth, brain weights and body weights of pups of protein restricted dams were similar to those of control pups. During the period of lactation, pups of restricted exhibited severely retarded body growth but only mildly retarded brain growth resulting in an elevated brain/body weight ratio. This relative macrocephaly was maximal at 10-20 days of age, declining completely by 35 days of age. The relative macrocephaly could not be accounted for by increased retention of water in the brain of the malnourished rats. Following weaning, pups were maintained ad lib on the diets fed their mothers. At adulthood brain/body weight ratios were normal in the protein restricted group.


[14 C]2-Deoxyglucose uptake marks systems activated by rewarding brain stimulation. Autoradiography of sections from the brains of anesthetized rats injected with [14C] 2-doexyglucose revealed neural systems unilaterally activated by rewarding electrical stimulation of the medial forebrain bundle. Since this new technique marks neural systems on the basis of their activity, it has great potential in functional neuroanatomy. The potential is easily realized in brain-stimulation studies, where systems may be driven to exceptionally high levels of activity.


Effects of hypothalamic and preoptic lesions on reproductive behavior in male rats. Adult male rats, which were selected on the basis of showing complete patterns of male copulatory behavior on two prior tests, were castrated six weeks prior to brain surgery. Animals were divided into three groups and given small bilateral lesions in the dorsomedial preoptic area (POA), ventromedial hypothalamus (VMH), or sham operations. Starting 10 days postsurgery, all animals were injected with estrogen alone and estrogen plus progesterone, and tested twice for lordosis behavior. Ten days following the female behavior tests, animals were injected daily with testosterone propionate for 13 days and tested for masculine sexual behavior on injection 5, 9 and 13. Low levels of lordotic behavior were observed for POA and VMH animals on both tests for female sex behavior and were comparable to sham operated animals. However, in terms of all dependent measures of male copulatory behavior, animals with VMH lesions showed significantly higher levels of male sex behavior with shorter latencies than sham animals across all three behavior tests. In contrast, POA lesioned rats showed little or no male sex behavior on any test and were significantly inferior to sham operated animals. Thus, the POA and VMH appear to exert excitatory and inhibitory control, respectively, over male copulatory behavior in male rats.


Effects of stressful procedures as ether anesthesia and intracranial injections on amino acid incorporation into brain protein. Ether anesthesia elevates plasma corticosterone levels considerably and interferes severely with the incorporation of centrally applied [3 H] leucine into brain protein. Only minor changes in leucine incorporation are observed in conscious rats with an implanted cannula in the third brain ventricle as compared to noncannulated controls. Injection through this cannula can be regarded as a minor stressful procedure comparable to subcutaneous injection both causing moderate elevations in plasma corticosterone levels. Injection through the cannula per se did not affect the leucine incorporation. In studies which require local application of the radioactive precursor, it is therefore recommended to avoid ether anesthesia and to use a preimplanted cannula in the brain ventricular system.


Reciprocal thalamo-hippocampal EEG augmenting and muscle responses in rabbits. Waxing and waning electrographic responses (augmenting) and primary evoked responses could be induced in restricted regions of hippocampus, thalamus, and skeletal muscle by bipolar, low-frequency (7-10 Hz), low-amplitude (35 mV-4V) stimulation of selected sites within the hippocampus or thalamus of rabbits. Induction of the immobility reflex (IR) (animal hypnosis) lowered the threshold and increased the amplitude of both kinds of responses. An additive enhancement of both kinds of responses was often produced by concurrent treatment with a tranquilizer and the immobility reflex. These results suggest the thalamus and the hippocampus have interacting modulating mechanisms which affect motor activity.


Hippocampal theta rhythm persists in the permanently isolated forebrain of the cat. In cats with high mesencephalic transections surviving for up to 90 days, the hippocampal EEG shows exaggerated percentages of 3-5 Hz theta activity. The theta rhythm has similar waveform and frequency characteristics to that seen in the intact cat and can be selectively enhanced or abolished by systemic physostigmine or atropine respectively. These data demonstrate (1) that the caudal brainstem is not essential for the spontaneous appearance of the hippocampal theta rhythm, and (2) the integrity of a major cholinergic system in the chronically isolated forebrain.


A method for x-irradiating selected brain regions in infant rats. A technique for immobilizing rat pups and irradiating selected regions of the head is described. As an example, measurements are given for the focal irradiation of the hippocampus. If animals of nearly the same weight are selected, several pups of the same age can be irradiated simultaneously.


C-21- and 6-hydroxylation of progesterone by rabbit liver subcellular fractions. In vitro C-21-hydroxylation of [3H]progesterone (P) has been demonstrated for the first time with rabbit liver microsomes and mitochondria. Deoxycorticosterone (DOC) was rigorously characterized as a metabolite of both mitochondrial and microsomal metabolism, whereas 6alpha-hydroxy DOC and 6alpha-hydroxy P were only identified as microsomal metabolites. 6beta-Hydroxy metabolites were also detected but were of less quantitative significance. Formation of 6alpha-hydroxy P and 6alpha-hydroxy DOC increased steadily between 5 and 120 min of incubation with the microsomal fraction, whereas DOC increased up to 30 min of incubation and then declined. Maximal yield of DOC was 25.9 and 22.5 pmol/mg protein with the mitochondrial and microsomal fractions, respectively.


The solution synthesis of sequential polypeptides as models for the double-stranded coiled-coil structure of tropomyosin. The syntheses of the three sequential polyheptapeptides [L-Leu-L-Glu-L-Ser-L-Leu-L-Glu-L-Ser-L-Lys)n, [L-Ala-L-Glu-L-Ser-L-Ala-L-Glu-L-Ser-L-Lys]n, [L-Ala-L-Glu-L-Ser-L-Leu-L-Glu-L-Ser-L-Lys]n and of the polytetrapeptide [L-Leu-L-Glu-L-Ser-L-Lys]n by solution methods are described. The syntheses were performed using a combination of a modified mixed carbonic anhydride method and an active ester coupling method. The N-hydroxysuccinimide ester was used as the active group for the polymerization of the monomers. These compounds were prepared as model polypeptides for the coiled-coil structure of tropomyosin.


Pars plana vitrectomy.

Pars plana vitrectomy. We describe our first 127 vitrectomies through the pars plana performed on 120 eyes for a variety of indications. The success rate in anterior segment disorders was 45% and in those of the posterior segment 34%. While in some cases the results were encouraging, in others they were disastrous. Some 12 eyes (10%) went on to lose perception of light.


The natural history of non-disciform ocular histoplasmosis. Nineteen of 21 asymptomatic individuals with non-disciform atrophic chorioretinal scars characteristics of the ocular histoplasmosis syndrome and identified in the Walkersville survey were re-examined three years later. During this period, of six subjects with peripapillary scars, one developed symptomatic serous detachment of the peripapillary retina; none of the three with macular or paramacular scars showed any change. Several peripheral scars showed increased pigmentation and others definite enlargement. One patient developed two new atrophic scars.


An eye screening program in a Chinese-Canadian community. A screening program staffed by ophthalmologists, ophthalmology residents, ophthalmic assistants, social workers and Chinese-speaking volunteers and directed at a Chinese immigrant community, was conducted at the Mount Sinai Hospital, Toronto. The Chinese population had been hesitant to use our hospital facilities and we hoped to overcome their fears, as well as to detect previously undiagnosed ocular problems. The program succeeded in finding many eye problems, some serious, and in encouraging this immigrant group to come for proper medical care. We describe the method of setting up and conducting such an undertaking, which involved the Departments of Ophthalmology and Social work, hospital administrators and volunteers from the community.


