[The embryonic pineal organ of Lacerta vivipara J. I. Differentiation of the cells of the sensory line (CSL). The gradient of morphological differentiation]. This paper deals with the cytological development of the cells of the sensory line (CSL) of the pineal organ in Lacerta vivipara J. from the embryonic stage 30 on to the third day after birth. The general results are diagrammatically represented in figure 29. Only from stage 35 on, a diversity of sensory line cells can be distinguished. During ontogenetic development, in the photoreceptor cells (P) secretory activity is not observed. From stage 38 on, the photoreceptive poles of these elements show a differentiation of disks while, from stage 37 on, their basal processes make synaptic contacts with dendritic outgrowths originating from intra-epithelial sensory nerve cells. The embryonic secretory rudimentary photoreceptor cells (SRP) are characterized by an intensive secretory activity. Our quantitative analysis reveals a highly significant increase, during ontogenetic development, of the number of dense secretory granules, stored in the basal processes of the SRP. The photoreceptive poles of the SRP, just like those of the P cells, show the differentiation of disks from stage 38 on. Only just after birth, the outer segments of the SRP become rudimentary. From the absence of characteristic synaptic contacts between the basal processes of the SRP and dendrites of the sensory nerve cells it is concluded that, during ontogenetic development, the SRP become rudimentary as photoreceptivity is concerned. During the ontogenetic development of the pineal organ in Lacerta vivipara, morphological signs pointing to regression of its photoreceptor function are not very marked. In showing a photoreceptive differentiation of the outer segments of the SRP, the present investigation agrees with phylogenetic studies by other authors and supports the concept of the presence of a sensory cell line in the vertebrate pineal organ (Collin, 1969 b).


Effect of the activation of alpha-adrenoreceptors on the synthesis and release of noradrenaline by peripheral adrenergic nerves in vivo. The synthesis and release of noradrenaline (NA) in the heart and submaxillary glands were studied in the rat following s.c. injections of oxymetazoline (50 mug/kg) or noradrenaline (500 mug/kg). NA release was evaluated from the decline in tissular specific radioactivity after administration of 3H-NA and NA synthesis by the estimation of the amounts of 3H-NA synthesized from 3H-tyrosine (TY) or 3H-Dopa, 30 min after the injection. Oxymetazoline treatment delayed the release of NA, the NA biological half-lives rising from 12 up to 36 hours in the heart and from 5.9 up to 21 hours in sub-maxillary glands. This inhibitory effect on NA release was interpreted as the consequence of the stimulation of alpha-adrenoreceptors. Thirty minutes after its injection, oxymetazoline increased both NA endogenous levels and 3H-NA amounts formed from 3H-TY: 3H-NA specific activities were not significantly altered. NA treatment led to an acceleration of NA release in the heart (NA biological half-life decreasing from 12 to 2.2 hours) but not in sub-maxillary glands. After injection of 3H-TY, the amounts of 3H-NA found in the heart and sub-maxillary glands were strongly reduced. Similar results were observed in the heart using 3H-Dopa as a precursor. These data are interpreted as the consequence of the removal of the newly synthesized 3H-NA by exogenous NA. The results obtained with oxymetazoline point out a dissociation between the NA release which is reduced and the NA synthesis which is unaltered. This indicates that NA synthesis rate by sympathetic nerve terminals is not immediately regulated by its release intensity. These data do not support the end-product feedback inhibition hypothesis according to which tyrosine hydroxylase is regulated by the intraneuronal NA concentration.


Evidence for involvement of central noradrenergic neurons in the cardiovascular depression induced by morphine in the rat. Morphine caused in the anaesthetized rat reduction in brain noradrenaline (NA) turnover, hypotension and bradycardia, similarly to the antihypertensive, alpha-adrenergic agonist, clonidine. All effects of morphine were antagonized by naloxone, as well as the alpha-receptor antagonist, yohimbine. In contrast, naloxone did not affect the circulatory depression and reduction in brain NA utilization by clonidine which both previously have been found to be antagonized by yohimbine. In contrast to clonidine, morphine even in high doses did not facilitate the flexor reflex activity of acutely spinalized rats. Pretreatment with protriptylin largely attenuated the circulatory depressive effects of morphine, as it has previously been found to block the corresponding effects of clonidine. Thus, the morphine-induced cardiovascular depressive effects are primarily elicited by activation of opiate receptors. However, the inhibition of brain NA neurotransmission by morphine appears critically involved in the mediation of the circulatory depression.


Distribution of monoamine oxidase (MAO) in relation to the hypothalamo-hypophyseal system of the teleost Clarias batrachus (L.). Varying degrees of monoamine oxidase (MAO) activity were noticed all along the hypothalamo-hypophyseal neurosecretory tract in C. batrachus. Intense activity was evident on the wall of the secretory cells of the adenohypophysis, neurons of the nucleus preopticus (NPO) and nucleus lateralis tuberis (NLT). However, MAO activity was also observed in the cytoplasm of some neurons in the ventromedian region of the NLT and groups of cells present in the neurohypophyseal ramifications of the pars intermedia. A strong accumulation of formazan granules in the median eminence (ME) and the neuroadeno interface lends further support to the view that C. batrachus has a ME of both the tetrapodan and the teleostean type. The distributional pattern of MAO in the hypothalamus and hypophysis suggests that monoaminergic fibres are probably involved in the secretory mechanism of the releasing factors and pituitary hormones.


Molecular biology of neurological and psychiatric disorders. I. Effect of parkinsonism, age, sex and L-dopa on platelet monoamine oxidase. Since there is substantial evidence for a nigrostriatal dopamine defect in Parkinson's disease and since monoamine oxidase (MAO) appears to be essential for the degradation of dopamine, we investigated whether this enzyme is involved in the pathogenesis of this disease or in the therapeutic action of L-dopa. To gain a solid basis for our analysis we studied some properties of platelet MAO, at present the only practical in vivo source for human MAO. Substrate and inhibitor pattern clearly pointed to a predominant B-type character of this enzyme. By using 3 substrates, m-iodobenzylamine, p-methoxybenzylamine, and tyramine, we found a marked age and sex difference in MAO activity. In untreated parkinsonian patients, platelet MAO was slightly reduced as compared with age- and sex-matched controls. Treatment with L-dopa induced a further reduction of platelet MAO activity in both sexes, but more in men than in women. We conjecture that the action of L-dopa on parkisonian patients is twofold: L-dopa is known to enhance the release of gonadotropins and thus to increase the production of sex hormones which in turn are capable of reducing MAO activity. Dopamine, formed from L-dopa, may thus have a better chance for survival in reaching the dopaminergic receptor. A new form of therapy, based on this concept, is proposed.


Acute effects of histamine on plasma prolactin and luteininzing hormone levels in male rats. Histamine injected into the 3rd ventricle of normal male rats at doses of 5-60 mug (free base) caused a marked release of prolactin. Responses were prevented by the antihistamine chlorpheniramine but not by atropine, methysergide or phenoxybenzamine. It thus seems that effects of histamine on prolactin are specific and not mediated by other neurotransmitters. Plasma LH remained normal after injection of low doses but it was decreased after high doses. The results obtained indicate a facilitatory role of histamine on prolactin release.


Pharmacological evidence for a selective antidopaminergic action of gamma-hydroxybutyric acid. D-Amphetamine (Amph) and p-chloroamphetamine (PCA) induced dose-dependent increases in oropharyngeal myocloniform twitch activity (MTA) in rats anesthetized with urethane. In doses of 80-120 mg/kg, gamma-hydroxybutyric acid (GHB) blocked Amph-induced MTA. The blockade was readily surmountable. Pretreatment with reserpine markedly enhanced the myoclonigenic effect of Amph and rendered it insensitive blockade by GHB, 160 mg/kg. PCA and tryptamine also effectively stimulated MTA, but unlike Amph were antagonized by low doses of the serotonin (5-HT) antagonist methysergide. In doses which blocked Amph, GHB failed to antagonize the myoclonigenic effect of PCA. It is concluded that: (a) the actions of Amph and PCA on MTA is less sensitive to GHB blockade than DA-mediated MTA; and (c) the GHB-Amph antagonism may be of a functional nature, i.e. result from a depression of the firing activity of DA neurons produced by GHB. Since reserpinization abolished the GHB effect on Amph-induced MTA, the functional integrity of granular DA binding and releasing mechanisms appears to be a pre-requisite for the antagonism between GHB and Amph.


A histochemical investigation of catecholamines in spinal cord injury. The catecholamine hypothesis of progressive spinal cord necrosis following mechanical trauma was investigated with the histofluorometric method. Forty-four adult mongrel dog were examined as control, L1 crush-injured, and crush-injured with prior T1 total transection groups. In crush injured dogs, catecholamines were present in a 1 cm length of white matter at the crush site, with the greatest accumulation in the deep lateral and ventral funiculi. Gray matter fluorescence was not enhanced. Prior transection did not abolish the intense accumulation of catecholamines at the site of the cord injury. We propose that the catecholamines accumulating at the cord injured site are not central in origin, but represent an uptake mechanism into white matter as a reflection of cord microperfusion.


Effect of pinealectomy on gonadotrophins in immature female rats. Pinealectomy, performed in new-born female rats, causes a temporary decrease in pituitary LH content between the 21st and the 30th day of age as compared with the controls. In sham-operated rats a smaller decrease is observed.


Alteration of protein metabolism in individual, identified neurons from Aplysia. A search for control mechanisms governing protein metabolism in neurons from Aplysia californica has uncovered two examples of altered patterns of newly synthesized proteins: (1) The pattern of newly synthesized proteins in the R2 neuron is altered when protein synthesis occurs at elevated temperatures (22-30 degrees C as compared with 13-15 degrees C). (2) The processing of newly synthesized 12,000 dalton (12k) material to 6-9,000 dalton (6-9k) size in the R15 neuron (Strumwasser, F. and Wilson, D.F. [1976], J. Gen. Physiol., in press) can be blocked by certain ion replacements. If acetate replaces chloride in the incubation medium during the synthesis of 12k material, an early step in the processing, prior to the actual breakdown of 12k material, is blocked. Experiments with RNA-synthesis inhibitors indicate that none of the mRNAs which code for abundantly synthesized protein species in the R2 or R15 neurons have short (less than 4 hr) half-lives. This result has implications for an earlier report of regulation of protein synthesis in the R15 neuron.


