A new method for quantifying ventricular regularization during atrial fibrillation.

Atrial fibrillation (AF) characteristically results in random variation of the intervals between successive ventricular depolarizations. However, when a patient with AF is treated with excessive amounts of digitalis, regular junctional rhythms may occur. The detection of "regularization" of the ventricular rhythm in patients with AF may signal early digitalis toxicity. In this paper, we describe a new method for quantifying the extent of ventricular regularization by the statistical analysis of the intervals between successive ventricular depolarizations (R-R intervals). This method yields a single index (Z score) which reflects the degree to which a sequence of R-R intervals deviates from a random distribution. Simulation studies demonstrate that our method is sensitive to "regularization" of as little as two to four percent of R-R intervals, even when equal intervals occur in small groups that might easily escape detection by visual electrocardiographic interpretation. Analysis of records from six nondigitalized subjects in AF shows that the sequence of R-R intervals is usually random, or very nearly so. Records obtained from the same patients when digitalized often demonstrate more regularized activity, reflected by an index (Z score) which is higher than expected from chance deviation if a random process is assumed. Preliminary data also suggeest that exercise is associated with substantial regularization of ventricular depolarization.


The syndrome of normal electrocardiograms, accessory pathways and paroxysmal tachycardias.

Tachycardias may be associated with the pre-excitation syndrome, a short PR interval or a prolonged QT interval. This report describes seven patients whose electrocardiograms (ECGs) did not reveal any of the above-named conditions. All of the patients presented with syncopal episodes, and the history of palpitations was elicited in five of the patients. His bundle electrogram studies in all of the patients showed an essentially unchanged AH interval with atrial pacing rates up to 180 beats/min. This can only be explained by a total bypass of the AV node. Two of the patients were also paced from the ventricle, and an unchanged pacing stimulus to A wave interval was observed. This signifies in these patients a functioning bypass pathway in the retrograde direction as well. Thus it would appear that pre-excitation cannot by eliminated as a diagnostic possibility even if the ECG is normal.


Interaction of oscillatory processes: the effects of subthreshold A.C. current on sinoatrial nodal rhythm.

In this study of interactions occurring within the heart, isolated superfused strips of rabbit atria, containing the sinoatrial (s.a.) node, were subjected to sinusoidal subthreshold current pulses of varied frequencies and intensities. A.C. current from an R.C. oscillator was applied through a Grass stimulation isolation unit, push-pull connection, and non-polarizing (Ag-AgCl-KCl-Tyrode Agar-Agar) electrodes. A Grass polygraph and tachometer were used to record the applied pulses and nodal firing rates; simultaneous magnetic tape recordings were obtained and used for data analysis. Suction electrode recordings and oscilloscope displays were used to determine how the cyclic impulses affected cellular activity. The s.a. nodal rhythm was modified by subthreshold A.C. current applications; when frequencies were low, firing rates of the node were modulated by the A.C. and mean rates were reduced. As frequencies were progressively increased, slow waxings and wanings in heart rate were produced. These periodic fluctuations were not readily correlated with either the A.C. frequency nor the intrinsic nodal rate, but were representative of the difference between the two. As applied current frequency neared the pacemaker's intrinsic rate, a synchronization occurred and the discharges locked in at a specific phase of the applied current alternation. This synchronization maintained during slight further increases in A.C. frequency but above a critical rate this relationship broke down and the waxing and wanings in frequency of pacemaker rate again developed. It was concluded that pacemaker action of the s.a. node is effected by integration of cellular activity through electron coupling.


Isorhythmic Dissociation--a "physiological" arrhythmia.

The behavior of the sino-atrial mechanism in isorhythmic dissociation (IRD) was studied in 21 patients, nine with spontaneous IRD and 12 with artificially pacemaker-induced IRD following electrode placement for heart block. Successive P-P, R-R and P-R intervals and blood pressure (BP) fluctuations were determined and graphically interrelated at control and during IRD. Several features were observed: a. IRD was present only when the independent ventricular rate was close to the atrial; b. P rate oscillations closely followed the P-R interval-dependent BP fluctuations (mean difference 30 mmHg) during IRD. In cardiogenic shock and in severe hypertension IRD could not be achieved easily; c. While during complete dissociation or during 1:1 A-V conduction the sinus rate was remarkably constant (2-4 beats/min variations), it showed marked oscillations (differences of 6-19, mean 13, beats/min) during IRD. All the data and calculations support the theory that in most instances of IRD, the arrhythmia is sustained by the normal physiologically active baroreceptor reflex arc.


The earliest electrocardiographic sign of acute transmural myocardial infarction.

A 43 year old man had serial 12-lead electrocardiograms (ECG) in the early phase of an acute anterior transmural myocardial infarction. In addition to the ST-segment elevation and hyperacute T waves, the patient's ECG displayed increase in the R wave voltage, decrease and final disappearance of the S wave, merging of the R wave with the elevated ST-segment and formation of monophonic curves. Such ECG patterns have been noted in the early phase of experimental coronary occlusion in the dog and in patients with Prinzmetal's angina. The clinical implication of this observation is discussed.


Intra-His bundle block in acute myocardial infarction. Report of two cases.

Two patients with acute intra-His bundle block, both secondary to myocardial infarction, are described. The diagnosis of the block was proved by means of His bundle recordings during the phase of complete atrio-ventricular (A-V) block. Two His bundle potentials, one (H) following each A wave and the other (H') preceding each QRS complex, were detected. In both cases, as well as in the few cases reported in the literature, the site of the infarction was in the inferior wall, an occurrence which shows the functional importance of the posterior blood supply to the His bundle. In both cases the block developed into a chronic form, requiring the implantation of a transvenous pacemaker in one case. This evolution suggests that the post-infarction intra-His bundle block may be due to irreversible anatomic damage.


Metabolic clearance of rat prolactin in the lactating and non-lactating rat.

The metabolic clearance of rat prolactin, assessed by the continuous infusion to equilibrium method, increased from 0-77 to 2-15 ml/min in lactating and from 0-65 to 1-75 ml/min in non-lactating rats as the infusion rate was increased from 100 to 472 ng/min. The clearance rate of rat prolactin did not increase when large doses of ovine prolactin were infused simultaneously with rat prolactin. The clearance rates computed from equilibrium levels of immunoreactive 131I-labelled rat prolactin in plasma were highly correlated with, but were considerably greater than, those computed from unlabelled rat prolactin which was infused simultaneously. In lactating and non-lactating rats, the clearance of each prolactin tested (RP-1, B-1, Nicoll's secreted and 131I-labelled) increased and had stabilized within the 30-35 min of infusion of each new higher dose of the hormone. The ability of the rat to clear quickly greater amounts of prolactin from the circulation as the infusion rate increases implies that plasma prolactin concentrations do not necessarily mirror the rate of prolactin secretion from the pituitary.


Concentration of prostaglandin F2alpha and steroids in the human corpus luteum.

The concentration of prostaglandin F2alpha (PGF2alpha), progesterone, pregnenolone, oestradiol-17beta, oestrone, androstenedione and testosterone was measured in corpora lutea obtained from 40 women at various stages of the menstrual cycle. The concentration of PGF2alpha was significantly higher in corpora lutea immediately after ovulation (26-7 +/- 3-9 (S.E.M.) ng/g, P less than 0-005) and in corpora albicantia (16-3 +/- 3-3 ng/g, P less than 0-005) than at any other time during the luteal phase. There was no correlation between the concentration of PGF2alpha, and that of any steroid. The progesterone concentration was highest in corpora lutea just after ovulation (24-9 +/-6-7 microng/g) and in early luteal groups (25-7 +/- 6-8 microng/g) but declined significantly (P less than 0-05) to its lowest level in corpora albicantia (1-82 +/- 0-66 microng/g). The concentration of oestradiol-17beta in the corpus luteum and luteal weight were significantly greater during the mid-luteal phase than at any other stage (concentration 282 +/- 43 ng/g), P less than 0-05; weight 1-86 +/- 0-18 g, P less than 0-005). The results indicate that regression of the human corpus luteum is not caused by a rise in the ovarian concentration of PGF2alpha in the late luteal phase of the cycle.


Sites of steroid production in ovine graafian follicles in culture.

The follicular components responsible for the synthesis of oestrogen, testosterone, and progesterone have been localized by studying in vitro the steroidogenic capacity of (1) intact follicles, (2) opened but undisturbed follicle walls, (3) isolated thecal shells, (4) granulosa cells and (5) co-cultures of thecal shells and granulosa monolayers. Oestrogen was secreted throughout the five-day culture period by intact follicles and explants of follicle wall. Neither the isolated thecal shell nor the membrana granulosa alone secreted oestrogen in vitro, but granulosa cells converted exogenous testosterone to oestrogen during the first few hours after explantation. A limited and transient production of oestrogen occurred in co-cultures of theca and granulosa. Testosterone was secreted in the presence of FSH in approximately equal amounts by intact follicle, follicle wall and thecal shells. No testosterone was secreted by the isolated granulosa cells. Progesterone was secreted by each cellular component but the highest output occurred where granulosa cells were grown in monolayer culture. The results indicate that the theca is the source of follicular androgen synthesis but that an interaction between theca and granulosa is required for the production of oestrogen. It is postulated that direct contact between two cell components is important in the modulation of steroidogenic function within the follicle.


Prostaglandin A2 at low rates of infusion restores the antidiuretic effect of vasopressin in lithium-treated rats.

To test the effect of prostaglandin A2 (PGA2) on renal function, infusions of PGA2 (0-7 ng/kg/min), arginine-vasopressin (AVP) (1-25 ng/kg/min) and PGA2 plus AVP were administered to male rats made resistant to the antidiuretic effect of AVP by pre-treatment with lithium. In non-lithium-treated control rats, AVP had its expected antidiuretic action but in lithium-treated rats neither urinary volume nor osmolarity was changed. Prostaglandin A2 alone had no effect on urine output in lithium-treated rats; AVP plus PGA2 infused together evoked a near normal antidiuretic response. This antidiuretic action of PGA2 contrasts with the diuretic action reported by others. However, our infusion rates were 300-4000 times lower than those of other workers and it is suggested that PGs may have opposite actions on the kidney depending on their concentration. The effect of indomethacin (a blocker of prostaglandin synthesis) on urine flow was tested in five groups of rats on different régimes of liquid intake. Urine flow was reduced in the three groups with the highest urine volumes before treatment, and increased in the two groups with the lowest urinary volumes, again indicating that PGs may have both diuretic and antidiuretic actions.