The presence of cell-mediated immunity in uveitis. We have attempted to demonstrate cell mediated immunity in cases of uveitis. We tested blood samples of patients for leucocyte migration inhibition (LMI) and lymphocyte transformation (LT). The gel diffusion test was used to detect humoral antibody. Allogeneic uveal, retinal and corneal antigens were prepared for the tests from eye bank eyes. The LMI and LT tests gave positive results in 9 out of 16 cases. In these 9 cases 8 were positive to retinal antigen, three with corneal antigen and only one was positive against uveal antigen. Humoral antibodies were not detected. We suggest that cell mediated autoimmunity is present but the relationship of this to the uveitis itself is obscure.


Increased scatter of responses as a precursor of visual field changes in glaucoma. A patient with ocular hypertension developed a glaucomatous field defect in the right eye 10 years after the initial examination. For several years preceding the appearance of the defect there had been scatter of threshold responses localized to the area where the defect was later found. We suggest that localized scatter may be an early sign of glaucomatous damage to visual function.


Anophthalmos. Report of two cases.

Anophthalmos. Report of two cases. Two infants were found to have bilateral anophthalmos and other congenital anomalies. Secondary anophthalmia was diagnosed in one patient who showed malformations of the brain and an absence of ocular tissues including the optic nerves. The other patient had degenerative (consecutive) anophthalmos; fragments of ocular tissues including the optic nerves were found in the orbits.


The visual field in indirect traumatic rupture of the choroid. Nine cases of indirect rupture of the choroid due to trauma were examined by indirect ophthalmoscopy, fluorescein angiography and static and kinetic perimetry. Our results indicate that the visual field defect cannot be correlated with the ophthalmoscopic picture as concerns shape, size, or location of the lesion. Seven of the 9 cases had a central scotoma and we demonstrated nerve involvement in 4 of the 9 cases. We do not know of other studies of the visual field in indirect traumatic rupture of the choroid.


Quality of care in hospital emergency departments and family physicians' offices. Indicator conditions were used to evaluate the quality of 686 episodes of care provided in two emergency departments and in five family physicians' offices. Overall, the care was considered adequate in 53% of the emergency department cases and in 40% of the cases dealt with in family physicians' offices, the difference being significant (P less than 0.01). Referrals were very common in both settings, and when quality was assessed solely on the basis of the care actually given by the primary-care providers the difference between the two settings disappeared. Half the observed deficiencies in care related to failure to document the findings from history-taking and physical examination. From these and earlier findings we conclude that the emergency department can be an appropriate setting for the care of nontraumatic illness.


Imported diseases: an assessment of trends. Increasing travel, migration and other forms of international exchange have given a new importance to imported diseases in Canada. This is reflected in the maintenance of an immigration medical screening program, the development of specialized clinics in major cities, increasing interest in tropical medicine and international health, and the designation of a national reference centre for parasitology.The introduction of a point system for immigration selection in 1967 gave rise to a burgeoning influx of people from developing countries that may have plateaued only within the past year. While tuberculosis is probably the single most important health problem in immigration, parasitic infections are of increasing concern. The popularity of overseas travel among Canadians is now also a major factor in the introduction of exotic diseases into Canada. Importation of disease by international trade is far less common than by travel and immigration.On a community health scale a system of monitoring trends of immigration to Canada and travel of Canadians to and from countries with a known risk would likely provide the best indicator of trends in disease importation. Thus, there was an increase of almost threefold (11.6% to 31.1%) between 1965 and 1975 in the proportion of immigration to Canada from countries with a malaria risk and a 2.78-fold increase between 1967 and 1974 in the overall amount of Canadian travel to such countries from which statistics were available.


Retinal detachment following hockey injury. Thirty-three cases of retinal detachment following hockey injury were seen during a 15-year period at the retina clinic of Maisonneuve-Rosemont Hospital, Montreal. Most injuries occurred in adolescents, the average age being 18 years. The mean interval between injury and preoperative examination was 3 years. Almost half of these young hockey players remained legally blind in the affected eye even after a successful operation. A helmet with a protective face visor is suggested as the best prevention against severe ocular damage such as retinal detachment.


Resuscitation from cardiopulmonary arrest during accidental hypothermia due to exhaustion and exposure. A 16-year-old boy with accidental hypothermia and cardiopulmonary arrest due to exhaustion and exposure was resuscitated after warming measures -- hot wet towels, hot water bottles, and hot water enemas and gastric lavage -- had increased his rectal temperature from 25.2 to 28.0 degrees C. Despite prolonged cardiopulmonary arrest, recovery was almost complete, with no evident cerebral damage. Cardiopulmonary resuscitation procedures should not be abandoned until the body temperature is more than 30 degrees C, because the prognosis in cases of accidental hypothermia without associated disease is excellent if cardiac function can be re-established.


[Percutaneous transheptic cholangiography with the skinny Chiba needle]. In 40 patients percutaneous transhepatic cholangiography was performed by means of the "skinny" Chiba needle. The intrahepatic bile ducts were visualized in 100% of the patients with dilated ducts and in 67% of those with ducts of normal calibre. The results compare to those in the literature and demonstrate the usefulness as well as the reduced morbidity of this new procedure. Therefore nonvisualization of the intrahepatic bile ducts by this method signifies that the ducts are not dilated.


Psychiatry and the dangerous sexual offender. A study of Dangerous Sexual Offenders, undertaken for the Canadian Law Reform Commission, reveals that about one-third of DSOs seriously threatened or actually endangered the life of the victim. One-third were moderately assaultive. The remainder, mostly homosexual pedophiles, were offensive but not physically violent. The role of psychiatrists, employed by the Crown in the process of securing an indeterminate sentence, is described. Most of them did not declare their role as "double-agents". Their expert testimony before the Courts also revealed a failure to discriminate between fact and opinion. Individual prejudice was, not infrequently, presented as the wisdom of the psychiatric profession. The life of DSOs in Canadian penitentiaries, is likely to be exceedingly brutal. Four of them have been murdured while in custody. Others have killed themselves or made determined attempts to do so. Since it is obviously unethical for psychiatrists to participate in any procedure which is likely to result in harm or the death of an individual, the author urges the Canadian Psychiatric Association to support the Law Reform Commissions' condemnation of the DSO legislation. As an interim measure psychiatrists should be urged not to collaborate in DSO cases.


Police negotiations. A new role for the community psychiatrist. This paper reviews the type of individual who might be involved in a hostage situation and police negotations. It singles out those clinical characteristics which are important in determining the management of the negotiations, and in doing so adds a plea for psychiatrists to become involved in an advisory role. By pointing out the need for psychiatrists and police to review some of the problems and determine a common approach before the situations arise, an additional characteristic is added to the role description of the community psychiatrist.


A high prevalence of affective disorder discovered in a "schizophrenia clinic". Fifty outpatients in a "schizophrenia clinic" were examined, and sixteen were found to be suffering from periodic affective disorders. Nine of these were given lithium carbonate, and eight responded well. Case histories illustrate three separate reasons for incorrect diagnosis. Examination of extensive old clinical notes of five of these patients suggests that the problems of diagnosis which have been described in the literature in the past, continue to represent obstacles to correct diagnosis. Suggestions for improvement are offered.