Effects of different ions on resting polarization and on the mass receptor potential of carotid body chemosensors. The carotid body and its own nerve were removed from cats anesthetized with sodium pentobarbital and placed in an air gap system; the carotid body was bathed in modified Locke's solution equilibrated with 50% O2 in N2, pH 7.43 at 35 degrees C. The sensory discharges, changes in "resting" receptor polarization and the mass receptor potential evoked by ACh or NaCN were recorded with nonpolarizable electrodes placed across the gap. Receptor potentials and sensory discharges evoked by ACh showed an appreciable increase in amplitude and frequency when the preparation was bathed in eserinized Locke. Eserine did not change appreciably the responses evoked by NaCN. Excessive depolarization elicited by either ACh or NaCN was accompanied by sensory discharge block. Removal of K+ ions from the bathing solution induced receptor hyperpolarization and an increase in the amplitude of the evoked receptor potentials. An increase of K+ concentration had the opposite effect. Reduction of Na+ or NaCl to one half, or total removal of this salt, induced an initial reduction and later disappearance of the sensory discharges, some receptor hyperpolarization and a reduction in the amplitude of the evoked receptor potential. Reduction or removal of Ca++ produced receptor depolarization, a marked depression of the evoked receptor potentials, an increase in the frequency of the sensory discharges and a reduction in the amplitude of the nerve action potentials. High Ca++ or Mg++ had little or no effect on action potential amplitude or resting polarization, but decreased sensory discharge frequency and the evoked receptor potentials. Total or partial replacement of Ca++ with Mg++ induced complex effects: (1) receptor depolarization which occurred in low Ca++, was prevented by addition of Mg++ ions; (2) the amplitude of the evoked receptor potentials was depressed; (3) the nerve discharge frequency was reduced as it was in high Mg++ solutions; and (4) the amplitude of the nerve action potentials was reduced as it was in low Ca++ solutions. Temperature had a marked effect on the chemoreceptors since at high temperatures the receptors were depolarized and the discharge frequency increased. The baseline discharge and responses evoked by ACh or NaCN were depressed at low temperatures. The results are discussed in terms of possible receptor mechanisms influenced by the different ions.


Creatine kinase isoenzymes in neuromuscular diseases. Determination of the creatine kinase isoenzyme pattern in 62 biopsy samples obtained from patients with neuromuscular disease revealed changes mainly in Duchenne muscular dystrophy. The BB isoenzyme was detected in 10 out of 17 cases with Duchenne muscular dystrophy and the relative amount of MB+BB isoenzyme was significantly increased in this group (P less than 0.005). In serum the MB isoenzyme was detected in all 28 cases with progressive muscular dystrophy and frequently also in other neuromuscular diseases. Among 152 control samples the MB isoenzyme was detected only in 2 cases. It is suggested that the finding of MB isoenzyme in the serum with normal or only slightly elevated total CK activity may be a further proof of neuromuscular disorder, but the finding is not specific for any particular disease.


Some quantitative morphological aspects of post-natal human cerebellar growth. Using a Quantimet 720 image analysing computer, the cellularity of the external and internal granular layer and the molecular layer has been measured in standard blocks of the lateral and central lobes of the cerebellum of apparently normal children. The DNA content of the nerve cells has also been measured and related to post-natal age. Standard cell concentrations per unit area have been established from birth to 14 years. The different lobules of the central lobe show different patterns of cellular development but all lobules reach their fully mature cellularity by 2 years. The maximum cellularity of the internal granular layer is maintained for several years, after which there is an apparent progressive reduction in the concentration of cells per unit area. Alterations in the DNA staining properties of the cell nuclei of the internal granular layer during normal development are presented.


Erythrocyte spectrin peak II phosphorylation in Duchenne muscular dystrophy. Duchenne muscular dystrophy (DMD) is a rapidly progressive crippling disease of young boys that is inherited as an X-linked recessive trait. Previous studies have demonstrated the usefulness of erythrocyte studies in exploring membrane abnormalities in inheritied muscular dystrophy. Erythrocyte spectrin peak II protein (m.w. equivalent to 220,000) was more highly phosphorylated under initial rate conditions in DMD than in controls. The extent of peak II phosphorylation was greater in DMD erythrocytes and a Na+ stimulated peak II phosphorylation effect (Avruch and Fairbanks 1974) was not found to account for the differences between DMD and controls. The phosphorylated state of spectrin proteins in the membrane was evaluated and no differences in DMD could be measured. The maximal transfer of phosphate from differences in DMD could be measured. The maximal transfer of phosphate from [gamma-32P]ATP to spectrin peak II accounts for approximately 5-10% of the total phosphate content of spectrin.


Polyacrylamide-gel disc electrophoresis of native cerebrospinal fluid proteins with special reference to immunoglobulins and some clinical applications. Polyacrylamide-gel disc electrophoresis has been applied to the fractionation of CSF samples obtained from 2m control subjects (range of age 16 to 77 yr, mean 41.0 yr) and from 157 patients with various neurological diseases, with the purpose of evaluating the diagnostic significance of separated protein bands. It was found that the immunoglobulins, with some exceptions, were fractionated in the G-zone which was defined as an area between the origin and 0.57 in terms of relative migration based on transferrin (RT). Fourty-four percent of the whole Bence Jones protein bands which were examined were detected in the area of RT 0.70-0.90. The normal values of CSF protein fractions were (means+/-SD):Pre-alb-zone, 10.97+/-2.31%; Alb-zone, 40.74+/-5.72%; A1-zone, 5.25+/-0.72%; A2-zone, 8.23+/-1.24%; B1-zone, 10.82+/-2.18%. B2-zone, 7.94+/-1.93%; G-zone, 16.05+/-2.49%. The following significant results were obtained: (1) When the total protein concentration (TP) of CSF is increased: the percentage of the Pre-alb-zone is lowered and that of the A1- and G-zones is increased in diseases such as neurosyphilis, infectious meningitis, brain tumour, multiple sclerosis, intervertebral disc protrusion and cerebral infarction. The A2-zone was diminished in cerebral infarction, and a similar change was seen in brain tumour with in addition a decrease of the B2-zone; (2) When the TP was normal: the percentage of the G-zone was increased in multiple sclerosis, brain tumour and intervertebral disc protrusion. In the latter 2 disorders the A1-zone also increased. This fraction also increased in the cases of cerebral infarction, whose mean age was, however, much higher than that of the control subjects.


Myofibrillar protein pattern in experimental myotonia in rats. Experimental myotonia was induced in rats by long-term administration of 20,25-diazacholesterol. Electrophysiological, morphological and biochemical investigations were carried out on m. soleus, m. extensor digitorum longus and m. gastrocnemius. The effect of 20,25-diazacholesterol administration on myofibrillar proteins was studied and a significant rise in the concentration of a protein presumed to be alpha-actinin was demonstrated in m. gastrocnemius. A change of the same character, not statistically significant, was observed in the m. extensor digitorum longus.


Abnormal tissue distribution of lead in amyotrophic lateral sclerosis. The lead content of cerebrospinal fluid (CSF) was found to be significantly elevated in 12 patients with amyotrophic lateral sclerosis, when compared to 28 control subjects having non-degenerative neurological disorders. The difference could not be explained as being merely secondary to blood-CSF barrier damage. A hypothetical model of the pathogenesis of the disease is advanced and the results are discussed in relation to this model.


Reactive hyperglycaemia in patients with acute stroke. Initial and follow-up fasting serum glucose levels following acute stroke were evaluated retrospectively in 392 selected hospitalized patients. Transitory reactive hyperglycaemia was observed in a large number of patients (28% of the total series) without a history of diabetes prior to the acute cerebrovascular event. The data from this group suggest a possible relationship between the impairment of carbohydrate metabolism and the type and location of stroke since both the frequency and severity of the hyperglycaemic response were higher in patients with haemorrhagic stroke and brainstem infarction as compared with cerebral infarction. The incidence and degree of the reactive hyperglycaemia were also related to the severity of the acute stroke. There were more comatose patients in the group showing this phenomenon. Initial serum glucose levels in the latter group were higher in unconscious patients than in alert ones. In addition, hospital mortality was significantly higher in these patients. Transitory reactive increases of serum glucose levels were also observed in the majority of patients with a history of overt diabetes prior to the acute stroke. The hyperglycaemic reaction following acute stroke may be attributed to several underlying mechanisms. These include: a non-specific reaction to acute stress and tissue injury with the associated autonomic, hormonal and metabolic alterations; uncovering of underlying latent diabetes by the acute stroke; increased secretion of growth hormone due to stroke-induced hypothalamic dysfunction; and irritation of the glucose regulatory centres in the hypothalamus and brain stem by blood-laden cerebrospinal fluid or local ischaemia.


A trial of antilymphocyte globulin in the treatment of chronic progressive multiple sclerosis. Twenty-three patients with chronic progressive multiple sclerosis (MS), resistant to steroid therapy, were treated with antilymphocyte globulin (ALG) and prednisone (30 mg by mouth daily). Twelve patients completed a full course of therapy (2 ml ALG i.m. daily for 2 weeks and 2 ml i.m. on alternate days for 2 weeks) and 6 others completed at least 2 weeks of daily injections. Six patients experienced an overall improvement of at least 15% using a comprehensive neurological scoring system. Three other patients had limited, but functionally useful improvement in specific neurologic functions. Six months after the completion of therapy, no patient had deteriorated to a level of function below that noted prior to treatment. Adverse reactions, which often necessitated stopping treatment, included fever, local inflammatory reactions, local rash, general malaise, mild anaphylactoid reactions, and enlargement and tenderness of regional lymph nodes. Because of the short duration of immunosuppression and the toxic side effects of ALG, we do not feel that ALG treatment yet deserves to be intorduced as a standard treatment in clinical practice. However, the improvement or arrest of progression seen in these patients who were deteriorating progressively despite steroid therapy would seem to justify a continued search for a safer method of suppressing immunity in MS patients.