Effect of sex and age at gonadectomy on the sebaceous response to progesterone.

The effect of progesterone on the rate of sebum secretion was examined in intact and gonadectomized rats. In intact, adult, male rats, progesterone administered for 3 weeks decreased sebum secretion; after castration of adult males, progesterone increased sebum secretion and an even greater response occurred in male castrated at 21 days of age. In intact, adult, female rats progesterone slightly increased sebum production. As in the male, the response was affected by the time of gonadectomy, a greater response occurring after spaying at 21 days compared with 10 weeks of age. Thus, the response to progesterone in the adult rat differs in intact males and females and is affected by changes in the endocrine environment induced by gonadectomy, especially near the time of puberty.


Binding and uptake of trypan blue by developing oocytes of Locusta migratoria migratorioides.

Resorbing oocytes are heavily stained by trypan blue injected into the haemolymph; this serves as a basis for a quick and convenient method for measuring the degree of resorption. Oocytes in the beginning of their development are most susceptible towards resorptive tendencies. The uptake of trypan blue by normally developing oocytes is proportional to the oocyte surface. From 'double-marker' experiments, in which trypan blue is injected into the haemolymph together with [3H]inulin (which does not bind to the oocyte membrane) it is estimated that the contribution of binding in the interiorization of trypan blue is in the order of 80%, under the conditions given. In vitro incubations show the interaction of trypan blue with the membrane to be electrostatic in nature.


An autoradiographic analysis of nucleic acid synthesis in the presumptive primordial germ cells of Xenopus laevis.

Microinjection of [3H]thymidine into Xenopus laevis embryos between late blastula (stage 10) and early tadpole (stage 44) showed that the presumptive primordial germ cells synthesis DNA between stages 10-33. The percentage of labelled cells was highest between stages 10 and 16, declined sharply between stages 22 and 26 and rose again between stages 26 and 33. The fluctuations in the labelling patterns together with increase in the number of presumptive primordial germ cells and direct observation of germ cells in mitosis suggested that the germ cells divide three times between stages 10 and 44. The first divisions probably take place during gastrulation (stages 10-12), the second relatively synchronously at about stages 22-24 and the third series again relatively synchronously about stages 37-39. This period of proliferative activity is distinguishable on the one hand from the cleavage divisions in which the number of germ cells does not increase and on the other hand from the next proliferative phase by a period of mitotic inactivity. Microinjection of [3H]uridine showed that the presumptive primordial germ cells synthesize RNA only in mid-gastrula to early tail-bud-stage embryos. There is no obvious simple causal relationship between RNA synthesis and the movement of the germ plasm to the nucleus, or with division of the germ cells or with their migration out of the  endoderm.


[Ultrastructure of the embryonic mouse sinus node at the early stages of development (author's transl)].

At early stages of development in the mouse embryo (12-13 days post-coitum) the cells of the sino-atrial node are homogeneous but are different to the atrial myocardic cells at this stage of development or a younger stage (9-10 days post-coitum). Sino-atrial node cells are small; they have many ribosomes, the myofibrillar material and the Golgi apparatus are poorly developed. Membrane contacts are represented by simple appositions and some fascia adherentes. These cells show many pinocytic invaginations and subsarcolemmic vesicles. From the 14th day post-coitum the sino-atrial node becomes heterogeneous. 'Clear cells' are present in the middle part of the node; they are characterized by their irregular shape and the poor development of their myofibrillar material 'Dark cells' are observed at the periphery of the node and seem related to myocardial type cells described in the sino-atrial node of the late mouse foetuses. Our observations do not support the existence of a 3rd cellular population, called by some authors: 'transitional cells'. The problem of the segregation between sino-atrial cells and myocardial cells is discussed.


Characterization of an organ-specific differentiator substance in the planarian Dugesia etrusca.

A substance which inhibits brain formation in decapitated regenerating planarians (Dugesia etrusca) was characterized and partially purified. The substance's inhibitory activity was followed during each purification procedure by adding freshly decapitated animals of a standard size to each fraction, and later measuring the resultant regenerated brain volume. The inhibitory activity remained in the supernatant after a 10000 g centrifugation of a cell-free homogenate. Most of the activity sedimented when the 10000 g supernatant was centrifuged at 32000 g. The degree of inhibitory activity increased with increased numbers of animals in the initial homogenate. The substance has an apparent molecular weight between 2 X 10(5) and 4 X 10(5) daltons. Digestion by pronase destroyed the activity, but treatment with RNase, DNase I, or lipase had no significant effect. The inhibiting substance has an isoelectric point (pI) of between 4-75 and 5-38 and migrates to the anode when electrophorezed in pH 6-8 buffer.


Temporary contacts formed between developing optic fibers in the chick.

Temporary junctions were observed between developing optic fibers of the chick embryo and were distributed along the entire length of the axons from the cell body to the tip of the growth cone. These junctions were present in all material studied between days E-3 and E-18, the latter being the start of myelin formation of the optic tract. Junctions between adjacent axons were focal in nature and showed a decrease in the size of the intercellular space caused by a close apposition of the plasma membrane. With the experimental techniques used final identification of these junctions could not be made but are thought to be of two types--the gap and occludens junctions. Temporary fasciae adherentes junctions were observed at the end of the axon, between the growth cone and adjacent neural tissue. Speculation was made on the functional role of these temporary junctions.


Development of a placental blood circulation in rat embryos in vitro.

Rat embryos explanted with their membranes at head-fold stage (9 1/2 days gestation) formed an allantoic placenta which enlarged in culture and developed a foetal blood circulation. Embryos explanted at early somite stages (10 1/2 days) also formed a growing allantoic placenta but only after removal of most of the ectoplacental trophoblast. Assays of total protein in the embryo and placenta suggested that, in the absence of a maternal blood circulation to the placenta, embryo and placenta compete for the respiratory and nutritional resources obtained through the yolk-sac.


Regulation of pre-natal haemopoiesis: evidence for negative feedback control of erythropoiesis in the foetal mouse.

The effects of medium conditioned by erythrocytes on in vitro differentiation of mouse prenatal erythroblasts were examined. Haem synthesis was inversely proportional to the concentration of erythrocyte-conditioned medium (ECM) in either presence or absence of erythropoietin (EP), but concentrations of ECM which limited haem synthesis to 50% of normal had no effect on changes in erythroblast numbers. ECM reduced uridine incorporation into RNA and limited the rise in incorporation due to stimulation by EP. ECM enhanced thymidine incorporation into DNA. This enhancement was additive with that due to EP, but appeared earlier. Thymidine labelling indices of liver cells were not changed by ECM in vitro. Serum from polycythaemic animals limited haem synthesis by EP stimulated foetal liver cells in vitro. These observations provide evidence for susceptibility of foetal liver erythroblasts to negative feedback control of differentiation, dependent on the concentration of circulating erythrocytes. Characteristic changes in kinetics of prenatal erythropoiesis in vivo can also be related to increasing erythrocyte concentration.


Pattern and polarity of sclerites in adult abdominal segments of Calliphora erythrocephala (Diptera): anlage rotation experiments.

The anlagen of imaginal histoblasts in the abdominal segments of Calliphora (higher Diptera) present an interesting problem, which bears on recent concepts employed in the consideration of spatial patterning in insects. They differ from imaginal discs with respect to larval organization and activity, and in the absence of the progressive pattern of genetic determination during the larval period, characteristic of imaginal discs. How is the adult pattern in the abdominal segments determined? The experiments presented here seek to clarify the spatial parameters involved in control of adult pattern and polarity in the adult segment. A series of 180 degrees rotations of hypodermal grafts bearing the anlagen singly, or in combination, or of larval intersegmental hypodermis, indicate that polarity is determined within the anlagen through interaction with local larval epidermis either before or during histoblast migration. The nature of the sclerites, too, is primarily carried by the anlagen rather than determined by intersegmental information. The whole question of 'determination of polarity' is set out more carefully than hitherto in the light of (a) observations of the movement of epidermal cells in other systems in response to disturbance of pattern, and (b) the obvious vectorial nature of the phenomenon, which cannot be a genetic matter, but one of cell axes and of the relation of cells to segment/organism. The demonstration that (i) hemitergite and hemisternite are primarily determined by the anlagen themselves, and not by larval intersegmental membranes; and (ii) evidence indicates an influence of epidermal cells of the larva on the differentiation (as well as polarity) of imaginal histoblasts, leads to the conclusion that neither of two models considered will account for the establishment of the adult abdominal pattern among the histoblasts at metamorphosis. These models are (a) of a segmental gradient, set by the intersegmental boundaries of the previous instar, to which imaginal cells respond by interpretation of positional information; and (b) of progressive compartmentalization of pattern within the anlagen, without reference to epidermal context.


Quantitative studies of the reactions to horizontal angular accelerations in axolotls. I. The head-turning reflexes of normal animals.

1. Artifically metamorphosed axolotls were exposed to both brief (impulse) and long-lasting horizontal angular accelerations on a turn-table. The animals responded with a head-turning reaction. 2. The general course of the reaction to impulse acceleration was independent of stimulus intensity. The velocity of the head movement first increased to a maximum exponentially and then decreased in a negative exponential manner. Stimulus intensity had a linear relationship to the mean maximum velocity and mean total angle covered by head-turning. The average velocity-time curves at various stimulus intensities differed only by a velocity factor. 3. During long-lasting constant accelerations the velocity of the head-turning increased to a maximum velocity in a sigmoid time-course and then decreased, first to a constant velocity, and then further. Mean values of the maximum velocity were correlated linearly with the stimulus intensity. 4. It was concluded that the head-turning reflexes in axolotls do not agree with the accepted movements of the vertebrate cupula and therefore are not a simple 'copy' of the afferent input. It is also suggested that the reaction threshold differes from that for the labyrinthine input.


The mechanism for co-ordinating metachronal limb movements between joined male and female Artemia salina during precopulatory behaviour.