The value of breast screening in women less than fifty years of age. In the four years our Breast Cancer Detection Demonstration Project has been receiving patients, 5,810 women under the age of fifty have been examined. Our findings definitely indicate screening of asymptomatic women by xeromammography is of advantage in this group whose greatest cause of death is cancer of the breast; 71.8% of their cancers were found by xeromammography. Of these 43.8% had in situ cancer and only 12.5% of those cancers found had axillary spread. This group should have a five-year cure rate of 87.1% rather than 63% as is the experience of unscreened women. The absorbed rads averaged 0.4632 to each breast per year. At the end of five years this would cause an estimated increase in risk from 7% to 7.162%. To increase survival rate by 24.1% against a theoretical increased risk of 0.16% is definitely worthwhile.


Radiation management of primary carcinoma of the vagina. This 15-year retrospective study includes 71 patients with diagnosis of primary carcinoma of the vagina treated at the University of Maryland Hospital, Radiation Therapy section from 1957 to 1970. The lesions were staged according to the system advocated by International Federation of Gynecology and Obstetrics (FIGO) with a minor modification (Perez et al.11). With the exception of Stage O, histologic diagnosis was 94% (60/64) invasive squamous cell carcinoma and 6.0% (4/64) adenocarcinoma. Of 71 cases who are eligible for a minimum five-year follow-up, the absolute five-year cure rate for various clinical stages is as follows: Stage O 100% (7/7), Stage 1 83.2% (5/6), Stage 11A 65% (13/20), Stage 11B 63.5% (7/11), Stage 111 40% (8/20), Stage IV 0% (0/7). The overall absolute five-year cure-rate for all stages combined was 56.3% (40/71). A comparable result and even better in some stages (II and III) as compared to several previous reports are thought to be due to the proper intergrated irradiation combining interstitial and intracavitary radium with external super-voltage beam. Furthermore, an aggressive radium implant to the vagina, paracolpium, and specifically to parametrium and pelvic wall in Stage II and III appears to be one of the keys to our good results. The technique of treatment, stage by stage, are being fully discussed along with a few complications and failures.


Adenosquamous carcinoma of the endometrium. An entity with an inherent poor prognosis? Mixed adenosquamous carcinoma of the endometrium have been reported in recent years to have a steady increase in incidence, extreme aggressiveness, poor responses to radiation therapy, and a low five-year survival (less than 20%). In the present report, 87 mixed carcinoma (MC) are compared with 260 pure adenocarcinomas (AC) and 29 adenoacanthomas (AA). There were no basic differences in incidence, clinical history, responses to radiation therapy, and prognosis for any of these three entities. Adenocarcinomas of the endometrium with and without squamous elements should be regarded and approached as any pure AC. There is an overall tendency for endometrial carcinomas to be at an early stage at diagnosis and the five-year survival regardless of pathologic type, stage, grade, myometrial invasion, and therapy is 80%.


Treatment failure sites according to irradiation technique and histology in patients with endometrial cancer. Three hundred and seventy-two patients with endometrial cancer treated from 1948 through 1969 and having complete follow-up were reviewed. All patients completed definitive therapy with preoperative irradiation and surgery or irradiation alone and have separated into two main groups: 1) those treated with irradiation by radium alone or 2) those treated with external irradiation plus diminished amounts of radium. Pathology material from each patient was reviewed by one pathologist. Treatment by radium alone led to fewer pelvic failures than did external irradiation plus diminished amounts of radium, when evaluated by stage, grade, and specific histology. Both irradiation modalities led to about the same incidence of failures due to distant metastasis only.


An analysis of distant metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. The charts of 5,019 previously untreated patients with squamous cell carcinoma of the upper respiratory and digestive tracts who completed treatment for cure from January 1948 through August 1973, were reviewed. These patients had no evidence of distant metastases when initially evaluated. Five hundred and forty-six patients developed clinical evidence of distant metastases. The overall incidence of distant metastases was 10.9%, varying from 3.1% for vocal cord cancers to 28.1% for cancer of the nasopharynx. The lungs and bones were the most common first sites of metastases, accounting for 52% and 20.3% respectively, whereas metastases to the mediastinum (2.9%) were rare. Forty-eight percent of the metastases were detected within nine months after treatment and 80% were detected within two years. The rate of distant metastases increased with the stage (2% for Stage I to 19.5% for Stage IV). The rate also increased with the T and N classification; however, the N stage had greater influence on the rate of metastases than the T stage. The incidence of distant metastases was significantly higher when there was a recurrence above the clavicles (16.7%) than when there was no recurrence (7.9%, less than 0.001). In patients whose primary lesion was treated by radiotherapy or surgery alone, the incidence was essentialy the same. Patients receiving postoperative irradiation had double the incidence of the preoperative group (20.1% vs 9.9%--p less than .005); however, the sequence of modalities was not randomized.


Local tumor hyperthermia in combination with radiation therapy. 1. Malignant cutaneous lesions. There is increasing evidence that the use of hyperthermia alone or in conjunction with other modalities may improve the therapeutic effectiveness of treatment of cancer. The present clinical studies were carried out to evaluate the response of normal and tumor tissues in patients with various cutaneous malignant lesions to repeated courses of hyperthermia alone or in conjunction with radiation therapy. Thirty-six patients with malignant cutaneous lesions (mycosis fungoides, Kaposi sarcoma, malignant melanoma, lymphoma cutis, and other metastatic skin lesions) have been studied. The heating methods used were: 1) temperature regulated water bath immersion; and 2) radiofrequency inductive heating. The normal tissue effects of the combined treatments of radiation and hyperthermia do not appear to be greater than those treated with radiation alone. The initial tumor regression rates were faster in patients treated with radiation plus hyperthermia than in radiation alone, particularly in patients with Kaposi sarcoma and lymphoma cutis. Among ten locally recurrent patients, seven showed significant prolonged benefits achieved by the combined treatments as compared with the radiation therapy alone. Fractionated hyperthermia alone caused significant tumor regression in four out of five patients. Possible mechanisms leading to the improved results from the combined treatments are discussed.


Emotional reactions to radiation treatment. Fifty patients sent to the Radiotherapy Service of the Mount Sinai Medical Center of New York City were interviewed by a psychiatrist. The focus of the initial interview was what they were told when referred for radiation. Although 60% were told by their doctors they had cancer, all arrived at the treatment center unprepared for the frequency, number, and procedure of treatment and for the efficacy of treatment by radiation. Patients believed that requiring radiation was very bad news. Radiation was feared as inherently damaging and quite possibly carcinogenic. Few expected it to be curative. Interviews after completing treatment revealed an incidence of depression and anxiety even greater than in the pre-treatment interviews, indicating that radiation treatment is stressful in itself. Fewer than one-third judged themselves improved by radiation. More than one-third felt worse and judged treatment to have been ineffective, not realizing their new distress resulted from side effects of radiation. Patients suffer irrational fears of damage and death because of erroneous preconceptions of radiation which doctors fail to correct. Ironically, the lay and medical concepts of the dismal manifestations and futility of radiation treatment are entirely false. In this series, only one patient suffered damage due to radiation. Sixty percent were free of signs of cancer at follow-up 18-36 months later.