Myelin composition in acute and chronic multiple sclerosis in relation to cerebral lysosomal activity. The neuropathology of 3 cases of acute multiple sclerosis was correlated with biochemical analyses. Astrocytosis was a characteristic feature of the diffuse demyelinating lesions in one case and lymphocytic cuffing characterized the well-defined plaques present in the white matter of the other two cases. No abnormalities were found in the protein or lipid composition of isolated myelin, despite a wide range of recovery. Nevertheless, the gel electrophoretic protein pattern of white matter adjacent to plaque areas showed selective loss of myelin basic protein. Lysosomal acid proteinase and beta-glucuronidase levels were very significantly increased in all white matter samples in which astrocytosis was a major neuropathological feature. Levels were less markedly raised in samples containing discrete active plaques. Enzyme changes were also found in the apparently normal white matter of 2 of the cases. Acid proteinase activity was in the normal range but the activities of beta-glucuronidase and acetylcholine esterase were elevated. The significance of these results in relation to glial cell activity in the early stages of demyelination is discussed.


Granulomatous angitis of the central nervous system. Case report and review. The nineteenth case report of granulomatous angiitis of the central nervous system is described in a 47-year-old patient, who survived 2 years with his disease. Problems with establishing the diagnosis are discussed. No single group of clinical symptoms or laboratory data exist for making a positive diagnosis during life, although a combination of certain nonspecific factors such as mental change, spinal fluid protein elevation and pleocytosis should be present before the diagnosis of granulomatous angiitis is entertained. Special blood tests and immunological studies and contrast procedures, as well as cortical biopsy have been of little value in establishing the diagnosis; instead, a leptomeningeal biopsy may be the procedure of choice. This patient, as well as the others given a trial of steroid treatment, demonstrated some obvious detectable clinical improvement. All patients treated with steroids have survived longer than any untreated patient suggesting that these drugs may be of some benefit.


Hyperphenylalaninaemia and experimental allergic encephalomyelitis. Previous suggestions to the effect that a reduced proportion of long chain and unsaturated fatty acids in the CNS as induced by experimental hyperphenylalaninaemia in young rats may alter the biochemical reactivity and stability of the myelin have been examined using experimental allergic encephalomyelitis (EAE). Lewis rats treated chronically with phenylalanine during development showed a higher susceptibility to EAE and a more severe course of the disease than their medium-treated litter mates. The possible implications of this observation for EAE as an experimental model of multiple sclerosis (MS) is discussed briefly in the light of the decreased levels of unsaturated fatty acids found in the CNS of MS patients.


Microdissection of peripheral nerve: collagen and lipid distribution with morphological correlation. Peripheral nerve is a complex tissue composed of endoneurial fascicles surrounded by perineurium and epineurium. We separated endoneurium from peri- and epineurium in human sural nerves by "endoneurial plucking", a method of microdissection. Endoneurial contents (axons, myelin sheaths, Schwann cells, vessels, and interstitial collagen) were cleanly separated in high yield from enveloping connective tissue, by both microscopic and biochemical criteria. Most of the nerve sulfatide and unesterified sterol was found in the endoneurial fraction while most of the collagen was in the peri-epineurial fraction. This microdissection method should prove useful in biochemical investigations of peripheral nerve.


Morphological observations on motor end-plates in rabbits with experimental myasthenia. The morphology of motor end-plates in rabbits immunized with Torpedo nicotinic acetylcholine receptor (nAChR) has been studied by light and electron microscopy. Rabbits were studied either after one period of paralysis, some in parallel with electrophysiological recordings of MEPPs and EPPs and of Naja naja alpha-neurotoxin binding properties or after recovery followed by a second paralysis. Changes in the sub-neural apparatus were noted after cholinesterase staining only in the latter group. Ultrastructurally, however, most end-plates in both groups contained a wide range of abnormalities. Many were similar in appearance to those observed in human myasthenia gravis (MG). This further supports the theory that immunized rabbits can be used as a model for myasthenia gravis. In the rabbits with 1 period of paralysis an acute stage of influence on the neuromuscular junction seemed to be present while simplified motor end-plates typical for human MG were mostly found in rabbits with 2 periods of paralysis. Short post-synaptic folds in conjugation with thickeneed membrane-bound vesicles at their tops, inside the basement membrane, were frequently observed. These were interpreted as if the crests of the folds containing nAChR had degenerated and had been budded off. If so, a large number of receptor sites had been lost which would be one possible explanation for the lowered capacity of the muscles to bind Naja naja alpha-neurotoxin. Membrane thickenings with projections and striations were interpreted as reflecting ACh receptors and were observed in the post-junctional membrane without proximity to the nerve terminal. The degeneration of the top of the post-synaptic folds and the occurrence of receptors at other locations within the motor end-plate will result in a widened distance between the nerve terminal and the receptors, which can explain previous interpretations of a presynaptic defect in MG.


Immunological observations on patients with Wilson's disease. In 19 patients with Wilson's disease we found an increased humoral immune response, i.e. a higher level of IgG and IgM, a higher titre of antibodies against Kunin's CA antigen and a depressed cell-mediated immunity i.e. a lower response to DNCB and E. coli in skin tests, lower lymphocyte transformation when stimulated by Con A, PPD, Candida albicans and streptokinase and a lower production of macrophage migration inhibition factor. The changes observed in the group of patients with liver cirrhosis caused by other facotrs than Wilson's disease were similar but less pronounced. We also found that leukocytes of patients with Wilson's disease have an impaired bactericidal activity and that copper ions have an inhibitory effect on some tests for cell-mediated immunity. It seems probable that immunological abnormalities in Wilson's disease are caused by liver cirrhosis but we cannot exclude an inhibitory effect of copper ions upon the immune response and an associated effect upon leukocyte metabolism.


The effect of hypocapnia and change of blood pressure on cerebral blood flow in men with cervical spinal cord transection. Cerebral blood flow (CBF) was measured by a 133Xe inhalation technique in 8 patients with chronic high spinal cord injuries. Six patients had a physiologically complete cervical cord transection and 1 subject had an incomplete C4-5 lesion but with evidence of interruption of sympathetic pathways. CBF and arterial blood pressure (BP) were measured in the supine position and then in the sitting, or feet up, position to produce a change of BP. In 4 patients CBF was measured during a suction manoeuvre applied to the lower half of the body to produce a fall of BP. There was no significant change of CBF in the patients during hypo- and hypertension. The response of CBF to hyperventilation for 5 min was measured in the supine position and did not differ significantly from that of 13 normal "control" subjects and 1 patient with a lesion at T2-3. It is concluded that the responses of the cerebral circulation to change of blood pressure and to hypocapnia are normal in patients with high spinal cord transection. The mechanisms involved in these responses are therefore independent of control via cervical sympathetic pathways.


On the development of CNS lesions in natural canine distemper encephalomyelitis. Acute lesions within spinal cord white matter have been studied by light and electron microscopy in 3 dogs suffering from the acute form of canine distemper encephalomyelitis (CDE). Prominent features of these lesions were viral inclusions, giant cell formation, cellular degeneration, myelin breakdown and phagocytic activity by cells believed to be derived from local glia. The viral inclusions occurred in giant cells, many astrocytes, macrophages and occasional oligodendroglia. Only suggestions of active viral replication from cell membranes were present. On the basis of the above features, these CDE lesions were classed as being acute. Perivascular inflammation and parenchymal invasion by haematogenous cells were lacking. However, older, gliotic, demyelinated lesions were always associated with inflammation. The pattern of demyelination in acute CDE lesions differed from those seen in other conditions, in particular the autoimmune demyelinating diseases. In acute CDE lesions, individual fibres became separated from others by rings of cells, the processes of which systematically stripped the myelin from the outer layers of the sheath inwards until a naked segment of axon remained. Some of the macrophages were recognisable as astroglia. Elsewhere, unequivocal astrocytes containing myelin debris were common. The results suggest that inflammation in acute CDE lesions is not a primary event, and that viral invasion causes breakdown of tissue which is accompanied pari passu by myelin destruction. The latter might be related to the non-specific release of host factors (viz. hydrolytic enzymes) or humoral factors during the cellular degeneration. Local cells appeared to participate in the process of myelin phagocytosis. Overt inflammation and damage by haematogenous cells were features only of chronic lesions and have been described previously in studies on chronic CDE lesions. The results are interpreted in terms of their relevance to the study of human subacute sclerosing panencephalitis, of which CDE is considered the animal analogue, and multiple sclerosis, the paradigm of the human demyelinating diseases.


Spinal muscle in scoliosis. Part 1. Histology and histochemistry. Histological and histochemical techniques were employed in a study of the spinal muscles from 35 adolescent scoliotic patients. Many abnormalities were found and, in general, the changes were indicative of denervation and neuropathy. None of the abnormalities were found at any one site more frequently than at any other, nor were they more often seen on one side or the other. None of the patients examined were normal at all sites of biopsy. These findings provide evidence of a neuropathic process being involved in the aetiology or progression of scoliosis. So-called "idiopathic" scoliosis may, perhaps, be the result of an otherwise sub-clinical lower motor neurone disorder.


Spinal muscle in scoliosis. Part 2. The proportion and size of type 1 and type 2 skeletal muscle fibres measured using a computer-controlled microscope. The development of the computer-controlled microscope system described has made it possible to estimate accurately the contribution made to the muscle fibre population by both Type 1 and Type 2 fibres. This method is more convenient, and at least as accurate as manual methods. It is also possible to measure the size of the individual fibres using this system. The system has been applied to this study of the spinal muscles in scoliosis. The results show that there is a difference in the ratio of Type 1 to Type 2 fibres in the spinal muscles on the 2 sides of the curve. The difference is found only at the apex of the curve. The results demonstrate that there are more Type 2 fibres on the concavity of the curve at the level of the apex. This difference is due to a disparity in the number of each fibre type rather than a difference in their relative sizes. The imbalance of Type 1 fibres at the apex of the curve may provide a sustained muscle pull on the spine so causing a curve convex to that side.


Clinical effects of cyclophosphamide in Guillain-Barré polyneuritis. (1) Fifteen patients with severe Guillain-Barré polyneuritis in progression were treated with cyclophosphamide in a total of 23 courses. The illnesses in 11 patients were monophasic, 2 were biphasic and 1 was of the chronic, relapsing variety; another was possibly biphasic. Length of illness prior to first course of cyclophosphamide was as follows: less than 1 week, 3; 1-4 weeks, 9; greater than 4 weeks, 3. (2) Progression stopped in association with 21 courses of treatment, in 6 before the treatment course was finished and in 15 an average of 3 days after the last dose. Improvement began during or following 19 courses. (3) Time when progression stopped, time from end of progression to beginning of improvement, and subsequent rate of recovery, suggest that cyclophosphamide made a significant contribution to the recovery processes in 13 patients. (4) Ultimate degree of recovery was not significantly different from that expected in conventionally treated patients with monophasic illnesses. (5) Reversible alopoecia was the only significant complication attributable to cyclophosphamide toxicity. (6) Our experience suggests that further evaluation of cyclophosphamide should include the use of controls and earlier treatment.