Male and female Artemia salina swim in tandem pairs before copulation and during this period the metachronal rhythms of the individuals are entrained. Artemia entrain to pulsatile water stimulation of the head at frequencies between 4 and 6 Hz. The antennules are mechano-sensitive. Antennular responsiveness to  phasic input is very probably the actual mechanism by which interorganism co-ordination is achieved, as mechano-stimulation of other Artemia structures, electro-stimulation and photo-stimulation are ineffective modes of entraining metachronal movements.


Neuronal mechanisms for object discrimination in the weakly electric fish Eigenmannia virescens.

The peripheral sensory basis for object discrimination was investigated in the weakly electric fish Eigenmannia virescens. Single unit recordings were made from the primary afferent fibres in the posterior branch of the anterior lateral line nerve while the local electric field (self-generated and stimulated) was modified by external resistance and capacitance shunts. Both fibre types (probability and phase coders) responded differentially to capacitance and resistance shunts of equivalent impedence. The degree of response differentiation between the two shunting conditions varied with the intensity of the electrical stimulus at the receptor. These data suggest that the primary electroreceptors can discriminatively encode the two electrical characteristics of 'objects'. However, since the response of primary electroreceptors also varied with the spatial orientation of the shunting electrodes, central structures must play an important role in object discrimination.


The locust jump. I. The motor programme.

A motor programme is described for defensive kicking in the locust which is also probably the programme for jumping. The method of analysis has been to make intracellular recordings from the somata of identified motornuerones which control the metathoracic tibiae while defensive kicks are made in response to tactile stimuli. Three stages are recognized in the programme. (1) Initial flexion of the tibiae results from the low spike threshold of tibial flexor motorneurones to tactile stimulation of the body. (2) Co-contraction of flexor and extensor muscles followa in which flexor and extensor excitor motoneurones spike at high frequency for 300-600 ms. the tibia flexed while the extensor muscle develops tension isometrically to the level required for a kick or jump. (3) Trigger activity terminates the co-contraction by inhibiting the flexor excitor motorneurones and simultaneously exciting the flexor inhibitors. This causes relaxation of the flexor muscle and allows the tibiae to extend. If the trigger activity does not occur, the jump or kick is aborted, and the tibiae remain flexed.


The locust jump. II. Neural circuits of the motor programme.

1. Neural circuits which co-ordinate the motorneurones of the meta-thoracic tibiae of the locust in jumping and kicking have been investigated. 2. The fast extensor motorneurone is reflexly excited by the subgenual organ, by a network of cuticle strain receptors, and by Brunner's organ. The subgenual organ and the cuticle strain receptors are excited by tension in the extensor muscle and mediate a positive feedback which could help to produce the burst of fast extensor spikes which precedes a jump or kick. Brunner's organ is stimulated by pressure from the flexed tibia, and will be excited by the initial flexion and throughout the co-contraction phase of a kick. 3. A central excitatory connexion from the fast extensor to the slow extensor ensures that extensor muscle tension is as great as possible early in the co-contraction phase of a kick. 4. A central excitatory connexion from the fast extensor to flexor motorneurones is confirmed. This ensures that flexor muscle tension is great enough to keep the tibia flexed when the extensor muscle tension starts to develop before a jump or kick. 5. Reflex excitation of flexor motorneurones occurs in response to an extensor muscle twitch when the tibia is flexed. This helps to maintain the flexor connexion. 6. A receptor, the 'lump receptor', which is stimulated by flexor muscle tension only when the tibia is flexed, can inhibit the flexor motorneurones and may activate the trigger system which allows the extension of the tibia in a jump or kick. 7. Recptors in the suspensory ligaments of the joint inhibit the fast extensor when the tibia extends.


Prothoracicotropic hormone in Manduca sexta: localization by a larval assay.

1. A new method for the assay of insect prothoracicotropic hormone (PTTH) is described, using fourth instar larvae of Manduca sexta. Larvae neck-ligated at a critical time to prevent release of PTTH from the head fail to undergo the next larval moult. Such ligated larvae moult to fifth instar larvae or larval-pupal intermediates after injection of brain homogenates from Manduca larvae, pupae or pharate adults. The degree of response is proportional to the concentration of brain homogenate injected. 2. The source of PTTH in the pupal brain is the dorsal region of the protocerebrum containing the lateral neurosecretory cells. Microhomogennates of single pieces of brain showed activity with this method. 3. PTTH activity in partially purified extracts is water soluable, stable to boiling for 10 min, and is destroyed by Pronase or trypsin.


The effect of the spacing of background elements upon optomotor memory responses in the crab: the influence of adding or deleting features during darkness.

1. Study was made of the effect of separation between stripes in the visual field upon responses which indicate memory of those stripes. 2. The amount of separation between white stripes had very little effect, whereas response strength and the amount of separation between black stripes were directly proportional. 3. The presence of extra, non-displaced black stripes prior to or following displacement reduced the size of the memory responses. 4. The effects of the amount of separation in the two cases were comparable. In both situations the separation affected only the responses to displacement of the stripe borders nearest to the extra stripe. 5. The effect of extra stripes present prior to displacement was in turn affected by the duration of the dark period, whilst the effect of those present during the post-displacement period was not. This accounts for the larger effect of extra stripes present during the psot-displacement period. 6. By expanding stripe width during darkness it was possible to distinguish between the effects of distance between stripes and the amount of white space separating them. Reducing white space while distance remains constant causes reductions in response strength, whereas reducing the distance between a memory zone and the white space between it and the neighboring stripe increased the size of the memory response.


The Mauthner-initiated startle response in teleost fish.

1. A characteristic behaviour, the 'Mauthner-initiated startle response', was recorded and quantitatively analysed with high-speed cinematography (200 frames/sec) after vibrational stimulation in 11 of 13 teleost species which possess Mauthner cells. 2. The latency of the response is 5-10 msec. This behaviour has: (a) an initial phase, the 'fast-body-bend', lasting about 20 msec and consisting of a stereotyped displacement of the head and tail to one side and (b), a second phase, the 'return-flip', consisting of a non-stereotyped flip of the tail to the opposite side. 3. Within 100 msec after the start of the Mauthner-initiated startle response, most fish were displaced 0-5-1-5 body lengths from their initial position. The variability of the animal's location after 100 msec suggests that the behaviour is adaptively non-predictable; 4. In goldfish, the Mauthner-initiated startle response could also be elicited by visual stimulation. 5. We conclude that the fast-body-bend is the direct result of activation of one Mauthner cell and its spinal motor neurone pool. 6. In four species we described examples of apparently non-Mauthner initiated startle responses.


Regulation of rectal secretion in saline-water mosquito larvae living in waters of diverse ionic composition.

1. Larvae of the saline-water mosquito Aedes campestris were adapted to three waters, all having an osmotic concentration of 700 mOsm, but differing in ionic rations. The (Na+Mg) SO4 medium was much moretoxic than the NAHCO3 or the NaCl media. 2. Ionic and osmotic concentrations of haemolymph and rectal secretion were measured in larvae adapted to all three media. The ratio of ionic concentrations in the rectal secretion reflected those in the external medium to which the larvae had been adapted, with the exception of SO42-, which was possibly replaced by HCO3-in the secretion. These differences in rectal fluid composition persisted even though all ligated recta were bathed in the same artificial haemolymph. 3. The Malpighian tubules were found to be the major site of SO42- excretion. In media containing high levels of NA+, Mg2+, K+, Cl- and HCO3-, the rectum secreted a hyperosmotic fluid containing these ions at concentrations several times greater than those found in the haemolymph. 4. These data provide the basis for speculation on the functioning of anal papillae in waters of diverse chemical composition.


The role of fetal calf serum in the primary immune response in vitro.

The mode of action of 2-mercaptoethanol (2-ME) on the primary immune response in vitro was investigated. Fetal calf serum (FCS) was preincubated with 2-ME and lyophilized to remove free 2-ME. This 2-ME-treated FCS was able to substitute the function of adherent cells in the primary immune response against sheep red blood cells (SRBC) in vitro; Fractionation of 2-tme-treated FCS on a Sephadex G-100 column showed that 2-ME acted on a high molecular serum component which after activation, could substitute for macrophages. In order to obtain a humoral immune response against SRBC in vitro, spleen cells require selected FCS. These "good" sera could be distinguished from "deficient" sera by their higher content of this 2-ME-activated factor. The height of the in vitro immune response to SRBC was dependent on the amount of activated factor added to the culture medium. FCS normally required in the culture medium could be completely replaced by the factor-containing fraction without deleterious effect on the culture medium. The factor should be added to the spleen cells during the first 24 h of culture and remain there for 72 h in order to obtain an optimal immune response. The factor could be partially absorbed by spleen cells but not by SRBC. The relationship between macrophage, 2-ME, and FCS in eliciting an in vitro primary immune response is discussed.


Bile pigment formation by skin heme oxygenase: studies on the response of the enzyme to heme compounds and tissue injury.

Skin heme oxygenase is locally elevated by stimuli such as tissue injury and injections of whole blood, myoglobin, and hematin. The enzyme activity is also increased at the proximity of the injection site of chemicals such as cobalt and cobalt-protoporphyrin-IX (cobalt-heme). Protoporphyrin-IX, the tetrapyrrole nucleus of type-b heme compounds, was ineffective in altering the enzyme activity in vivo. The developmental pattern of heme oxygenase in skin was compared to that of the enzyme in liver. The enzyme activity in both organs was greatest during the 1st postpartum wk and declined to adult levels after 2 wk. The physiological implications of the increased activity of skin heme oxygenase are discussed, and it is concluded that the activity of the hepatic heme oxygenase system and that of the skin are regulated by the same mechanism.


Studies on congenital osteopetrosis in microphthalmic mice using organ cultures: impairment of bone resorption in response to physiologic stimulators.

The mechanism of congenital osteopetrosis in microphthalmic (mi) mice has been examined in bone organ cultures. Resorption was measured by the release of previously incorporated 45Ca in fetal long bones and newborn calvaria from mi mice and heterozygous or homozygous normal litter mates. Bones from mi mice showed a generalized resorption defect with decreased spontaneous or control resorption and failure to respond to parathyroid hormone (PTH), prostaglandin E2, 1,25 dihydroxy vitamin D3, vitamin A, or osteoclast activating factor (OAF) from human peripheral leukocytes or mouse spleen cells. Bones from heterozygotes showed a smaller response to PTH than bones from homozygous normals. Mutant bones failed to show an increase in lysosomal enzyme release in response to PTH or vitamin A, agents which increased release from bones of homozygous normals. Proline incorporation into collagenase-digestible protein was similar in cultures of normal and mutant bone and was inhibited by PTH and OAF. These results indicate that congenital osteopetrosis in mi mice is due to a generalized defect in the function and hormonal response of osteoclasts and suggests that this cell line is separate from the osteoblast cell line which shows no impairment of hormonal response.