Radioiodine I-31 therapy in the management of thyroid cancer. A prospective study. The therapeutic value of I-131 ablation therapy following thyroidectomy for thyroid cancer was evaluated in 54 patients in a prospective study of 25 years. Thirteen (24%) patients had follicular, 24 (44%) papillary, 13 (24%) mixed papillary-follicular, two (4%) Hurthle cell and two (4%) had undifferentiated cell type tumor. Twenty-four (44.5%) patients had metastases at the time of I-131 therapy mainly to cervical and mediastinal lymph nodes, and less frequently to bone, brain, lung, and liver. After surgical thyroidectomy, the mean cumulative dose of I-131 required to achieve therapeutic ablation of functioning post-surgical remnants or tumor metastases was 163.4 mCi. The recurrence rate for patients with metastases was 56% and those without metastases was 25%. Ten patients showed recurrence of I-131 accumulating tissue five to 10 years after initial total ablation. The total mean cumulative dose of I-131 administered for both followup diagnostic studies, and initial and follow-up therapy was 245.3 mCi. Seven deaths were attributable to thyroid cancer, five with differentiated and two with anaplastic cell type tumors. Three of the four patients with differentiated cell type tumors had metastases to brain or bone. Their response to therapy was similar to those patients with anaplastic cell type tumors. In contrast, there were no deaths due to thyroid cancer when total ablation was achieved and maintained. After ablation, all patients were maintained on maximum tolerated doses of thyroid extract or thyroxin. No significant complications attributable to the therapeutic doses of I-131 employed in this series were noted.


Placental proteins and their subunits as tumor markers in prostatic carcinoma. Sixteen patients with Stage D adenocarcinoma of the prostate were prospectively evaluated for the presence of human placental lactogen (hPL), placental alkaline phosphatase (PAP), and human chorionic gonadotropin (hCG). Ectopic production of hCG was found in one of the 16 cases and is described in detail. Serial serum hCG levels in that patient mirrored his course more reliably than concomitant acid phosphatase levels. Serum estradiol, testosterone, the hCG-alpha subunit, hPL and PAP were not elevated. There was a minimal elevation of serum FSH. There were no elevations of the other placental proteins in ten evaluable cases. A retrospective evaluation of serum bank specimens from 47 patients with prostatic carcinoma revealed no elevation of the placental proteins hPL, hCG-beta, and hCG-alpha. To our knowledge this report documents the first case of a chorionic gonadotropin-producing prostatic carcinoma appearing the literature.


Spindle and epithelioid cell nevi in children and adults. A review of 211 cases of the Spitz nevus. A large series of 211 Spitz nevi is reviewed. 30% of the lesions were from patients 20 years of age and over. The trunk and lower extremity were most commonly involved. There were no significant histologic differences between cases from adults and children. Features which may help in differentiating atypical Spitz nevi from malignant melanoma include the presence of some nevus cell maturity at the base, an absence of atypical mitoses, no significant upward epidermal spread and the nuclear chromatin pattern.


Vaccinia necrosum complicating immunoblastic sarcoma. A 59-year-old man is presented who had immunoblastic lymphadenopathy which evolved over a three-year period into immunoblastic sarcoma. His course was complicated by vaccinia necrosum, which necessitated prolonged therapy with Marboran and vaccinia-immune globulin. The persistence of virus was documented at autopsy by positive viral culture and ultra-structural examination. This case illustrates the potential hazards of administration of live viral vaccines to an immune compromised host presumed to be in remission and suggests that the continued activity of viral infection may signal the unsuspected persistence of underlying disease.


Central nervous system infections in patients with cancer. Changing patterns. Central nervous system infections in patients with cancer at Memorial Sloan-Kettering Cancer Center from 1971 to 1974 were surveyed and compared with a previous survey from 1955 to 1970. The two periods were similar in that: 1) There was a high incidence of CNS infection in patients with lymphoma, leukemia, and head and spine tumors, 2) specific organisms tended to infect patients with certain primary neoplasms, and 3) fungal infections were common and difficult to diagnose. The two periods differed in that: 1) the overall incidence of CNS infection was lower in 1971 to 1974, 2) there was a decreased  incidence of cryptococcal meningitis, and 3) there was an increase in Listeria monocytogenes meningitis. Early recognition of CNS infection and aggressive therapy appears to increase survival.


Pheochromocytoma with angiomatous features. A case report and ultrastructural study. A functional pheochromocytoma of the adrenal gland but with an angiomatous histologic pattern was studied by light and electron microscopy. Although this tumor had typical clinical and gross anatomic features, its light microscopic appearance was unique and, to our knowledge, has not been previously described. Fine structural study provided insight into the intracellular pathways of catecholamine granule formation.


Ultrastructure and biochemistry of thyroid carcinoma. Thirty-two thyroid tumors, 9 benign, 23 malignant, and 12 samples of normal thyroid tissue were examined by light and electron microscopy. Thyroglobulin content was also measured in the tissues and, in a limited number of cases, enzymatic activities were determined, such as thyroid peroxidase-iodinase, acid protease, and deiodinase. The presence of significant amounts of 19S, 27S and 12S thyroglobulin was well correlated with the ability of the tumors to accumulate radioiodine. It is suggested that the presence of thyroglobulin be used as a marker of potential function of thyroid carcinoma. Two types of ultrastructural changes were observed in thyroid carcinoma. The first one was interpreted as accompanying the progressive loss of function of thyroid tumors, and was represented by the modifications of highly specialized structures such as RER, lysosomal dense bodies, colloid, etc. The second one is suspected to reflect the malignant transformation of the follicular cell. This concerned namely the nuclei, mitochondria, and intracytoplasmic inclusions. These changes may have a diagnostic value since they were not observed in benign conditions.


Prolonged survival after immunotherapy (irradiated cancer autografts) or mammary cancers, assessed by a measure of therapeutic deficiency. Sixteen women, twelve with stage 2 and four with stage 3 mammary cancers, were given autografts of irradiated cancer cells immediately after simple mastectomy and before postoperative radiotherapy, as a pilot trial with entry limited for ethical and operational reasons. Entry was based upon the presence of the poor prognostic features of tumor diameter exceeding 4 cm, fixation to skin or fascia or presence of axillary lymph nodal metastases. Actuarial survival curves for a period of six years show significant (p less than 0.01) prolongation of survival of the small autografted group (63% at six years) compared to that (30% at six years) of 139 ungrafted stage 2 mammary cancer patients treated by mastectomy and postoperative radiotherapy. The concept of deficiency of a treatment based upon person-years lived is introduced and used to analyze the data. The observations and analyses support the theoretical concept that irradiated autografts of cancers may sensitise residual cancer to subsequent conventional radiotherapy and in the process can activate systemic immunological restraints.


Focal myositis.

Focal myositis. Focal myositis, a new distinct clinicopathologic entity, is a benign inflammatory pseudotumor of skeletal muscle. Based on a study of 16 cases, the disease which affects both children and adults typically evolves over a period of several weeks as a localized painful swelling within the soft tissue of an extremity. At surgery the lesion is frequently considered a neoplasm, appearing pale in color and poorly demarcated from the surrounding muscle. Histologically there is lymphocytic infiltration of the perimysial and endomysial spaces, scattered muscle fiber necrosis and regeneration, and interstitial fibrosis. The etiology is unknown, but a history of trauma or family background of a similar disease was specifically excluded. Although polymyositis may be suspected initially because of muscle pain and inflammation, the process remains confined to a single area and signs of systemic disease are not encountered. Follow-up information obtained 2--6 years after surgery indicates no recurrence of the lesion in any of 16 cases.