Chronic neurologic disease in Theiler's virus infection of SJL/J mice. This study demonstrates that most SJL/J mice inoculated intracerebrally (IC) with 1000 suckling mouse 50% mean lethal doses of Theiler's encephalomyelitis virus (TMEV) develop flaccid paralysis 10-21 days after infection when there is acute spinal cord gray matter involvement (early disease). Surviving mice later develop a distinctive chronic neurologic disorder which is associated with marked mononuclear cell infiltrates and active demyelination in spinal cord white matter (late disease). Moreover, about one-fourth of infected animals only develop signs of late disease which may begin after an incubation period as long as 2 and a half months. Affected mice are less active, incontinent, and have a waddling, spastic gait. Minimal stimulation induces prolonged extensor spasms of all limbs. These late-developing manifestations of chronic TMEV infection are progressive and clinical remissions have not been observed. The effect of persistent CNS infection on general development was monitored by weekly measurement of body weight; however, the growth of chronically-infected mice was found to parallel that of control animals.


Analysis of serum immunoglobulins in hereditary sensory radicular neuropathy. Serum and salivary immunoglobulins were studied in 11 members of a family including 3 patients with hereditary sensory radicular neuropathy (HSRN) in 1 of whom serum immunoglobulins were measured over a period of about 6 years. It was confirmed that serum IgA and IgG levels rose as the disease progressed. Although our results do not agree, in part, with the findings of Whitaker et al. (1974) who reported an increase in IgA alone, the present study suggested that such dysimmunoglobulinaemia deserves further study. Whether dysimmunoglobulinaemia is a primary phenomenon related to the development of HSRN or simply a secondary change remains to be further explored.


Two patterns of results in polyneuropathies investigated with the H reflex. Correlation between proximal and distal conduction velocities. The Hoffman (H) reflex of the soleus muscle has been used to study peripheral neurological disorders in 79 cases of chronic renal insufficiency prior to the initiation of haemodialysis, and in 94 cases of chronic alcoholism. In both groups, care was taken to ensure that the subjects examined could not be suspected of any other type of neuropathy. The results have been compared with those obtained in 42 normal subjects. The nerve conduction velocity in the reflex pathway was evaluated by an H index formula in which the conduction time (interval between M and H responses) is related to the length of the nervous pathway (a function of the subject's height). This method demonstrated a marked reduction in the conduction velocity of the proximal parts of the peripheral nerves, in both uraemic and alcoholic subjects. The maximal amplitude of the reflex response was evaluated in relation to the maximal amplitude of the direct motor response (H max/M max). It was shown that this ratio diminishes very greatly and very rapidly in the course of alcoholic polyneuritis, while, at comparable conduction velocities, the amplitude of the reflex response is much less changed in chronic renal insufficiency. These results prove that there is a noteworthy difference between uraemic and alcoholic polyneuropathy. Its significance is discussed in the context of currently knwon histopathological and electrophysiological data on the polyneuritides. From a practical point of view, the H reflex appears to be an effective tool for the investigation of peripheral neuropathy in man.


Neurochemical findings in a perinatal sudanophilic leukodystrophy rich in steryl ester. Neurochemical and neuropathological studies have been made of a 10-day-old child who suffered from a sudanophilic leukodystrophy. The brain white matter contained abundant sudanophilic material. The patient's grey matter total cholesterol content was 30% higher than whole brain tissue derived from a comparable control. White matter cholesterol content was more than double the control value. Nearly 80% of the white matter cholesterol was esterified. Subcellular fractionation of the white matter resulted in a "floating fraction" rich in cholesteryl ester. The steryl ester fatty acid composition was not typical of control tissue or demyelinating tissue. Patient phospholipid fatty acid composition patterns differed from control, but white matter galactolipid fatty acid composition appeared normal. Cholesteryl ester hydrolase activity appeared normal. Myelin and myelin-like fractions, isolated from diseased and normal brain tissue, were of a primitive developing nature but appeared to be comparable. The findings indicate a neonatal sudanophilic leukodystrophy which doubtless began in prenatal life and which was rich in cholesteryl ester. The aetiology of the leukodystrophy is unknown.


Aspects of cortical organization related to the geometry of neurons with intra-cortical axons. Using the Golgi method, cells with intra-cortical axons in the visual cortex of young mice were classified according to defined geometrical axonal shapes. This study principally describes a computer technique and its application to the study of neuronal morphology. Neurons were converted in a sequence of three-coordinate points which were stored in digital form on magnetic tape. From the stored data and total real length in space of dendrites and axons was obtained and the results compared in two groups of mice raised under different conditions. Preliminary observations show short axonal lengths in mice raised in darkness. Using Eulerian coordinate transformations, reconstructions of individual neurons and of groups of several neurons and fibres were obtained by generating displays of different views after rotation around the horizontal axis. Reconstructed pictures were compared with their corresponding original drawings in order to describe particular aspects of cortical organization.


The openings of the central canal in the filum terminale internum of some mammals. Openings of the central canal in the filum terminale internum of the rabbit, guinea pig, and rat have been studied by light and electron microscopy. There were two openings in the rabbit, two or three in the guinea pig, and one in the rat. They opened dorsally and were of two types; one type was without a pial covering, the other with a pial covering. In both types, a focal junctional apparatus associated with increased density of the subjacent cytoplasm was observed between the pial cell and the ependymal cell at the margins of the opening, where the basal lamina on the surface of the filum terminale showed a characteristic ending for each species. Injections of india ink into the lateral ventricle of the brain indicated that the cerebrospinal fluid of the ventricular system drains out of the central canal by way of these openings, into the subarachnoid space. Reissner's fibre of the rabbit and rat consisted of a mass of moderately electron dense fibrous material containing many small vesicles in the central canal of the filum terminale. This mass passed through the openings into the subarachnoid space and continued into the subdual space.


A nucleolus-associated coiled body.

A nucleolus-associated coiled body. One or two healthy structures frequently have been observed attached to nucleoli in facial motor neurons of the golden hamster. These round-to-oval structures, called "coiled bodies", were seen at 15, 19, and 24 days postnatal and in the adult, both in normal neurons and in chromatolytic neurons which had been axotomized 4 days previously. With one exception, the coiled bodies were seen to be attached via fibrillar material to the nucleolar periphery. Although the numbers of coiled bodies may be altered during neuronal maturation and as a result of axon section, the bodies revealed no structural alterations that could be attributed to developmental age or to experimental trauma.


Acetylcholinesterase activity of synaptic structures in the spinal trigeminal nucleus. The electron microscope has been used to study the localization of acetylcholinesterase (AChE) activity in the spinal trigeminal nucleus of normal cats with special emphasis on the distribution near synaptic structures. Reaction product is found around both round and flattened synaptic vesicle-containing axon terminals, particularly in synaptic clefts and often specifically associated with the presynaptic, or less frequently the postsynaptic membrane. The presence of reaction product at these specific sites suggests that these are areas of high AChE activity and that acetylcholine may be important in neurotransmission in these regions.


Potential of Schwann cells from unmyelinated nerves to produce myelin: a quantitative ultrastructural and radiographic study. In adult mice, most fibres in the cervical sympathetic trunk (CST) are unmyelinated whereas a large proportion of sural nerve fibres are myelinated. This study of nerve grafts in syngeneic mice was designed to determine if Schwann cells originating from the unmyelinated CST would produce myelin when in contact with regenerating axons of the sural nerve. Quantitative microscopy of triated thymidine-labelled CST segments grafted to unlabelled sural nerve stumps revealed that, one month after grafting, previously unmyelinated grafts contained many myelinated fibres. By phase and electron microscope radioautography, nearly 40% of the myelin-producing cells in the reinnervated graft were shown to have originated in the unmyelinated CST. These findings indicate that Schwann cells originating from unmyelinated fibres are able to differentiate into myelin producing cells.


Ultrastructural study of plasma membrane GM1 in neuroectodermal cells using cholera-peroxidase. Cholera toxin was coupled to peroxidase to yield a highly specific marker for GM1 gangliosides. Study of embryonic brain cells in culture revealed intense binding of cholera-peroxidase by plasma membranes of both neurons and glial cells. In contrast, long-term monolayer glioblastoma cultures, including one producing C-type virus, revealed virtually no labelling of their plasma membranes. Such cells were shown to be capable of incorporating exogenously applied GM1 into their plasma membranes. Studies with fixed brain and synaptosomal fractions were in accord with results on embryonic brain cells in culture, and autoradiographic findings with 125I cholera supported observations made utilizing cholera-peroxidase. From our studies there is some indication that long-term propagation in vitro alters the plasma membrane GM1.


Morphological aspects of the elimination of polyneuronal innervation of skeletal muscle fibres in newborn rats. The ultrastructure of neuromuscular junctions of rat soleus muscles 1-40 days postnatally was examined for possible morphological correlates of the transient polyneuronal innervation which is present in newborn rats. Several vesicle-laden profiles of terminal axons are seen to contact each muscle fiber up to 8 days postnatally. Axon terminals often lie close together, without Schwann cell intervention. Between days 8 and 16 the number of profiles of terminals on each muscle fibre is reduced, and both Schwann cells and ridge-like extensions of muscle fibre cytoplasm intervene between and separate axon terminals. No signs of degenerating intramuscular axons or axon terminals could be found. It is suggested that the redundant terminals are eliminated by retraction into the parent axons. This process is apparently accomplished without any morphological signs of degeneration.


Peripheral nerve glycoproteins and myelin fine structure during development of rat sciatic nerve. Developmental changes in relative amounts of peripheral nerve proteins and glycoproteins have been correlated with the degree of morphological myelination at various ages during the first 25 postnatal days in rat sciatic nerve. At birth there is virtually no major myelin glycoprotein (P0), but there is a protein which migrates to the same point on sodium dodecyl sulphate (SDS) polyacrylamide gels as the small myelin basic protein (P2). During the time myelin is being formed in the nerve, the P0 protein increases and the P2 protein appears to decrease in relative amount in the nerve. The accumulation of P0 protein in the nerve correlates extremely well with the degree of myelination in sciatic nerve. At 4-6 days postnatal, smooth membrane profiles are observed which are located within axons and in the inner Schwann cell cytoplasm. Such profiles are also observed to fuse with the axolemma-Schwann cell interface. The profiles may represent membrane material being added to or deleted from the axolemma or myelin during myelination.