[A new method for the preparation of linear polyacrylamide gradients (author's transl)].

Continuous linear gradients improve electrophoretic separations in polyacrylamide. They are obtained by overlayering equal volumes of two monomer solutions with different acrylamide concentrations, namely 180-260 and 23-50 g/l, in the usual gel tubes. The tubes are tilted 3-10 degrees to the horizontal, and rotated around their longitudinal axis until the parts of both solutions in contact are mixed homogeneously. Subsequent polymerization takes place in the vertical position. The more concentrated lower solution contains 4-nitrophenol, so that the final polymer concentration at any point of the gel can be measured densitometrically. The construction and handling of the rotation device are simple and yield highly reproducible results. This versatile method was evaluated for the separation of proteins, lipoproteins, and enzymes in human serum and yields 27-30 protein fractions by additional use of a pH-gradient.


Surface parasitism by Mycoplasma pneumoniae of respiratory epithelium.

Identification of the attachment factor on virulent Mycoplasma pneumoniae organisms which permits surface parasitism of respiratory epithelium was attempted. Brief pretreatment of M. pneumoniae monolayers with protease prevented mycoplasma attachment ot sensitive host cells without reducing viability of the microorganisms. Gel electrophoretic analysis of mycoplasma proteins before and after exposure of intact mycoplasmas to protease revealed the absence of a major protein species (P1) in enzyme-treated preparations while other protein bands with the exception of P2 were virtually unaffected. The absence of P1 correlated with the failure of enzyme-treated mycoplasmas to attach to tracheal explants. P1 regeneration after protease treatment of mycoplasma monolayers was directly associated with reattachment capabilities in M. pneumoniae. Erythromycin inhibited P1 resynthesis, thus preventing resumed attachment activity by mycoplasmas. Lactoperoxidase-catalyzed iodination of intact M. pneumoniae organisms further confirmed that P1 was an external membrane protein and suggested that his surface component was required for the successful membrane-membrane interaction between host and parasite.


[Enzymatic determination of total cholesterol with the Greiner Selective Analyzer (GSA-II) (author's transl)].

A fully enzymatic method to determine total cholesterol in serum is described. The method appears especially suitable for adaptation to discrete mechanical analyzers either of the single channel or the multi-channel type. The method uses the enzymes cholesterol esterase (EC 3.1.1.13), cholesterol oxidase (EC 1.1.3.6) and peroxidase (EC 1.11.1.7) with 4-aminophenazone and phenol as substrates in the indicator reaction. The method was adapted to the Greiner Selective Analyzer GSA-II. For this purpose the critical parameters of the reaction were intensively examined. The complete reagent is stable within the GSA II dispenser at 4 degrees C for at least 1 week. By omitting cholesterol oxidase in the blank reagent a sample bland and a partial reagent blank are obtained. Within a range up to 10.4 mmol/1 (4.0 g/l) the maximum colour is developed within 6 minutes. The calibration factor was stable for 4 months. The method allows absolute measurements. At concentrations between 2 and 4 mmol/1 within-batch precision ranged from 0.5 to 1.4%. Precision from day to day for the same control sera amounted to 2.8; 2.0; 2.7 and 2.0% for a period of 3 months. Examination of accuracy yielded satisfying results. Ascorbic acid in the physiological range did not alter results to a significant extent. Catalase or novaminesulfone added in vitro did not interfere. Optical interferences by bilirubin, hemoglobin or turbidity are compensated by a sample blank. A comparison of results with the enzymatic method of Roeschlau et al. (Z. Klin. Chem. Klin. Biochem. 12, 226 (1974)) yielded satisfactory agreement. The limits of detection of the present method can be lowered by a factor of 2.2 by replacing phenol by dihalogen phenols.


Eye movements and over rehearsal in wood recall.

Rates of overt rehearsal and eye movement were compared to each other, and were also compared as predictors of immediate and delayed recall, using practiced subjects who studied lists of eight simultaneously presented words. The correlation between number of eye fixations per word and number of rehearsals per word was greater in immediate than in delayed recall. Also, the number of fixations exceeded the number of overt rehearsals, especially under delayed-recall conditions. However, both overt rehearsals and eye movements were slower in delayed recall. The number of overt rehearsals and the number of fixations per word were good predictors of immediate recall, but neither was highly correlated with delayed recall. Engaging in overt rehearsal had the following effects: It slowed down eye movements, seemed to bias the subject toward a serial learning strategy, improved immediate recall, and did not reduce delayed recall. It was concluded that total looking time was the best predictor of long-term retention and that recall performance following overt rehearsal was different from recall performance following silent study.


Eyelid response topography in differential interstimulus interval conditioning.

The problem of conditioned eyelid discrimination was investigated with a differential interstimulus interval (ISI) conditioning procedure. In two groups, conditioned stimulus (CS) lights presented in the left or right visual fields signaled ISIs of 800 or 1,200 msec before delivery of an airpuff unconditioned stimulus. Two additional groups received one or the other ISI with both CSs. Somewhat unexpectedly, none of the response-frequency or topography measures showed evidence of conditioned discrimination in the differential ISI groups. Instead, the latencies and puff-attenuating topographies of responses were much more appropriate to the ISI given on the preceding trial, n--1, than to the ISI cued on trial n. Neither the absence of conditioned discrimination nor the presence of ISI sequential effects was related to subjects' reported awareness of the CS-ISI contingencies, suggesting that the overriding process was a relatively "automatic" shaping and reshaping of responses in accord with recent ISI experience. These results are discussed in terms of the complex stimulus- and response-processing requirements of the task. Across all four groups there was some evidence of a relative excitatory response bias to CSs presented in the right visual field, and it was found that voluntary-form responders (but not conditioned-form responders) initially gave more alpha responses to the right-field CS than to the left-field CS. These results were examined for possible hemispheric processing implications.


The effect of 5-bromodeoxyuridine on the postnatal development of the rat testis.

The effects of 5-bromodeoxyuridine (BrdU) on postnatal testicular development were studied in rats treated on the second, third and fourth days of life. Testes were removed for study at 5, 15 and 35 days of age. Body weights and diameters of seminiferous cords and tubules were significantly less in the treated than control animals. At 15 days of age fewer pachytene spermatocytes were present in treated animals. At 35 days of age the testes of treated animals contained fewer canalized cords. Spermatids exhibited an altered distribution of chromatin material, contained less agranular endoplasmic reticulum and fewer mitochondria, and had not yet developed tails. Sertoli cells and Leydig cells of treated animals contained less agranular endoplasmic reticulum and more lipid droplets than the normal.


Abnormal morphogenesis of feather structures and pattern in the chick embryo integument. II. Histological description.

The development of skin and feathers in highly feathered scaleless mutants and normal Single Comb White Leghorn chick embryos was analyzed histologically. In addition, the growth of mutant feathers in chorioallantoic membrane culture is reported as a verification of several inferences made from observations of serially staged fixed specimens. The most striking feature of scaleless high line feather development is the widespread appearance of condensed or nearly condensed dermis. The discrete arrangement of normal placodes with underlying condensed dermis is replaced in the mutant by a heterogeneously shaped group of extremely large islands of columnar ("placodized") epithelium as long as 3,000 micron. The shape and extent of the condensed areas of dermis reflect the shape and extent of the overlying "placodized" epithelium. The polarity of the epidermis in normal feather germs, i.e., thicker epidermis on the posterior surface, is absent in mutant feather germs. This absence of epidermal polarity is reflected in the aberrant outgrowth of the mutant feather primordial. In the mutant, the basal cell layer of the epidermis invades the dermal core of the aberrant feather germs and may form barb vane ridges or feather sheaths. This process had no counterpart in the development of normal down feathers.


Regeneration of the retina in the adult newt, Triturus cristatus, following surgical division of the eye by a post-limbal incision.

An autoradiographic and histological study of retinal regeneration following a post-limbal ocular incision, in Triturus cristatus, is described. In these cases there is a major contribution to the regenerating retina from both the anterior complex (pars ciliaris retinae: ora serrata) and the retinal pigment epithelium. The tissue derived from the anterior complex can independently differentiate into retinal tissue if the anterior and posterior parts of the regenerate do not join. This contrasts with the situation following a limbal incision to the eye where the regenerative response of the anterior complex is inhibited. The significance of labelling patterns in the regenerating retina, following administration of 3H-thymidine, is discussed.


Inhibition of epidermal cell migration by concanavalin A in skin wounds of the adult newt.

Pigment cell migration was used as an indicator to study the effects of the plant lectin, concanavalin A (con A), on epidermal cell closure of skin wounds. Continuous immersion of wounded animals in 10-100 microng/ml of con A greatly slowed but did not stop epidermal cell migration. Thus, untreated animals closed wounds in 12 to 24 hours while some treated wounds were still open after three days. Removal from con A after 24 hours, allowed inhibited wounds to close faster than those left in con A. Brief (30-minute) immersion of wounded animals in con A, either before or after migration had begun, suppressed closure for four to eight hours, demonstrating that the affinity for con A persists as epidermal cells migrate. When the left forelimb of bilaterally wounded animals was immersed in con A, it caused suppression of migration only on the immersed side, indicating a local rather than systemic site of action. Mixture with its competing sugar, alpha methyl D mannoside, abolished the effects of con A. The mechanism by which this lectin suppresses epidermal cell migration is unknown but clearly involves binding of the molecule to glycoprotein or glycolipid receptors on the cell surface.


Further studies on the biology of an antiviral factor (AVF) from virus-infected plants and its association with the N-gene of Nicotiana species.