Some observations concerning the demographic and geographic incidence of carcinoma of the lip and buccal cavity. The geographic and demographic data obtained during the Third National Cancer Survey have provided a perspective on etiologic factors and incidence trends for cancers of low frequency. The incidence of cancer of the lip, oral cavity and skin from this survey was compared to similar studies in 1947 and intra-regional patterns in one area of the Third National Cancer Survey (Dallas-Fort Worth Metropolitan SMSA) were evaluated. The average age-adjusted annual incidence of cancer of the lip in white men in this latter area was 11.5 per 100,000 (based on 1950 population standard), 2-fold greater than that geographic area with the second highest incidence and approximately 3-fold greater than in all the other areas. The incidence in white women was only 8% that seen in white men. Intra-regional differences of similar populations were seen with the incidence in Fort Worth men being 50% greater than in a similar population in Dallas. Incidence trends over the past 2 decades reveal a significant decline in the incidence of oral cavity cancer and a slight decrease in lip cancer. Comparisons of the incidence of lip cancer did not correlate with the incidence of skin cancer nor with geographic latitude in the other survey areas. The studies fail to support the classical implication of actinic radiation as the primary etiologic factor in lip cancer incidence.


The increasing incidence of breast cancer in Alberta 1953-1973. The incidence of female breast cancer in Alberta increased steadily by one case per 100,000 per year from 1953 to 1973 to a current rate of 68.6 per year when adjusted to the 1950 U.S. population. Incidence rates of breast cancer in Alberta and Saskatchewan were identical after population adjustment. The incidence increased in women over 40, implicating an increase in the postmenopausal type of breast cancer. Birth cohort analysis showed increased age-specific incidence rates in middle-aged women occurring in successive cohorts from 1903 to 1918, a result similar to that found in Saskatchewan, Connecticut, and Finland. The menopausal hook is disappearing in Alberta data, apparently due to cohort-specific increases in incidence. Possible etiological factors involved in these incidence changes are discussed; a detailed analysis of specific etiological factors is currently underway on over 3,000 patients with malignant or benign breast disease who were examined at the Dr. W. W. Cross Cancer Institute in Edmonton from 1971 to 1974.


Progress in manual breast examination.

Progress in manual breast examination. Manual breast examination, despite recent advances in mechanical screening devices, remains a primary diagnostic procedure for early detection of breast cancer. The potential effectiveness of breast self-examination for reducing mortality relies on the effectiveness of a technology for training women to detect small tumors through manual palpation. Research indicates that although the regular practice of breast self-examination can lead to the detection of small tumors, current training methods are inadequate to ensure proper performance and maintain regular practice. An alternative interdisciplinary research and training approach, involving medicine, biomaterials engineering, psychophysics, and experimental psychology, is suggested. A dynamic lifelike breast model with variable lumps would provide the basis for generating systematic data regarding the factors affecting detection of small lumps and lead to development and evaluation of efficient and effective methods to teach manual examination.


Retrograde lymphatic spread and ischemia of the forearm and hand--rare complications of carcinoma of the breast. A case of ischemia of the forearm and hand with resulting necrosis three years following simple mastectomy and radiation therapy for breast carcinoma is reported. Histologic sections of the mid-forearm amputation specimen showed extensive lymphatic involvement by tumor. The latter process is judged to have been one of retrograde lymphatic extension.


Clinical and prognostic features of a rapidly progressing breast cancer in Tunisia. Clinical and radiographic examination of 581 patients with histologically verified breast cancer has permitted us to define a subgroup having a significantly poorer prognosis than other patients. Their condition, called "poussée évolutive" (rapidly progressing), is characterized by rapid tumor growth and/or inflammation adjacent to the tumor. Statistical analysis of the survival of M0 patients (412 of the 581) shows that the diagnosis of "poussée évolutive" provides prognostic information beyond that given by T and N classifications and after delay between initial symptoms and diagnosis have been considered. Six years of clinical experience with this condition are discussed.


Rhabdomyosarcoma of lung arising in congenital cystic adenomatoid malformation. An asymptomatic congenital cystic adenomatoid malformation of lung discovered at age 18 months, and unchanging for 14 months prior to its removal, was found to harbor a small embryonal rhabdomyosarcoma following excision. With lobectomy and chemotherapy, the tumor-free interval has now exceeded three years. The case represents a well-documented occurrence of malignant tumor arising within a congenital malformation, an association that is unlikely to be the result of chance.


Prognosis in malignant melanoma of the skin. Significance of stage of disease, anatomical site, sex, age and period of diagnosis. The prognosis in malignant melanoma of the skin has been studied in relation to stage, anatomical site, sex, age and period of diagnosis. A total of 2,956 cases diagnosed in Norway 1953-1971 were analyzed. The final date of follow-up was December 31, 1973. The disease is amenable to cure for localized as well as nonlocalized cases, the cure rates being about 60% for the former and 15% for the latter group. Even within the group of localized cases large deviations in prognosis were found, the survival rates varying according to anatomical site, sex and age. The interaction between sex and age in prognosis is discussed in detail. A rise in survival was observed from the period of diagnosis 1953-1963 to that of 1964-1971. Detailed analysis points to earlier diagnosis or therapeutic progress in the later study period rather than a lower degree of malignancy of registered cases.


Methotrexate compared with placebo in lung cancer. Two hundred thirty-nine patients with microscopically proven, inoperable bronchogenic carcinoma were allocated at random to receive twice weekly I.M. injections of either methotrexate at "high dose" of 0.06 mg/kg/dose or methotrexate at "low dose" of 0.2 mg/kg or visually indistinguishable placebo in the same volume of 0.1 ml/kg for four months. Twelve patients were invalidated for procedural reasons. Objective response (greater than or equal to 50% tumor regression) was dose-related with 21% of 48 patients with measurable disease on high -ose, 11% of 37 patients on low dose, and 6% of 32 patients on placebo. Corresponding response rates for epidermoid carcinoma were 35% of 23 patients, 9% of 11 patients, and 0 of 13 patients. Responders in the two treatment groups had a three to four fold increase of median survival (p less than .05). Non-responders on high and low dose methotrexate lived as long as patients on placebo. Leukopenic patients in all three treatment groups lived substantially longer than patients without leukopenia less than 4,500/mm3, irrespective of presence or absence of objective response. All three regimens were well tolerated. None of the patients had life-threatening toxicity. It is concluded that methotrexate at "high dose" is a potentially useful drug for temporary palliation of epidermoid carcinoma of the lung.


Malignant pheochromocytoma with features suggesting the Brown-Séquard syndrome. A case report. A case of malignant pheochromocytoma arising from the abdominal preaortic chromaffin tissue is presented. Of particular note is that right hemiplegia associated with sensory disturbances, compatible with the Brown-Séquard syndrome, was an outstanding early clinical manifestation. The patient finally developed signs of complete transection of the spinal cord which was caused by metastasis of the tumor to the cervical spines. The neurological abnormalities observed in the present case were so unusual in pheochromocytoma as to lead initially a diagnosis of cord tumor. Autopsy findings well supported the clinical diagnosis. Cases like this have not been reported so far.