Activity and excitability to electrical current of cortical auditory receptive neurons of awake cats as affected by stimulus association. 1. Unit activity and excitability were studied at the midlateral and suprasylvian cortex of naive, blink-conditioned and "randomization" cats. The latter received the same CS and US as did the conditioned animals, but in random temporal order and with random intertrial intervals with mean comparable to that used for conditioning. The randomization group failed to develop a blink CR. 2. With conditioning, spontaneous and evoked unit discharges were increased above levels found in naive animals. Correspondingly, levels of extracellularly injected current required to elicit a spike discharge were lower in conditioned than in naive animals. In addition, in the conditioned animals, the degree of enhancement of evoked activity and excitability was found to be greatest in the units that responded to the CS, as opposed to units that responded to another auditory stimulus of equal intensity but of no special behavioral significance vis-a-vis the conditioned reflex. 3...


Effect of early exposure to patterned sound on unit activity in rat inferior colliculus. 1. Young rats were exposed to one of two patterns of sounds for 5 h daily during the first 4 mo of life. The up pattern consisted of a tone swept from 6 to 9 kHz in 1 s alternated with a 1-s noise burst. The down pattern differed in that the sweeps were from 9 to 6 kHz. 2. A pattern evoked more spikes, on the average, from units in the inferior colliculus of rats exposed to that pattern than from units in animals exposed to the other pattern. 3. The exposure effect was most pronounced in the unit responses to the noise-burst segment within a pattern suggesting a long-lasting, malleable influence of the tone sweep which defined the pattern. Responses to pattern noise components were less for both exposed groups than for the unexposed controls, suggesting that inhibitory mechanisms were responsible for the pattern discrimination evident in the responses of the exposed unit population. 4. Unit responses in unexposed rats were somewhat more selective for the down pattern so that the resulting shift in response selectivity was relatively more apparent for exposure to the up pattern. 5. While control and down-exposed units generally responded more to both the tone sweep and noise burst in one pattern, a large proportion of the up-exposed unit population continued to favor the down over the up-swept tone, but responded more to the up-pattern noise bursts. This suggests that the unit responses to the noise bursts did not simply reflect prolonged responses to the tone sweeps. 6. No similar effects were seen for units from mothers similarly exposed to the same patterns.


Regulatory actions of human stretch reflex. 1. The stretch reflex in the elbow flexor musculature was studied in 23 human subjects. The subjects were required to establish an initial force equivalent to 10% maximum at a prescribed initial length; mechanical disturbances delivered at random times increased load force to 15% or reduced it to 5%. We measured arm force, displacement, and EMG (usually biceps); acceleration was calculated from displacement, and average responses from sets of 10 like trials. 2. Modification of the stretch reflex was studied by comparing average responses obtained with different instructions, but with the same disturbance. The usual introductions were "compensate for arm deflection" and "do not intervene voluntarily". The initial response did not depend on instruction; changes in response that depended on instruction began abruptly after a latent period which ranged from 70 to 320 ms (measured from force and acceleration), depending on conditions and subject. The latency became longer (10-50 ms) and more variable when the subject did not know the direction of disturbance in advance. This and other observations indicate that modifications of the stretch reflex are not produced by servo actions. They are produced by triggered reactions, which occur at both short and long latencies and which have properties resembling the movements produced in a reaction-time task. 3. We confirmed that most subjects can suppress triggered reactions when the instruction calls for no intervention, leaving an unmodified reflex response. This response consists of a compliant deflection of the arm in the direction of the disturbance. 4. The compensatory actions associated with unmodified stretch (and unloading) reflexes were assessed from EMG responses of biceps. During a 300-ms transient phase, EMG changes were notably asymmetric when responses to symmetric disturbances were compared. Increased force stretched biceps and produced a prominent increase in EMG, whereas decreased force allowed biceps to shorten and produced either an EMG decrease of smaller magnitude or an actual increase. These asymmetric reflex actions produced quite symmetric mechanical responses (arm displacements and forces), which implies the existence of and compensation for nonlinear muscle mechanical properties. This result is discussed in relation to the hypothesis that the function of the stretch reflex is to compensate for variations in muscle properties, thus maintaining stiffness. 5. Effective control of muscle length or joint position does not result from servo action by the stretch reflex. Errors in position are corrected only when triggered reactions are superimposed on the reflex response.


Angiographic study of the growth of intracranial aneurysms. The authors have attempted to assess whether there is any standard rate of growth of intracranial aneurysms. Angiographic studies were performed on 67 patients with 82 aneurysms with intervals between angiograms ranging from a few days to 10 years. Examination of these records showed no consistent rate of change in size, possibly partly because of inherent inaccuracies in the method, which are discussed. The clinical reasons for the repeat studies are briefly mentioned. It is concluded that it is unwise to wait and see what may happen to any but perhaps the smallest aneurysm.


Lateral extracavitary approach to traumatic lesions of the thoracic and lumbar spine. The lateral extracavitary approach to the spine was used for resection of displaced bpne and disc located anterior to the dura in 62 patients with traumatic lesions of the thoracic and lumbar spine. Fifty-two patients had closed vertebral fractures and 10 had gunshot wounds. The spinal cord was involved in 44 patients, and the cauda equina in 18. A spinal subarachnoid block was demonstrated in 17 of 57 preoperative gas myelograms. Evoked potential recordings, although related to preception of joint rotation, tended to reflect the overall neurological condition and had some prognostic value. Significant improvement followed surgery in 46 patients with incomplete neurological lesions, and one was transiently worse. Before operation 18 patients were able to walk; nine with assistance and nine without. After operation 47 patients were able to walk; 12 with assistance and 35 without. Adequate bladder function was present in 17 patients before surgery, and in 44 after surgery. A laminectomy had been done previously in 16 patients, 11 of whom improved significantly after anterior resection. Spine fusions were required in 26 patients, five of whom had a prior laminectomy. The major factor in the pathogenesis of the incomplete neurological deficit appeared to be distortion of the cord and roots by displaced bone and disc. Consequently, the primary object of treatment was the restoration and maintenance of normal anatomical relationships between the spinal cord or cauda equina and the spinal canal.


Prediction of mobility gains in patients with cervical spinal cord injuries. A measure of mobility for patients with spinal cord injuries is introduced that is very useful in determining patient recovery. The index is used to obtain a prediction equation for motor skills 1 year after injury. Important predictor variables identified include the patient's sex, rectal status, total reflexes, two treatment combinations, motor and sensory neurological history since injury, neurological status, and initial mobility score. Interpretations are made to explain the meaning of the contributions of these variables and show the usefulness of the prediction equation.


Myelotomy for control of mass spasms in paraplegia. A new myelotomy knife is described and a procedure, designed to sever certain reflex connections while preserving as many corticospinal connections as possible, is presented. Through intermittent dorsal midline incisions the gray matter lateral to the central canal is severed bilaterally under the microscope from L-1 to S-1. This procedure relieved mass spasms and hyperactive reflexes in 14 paraplegic or tetraplegic patients, but preserved postural reflexes and whatever voluntary motor power the patients had prior to myelotomy. Before myelotomy all patients were bedridden. Afterward nine patients were able to use a wheel chair and five were able to walk with the use of parallel bars or crutches.


Brain abscess caused by Salmonella typhi. Case report. The authors report a rare case of a brain abscess associated with osteomyelitis caused by Salmonella typhi that remained in contact with human tissues for 33 years without losing its virulence.


Primary Burkitt's lymphoma of the frontal bone. Case report. The author reports a case of recurrent Burkitt's lymphoma in the left frontal region with extradural extension. Craniotomy was performed to relieve rapidly progressive intracranial compression. The patient received cytotoxic treatment postoperatively, with remarkable regression of the tumor.


Complications of halo-pelvic traction. Case report. When halo-pelvic traction is applied at a rapid rate it may induce cranial nerve palsies. The sixth, ninth, and tenth cranial nerves appear to be the most vulnerable. A proposed etiology is the stretching of these nerves resulting in a compromised blood supply with a consequent temporary paralysis which usually improves within 8 to 10 weeks.


New 68Ga-labeled skeletal-imaging agents for positron scintigraphy. The present skeletal-imaging agents labeled with radiogallium rely upon carrier gallium to augment bone uptake; no gallium-labeled bone-imaging agent free of this disadvantage is available. In attempts to develop such agents, we prepared 68Ga-ethylenediaminetetramethylene phosphonate (68Gs-EDTMP) and 68Ga-diethylenetriaminepentamethylene phosphonate (68Ga-DTPMP) and determined their biologic distributions in rats and dogs. These compounds combine the bone-seeking characteristics of phosphonic acid and the complexing ability of EDTA and DTPA analogs. The chelates are administered without gallium carrier. In rats, 50-60% of the carrier-free dose accumulates in bone at 1 hr after intravenous injection, while 25--30% is excreted through the urine. In dogs, at 3 hr after intravenous injection 35% is found in bone. Although the general patterns of organ distribution of the two 68Ga chelates are similar, 68Ga-EDTMP appears superior because of its faster blood clearance. Bone images obtained with this compound in dogs, using a multidetector positron camera, are presented. The optimum time for imaging was found to be 2.5--3 hr after injection.


A new nuclear medicine scintillation camera based on image-intensifier tubes. A large-field scintilation camera for nuclear medicine application has recently been developed by Old Delft. The system is based on a large-field image-intensifier tube preceded by a scintillator mosaic. A comparison is made with present state-of-the-art scintillation cameras in terms of modulation transfer function (MTF) and sensitivity. These parameters, which determine the performance of scintillation cameras, are not independent of each other. Therefore, a comparative evaluation should be made under well-defined and identical conditions. The new scintillation camera achieves considerable improvement in image quality. In fact, the intrinsic MTF of the new camera is rather close to unity in the spatial frequency range up to 1 line pair per centimeter (1p/cm). Further improvement would require a fundamentally new approach to gamma imaging, free of the limitations of conventional collimators (e.g., coded-aperture imaging techniques).