The antiviral factor (AVF) from virus-infected plants, purified on polyacrylamide gels, could be labelled with radioactive phosphorus and its activity could be eluted from the gels. The radioactivity and the antiviral activity were co-purified and thus co-electrophoresed; hence, the previously reported radioactive zone (Antignus, Sela & Harpaz, 1975) can be regarded as AVF. The production of AVF requires both the presence of the N-gene in the plant as well as virus infection. AVF production is inhibited by actinomycin D, but its activity is not affected by this drug. AVF production is correlated in time with the development of virus resistance in a local-lesion host. AVF inhibits TMV multiplication in infected leaves and suppresses virus synthesis almost totally in a local-lesion host. Some AVF is also produced when Nicotiana glutinosa L. is infected with a non-localized virus, but to a much lesser extent and at a later stage of infection. The production of AVF in N. glutinosa is not blocked at 30 degrees C. even though TMV is no longer localized at this temperature.


Fine structure of the cerebellum of "staggerer-reeler", a double mutant of mice affected by staggerer and reeler conditions. I. The premature disappearance of the external granular layer and ensuing cerebellar disorganization.

It was reasoned that cerebella of mice carrying both staggerer and reeler conditions, called double mutant, might accentuate some of the anomalies observed in single mutants, thus revealing further details otherwise undetectable. As expected, the cerebellar hypoplasia, the paucity of fissures, granule cells and interneurons of the molecular layer, and the external granular layer hypoplasia, common in both staggerer and reeler, were much more pronounced in double mutant. However, the most striking feature of the double mutant cerebellum was the premature disappearance of the external granular layer. The external granular layer is smaller both in staggerer and reeler as compared to the normal but it persists beyond the normal time (around day 15). In double mutant, however, the external granular layer disappeared by day 7 or 8, reducing the density of granule cells even further. This observation was interpreted as indicating that both the staggerer and reeler genes effect the premature disappearance of the external granular layer. Most of the gross cerebellar anomalies in double mutant such as cerebellar hypoplasia, paucity of fissures and Purkinje and Golgi epithelial cell disalignment could be explained as the result of this premature disappearance of the external granular layer. On the other hand, anomalies of Purkinje cells and Bergmann fibers, which are also present both in staggerer and reeler, did not follow the same additive change.


Fine structure of the cerebellum of "staggerer-reeler", a double mutant of mice affected by staggerer and reeler conditions. II. Purkinje cell anomalies.

Purkinje cells in double mutant were very similar to those in staggerer both at days 7 and 15, and could not be distinguished from staggerer Purkinje cells by morphological criteria. They were small and immature looking, and their nuclei were invariably eccentric in position both at days 7 and 15. The typical funnel stage was not observed at any time. Somatic spines and their synapses were extermely rare at day 7 when they are abundant in the normal, but they were present at day 15 with typical synapses with climbing fibers. Dendritic spines were also present at day 15 although extremely infrequent, and they showed synapses both with parallel and climbing fibers. More often, however, parallel and climbing fibers were found in synapsis with the smooth surgace of these dentrites. These observations were in close agreement with those of staggerer Purkinje cells. The persistence of staggerer Purkinje cell soma anomalies in double mutant was interpreted as indicating that these anomalies are specific effects of the staggerer gene, being relatively free from environmental influences.


Fine structure of the cerebellum of "staggerer-reeler", a double mutant of mice affected by staggerer and reeler conditions. III. bergmann fiber anomalies.

Bergmann fibers and the distribution of Golgi epithelial cells were significantly altered in staggerer, reeler and double mutant (affected by both staggerer and reeler conditions). However, the Bergmann fiber anomalies in double mutant were not identical to those of either staggerer or reeler. A comparison of these anomalies with the anomalies described in weaver revealed that the developmental patterns of Bergmann fibers are distinct in all four cerebellar mutants just as are the cytoarchitectural anomalies of these cerebella. The results of the present electronmicroscopic examinations of Bergmann fibers in staggerer and reeler were in good agreement with the findings made with the immunofluorescence technique. There was, however, one important discrepancy between these two sets of observations. Immunofluorescent astrocytic fibers were nearly absent in 21 and 26 day old staggerers while Bergmann fibers were structurally present in nearly normal numbers both at days 21 and 31. A possible reason for this discrepancy was discussed.


H3T-labelled blood cells in the CNS response to axotomies at various times after isotope injection.

Numerous investigators, using tritiated thymidine to label mononuclear blood cells, have proposed a hematogenous origin for some of the reactive cells responding to injury in the CNS. However, two questions have remained unanswered: recirculation of H3T at the time of injury with labelling of proliferating local cells; and local reutilization of label released from degenerating cells. In a recently reported experiment using bilateral injuries made at different times (24), a large number os labelled cells responding to the second injury resulted from mitosis of cells already reacting to injury on the contralateral side. Additionally, the possibility that some of the labelled cells could have been newly drived from blood was not ruled out. The present experiment was designed to further explore this possibility. To minimize the problems of H3T recirculation and reutilization, the isotope was injected 3 to 17 days before nerve injury in some of the animals. At sacrifice, labelled cells were found in the nucleus of the injured nerve up to 36 days after isotope injection, with the peak of the reaction occurring at 9 days. Since the isotope was injected 3 to 17 days before injury and because there was no source of reactive cells on the contralateral side, it was felt that these labelled cells were newly derived from blood.


Granulovacuolar degeneration in the ageing brain and in dementia.

Quantitative morphometry with a sampling stage light microscope was performed to determine the severity of granulovacuolar degeneration of hippocampal neurones in serially sectioned temporal lobe from mentally normal subjects of different ages and from demented patients. The degree of granulovacuolar change in control brains increased slightly with increasing age; the "granulovacuolar index" of cases with Alzheimer's disease exceeded by many times that of age-matched controls. This significant difference was demonstrable whether the granulovacuolar severity was expressed as number of affected cells per volume of cortex analysed, or as the percentage involvement of total neurones counted in the hippocampus. The posterior half of each dement's hippocampus was found to be more susceptible to this augmented granulovacuolar degeneration than the anterior half, a selectivity already observed for neurofibrillary tangel formation in the same material.


Attempts to induce chronic experimental allergic neuritis in strain 13 and Hartley guinea pigs.

An attempt has been made to develop a model of chronic experimental allergic neuritis (EAN) using juvenile and adult inbred (Strain 13) and Hartley guinea pigs sensitized with peripheral nerve in complete Freund's adjuvant. Animals were followed clinically for periods ranging from 2 to 44 weeks postinoculation and then sacrificed for light and electron microscopy. Out of a total of 39 animals, 16 showed either clinical signs or had histopathologic changes. The remaining 23 guinea pigs were free of any disease. The animals' age at inoculation and strain did not seem to affect either the clinical course or ultimate histopathologic changes. The 7 animals that had clinical EAN displayed signs ranging from weight loss and soiling to quadriparesis (one animal). The histologic changes consisted of meningeal and perivascular inflammation as well as peripheral nervous system (PNS) and central nervous system demyelination and remyelination. An interesting abnormality seen the nerve roots of several animals was the proliferation of Schwann cells around remyelinated PNS fibers reminiscent of the "onion-bulb" formations seen in human hypertrophic neuropathies. Because of the lack of ongoing demyelination, onion-bulb formation appeared in this case to be a secondary proliferation of Schwann cells after a single primary episode of demyelination. It is concluded from the present study that despite some interesting histopathologic changes, the animals studied were largely resistant both to acute as well as chronic EAN.


Methylazoxymethanol-induced aberrant Purkinje cell dendritic development.

Purkinje cell dendrites develop with a specific orientation and relationship to related neurons and glia. Their dendritic spine postsynaptic membrane specialization may, in turn, require a permanent presynaptic contact by parallel fibers. To determine whether changes in the surrounding cells influence the normal development of the cerebellar Purkinje cell dendrites and spine specializations, destruction on the differentiating cell layer was induced in the postnatal mouse by administration of methylazoxymethanol acetate (MAM) (0.05 micronl/gm body weight) at day zero. The Purkinje cells were examined by light and electron microscopy on the tenth postnatal day. The midsagittal surface area of the cerebellar vermis in treated animals was reduced by an average of 60%. MAM-induced granule cell depletion and Purkinje cell dislocation were observed by light microscopy. When compared to controls, examination following Golgi impregnation revealed random orientation of Purkinje cell apical poles, and multiple primary dendrites of reduced length with few branches, branchlets and spines. Vertical processes of Golgi epithelial (Bergmann) cells were obliquely directed, reduced in length and complexity in MAM-treated mice. Ultrastructural examination revealed naked Purkinje cell dendritic spine specializations in both groups. Although necrotic debris persisted in astrocytes and macrophages, degenerating presynaptic terminals were not found. This study suggests that permanent presynaptic contact by parallel fibers is not essential for spine development. Astrocytic reactions to injury, in association with the reduced folial expansion, may have contributed to the observed abnormalities and disorientation of the Purkinje cells. The data suggests that Purkinje cell dendritic development may be strongly influenced by changes in surrounding cells.


Neuropathological effects of intracerebral platinum salt injections.

Multiple intracerebral injections of a mixture of platinum salts were made in 9 adult cats and the brains studied by light and electron microscopy at 5-12 days post injection. At the center of the lesions normal cortical architecture was completely replaced by edematous areas containing lipid-laden macrophages and cellular debris. The lesion periphery was characterized by perivascular edema and degenerative changes including cytoplasmic lipid inclusions and vacuolations with selective vulnerability of neurons. Membranous cytoplasmic bodies (MCB), zebra bodies and multiple nucleoli were observed in several cell types. This ultrastructural pattern, mimicked to some extent, that observed following electrical stimulation of brain following chronically implanted platinum and rhodium electrodes. The induction of zebra bodies and MCB, both of which are morphologic features of human neurolipidoses associated with congenital enzyme deficiencies, suggests an inhibitory effect of platinum on brain enzymes. Functional electrical stimulation of brain and other organs is currently being employed in a wide variety of clinical applications (14, 15). A mandatory consideration is that of the long-term effects of the stimuli as well as the electrodes themselves on the tissues involved. The histological effects and mechanisms of tissue damage following chronic application of electrical stimuli to brain have been the subject of several investigations in this laboratory (1, 14-18). Factors contributing to neural damage induced by electrical stimulation include noxious products resulting from electrode dissolution. In vitro studies employing electrochemical (3,9) and scanning electron microscopy (6) techniques have established that erosion of noble metal electrodes occurs, even when passing relatively small stimulation currents. Such electrode dissolution is of particular importance in long term applications of neural prostheses. The present study was initiated to assess the contribution of platinum electrode erosion products to neurla damage following electrical stimulation of brain, specifically to distinguish morphological changes resulting directly from electrode solubilization as opposed to electrical factors. Accordingly, intracerebral injections of graded volumes of platinum salts were made in an attempt to stimulate the presence of platinum electrode dissolution products.