Small bowel perforation secondary to metastatic carcinoma of the lung. This is a report of small bowel perforation secondary to a metastasis from a primary adenocarcinoma of lung in a 62-year-old woman five months after resection of the primary tumor. She had received radiation therapy and corticosteroids after surgery. Features of this and five previously reported cases are discussed. Modern therapy may alter the course of pulmonary cancer resulting in more frequent observation of this rare complication.


Relationship of host immune status to tumor cell arrest, distribution, and survival in experimental metastasis. The kinetics of initial arrest in organs, distribution, survival, and fate of 125I-iododeoxyuridine-labeled B16 melanoma tumor cells injected intravenously into normal, tumor-sensitized and immune manipulated syngeneic and allogeneic mice were investigated. Groups of animals were killed at intervals ranging from two minutes to 14 days after intravenous tumor cell injection. Lungs, liver, spleen and blood were collected from each animal and processed so that radioactivity associated with DNA of tumor cells viable at the time of sacrifice could be monitored. The following conclusions can be made: initial tumor cell arrest in organs is influenced by the host immune status but it does not correlate with the survival kinetics or development into tumors. The same tumor, which was rejected in mice after a subcutaneous tumor challenge, grew in the lungs after intravenous injection. Therefore, rejection of a subcutaneous challenge as the sole criterion of host immunity to neoplasms should be questioned. Allogeneic animals are not appropriate for use as a model system for the study of experimental metastasis. Animals sensitized to a tumor exhibit kinetic patterns of tumor cell arrest and survival that differ from normal syngeneic hosts.


Medulloblastoma. A review of the LDS hospital experience. A review of 14 patients with an initial diagnosis of medulloblastoma treated with irradiation therapy is presented. Follow-up data are available on all patients. When one evaluates those patients who were treated with total CNS irradiation in ours and other institutions, an excellent five-year survival of approximately 70% is observed. The point of significance is that the dose to the spinal axis was in the range of 2500 rads for the majority of the survivors with a boost to the posterior fossa between 4500 and 5000 rads. Only one patient had metestetic disease, and that was a patient who had a ventricular atrial shunt placed initially for control of increased intracranial pressure. These survival data add to already published data from Hope-Stone and others reporting excellent five-year survival with total CNS irradiation and are contradictory to the reports of approximately 40% five-year survival. The implications of the following review are that one can question the necessity of taking all patients with medulloblastoma to 3500 rads to the spinal column. We would suggest that if no clinical or laboratory evidence exists for spinal involvement, the use of a low dose to the spinal column of approximately 2500 rads decreases the potential for spinal column arrest in this young group of patients.


Cancer patients: knowledge and attitudes. Fifty patients undergoing treatment were interviewed on what they knew about radiotherapy and their attitudes towards their disease and those treating their disease. Ninety-four percent used the word "cancer" or "malignant tumor" to describe the reason for being treated. All patients were told their diagnosis by the physician who referred them for therapy. Nineteen patients remembered feeling frightened by the equipment at first, but all had a lessening of anxiety with time. All patients perceived the role of the radiation technologist as that of operating the treatment machine and spoke only about trivialities to them. Eighty percent felt that the radiotherapist gave them satisfactory information about their treatment before commencing treatment. In contrast, the referring physician was thought to have been of no help in preparing for the experience of undergoing radiotherapy by 52% of those interviewed. Eighty-two percent of the patients expressed the opinion that both the referring physician and therapist were not the people to whom they would bring emotional problems. Therefore, mental health professionals could make a major contribution in the total program if they were involved in the day to day care of patients receiving radiotherapy.


Significance of the vertebral venous (Batson's) plexus in metastatic spread in colorectal carcinoma. Recently studies of bone metastases in colorectal carcinoma by radionuclide scanning are reviewed. A frequency of 33--61% has been reported using the more recently available bone scanning tests. The commonly accepted frequency of bone metastases from colorectal carcinoma by x-ray or anatomic studies is 5%. This much higher frequency currently being reported must still be established by additional studies. However, if the much high frequency currently being reported is firm, they suggest a much greater importance of the Vertebral Venous Plexus in tumor spread than heretofore suspected for colorectal carcinoma.


Behavioral therapy: its application to reduce disruptive behaviors of the elderly in nursing homes. Nurses who care for the elderly in nursing homes and auxiliary hospitals have many goals. They provide for the health, recreational, social and emotional needs of their patients. They also strive to increase their patients' levels of self-care and self-respect. Unfortunately, because many patients exhibit disruptive behaviors--striking staff or other patients, throwing temper tantrums, lying on the floor in corridors, refusing to take medication and so on, these desirable goals cannot always be met. What nurses need, in addition to their specialized, medically oriented training, is training in a consistent strategy for handling these problems. Behavioral therapy provides this strategy.


Methylation analysis of neuraminic acids by gas chromatography-mass spectrometry. The permethylated methyl glycoside methyl esters of N-acetyl- and N-glycolyl-neuraminic acids and of N-acetylneuraminic acid 8-acetate have been analyzed by g.1.c.-mass spectrometry. Fragmentation of the neuraminic acid derivatives in electron-impact mass spectrometry has been studied by deuterium labelling. The results were applied in the methylation analysis of neuraminic acids from gangliosides of brain and kidney.


1,6-anhydro-1(6)-thio-L-iditol and -D-mannitol, and some derivatives thereof. Starting from 1,2:5,6-dianhydro-3,4-O-isopropylidene-L-iditol (1) and -D-mannitol (6), respectively, the corresponding 1,6-anhydro-1,(6)-thio derivatives (2a and 7a) were synthesized. The discrepancy in the yields obtained, as well as the different behavior of their methylated derivatives (2e and 7c) towards acid hydrolysis, could be explained by steric factors. The di-O-mesyl derivatives 3d  and 12c were unstable compounds, and showed no ulcerostatic activity, unlike the D-glucitol analog.


[13C and 1H NMR of (1 goes to 6)-beta-D-glucan, linear oligosaccharides and their corresponding cyclic forms]. The results of 1H-n.m.r. and 13C-n.m.r. studies of linear and cyclic oligosaccharides in the series of gentiodextrins, both in their hydroxylated and acetylated form, were compared to those obtained for the corresponding natural or synthetic polysaccharide. The 13C-signals of each D-glucopyranose unit of acetylated oligosaccharides are more distinct than those of the parent hydroxylated compounds. In order to relate the change of the various signals with the degree of polymerization, gentiotriose undecaacetate, enriched in 13C at C-1'', was prepared, as well as gentiotetraose tetradecaacetate selectively labeled at C-1'' and C-1'''. A (1 leads to 6)-beta-D-glucan having a D.P. of approximately 10 was chemically prepared. During the course of the polycondensation, the 2,3,4,2',3',4'-hexa-O-acetyl-di-beta-D-glucopyranosyl 1,6':6,1'-dianhydride, and the 2,3,4,2',3',4',2'',3'',4'',2''',3''',4'''-dodeca-O-acetyl-tetra-beta-D-glucopyranosyl 1,6''':6,1'''-tetraanhydride, respectively, were formed.