Procedures for receiving and opening packages containing radioactivity. A concise set of procedures is presented to aid laboratory personnel in complying with Part 20.205 of Title 10, Chapter 1, of the Code of Federal Regulations, concerning the receipt and monitoring of radioactive materials. Because these regulations were written for a large and diverse community of licenses, they are difficult to implement on a day-to-day basis. The procedures presented here reduce the regulations to an operationally functional form.


A simplified radiopharmaceutical accountability record-keeping system. A comprehensive system has been developed to ensure that a patient receives the proper radiopharmaceutical dose and that records of accountability are conveniently maintained. A radiopharmacy assay/utilization record serves as the control document for source products and derived new products. Color-coded numbered labels are used to maintain accountability among source products, derived products, prescriptions, logbooks, and patient doses. These measures have proved effective in simplifying documentation, minimizing dose-administration errors, and providing for radiopharmaceutical accountability.


Quenching curves: solutions by second-order polynomial regression. This paper describes an inexpensive practical approach for the automated computation of quench corrections in beta-scintillation experiments, using a table-top calculator. This approach applies a second-order fit, ax2 + bx + c = y, where x is the channel A/B ratio for known quench standards and y describes efficiency. There is excellent agreement between measured values and the polynomial expression for most experimental A/B ratios.


Color functional images of the cerebral blood flow. Functional gamma imaging, in color, was established for regional cerebral blood flow (rCBF) using 133Xe. During 10 min after intracarotid injection of 133Xe in saline, 60 picture frames of the 133Xe clearance curve for the entire hemisphere were obtained. After nine-point smoothing, the rCBF for each of the 4,096 picture elements was calculated by two methods: the half-time method and the height-over-area method. Both the 133Xe clearance half-times and the calculated CBF values were displayed, using 13 steps of color, as functional CBF images of the brain. Images of peak count and total count were also displayed on the same frame of the color television. Forty-six studies, performed on 37 patients with various cerebral disorders, were divided into two types: diffuse and focal. In the diffuse type, a decrease in CBF was noted in cases of normal-pressure hydrocephalus; successful ventriculoperitoneal shunt operations were followed by recovery of CBF. Occlusion of the middle cerebral artery showed up as a wedge-shaped area of decreased CBF, even when the conventional brain scan looked normal. Increased perfusion to a tumor was frequently associated with decreased CBF in the rest of the lateral hemisphere; such a decrease could be improved by surgical removal of the tumor.


Origin and location on the oral activity in sequential salivary gland scintigraphy with 99mTc-pertechnetate. Conflicting views exist regarding the origin and location of the oral radioactivity seen in salivary gland scintigraphy with 99mTc-pertechnetate. The normal accumulation of oral activity was studied in a series of healthy subjects by sequential scintigraphy (anterior and lateral views) after intravenous injection of 2 mCi of 99mTc-pertechnetate. Ligation of the parotid ducts and/or cannulation of the submandibular ducts, which prevented their secretions from reaching the oral cavity, established that the oral activity was due entirely to radioactive saliva secreted by the parotid and submandibular glands. Pertechnetate mouthwash studies confirmed that radioactive saliva is absorbed to oral mucosa and that adsorption to the lingual mucosa in the major contributor to the oral activity. Pertechnetate uptake in sublingual and minor salivary glands of the oral cavity was not visualized, thereby invalidating scintigraphy in the study of these glands. In the diagnosis of salivary gland disorders, oral activity is a useful indicator of major salivary gland function.


A simplified approach to radionuclide venography: concise communication. A simplified method has been developed for performing radionuclide venography. The method makes use of the scintillation camera and a synchronized whole-body scanning bed. This technique permits a more integrated presentation of the data and is performed in conjunction with a standard ventilation-perfusion lung study. The total amount of 99mTc tracer injected is 2 mCi.


Diagnostic scintigraphic sign in epidural hematoma at the vertex: case report. Brain scintigraphy was described in a case of vertical (biparasagittal) epidural hematoma confirmed by contrast angiography. The anterior dynamic and static studies showed inferior displacement of the superior sagittal sinus, diagnostic of an epidural collection. Delayed static anterior and lateral images showed an increased vertical uptake with a crescentic and straight inner contour, respectively. A transaxial computed tomographic scan was negative.


The rim sign in epidural hematoma: case report. A case of epidural hematoma of 7 days' duration showed a rim sign in the dynamic and static brain images. The significance and value of a rim sign are discussed.


Abnormal rapid-sequence imaging in a patient with subdural empyema: case report. Static brain images in a patient with subdural empyema showed findings similar to those of a subdural hematoma. The rapid-sequence study, however, showed increased peripheral activity on the affected side. Since this finding suggested an inflammatory process, further neuroradiologic evaluation and immediate surgical treatment were undertaken. The significance of the rapid-sequence study in subdural empyema has not been reported previously.


Primary and secondary carcinomata with focal nodular hyperplasia in a multinodular thyroid: case report. A patient is described whose multinodular thyroid gland was found to have a primary papillary adenocarcinoma, a metastatic renal-cell carcinoma, and focal nodular hyperplasia. To our knowledge, this is the first case report of such an unusual combination. In a patient with known malignancy elsewhere, the possibility that a recent thyroid mass may be a metastasis should be considered.


"Owl eye" sign in thyroid nodule of papillary carcinoma: case report. A cold area within a benign autonomous thyroid nodule comprises the "owl eye" sign. A case of thyroid carcinoma is presented whose scan appearance simulates that of a benign autonomous nodule with the "owl eye" sign.


Technetium-99m labeling of human monocytes for chemotactic studies. Although the current use of 51Cr for the evaluation of monocyte chemotaxis has yielded encouraging results, certain properties of this radionuclide leave room for improvement. Technetium-99m was evaluated as an alternative label for this purpose. A cell loss of 50% was found, but the recovered cells showed excellent viability and function. Chemotaxis was measured using a modified Boyden's chamber and a lymphocyte-derived chemotactic factor. The chemotactic properties of 99mTc-labeled human monocytes were preserved, and an excellent correlation between radioactive measurement and microscopic counting of migrating cells was observed.


Localization of skeletal-imaging 99mTc chelates in dead cells in tissue culture: concise communication. Screening new agents for imaging myocardial infarcts and investigating the mechanism of cellular uptake and subcellular localization of these agents prompted us to develop a necrosis model in tissue culture. Live cells obtained from exponentially growing cultures and dead cells obtained from nutritionally depleted plateau-phase cultures were incubated with 99mTc-pyrophosphate, 99mTc-hydroxyethylene diphosphonate (99mTc-HEDP), 67Ga-citrate, and 45Ca-HEDP. For the bone-seeking 99mTc chelates, the ratio of dead to live cell radioactivity was 15--20 after 1 hr of incubation. On the other hand, no preferential binding of 67Ga-citrate was observed, indicating that the mechanism of 67Ga localization in infarcts is different from that of the 99mTc chelates. The death cells accumulated only twice as much 45Ca-HEDP or 45Ca-pyrophosphate as did live cells, possibly due to the carrier effect of calcium in the medium. The receptors for 99mTc chelates could be partially blocked by preincubating the dead cells with microgram amounts of Na-HEDP. Heat-denaturation of live cells also increased the localization of 99mTc-HEDP in the cells, and this uptake was proportional to the duration of heating. Bone-seeking 99mTc chelates could be used for marking dead cells instead of conventional staining methods.


Dietary fat level as affecting running performance and other performance-related parameters of rats restricted or non-restricted in food intake. The effect of food energy density on certain physical performance characteristics of rats was studied during ad libitum and weight-restricted feeding. After a 16-week treadmill training period, 48 young adult male Long-Evans rats were divided into six groups, receiving 20%, 40% or 70% of energy as dietary fat and fed ad libitum or 40% by weight of average ad libitum intake. They were run to exhaustion once a week. Increased dietary fat level was not correlated with superior running performance at either food intake level, although during restricted feeding the high fat group received 40% more energy than the low fat group. Lower body weight was correlated with increased running performance at both food intake levels. The rate of performance increase with decreasing body weight during food restriction was significantly higher for the low fat than for the high fat group. Water consumption was considerably lower during restricted than during ad libitum feeding. Plasma glucose was lower when the 70% fat diet was fed than when compared to the other fat diets at both levels of food intake, lower from day 8 on of restricted that during ad libitum food intake, and lower on day 15 than on day 8 of the restricted intake.


Influence of fat level and type of carbohydrate on the capacity of pectin in lowering serum and liver lipids of young rats. The effect of pectin on lowering cholesterol and fat concentration in tissues of the rat was investigated in relation to the level of fat and the type of carbohydrate. Groups of rats were fed nutritionally complete diets containing equal protein: energy, varied with 5% (low-fat, 2% corn oil plus 3% beff tallow) or 20% (high-fat, 2% corn oil plus 18% beef tallow) fat and cornstarch or sucrose as carbohydrate for 2 weeks. Although there were no interactions, the feeding of pectin reduced the cholesterol level in liver and serum from dietary cholesterol to a greater degree in rats fed the low-fat than in those fed the high-fat diet. This effectiveness also varied with type of carbohydrate. In the low-fat diet, this effectiveness was higher with sucrose than with cornstarch, but in the high-fat diet, it was reversed. The size of perirenal fat pads and the concentrations of total liver lipid and cholesterol were less in rats fed the high-fat pectin diet than in those fed the high-fat diet without pectin, indicating that pectin also had an ability to lower fat absorption. When the level of serum alkaline phosphatase was lowered, pectin was more effective in lowering cholesterol level. This phenomenon, however, seemed due to the type of carbohydrate and fat rather than the cholesterol in the diet. Dietary cholesterol had no effect on the size of perirenal fat pads, but increased liver lipid content greatly in rats fed the high-fat diet. Dietary pectin increased the rate of removal of serum cholesterol, and a similar trend was shown in liver cholesterol which had accumulated from the pre-fed hyper-cholesterol diet.