The choroid plexus in passive serum sickness.

Immunofluorescent microscopy of the choroid plexus revealed the presence of rabbit IgG and either rat or mouse C3 in a high percentage of young male Wistar rats and CF1 mice who had received intravenous injections of preformed BSA-rabbit anti BSA complexes over a 3 day period. Electron dense deposits were observed in the basement membrane region of the choroid plexus in these animals. These findings were comparable to those noted in their renal glomeruli. This is the first description of involvement of the choroid plexus in passive immune complex disease. This experimental model is rapidly inducible and should be of value in future pathophysiological studies of this important structure.


Surgical management of unruptured asymptomatic aneurysms.

The natural history of unruptured asymptomatic aneurysms in nuclear. Because of this uncertainty regarding risk of ultimate enlargement  and/or hemorrhage, and in view of the significant mortality and morbidity traditionally involved in aneurysm surgery, clinicans have varied in their advocacy of surgical management of such lesions. Forty-nine consecutive patients harboring 52 such aneurysms were treated surgically over a 57-month period. There were no surgical deaths and morbidity was within acceptable limits. Patient population characteristic and surgical technique are discussed.


Mechanical and physiological effects of dentatotomy.

The role of the dentate ligaments in the pathogenesis of myelopathy secondary to disease conditions that alter the normal biomechanics of the spinal canal was studied in 14 dogs. The effects of posterior cord elevation on somatosensory evoked potentials (SSEP's) and tension requirements were compared before and after dentate ligaments section in acute experiments. At levels of posterior elevation usually within the confines of the canine canal, the dentate ligaments were the most significant element increasing tension requirements and SSEP alternations. Human cadaver studies also showed an approximate 50% reduction of force after dentatotomy. These findings suggests that after dentate ligaments section the applied tension is distributed over a longer segments of the cord with a reduction in tension and disruption of axonal conduction at the level at which the force was applied.


Dural posterior fossa AVM producing raised sagittal simus pressure. Case report.

A patient with raised intracranial pressure secondary to a dural arteriovenous malformation (AVM) of the posterior fossa is presented. Direct shunting of arterial blood into the transverse sigmoid sinus caused a considerable increase of the sagittal sinus pressure (SSP) and elevation of intracranial pressure (ICP). Both ICP and SSP returned to normal values following obliteration of the dural AVM by selective embolization.


Neuroepithelial cyst of the fourth ventricle. Case report.

Developmental cysts lined by neuroepithelium are a distinctive form of neural tube dysgenesis. Neuropathological study of fourth ventricular cysts that caused symptomatic hydrocephalus indicated its neuroepithelial origin. The cyst arose from the ventral surface of cerebellar vermis. Evagination of the rhombencephalic roof and entrapment of a ventricular diverticulum beneath the cerebellar anlagen is proposed as a mechanism responsible for the extraordinary occurrence of neuroepithelial cysts within the fourth ventricle.


Intracranial aneurysm in infancy. Case report.

Angiography demonstrated an aneurysm of the left anterior cerebral artery in a 4-month-old baby who was admitted for subarachnoid hemorrhage. A surgical cure with long-term follow-up course was achieved. Clinical and pathogenetic aspects are presented. The rarity of such lesions in childhood and their successful surgical treatment are discussed briefly.


Early diagnosis of myocardial infarction in the dog with 99mTc-glucoheptonate.

Early gamma imaging of acute experimental myocardial infarcts was evaluated in mongrel dogs with 99mTc-glucoheptonate. From 15 to 20 mCi were injected between 1 and 27 hr after coronary artery occlusion. Nine dogs imaged 3 hr after injection (4 hr after occlusion) showed unequivocal uptake in the region of the infarct. Fifteen dogs imaged 5-7 hr after injection (6-8 hr after occlusion) showed sufficiently well-defined regions of abnormal uptake so that planimetry could be performed reliably. Five animals imaged serially showed improvement of the image only up to about 5-7 hr after injection. Infarct-to-normal myocardium and infarct-to-blood ratios were slightly higher in dogs injected 15-27 hr after infarction than in those injected 1 hr after infarction, implying that equally good results can be obtained with injection and imaging of 99mTc-glucoheptonate at any time within the first day. No other infarct-labeling radiopharmaceutical shares this capability for the early detection a delineation of acute infarcts.


Hand images: normal and abnormal.

Supplemental hand scintigrams with abnormal features were obtained from 29% of patients (134 of 463) who were referred for routine minified bone imaging with 99mTc-Sn-polyphosphate. A wide spectrum of normal activity distribution ranging from well-defined to "wash-out" images is described in 329 cases (71%). In the abnormal images of the joints and individual bones, the changes--although not always characteristic of some particular disease--may often suggest a diagnosis and/or its pathophysiologic status. The joints with heavy uptake correlate well with the presence of active clinical findings, e.g., in the arthritides. The bone feature associated with metabolic disease, especially when full-blown, may be fairly characteristic. A potential application is in the assessment of digital circulation, particularly in obliterative vascular diseases such as scleroderma, Buerger's disease, chronic neuropathies, and possibly other collagen or vascular diseases that involve the hands. Interesting images, probably of somewhat limited usefulness, are observed in some congenital anomalies, fractures, camptodactyly, contracture deformities, unilateral lymphedema after mastectomy, etc.


Diagnosis of osteoporosis: usefulness of photon absorptiometry at the radius.

The photon-absorption method (Cameron-Sorenson) is commonly used in the diagnosis of osteoporosis to measure bone mineral in appendicular bones. Although this method gives accurate and reproducible results when applied to the distal radius and midradius, separation between osteoporotic patients and age-matched normals was less than satisfactory because of a large overlap. By contrast, a radiographic index based on the pattern of trabecular bone at the proximal femur (Singh index) gave a better separation between the two populations. The Singh index discriminates better, probably because osteoporotic patients have a greater proportion of loss of trabecular bone of the axial skeleton than of cortical bone of the appendicular skeleton.


Gallium bone scan in myelofibrosis: case report.

When gallium is injected into a patient who has received many transfusions, the resultant scan appears similar to a bone scan with renal excretion. This case report presents a 51-year-old man with myelofibrosis and myeloid metaplasia. Gullium-67 and 52Fe scans with 99mTc-pyrophosphate bone scintigrams are included.


Utility of bone scanning in disseminated coccidioidomycosis: case report.

Five cases of disseminated coccidioidomycosis (DC) are presented, to illustrate the complementary nature of bone scanning and radiography in the assessment of skeletal involvement. As shown in other unflammatory and neoplastic processes, bone scanning is more sensitive than radiography in the detection of early skeletal disease, but correlation with radiographs remains a necessity.


An evaluation of 99mTc-labeled hepatobiliary agents.

Scintigraphic imaging of the hepatobiliary system has been significantly improved with the development of 99mTc-labeled compounds. Two of the most promising agents, pyridoxylideneglutamate and HIDA, each formed the basis for the development of a group of structural analogs. Condensation of pyridoxal with leucine and arginine (in place of glutamate) produced pyridoxylideneleucine and pyridoxylidenearginine. Since increasing the molecular weight and the lipid solubility of compounds tends to enhance their biliary excretion, several new IDA derivatives were synthesized by altering the lipophilic substituents on the ring of HIDA. The substitutions included ethyl and ethoxy groups as well as iodine. All compounds were compared with 131I-rose bengal using a baboon model that allowed blood, bile, and urine collection.


Pathologic changes in the lungs of mice following injection of human albumin microspheres.

Mice injected with 131I-human albumin microspheres equivalent to 10-20 or 200 human doses were sequentially killed over a 12-day period. About 90% of the microspheres initially lodged in the precapillary arterioles and capillaries of the lungs. Their pulmonary clearance was essentially complete after 3 days. Occlusion of the vessels always led to focal hyperemia of the surrounding tissue and to slight hemorrhage into the alveoli. This was followed, though less frequently, by perivascular nodular inflammtion. Hemorrhagic infarcts were quite uncommon and occurred only after the massive doses. Some emboli underwent organization, but most were resolved. Circulatory disturbances and perivascular inflammation receded in about 1 week and seldom led to obliteration of the involved vessels. Hemorrhagic infarcts were converted into minute scars. Twelve days after injection of microspheres in massive doses, the only findings were post-inarct scars and obliterated vessels, which were sparse and difficult to detect. The lower doses of microspheres did not leave any detectable residues.


Inexpensive scintillation camera study device.

A commerically available inexpensive calculator was modified and mounted next to one of the display oscilloscopes on a scintillation-camera console. This enabled the technologist to dial in each patient's identification number, which then appeared on every frame of the 35-mm film used. By using this device, labeling errors have been reduced to a minimum.


Segmental analysis of Ti-201 stress myocardial scintigraphy.

Thallium-201 scintigraphy of the exercised myocardium was performed in 70 male patients admitted for coronary arteriography and left-ventricular angiography. Left ventricular scintigrams were collected in left lateral, left anterior oblique (65 degrees, 45 degrees, and 25 degrees), and anterior views, and the images were divided into eight segments: apical, anteroseptal, anterior, antero-lateral, posterolateral, posterior, inferior, and posteroseptal. A correlative study between segmental hypoperfusion on scintigram and coronary-artery stenosis visualized by contrast artriorgraphy allowed selection of specific segments for each main coronary artery. Hypoactivity in the apical and posterior segments did not appear reliable. Using selected segments, we were able to identify LAD disease in 84%, LCx disease in 49%, and RCA disease in 79% of documented significant stenosis, with specificity of 95%, 89%, and 88%, respectively. Coronary-artery disease could be detected in 95% of patients having more than 50% coronary-artery stenosis, with 93% specificity. In most cases, patients with two-vessels disease and three-vessel disease could not be distinguished from each other. Multiple-vessel disease suggested by segmental analysis of myocardial scinitgrams after exercise was confirmed artriographically in 88% of the patients, but 52% with scintigrams suggesting signle-vessel disease had, in fact, multiple-vessel disease.