Synthesis of some purine and pyrimidine nucleosides of 3-amino-2,3,6-trideoxy-L-lyxo-hexopyranose (daunosamine). The daunosaminyl analogue of the antibiotic puromycin and the nucleoside derivatives of daunosamine with adenine, thymine, and cytosine have been synthesised. The nucleoside derivatives of 6-dimethylaminopurine, thymine, and cytosine were prepared by melting the protected daunosamine with the protected base in vacuo. Daunosaminyladenine was obtained by condensing N-trifluoroacetyl-O-trifluoroacetyl-alpha-daunosaminyl chloride either with N6-benzoyl-9-chloromercuryadenine in boiling xylene or with N6-benzoyladenine in dichloromethane at room temperature in the presence of a molecular sieve. In each reaction, the beta-anomeric nucleoside was obtained, as shown by p.m.r. data. The protecting groups were removed with barium hydroxide or methanolic ammonia to give the free aminonucleosides in good yield. 9-beta-Daunosaminyl-6-dimethylaminopurine was coupled to N-benzylocyxcarbonyl-O-methyltyrosine, giving, after hydrogenolysis, the daunosaminyl analogue of puromycin.


Derivatives of 2,3-anhydro-DL-threitol, 2,3-anhydroerythritol, 2,3:4,5-dianhydrogalactitol, and 2,3:4,5-dianhydroallitol. alpha, omega-Disubstituted derivatives of 2,3-anhydro-DL-threitol (2), 2,3-anhydroerythritol (4), 2,3:4,5-dianhydrogalactitol (8), and 2,3:4,5-dianhydroallitol (12) have been synthesised by epoxidation of the appropriate alkeness and dienes. Benzyloxy carbonyl groups were used for protecting the primary hydroxyl groups during epoxidation.


A new chemical synthesis of 2-amino-(N-D-ribofuranosyl)acetamide 5'-phosphate. 2-Amino-(N-D-ribosyl)acetamide 5'-phosphate (GAR,10) has been prepared in a readily scaled-up synthesis from 2,3-O-isopropylidene-D-ribofuranosylamine p-toluenesulfonate (3) by condensation with the mixed anhydride of N-)benzyloxy-carbonyl)glycine, followed by phosphorylation with 2-cyanoethyl phosphate and removal of the protecting groups. By varying the conditions, the alpha-4 and the beta-5 anomers could be obtained and separated from each other. Anomerization occurs upon removing the O-isopropylidene group from either 7 or 8, so that the final compound (10) is an equimolar mixture of both anomers, of which only one is active toward GAR-transformylase.


Ultrastructural alterations in ciliary cells exposed to ionizing radiation. A scanning and transmission electron microscopic study. Early effects of ionizing radiation were investigated in an experimental in vitro system using the ciliary cells of the tracheal mucous membrane of the rabbit, irradiated at 30 degrees C and at more than 90% humidity. The changes in physiological activities of the ciliary cells caused by irradiation were continuously registered during the irradiation. The specimens were examined immediately after irradiation electron microscopically. The morphological changes in irradiated material after 10-70 Gy are compared with normal material. After 40-70 Gy, scanning electron microscopy revealed the formation of vesicles on cilia, and club-like protrusions and adhesion of their tips. After 30-70 Gy, a swelling of mitochondrial membranes and cristae was apparent transmission electron microscopically. The membrane alterations caused by irradiation are assumed to disturb the permeability and flow of ATP from the mitochondria, which in turn leads to the recorded changes in the activity of the ciliated cells.


Macrophage-lymphocyte cluster formation in the medullary sinus of lymph node after immunization with sheep red blood cells (SRBC). Normally the lymphatic sinuses of the lymph node are loosely packed with lymphocytes and free macrophages as well as with macrophages adhering to the fibrocellular trabeculae. After immunization with SRBC cluster formation occurs in the medullary sinuses of rats between a central macrophage and peripherally located lymphocytes. These rosette-like clusters are nearly identical with the clusters found during primary and secondary immune response against SRBC in vitro and seem to be the in vivo equivalent for the same immune response.


Regeneration in the central nervous system of a pulmonate mollusc, Melampus. The left cerebral ganglion was ablated from 72 anesthetized, adult Melampus bidentatus (Mollusca: Pulmonata). Skin incisions were well healed and normal feeding and locomotion observed four days after surgery. Dissections of animals sacrificed weekly showed that most nerves and connectives regrew within 30 days, attaching to the swollen end of the major labial nerve. The enlarged end of this nerve later developed into a distinctive bud; some of these buds contained cell bodies as soon as 42 days after surgery. As the first known report of central nervous tissue regeneration in molluscs, this study points to the need for controls in experiments involving section or ablation of nervous tissue in molluscs.


Specializations of the outer mitochondrial membrane during oocyte development. A coating of electron dense material is present on the cytoplasmic surface of outer mitochondrial membranes in medium-sized hamster oocytes. The coating is not present at earlier or later stages of oocyte development. Its possible relationship to the synthesis and transport of mitochondrial protein is discussed. Associations between endoplasmic reticulum, ribosomes, glycogen and the outer mitochondrial membrane are also described and discussed.


Intra- and extraganglionic nerve endings formed by neurosecretory cells of the cerebral ganglion of the earthworm (Lumbricus terrestris L.). In the cerebral ( = supraesophageal, suprapharyngeal) ganglion of the earthworm, a number of neurosecretory Gomori-positive perikarya are bipolar; others are unipolar, or multipolar. Some of the neurosecretory cell processes project centrally into a fibrous zone; peripheral processes enter small nerves which leave the dorsocaudal aspect of the ganglion. In the central fibrous zone, the neurosecretory fibers form varicose Gomoripositive terminals. Here, also zinc-iodine-osmium (ZIO)-positive fibers and monoamine fluorescent fibers are found. With the electron microscope, nerve terminals containing synaptic vesicles and either large neurosecretory "peptidergic" granular vesicles (diameter more than 1500 A), or smaller granular vesicles (diameter about 1300 A, or 900 A) are observed. These axon endings mainly form axo-dendritic synapses. "Peptidergic" profiles are both pre- and postsynaptic. Some of the extraganglionic "peptideric" fibers appear to terminate around vessels, but most of them form terminals on the visceral muscle cells which surround the ganglion. We think that the central neurosecretory processes communicate with the fibers of the synaptic zone of the ganglion. The peripheral neurosecretory "peptidergic" fibers are supposed to form a primitive neurohemal area and/or to function as vasomotor nerves. The fibers innervating the visceral muscle cells may represent vegetative nerves.


Oögenesis in a marine teleost, Blennius pholis L. Oögenesis in the oviparous marine teleost, Blennius pholis L., is examined. Eleven developmental stages are identified by ultrastructural observations when changes in the distributions of the organelles and inclusions are described. An exogenous source for the protein yolk precursors is indicated, but less clear is the endogenous contribution. Changes in the follicle epithelium are described together with the formation of the zona which is considered to be follicular in origin. Two types of follicle cell are distinguished and these probably function differently in the process of zona formation. The zona becomes divided into the externa and interna, the latter probably resulting from the chemical ordering by disulphide bonding of the proteinaceous material of the former.


Endocytosis and aspects of autophagy in the foot epithelium of the slug Agriolimax reticulatus (Müller). The foot epithelium of the slug Agriolimax reticulatus (M) can function as a digestive epithelium and possesses a vacuolar system in which heterophagic and autophagic material is hydrolysed. Using ferritin and peroxidase as markers, the process of endocytosis has been demonstrated at the level of the electron microscopy. The mechanisms involved with the uptake of each marker differed in that ferritin was confined to fairly large vacuoles, while peroxidase was present in smaller pinocytotic vesicles which ultimately fused to form larger vacuoles or multivesicular bodies. Cytochemical tests for acid phosphatase revealed that the latter bodies acquired hydrolytic enzyme to become secondary lysosomes. Acid phosphatase was also localized in the Golgi apparatus of the epithelial cells. In addition to the endocytotic activity, evidence of autophagy was found in the epithelial cells and this process was apparently enhanced during starvation.