Metallothionein and its relationship to the metabolism of dietary zinc in rats. Metallothionein (MTN), a low molecular weight cytoplasmic metalloprotein has previously been implicated in the metabolism of Zn. Experiments were conducted with rats to determine the effect of feeding varying levels of dietary Zn for short periods on the increase or decrease in MTN-bound Zn. The results indicated that MTN-Zn in both liver and intestinal mucosal cytosol responded rapidly to an altered dietary Zn level and that serum Zn was directly related to the appearance of MTN. 65Zn absorption also responded rapidly to a change in dietary Zn and was inversely correlated with intestinal mucosal MTN-Zn. Hepatic 65Zn uptake appeared to be directly correlated with liver MTN-Zn. A 24 hour fast increased MTN-Zn in rats fed two different levels of Zn except in those rats that were previously treated with actinomycin D. The antibiotic, which blocks DNA-dependent RNA synthesis, appeared to block Zn uptake from blood to the liver. These findings offer support for the involvement of MTN in zinc metabolism.


myo-Inositol metabolism during lactation and development in the rat. The prevention of lactation-induced fatty liver by dietary myo-inositol. Effects of dietary myo-inositol deprivation were examined during prenatal and postnatal development and during lactation in the rat. The deficient diet contained no detectable myo-inositol while the supplemented diet contained 0.5% (w/w) myo-inositol while the supplemented diet ct contained 0.5% (w/w) myo-inositol at the expense of sucrose. Both diets contained 25% casein, adequate amounts of all known vitamins, choline, and essential fatty acids as well as 0.5% (w/w) phthalylsulfathiazole to depress myo-inositol contribution to the diet by microorganisms. Pregnant rats of the Holtzman strain were fed the respective diets during gestation and lactation, and pups were fed the corresponding diet after weaning until 3 months of age. There were no significant differen-es in body weight between experimental groups. Supplementation of the diet with myo-inositol significanly increased the levels of myo-inositol in plasma, liver, kidney, and intestine of pups at all ages examined, and significantly increased the levels of myo-inositol in the milk and mammary tissue during lactation. During lactation, the myo-inositol deprived dams developed severe fatty livers (31% w/w) characterized by diminished phosphatidyl-inositol (50%) and total phospholipid phosphorus (57%) levels as compared with controls. After weaning, the liver lipid content of the myo-inositol deprived dams returned to normal (4.5%). The data suggest that a possible threshold level of free myo-inositol (approximately 0.15 mumoles/g lipid-free tissue) was required to prevent fatty liver in lactating dams under these dietary conditions. Effects of the deficient diet on fertility were also examined. Based on sperm count and production of offspring, there were no differnences between the experimental and control males. Females of both groups showed equal ability to produce offspring.


Absorption of dietary beta-sitosterol in laying hens and its incorporation into the egg. Studies were undertaken to determine the dietary beta-sitosterol absorption in laying hens and its incorporation into the egg. Hens were divided into four groups and fed a commercial low-fat laying diet. Group 1 served as controls; the diet of group 2 was supplemented with 10% corn oil; group 3 with 4% plant sterols (emulsion in carboxymethylcellulose); group 4 with 10% corn oil and 4% plant sterols. The daily beta-sitosterol intake of hens in groups 1, 2, 3 and 4 was 0.036 g 0.095 g, 2 g and 2.56 g, respectively. After consuming the diets for 30 to 40 days, cholesterol and beta-sitosterol contents of the eggs were estimated by gas liquid chromatographic and mass spectrometric methods. Feeding corn oil with and without plant sterols increased cholesterol content of the eggs, while feeding plant sterols alone had no effect on egg cholesterol levels. The beta-sitosterol content of eggs from groups 1 and 2 was similar (60-66 mug/g yolk) and feeding plant sterols increased the beta-sitosterol content to a very small extent (82-90 mug/g yolk). Studies on the dietary beta-sitosterol and cholesterol absorption indicated that there was very little absorption of beta-sitosterol. In control hens, beta-sitosterol absorption was about 7% compared to 81% cholesterol absorption. Plant sterols feeding did not affect the beta-sitosterol absorption but reduced cholesterol absorption by 40%. Feeding corn oil alone did not affect cholesterol absorption. Failure to detect any significant amount of beta-sitosterol in these hens. At the peak radioactivity deposition in the eggs, only 2% of the absorbed beta-sitosterol radioactivity was found in the eggs of group 4 compared to 5% found in group 1, while cholesterol radiioactivity was nearly 4 to 5 times in both groups. These data suggested that laying hens synthesized specific lipoproteins for deposition in yolk.


Characteristic inhibition of in vitro swelling of purified rat liver mitochondria induced by Ca2+ or thyroxine by feeding rats a low casein diet. It has been shown previously by the author that the structure of rat liver mitochondria is changed by a low casein diet. In the present experiments, using the free fatty acid producing substances Ca2+ and thyroxine, and the free fatty acid sodium oleate, the influence of a 4% casein diet on the in vitro swelling process of purified rat liver mitochondria was investigated by following the decrease in optical density at 520 nm after addition of one of the swelling agents. Swelling due to hypotonicity was also investigated. Rats were fed the test diets for 80 to 100 days. Mitochondria were purified by washing three times; after each wash the isotonic suspension was centrifuged at 3,000 X g for 6 minutes. The results show that the in vitro swelling of mitochondria induced by Ca2+ or thyroxine was inhibited greatly in the early period of swelling in rats fed a low casein diet. By comparison to this, there was not a notable effect of a low casein diet on the rate of swelling induced by sodium oleate. But in the case of sodium oleate, the values of optical density were always higher in rats fed a low casein diet, and the differences between two groups were always significant. Swelling due to hypotonicity was not affected at all by a low casein diet.


The biotin requirement of rats fed 20% egg white. The biotin requirement of rats fed a diet based upon 62.4% sucrose, 20.0% egg white and 10.0% corn oil was determined using growth for 60 days as the cirterion. Maximal growth and maximal concentration of cholesterol in plasma occurred when the diet contained 2.00 mg biotin/kg. Growth depression was noted in one of two experiments in which 3.00 mg of biotin was present per kg of diet.


Maternal protein malnutrition during gestation alone and its effects on plasma insulin levels of the pregnant pig, its fetuses and the developing offspring. The effects of restricting protein intake on plasma insulin were studied in pregnant pigs, fetuses and the developing offspring. Pregnant pigs were fed diets containing 18%, 3% or 0.5% protein throughout the gestation period. At 10, 13 and 15 weeks of gestation, fetuses were removed from the uterus after bleeding the dam. Plasma samples were used for insulin determination by a radioimmunoassay procedure. At week 15 of gestation, plasma insulin levels were significantly higher in pregnant pigs fed 18% protein and also in their fetuses than in the other two groups. There was a high correlation between fetal insulin level and fetal growth rate (r = 0.84). Two-day-pld pigs from another set of pregnant pigs fed the diet containing 18%, 3%, or 0.5% protein during gestation were cross-fostered to control nursing dams and weaned at 4 weeks of age to a standard diet. Plasma smaples obtained at regular intervals were used for insulin determination. Offspring of pigs fed 0.5% protein during gestation had consistently low insulin levels in postnatal life in spite of cross-fostering and standard feeding after weaning. It appears that one of the stimuli which control maternal insulin secretion and placenta transfer is the maternal protein intake while severe maternal protein restriction might contribute to the low levels of insulin in the progeny during postnatal life.


Effect of glycerol on lipogenic enzyme activities and on fatty acid synthesis in the rat and chicken. The influence of glycerol on the rates of fatty acid snythesis in liver slices from rats and chickens in pieces of adipose tissue from rats was first studied. Then the effect of dietary glycerol on lipid metabolism in rats and cheickens was examined. Media containing 3 or 10 mM glycerol depressed the rate of glucose conversion to fatty acids in rat liver slices. However, media containing up to 25 mM glycerol did not influence the rate of fatty acid synthesis in chick liver slices. The inhibitory action of glycerol in rat liver slices might occur at the level of glucose (or glycogen) conversion to pyruvate because glycerol did not inhibit pyruvate or acetate conversion to fatty acids. Rats and chickens were fed glycerol containing diets for either 3 days or 3 weeks. Feeding diets containing 20.5 parts glycerol (22% of dietary energy) to rats or chickens did not influence the growth rate of the animals. However, substitution of 42.2 parts glycerol (43% of dietary energy) for glucose in the diet significantly depressed food intake and growth rate in both rats and chickens. The activities of citrate cleavage enzyme, fatty acid synthetase and malic enzyme in livers of rats fed the glycerol-containing diets were dramatically increased. However, this stimulation of enzyme activity occurred without a concomitant increase in the in vivo rate of fatty acid synthesis in the rat liver. In the chicken, unlike the rat, dietary glycerol did not stimulate but instead decreased hepatic malic enzyme and fatty acid synthetase activities. No significant differences in adipose tissue lipogenic enzyme activities or in the rates of fatty acid synthesis were observed in rats fed glycerol-containing diets. The lipogenic response to glycerol feeding depends on the species as well as the organ.


Leukocyte transketolase activity as an indicator of thiamin nutriture in rats. The purpose of this study was to evaluate the possibility of using leukocyte transketolase activity (TKA) as an index of thiamin status. It was shown previously that hepatic TKA in rats is altered by changes in the type and amounts of carbohydrate, protein, and fat in the diet. It was, therefore, essential to determine whether leukocyte TKA in rats is affected by dietary factors other than thiamin intake. Hepatic TKA and leukocyte TKA both varied with dietary thiamin intake; maximum activity was attained when the diet contained 3 to 4 mg thiamin/kg diet. Administration of oxythiamin resulted in decreases in TKA in both liver and leukocytes. The changes in leukocyte and hepatic TKA induced by varying degrees of thiamin deficiency were closely correlated. The responses of thiamin content were also closely correlated in liver and leukocytes. However, only hepatic TKA was altered by increasing the fat or protein content of the diet or by substituting fructose for glucose. None of the dietary manipulations studied except the production of thiamin deficiency had any effect on leukocyte TKA. We conclude from our results that leukocyte TKA is a sensitive and specific indicator of thiamin nutriture in rats.


The role of thiamine on excitable membrane of crayfish giant axon. Electrophysiological and biochemical studies were performed to determine the role of thiamine in the excitable membrane of the crayfish giant axons, as it has been suggested that thiamine plays a role in the excitability of the membrane which is unrelated to the metabolic process. Thiamine (5mM) significantly increased the rising rate of the action potential without affecting the resting membrane potential and threshold potential. A recovery of the enhancement was evidenced by a wash of the axon with physiological solution. Pyrithiamine (10 mM) reduced the rising rate of the action potential without affecting the membrane and threshold potential. The reduction of dV/dt by pyrithiamine remained unchanged after a wash of the axon with physiological solution, while dV/dt increased after thiamine treatment. The amount of thiamine found in the crayfish axons was comparable to that observed in the rat sciatic nerve. In addition, pyrithiamine reduced the thiamine content in axons and protein binding thiamine of the axons. It is thus concluded that thiamine in the excitable membrane of crayfish axons plays a significant role in production of the action potential and is essential for maintaining the membrane excitability of crayfish axons.