Comparison of different noninvasive methods of infarct sizing during experimental myocardial infarction.

This study evaluated the accuracy of several noninvasive infarct-sizing techniques in 12 awake, unsedated dogs with multivessel coronary obstructions and acute anterior myocardial infarcts. Estimations of infarct size by scintigraphy with technetium-99m Sn pyrophosphate (Tc-PP), serum creatine phosphokinase (CPK) release, peak serum myoglobin levels by radioimmunoassay, and precordial ECG mapping were compared and correlated with histologic measurements of infarct size. The comparisons indicate that precordial ST segments mapping, serum CPK release measurements and peak serum CPK, peak serum myoglobin, and Tc-PPi myocardial scintigraphy all provide approximate estimates of infarct size in this model. Each technique also has certain important limitations, however, including: (A) precordial mapping is relatively insensitive in the identification of small anterior infarcts, (B) serial serum CPK release measurements when obtained for only 24 hr after infarction tend to underestimate large anterior infarct size, and (C) Tc-PPi myocardial scintigrams may fail to recognize anterior infarcts less than 3 gm in size and may overestimate the size of small predominantly subendocardial infarcts. The findings also show that the closest estimate of histologic infarct size in this model was provided by combining two of the noninvasive techniques (precordial mapping to identify sites with 2 or more millimeters of ST segments elevation and Tc-PPi myocardial scintigrams) rather than by relying exclusively on any one technique alone.


Comparison of Ga-67 citrate images obtained with rectilinear scanner and large-field Anger camera.

Two methods for Ga-67 citrate imaging were compared on 20 patients. Scans were performed using approximately equal procedure time with two instruments: (A) a dual 5-in. rectilinear scanner with medium-energy collimator, with a single window spanning both the 93-keV and the 185-keV spectral peaks; and (B) a large-field (15-in. diam) Anger camera equipped with moving table, medium-energy collimator, and three windows covering the 93-keV, 185-keV, and 300-keV peaks separately. Sixteen abnormal sites and 24 normal sites were selected for comparison. Each site was evaluated by four physicians experienced in interpreting Ga-67 citrate images. The observers performed significantly better using the images obtained with the large-field camera (three windows) than with the dual 5-in. scanner (single window).


Gastroesophageal reflux: a potential source of confusion in technetium thyroid scanning:case report.

Technetium-99m as pertechnetate, excreted into the stomach after intravenous injection and refluxed as high as the cervical esophagus can present a confusing picture during thyroid scintigraphy if one is not aware of this possibility. The typical appearance of refluxed tracer is presented, and a simple method for eliminating the confusion is suggested.


Quantification of flow in a dynamic phantom using Rb81-Kr81m, and a Nal detector.

Blood flow can be measured by monitoring the count rate of Krypton-81m after its parent, Rubidium-81 (a potassium analogue), has been deposited in the tissue. The steady-state Kr-81m count rate reflects both production by decay of Rb-81 and washout due to blood flow. Its use is theoretically superior to that of Xenon-133 for quantification of blood flow (cc/min per 100 gm) since: (1) multiple flow measurements can be obtained from a single arterial injection, (2) flow-dependent changes in the count rate of Kr-81m provide a steady-state measure of specific flow, and (3) errors due to uptake in fat are eliminated. The count rate of Kr-81m was measured as a function of flow in a dynamic phantom with a NaI crystal, suing both pure cyclotron-produced Rb-81 and commercially available samples with as much as 25% contamination from Rb-82m. The phantom was calibrated by measuring the flow-rate constants with Xe-133. No significant difference was found between the flow-rate constant measured with three pure samples. The ratio of the zero-flow Kr-81m count rate to the rate observed in the presence of flow showed excellent correlation with calibrated flow over a range of rate constant from 0 to 0.02 sec (-1). This study suggests that regional specific flow can be measured in vivo with currently available Nal detecting systems after the intra-arterial injection of Rb-81.


Rapid, rigorous computation of modulation transfer function on a pocket calculator.

This article describes a method for the rigorous calculation of modulation transfer function (MTF) of a collimated scintillation detector using a programmable pocket calculator. The calculation utilizes a normalized discrete Fourier transform (DFT) of the line spread function (LSF) including real and imaginary terms. A method is described for recording the LSF using an Anger camera and multichannel analyzer (MCA). The procedures for recording of the LSF and calculation of the MTF are therefore performed independently of a computer, allowing nuclear medicine laboratories without access to a computer, allowing nuclear medicine laboratories without access to incorporate MTF studies into their quality-assurance programs. The results obtained using the pocket calculator were compared with those using a PDP-12 minicomputer. The pocket calculator was slightly more accurate, since it does not suffer from the round-off errors of the PDP-12. The time required to plot an 11-point MTF curve using the pocket calculator was 5 min, using the PDP-12 0.5 min.


Effect of dietary DL-ethionine on egg laying and activities of cytoplasmic and mitochondrial L-glycerol 3-phosphate dehydrogenases in liver and kidney of Japanese quail, Coturnix coturnix japonica.

The effect of dietary DL-ethionine on egg laying and activities of succinate dehydrogenases, cytoplasmic and mitochondrial L-glycerol 3-phosphate dehydrogenases, in liver and kidney of Japanese quail, Coturnix coturnix japonica was investigated. When quail at full laying were fed a diet supplemented with DL-ethionine at 0.05%, 0.10%, 0.15% and 0.30% (w/w), respectively, apparent DL-ethionine concentration dependent inhibitions of egg laying rate, weights of ovary and oviduct, and egg weight were observed. At the 0.30% level, activity per g tissue of cytoplasmic L-glygerol 3-phosphate dehydrogenase from liver and kidney decreased to about one-half of the initial activity. A significant difference in the activity of mitochondrial L-glycerol 3-phosphate and succinate dehydrogenase from liver and kidney was obtained between the control and the DL-ethionine fed quail, respectively. These results indicated that dietary DL-ethionine inhibits egg laying and activities of L-glycerol 3-phosphate dehydrogenases and succinate dehydrogenase of both liver and kidney of Japanese quail.


Effect of tryptophan or phenobarbital administration on hepatic polyribosomes and protein synthesis in rats force-fed a complete or threonine-devoid diet.

Young rats were force-fed a complete or threonine-devoid diet for 3 days. Prior to killing on the fourth morning rats of each group were treated with l-tryptophan (30 mg/100 g body weight) 2 hours before killing or with sodium phenobarbital (8 mg/100 g body weight) 14 hours before killing. Rats force-fed the threonine-devoid diet revealed increased aggregation of polyribosomes (sucrose density gradient analyses) and increased protein synthesis (in vitro [14C]leucine incorporation into protein) in the livers in comparison to that in the livers of rats force-fed the complete diet. Plasma total tryptophan levels were decreased and plasma free tryptophan as a percentage of total plasma tryptophan was increased in rats force-fed the threonine-devoid diet for 3 days. Administration of tryptophan or of phenobarbital stimulated polyribosomal aggregation and in vitro protein synthesis of the livers of rats force-fed the complete or the threonine-devoid diet. These stimulatory effects incuded by tryptophan or phenobarbital were most marked in rats force-fed the threonine-devoid diet. Hepatic tryptophan pyrrolase activity was stimulated to similar degrees following the administration of tryptophan to rats force-fed the complete or the threonine-devoid diet.


Bovine milk xanthine oxidase, blood lipids and coronary plaques in rabbits.

The effects of prolonged intravenous  administration of bovine milk xanthine oxidase (EC 1.2.3.2.) on blood lipids and arterial integrity were measured to determine if the administration of this enzyme produces metabolic changes conducive to plaque formation. New Zealand White rabbits were injected intravenously with bovine milk xanthine oxidase at 4-day intervals during a 13-week test period. At the end of the test period, the rabbits were killed and blood, heart, aorta, liver, and kidneys were collected and evaluated. Rabbits injected with phosphate buffer or acid-denatured xanthine oxidase for the same length of time served as negative controls. Additional rabbits fed a diet containing 3% added cholesterol for the same time period served as positive controls. The administration of xanthine oxidase in large amounts over a prolonged period did not alter serum cholesterol or triglyceride levels and did not reduce plasmalogen levels in the aorta or heart. Xanthine oxidase administration did not induce arterial plaque formation. Cholesterol feeding over the same time period increased serum cholesterol levels, reduced liver xanthine oxidase activity levels and resulted in a marked development of arterial plaques. Althouth xanthine oxidase activity was found in liver from all rabbits, enzyme activity was not detectable in aorta, heart or kidneys from any rabbit. Free or complexed bovine milk xanthine oxidase could not be demonstrated in heart, aorta, liver or kidneys from any of the rabbits with immunodiffusion or with immunofluorescent techniques. The study showed that when large intravenous doses of bovine milk xanthine oxidase were given to rabbits, the enzyme was not deposited in heart, aorta, liver or kidneys. The study also showed that large intravenous doses of xanthine oxidase over prolonged periods did not deplete arterial or coronary tissue plasmalogens, and did not induce arterial plaque formation.


Effect of supplementation of methionine and threonine to a protein free diet on urinary excretion of nitrogen and tissue free amino acids in rats.

It was previously reported that methionine and threonine supplementation to a protein free diet had a greater nitrogen sparing effect than methionine supplementation along. The reduced urinary nitrogen excretion by methionine and threonine is due to the reduced excretion of urea. In the present study, the changes in tissue level of free amino acids and ammonia were investigated. Ornithine is one of the urea cycle inter-mediates and may play an important role for urea formation, therefore the liver concentration of ornithine was also determined. The contents of ammonia in plasma were the same in these two groups and the ammonia content in liver of rats fed the control diet was smaller than that of rats fed the protein free diet supplemented with methionine and threonine. The contents of some amino acids in tissues were significantly reduced. The concentrations of aspartic acid, glutamic acid, alanine and serine in plasma and liver of rats fed the protein free diet supplemented with methionine and threonine were, particularly, significantly reduced as compared with those of rats fed the protein free diet. In addition to the decrease of free amino acids which are considered to be nonspecific nitrogen carriers from the peripheral tissues, the concentration of ornithine in liver was also significantly reduced. The results suggest that the decreased migration of free amino acids from peripheral tissues to the decreased level of liver ornithine would efficiently reduce the urea formation in rats fed the protein free diet supplemented with methionine and threonine.