Tritiated thymidine autoradiographic study on the origin and renewal of argentaffin cells in the pyloric gland of hamsters. The origin and renewal of the argentaffin cells in the pyloric glands of hamsters were studied by flash, cumulative and pulse labelling autoradiography with 3H-thymidine. The argentaffin cells were identified by the Diazo Method using Fast Red B Salt. By flash labelling autoradiography, it was shown that the argentaffin cells located from the middle to the lower level of the pyloric mucosa were not labelled with 3H-thymidine, indicating that this cell type has no proliferative activity. On the 10th and the 20th day of cumulative labelling, 31% and 63% of the argentaffin cells in the gland were found to be labelled, respectively. The labelled argentaffin cells were concentrated in the upper part of the gland (around the region of the isthmus), and no label was found over nuclei of the cells at the lowermost level of the gland. These labelled cells were shown to undergo a downward migration in the days following pulse labelling. They were replaced by unlabelled (and weakly or very weakly labelled) cells which arose at the region of the isthmus. The argentaffin cells in the pyloric gland are thought to arise from epithelial precursor cells at the region of the isthmus. The labelled argentaffin cells in the gland were found to decrease in number almost exponentially after pulse labelling. This indicates that the life span of argentaffin cells is not fixed, but their renewal conforms to the "random loss system". The half time of turnover of this cell population was 15 days on average.


Neuritic growth cone and ependymal gap junctions in the feline subfornical organ during early development. Intercellular contacts in the subfornical organ (SFO) of kittens 3, 16, and 29 days old were studied in thin sections and by the freeze-etch method. Gap junctions appeared between growing nerve processes and target cells. The junctions were interspersed between immature synapses lacking mitochondria as well as full pre- and postsynaptic membrane specializations. Gap junctions were seen on filopodia as well as on more mature processes. The morphology of these junctions was typical of those described earlier but they were of small size (0.2-0.3 micron). Gap junctions of peculiar form were also seen between ependymal elements in the SFO at 16 days. These were of large size (0.5-0.8 micron) and were often of segmented character. This segmentation consisted of bands 3-4 particles in width with a center-to-center spacing of 90 nm with particle free corridors between corresponding to the width of about two rows of particles. The margin of the group might be circumscribed by a row of particles. Although gap junctions of large size were seen between ependymal cells in thin section, features corresponding to the particle free corridors have not been observed to date.


Spermatogenesis and the role of Sertoli cells in the freshwater snail Biomphalaria glabrata. The various stages of spermatogenesis and the Sertoli cells of Biomphalaria glabrata were studied with histochemical and electron microscope techniques. During spermatogenesis a manchette of microtubules is formed around the nucleus and the mid-piece of the spermatids. This manchette becomes helically coiled and probably plays an important role in the spiralisation of the nucleus and of the mitochondrial sheath. During spermatogenesis so-called chromatoid bodies (CB) occur, which consist of arginine-rich proteins. These CB disintegrate during the early spermatid stage. The results suggest that the CB are either involved in histone transition or in the formation of microtubules. The remaining cytoplasm of the spermatids is phagocytised by the Sertoli cells. Apparently this process of phagocytosis is an important part of the mechanism of spermiation. Morphological measurements of the Sertoli cells showed that the relative volume of most organelles decrease during spermatogenesis, indicating a general decrease in cell activity. Possible functions of the Sertoli cells, such as transportation and nutrition of spermatogenic cells and hormone production, are discussed. It is concluded on the basis of the histochemical and ultrastructural observations that the Sertoli cells are involved in the nutrition of spermatogenic cells. It seems unlikely that they are hormone producing cells.


Ultrastructural changes in rat hypothalamic neurosecretory cells and their associated glia during minimal dehydration and rehydration. A quantitative ultrastructural study was performed to determine the changes in the neurosecretory neurons of the supraoptic (SON) and circularis (NC) nuclei following 4-24 h of water deprivation (WD) and subsequent rehydration (12 and 24 h). In both nuclei, the amount of direct soma-somatic contact increased throughout WD, apparently by retraction of fine glial processes from between the cells. Rehydration reversed these changes. The number of smaller (less than 1600 A) neurosecretory granules (NSG's) decreased in both nuclei at 4 h of WD but returned to control levels by 24 h of WD and remained so during rehydration. Larger (less than 1600 A) NSG's decreased in number at 4 h of WD in SON and then returned to control levels by 24 h of WD and remained the same throughout rehydration. In NC, these NSG's did not change in number with WD, but significantly increased between 12 and 24 h of rehydration. No cells with dilated rough endoplasmic reticulum were seen in NC during this study. In SON, however, the percentage of such cells increased at 4 and 12 h of dehydration only to decrease to control levels at 24 h of dehydration and throughout rehydration. Lysosomes decreased at 4 h of dehydration in SON and returned to control levels thereafter. In NC, lysosomes tended to decrease with dehydration and increase with rehydration. These findings indicate that detectable morphological changes take place in the course of alterations in hydration state that are well within the physiological range.


Tubules invaginating from the sarcolemma in the subneural region of muscle fibers. Sarcoplasmic tubules invaginating from the sarcolemma of the subneural region of muscle fibers are described in Atlantic hagfish and rat. In rat, the tubules invaginate from the bottoms of the secondary synaptic clefts. The density of tubule openings may be higher than the density of T-tubule openings elsewhere along muscle fibers.


Correlations between ultrastructural features and contraction rates in rotiferan muscle. I. Preliminary observations on longitudinal retractor muscles in Trichocerca rattus. The Rotifer Trichocerca rattus has striated longitudinal retractor muscles. These muscles can be divided into two categories: 1. The central and ventral retractor muscles which, after fixation, are found in a supercontracted state: they probably contract very quickly. 2. The lateral retractor muscles which are in a relaxed state after fixation. However, if the animal is mechanically stimulated before fixation, these are also fixed in a contracted state: so, normally, these muscles probably contract more slowly than the first category. In the relaxed state, thin myofilaments of the lateral retractor muscles are folded at the I band level; this a consequence of their compression provoked by the contraction of central and ventral retractor muscles. In muscles of the first type, the thick myofilaments are shorter (less than 2 mu) than in the second type (2.5 mu).


Granular cells in the connective tissue of Helix pomatia L. (gastropoda, pulmonata). Histochemistry, ultrastructure, and results of polyacrylamide electrophoretic investigations. Granular cells (cells crowded with colourless granules staining with paraldehyde fuchsin according to Gomori-Gabe and not containing calcium) are independent cells in the connective tissue of Helix pomatia. Histochemical data suggest that the granules are rich in sulfhydryl-containing proteins, but lack biogenic monoamines. Electron microscopic investigations confirm the supposed secretory activity of the granular cells. Secretory proteins are presumed to be synthetized in the endoplasmic reticulum and condensed in the Golgi apparatus giving rise to the granules. Extrusion occurs by exocytosis. Electrophoresis of homogenates, prepared from tissues containing numerous granular cells, results in the separation and identification of a secretory protein from the granular cells. An electrophoretically homologous protein is recognized in the hemolymph, but in very small quantities. Our findings and the work of others suggest the involvement of granular cells in neuroendocrine events.