Absorption, utilization and clinical effectiveness of allithiamines compared to water-soluble thiamines. Oral administration of lipid-soluble allithiamines [thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide (TTHF)] rapidly increased thiamine activity in whole blood, red blood cells, cerebrospinal fluid, and urine in normal and thiamine-deficient subjects. These thiamine congeners also restored red blood cell transketolase to normal in alcoholics with thiamine deficiency. Such repletion equaled that produced by parenteral, water-soluble thiamine hydrochloride (THCl) or thiamine pyrophosphate (TPP). Oral administration of water-soluble thiamines (THCl, TPP) neither elevated thiamine activity in biological fluids nor restored transketolase activity to normal in alcoholics with thiamine deficiency presumably due to their rate-limited intestinal transport. Oral administration of TPD eliminated lateral rectus palsy in patients with Wernicke's encephalopathy. Orally administered allithiamine vitamers are therefore recommended for prophylaxis and treatment of thiamine deficits because while having essentially the same biological properties as parenterally administered water-soluble thiamines they have not produced any untoward effects after long-term administration and are far more efficiently utilized.


Reactivation mechanisms of thiamine with thermostable factors. It was observed, in vitro, that the water extract of the fermented-tea customarily chewed by Thai people has a similar thermostable thiamine-inactivating factor to that found in the water extract of fern. It was also observed that the percentage of thiamine disulfide formed from thiamine with some flavones, catechol, pyrogallol, caffeic acid, dihydroxyphenylalanine, and hemin is greater at pH 7.5 than at pH 7.0. With some flavonoids, such as quercetin, rutin, and 6,7,4'-trihydroxyisoflavone, and pyrogallol, hemin, catechol and caffeic acid at pH 7.5, around 30-100% of thiamine is changed into thiamine disulfide. Water extract of shiitake, okra, coffee, black tea and fukinoto have only weak activities of thermostable thiamine-inactivating factors as a large percentage of thiamine disulfide is formed from thiamine even at pH 7.0. 2-Methyl-4-amino-5-aminomethylpyrimidine was isolated from the reaction mixture of 1 g thiamine with 20 mg catechol (1:0.5 mole) at pH 7.0, 45 degrees C, and identified with the synthesized pyrimidine.


Effect of field size on red--green color mixture equations. Red-green color mixture equations were measured in 10 color-normal observers for fields of view varying from 30' to 10 degrees. The G/R mixture decreases continuously as field size is increased. The data are consistent with the interpretation that the cone visual photopigments decrease exponentially in effective optical density as the field size is increased.


Luminance and opponent-color contributions to visual detection and adaptation and to temporal and spatial integration. We show how the processes of visual detection and of temporal and spatial summation may be analyzed in terms of parallel luminance (achromatic) and opponent-color systems; a test flash is detected if it exceeds the threshold of either system. The spectral sensitivity of the luminance system may be determined by a flicker method, and has a single broad peak near 555 nm; the spectral sensitivity of the opponent-color system corresponds to the color recognition threshold, and has three peaks at about 440, 530, and 600 nm (on a white background). The temporal and spatial integration of the opponent-color system are generally greater than for the luminance system; further, a white background selectively depresses the sensitivity of the luminance system relative to the opponent-color system. Thus relatively large (1 degree) and long (200 msec) spectral test flashes on a white background are detected by the opponent-color system except near 570 nm; the contribution of the luminance system becomes more prominent if the size or duration of the test flash is reduced, or if the white background is extinguished. The present analysis is discussed in relation to Stiles' model of independent eta mechanisms.


Cryoimmunoglobulin IgGk with microtubular ultrastructure associated with pyoderma gangrenosum. Recurrent gangrenous leg ulcers were associated with a monoclonal IgGk cryoglobulinaemia, though without overt myeloma. Cryoprecipitation of the serum in vitro gave a reversible gel with microtubular structure, built from the monomer and with a high degree of order. The same structure was found distending the superficial vessels of the ulcer biopsy, as well as extravascularly. There was no vasculitis, and luminal obstruction appeared responsible for the ulceration. Microtubular structures occur in nature among diverse proteins and viruses. The protein studied here is similar to a reported instance of myeloma cryo-IgGk.


Cardiac biopsy in skeletal myopathy: report of a case with myocardial mitochondrial abnormalities. Transvenous right ventricular endomyocardial biopsy in an 11-yr-old boy with a proximal skeletal myopathy and a cardiomyopathy, has shown a major increase in mitochondrial size and numbers on electron-microscopic morphometry, with formation of unique ring-shaped mitochondria in cardiac muscle cells. The significance of this finding and the use of cardiac biopsy in children are discussed.


Aspirin damage in the rat kidney in the intact animal and after unilateral nephrectomy. Aspirin caused epithelial hyperplasia, papillary necrosis with calcification and cortical changes in the rat kidney. After unilateral nephrectomy the lesions appeared more rapidly and were more severe. In the electron microscope the earliest changes were observed in the interstitial cells.


Inflammatory cells in duct-ligated salivary glands of the cat: a histochemical study. Inflammatory cells were studied in submandibular, sublingual and parotid glands of cat following ductal ligation. Macrophages were seen within the parenchyma and associated with extravasated mucin, and were possibly of importance in removing secretory material. Neutrophils were seen interstitially and within the parenchyma. Eosinophils were involved in an initial inflammatory response in interstitial tissue. Fibrous connective tissue was more apparent.


Histologic study of biliary fibrous remnants in 48 cases of extrahepatic biliary atresia: correlation with postoperative bile flow restoration. The fibrous remnants of bile ducts that were removed at surgery for extrahepatic biliary atresia were studied by serial section. Forty-eight specimens were classified into three types on the basis of histopathologic changes in the proximal portions of the speciments from the vicinity of the porta hepatis: (1) connective tissue without glands or other epithelial structures (15 cases); (2) connective tissue containing glands lined with cuboidal epithelium (15 cases); (3) connective tissue containing central biliary ducts and peripheral glands (18 cases). Histopathologic changes in sections from distal portions of the specimens did not conform to this classification. A precise correlation of prognostic significance could not be established between these histologic data and postoperative restoration of bile flow, although failure to restore flow was encountered most frequently in cases without demonstrable ducts or glands (TYPE 1).


Functioning thyroid masses in childhood and adolescence. Clinical, surgical, and pathologic correlations. Six girls, aged 5 to 15 years, presented with thyroid masses in otherwise nonpalpable thyroid glands and with normal serum thyroxine levels. Scintiscanning before and after TSH stimulation confirmed the presence of autonomous nodules in the four adolescents, of whom two had elevated T3 levels. Surgical exploration revealed adenomatous thyroid hyperplasia in three of the girls and papillary adenocarcinoma in the fourth. Scans in the other two girls revealed absence of the left lobe. One of them proved to have agenesis of the left lobe with enlargement of the right lobe because of lymphocytic thyroiditis. The other girl had an ectopic thyroid with chronic inflammation. A thorough diagnostic evaluation of single or multiple functioning thyroid masses in children and adolescents is essential in establishing the correct diagnosis. The possibility that carcinoma can occur in autonomous nodules as well as in hemiagenesis and ectopic thyroid tissue is discussed. An approach to the management of functioning thyroid masses in the pediatric age group is proposed.


Circulating bound and free estradiol and estrone during normal growth and development and in premature thelarche and isosexual precocity. Serum concentrations of unconjugated estrone, estradiol, and free estradiol, were determined in normal neonates, prepubertal children, adolescents, and adults. The values were compared with those obtained in children with premature thelarche and female sexual precocity. Unconjugated E1 and E2 fell rapidly, and the percentage of FE2 more gradually during the neonatal period and remained low prepubertally. During adolescence girls had greater increases in E1 and E2 while the percentage of FE2 was higher in boys. In premature thelarche  only the FE2 was significantly increased. In sexual precocity E1, E2, and FE2 were elevated. Reference standards are provided in Tables I and II for use in the diagnosis of conditions with under- or overproduction of estrogens during growth and development.


Antibody deficiency and alopecia.

Antibody deficiency and alopecia. Three patients are described with antibody deficiency, recurrent infections, and alopecia. One patient had congenital agammaglobulinemia; the other two patients, a brother and sister, had an incomplete antibody deficiency syndrome. The loss of hair in each patient was total; the history was typical of alopecia areata. The association of alopecia and antibody deficiency has not previously been described to our knowledge in children.


Deficiency of adenosine deaminase not associated with severe combined immunodeficiency. The 12-year-old Kung (""Bushman'') boy from South West Africa who has marked deficiency of red cell adenosine deaminase has been found to have 2 to 3% of enzyme activity in red blood cells, 10 to 12% in leukocytes, and 10 to 30% in cultured fibroblasts. The enzyme has ADA 1 electrophoretic mobility: SV40 transformation of cultured fibroblasts caused a decrease of ""tissue ADA'' and an increase in ""red cell ADA'' isozymes. A battery of investigations revealed that the child has normal humoral and cellular immunity. A family study showed that a sibling had the same level of red cell ADA and the parents had intermediate levels. Studies of the Kung population from which the child comes have shown that the allele responsible for the condition, and which we designate ADA8, is polymorphic.


The chondro-osseous dysplasia of adenosine deaminase deficiency with severe combined immunodeficiency. Three children, two of them siblings, with severe combined immunodeficiency and adenosine deaminase deficiency died within the first six months of life from the complications of acute bacterial infections. Subtle radiographic abnormalities were seen at the costochondral junctions, at the apophysis of the iliac bones, and in the vertebral bodies. At autopsy, the thymus showed evidence of early differentiation and, in one instance, aborted Hassall's corpuscles. Histologic study of the bone disclosed lack of organized cartilage columnar formation, large lacuni containing hypertrophied cells, and lack of trabecular formation with uninterrupted areas of calcified cartilage. These changes are distinctly different from those observed in the metaphyseal chondrodysplasias or in other chondrodystrophies.


Infection of the urinary tract after anti-reflux surgery. Two hundred twenty-three children who underwent anti-reflux surgery were evaluated. Pyelonephritic scarring was more apt to occur with greater degrees of reflux. Postoperative infection was principally confined to the bladder and occurred primarily in females. The beneficial effect of anti-reflux surgery is discussed.