Xylitol infusion and oxalate formation in rabbits.

Oxalate levels in the plasma and urine fractions of fasted normal, oxythiamin treated (20 mg/kg) and 4-deoxypyridoxine treated (300 mg/kg) rabbits were determined following infusion with either xylitol or glucose at a dose of 2 g/kg body weight. Biochemical determinations showed that transient thiamin or pyridoxine deficient states had been induced in the antivitamin treated rabbits. In the first 24 hour following infusion with either carbohydrate, urinary oxalate levels remained within the normal range for all  groups. Oxythiamin hastened the appearance of the transient, elevation in plasma oxalate concentrations seen in rabbits after infusion with glucose. After xylitol infusion, the elevation of plasma oxalate was not significnatly above normal. 4-Deoxypyridoxine enhanced peak plasma oxalate levels above those of controls for both sugars. Glucose, at an equivalent dose to xylitol, resulted in higher plasma oxalate levels than xylitol for all groups. Infusions of [U-14C]xylitol and [U-14C]glucose solutions into 4-deoxypyridoxine treated rabbits demonstrated a conversion of the administered radioactive carbon into 14C oxalate of 0.01% with a high dilution of the specific activity. The results suggest that oxalate production from xylitol is negligible; any toxicity related to xylitol administration is not a consequence of oxalate production.


Relation between liver amino acid-catabolizing enzymes and free amino acids of liver and plasma in adult cockerels fed diets containing graded levels of protein.

Activities of liver amino acid-catabolizing enzymes and liver and plasma free amino acid concentrations in adult cockerels fed diets containing 3% to 21% casein were determined 2 hours after a meal. Liver tryptophan pyrrolase activity and liver tryptophan increased with an increase in dietary casein level, but plasma tryptophan decreased with the increase dietary casein level. As the dietary casein level increased, liver lysine-ketoglutarate reductase activity decreased, but liver and plasma lysine increased proportionally, and the rate of increase was larger in the plasma than in the liver. Liver phenylalanine hydroxylase activity increased with the increase in dietary casein level from 3% to 12%, and thereafter remained unchanged. Reflecting the change of this enzyme, phenylalanine increased in the liver and decreased in the plasma with the increase in dietary casein level from 3% to 12%, and thereafter the rate of increase in liver phenylalanine became small and plasms phenylalanine increased. Liver tyrosine was not influenced by the dietary casein level, whereas plasma tyrosine increased sharply from 3% to 12%, and thereafter the rate of increase decreased. Thus, the difference between liver and plasma free amino acid responses might be due to the changes in the activities of liver amino acid-catabolizing enzymes.


Reduced DNA synthesis in zinc deficiency: regional differences in embryonic rats.

Zinc deficiency during prenatal life results in a high incidence of gross malformations especially of CNS. Reduced 3H-thymidine incorporation into rat embryos has previously been reported in zinc deficient rats. The effect of zinc deficiency on regional DNA synthesis in the 12 day rat embryo was therefore investigated. Zinc deficiency was achieved by feeding normal pregnant rats a diet containing 0.4 ppm zinc from day 0 to day 12. Pair-fed controls received a diet containing 100 ppm zinc. Dams were injected with 3H-thymidine on day 12 and embryos removed 1 hour later. In embryos from zinc deficient dams, there was a lower incorporation of 3H-thymidine into DNA in the head regions than in comparable regions from ad libitum and pair-fed controls. Total DNA and RNA contents in the head and body regions of embryos from zinc deficient dams were lower than respective regions of pair-fed controls, but the greatest deficit occurred in the head region. Replacement of zinc 28 hours prior to injection of the label increased the low incorporation of 3H-thymidine/DNA in the head region of zinc deficient embryos. Autoradiographs of the head region indicated that reduced uptake of 3H-thymidine and reversal by zinc replacement occurred mainly in the developing CNS. These results demonstrate that the reduction in DNA synthesis resulting from zinc deficiency can be reversed by zinc alone, and that zinc deficiency in the mammalian system does not result in a general reduction in DNA synthesis in all tissues, but the head region is more vulnerable to reductions in zinc than the body region. The observation that DNA synthesis in the head region is reduced by zinc deficiency more than is the rest of the body may explain the increased vulnerability of the CNS to prenatal zinc deficiency.


Abnormal prenatal lung development resulting from maternal zinc deficiency in rats.

The effect of maternal zinc deficiency during gestation on fetal lung development was studied. Sprague-Dawley rats were fed from the day of mating (day zero) a zinc deficient diet (0.4 +/- 0.1 ppm zinc) ad libitum, or a zinc supplemented control diet (100 ppm zinc) either ad libitum or with restricted intake. Fetuses were removed by cesarean section on days 17 to 21 of gestation. Fetuses of zinc deficient dams had smaller lungs both in absolute weight and relative to body weight on all days than did either ad libitum-fed or restricted-intake controls. On days 20 and 21 of gestation, concentration of fetal lung lecithin and phosphatidylethanolamine was lower in zinc deficient fetuses than in control groups, indicating a reduced production of pulmonary surfactant. The lecithin to sphingomyelin ratio of amniotic fluid was lower in zinc deficient rats than in controls on days 19, 20, and 21 of gestation. On days 18 through 21 of gestation, fetal lung DNA concentration in zinc deficient fetuses was lower than in controls, but there were no differences in fetal lung zinc concentration. Histological examination of lungs from zinc deficient fetuses at term showed air spaces that were slightly collapsed with smaller lumina of the alveolar ducts than in controls.


Effects of branched-chain amino acid antagonism in the rat on tissue amino acid and keto acid concentrations.

Growth rate, plasma amino acid, and alpha-keto acid concentrations and activities of the branched-chain amino acid degradative enzymes of rats were measured. Effects of ingestion of excessive amounts of branched-chain amino acids on these variables were determined. Excessive intake of a single branched-chain amino acid led rapidly to elevated plasma concentration of both the amino acid administered and its corresponding alpha-keto acid and, if the rats had previously been fed a low protein diet, to an increase in liver branched-chain alpha-keto acid dehydrogenase activity. Only leucine caused, in addition, marked growth and food intake depression and decreased plasma isoleucine, valine, alpha-keto-beta-methylvaleric acid and alpha-keto isovaleric acid concentrations. The growth depression was associated food intake depression and could be moderated by addition of isoleucine and valine to the diet. The decreases in plasma isoleucine, valine, alpha-keto-beta-methylvaleric acid and alpha-keto isovaleric acid were not caused by increased degradation of these metabolites to carbon dioxide as branched-chain amino acid oxidation rates in vivo were unchanged by leucine loading and the degradative enzymes were unchanged in adequately fed rats. The decreased concentrations of these amino and keto acids may be the result of decreased protein degradation or increased protein synthesis, possibly mediated by insulin.


Methotrexate hepatotoxicity in children with leukemia.

Percutaneous liver biopsy was performed on seven children with acute lymphocytic leukemia who had received maintanance chemotherapy with high-dose intravenous methotrexate for 1 1/2 to 2 1/2 years. Portal fibrosis was found in four of the seven children and in an additional patient treated with oral methotrexate. Serial tests of liver function and 99mtechnetium-sulfur-colloid scans did not accurately identify children with hepatic fibrosis. Clinical evidence of liver disease was not seen.


PKU as a factor in the development of self-esteem.

Self-esteem of ten children with phenylketonuria was compared with that of seven unaffected siblings of children with PKU in a total of 11 families. Ages of the nine girls and eight boys ranged from 8 to 15 years. The study examined several variables that might affect self-esteem. From this study, it appears that PKU status and lowered IQ together contribute to lowered self-concept and that PKU status alone (i.e. with the effects of IQ removed) has a strong tendency to influence self-esteem.


The association of familial liver disease, subepidermal immunoproteins, and membranoproliferative glomerulonephritis.

Herein we report a new familial form of hepatic disease. Each of the four patients had splenomegaly, hypersplenism, a small liver, biochemical evidence of hepatic excretory dysfunction and hepatocellular damage, kidneys without demonstrable cysts, and normal blood pressue. An evaluation of serum immunoproteins, autoantibodies, histocompatibility antigens, and mixed lymphocyte reactivity further defined the immunologic features of this syndrome. Extrahepatic manifestations included a papulosquamous dermatitis with deposition of immunoglobulins and complement in both normal and abnormal skin, a membranoproliferative glomerulonephritis with subendothelial deposits, arthritis, and pericardial, pleural, and synovial effusions.


Severe glomerulonephritis complicated by coagulopathy: treatment with anticoaguland and immunosuppresive drugs.

Serial determinations, using plasma fibrinogen gel chromatography as well as standard methodology, demonstrated that six children with severe glomerulonephritis, characterized on renal biopsy by glomerular necrosis and crescent formation, had persistent evidence of intravascular coagulation. Based on these observations, therapy with anticoagulants and azathicoagulants and azathioprine was instituted for one year; treatment with anticoagulants was continued for a second year. Anticoagulant therapy was initiated with heparin, followed by oral anticoagulation with phenindione and dipyridamole. In contrast to our earlier experience with similar patients, each of the present patients improved. Urinalyses returned to normal and glomerular filtration rates to near normal values in all patients at the end of the treatment period and have remained so for up to 3.9 years since treatment has been completed. Post-treatment biopsies showed remarkable improvement, with virtually no glomerulosclerosis even in patients who had had a high incidence of glomerular crescents before treatment. It is suggested that the therapeutic regimen favorably influenced the natural history of disease and that plasma fibrinogen chromatographic findings may be helpful in selecting patients likely to benefit from the use of anticoagulant therapy.


The dysmature infant. Associated factors and outcome at 7 years of age.

Dysmaturity, diagnosed according to the Clifford criteria, was studied for the first time in a black population. The infants and matched control subjects were participants in the Collaborative Perinatal Study in Philadelphia from birth to 7 years of age. The incidence of dysmaturity was 25/1,000 live births; more boys than girls were born dysmature, reversing the normal male/female ratio found among black infants in the Collaborative Study as a whole. The condition was more common among post-term infants but did occur in earlier gestational weeks. The overall characteristics of the condition among this black population did not differ from those previously reported among white populations of various races. Surviving infants developed mentally and physically as well as control subjects. No prenatal or environmental characteristics were found that distinguished mothers of dysmature infants from those of nondysmature infants.