Androgen-controlled specific proteins in rat epididymis. The pattern of proteins in the soluble fraction of the cytoplasm of the rat epididymis was studied by acrylamide gel electrophoresis. The components of five distinct bands, labelled A, B, C, D and E, were found to be sensitive to changes in androgen in the blood. Castration for 14 days produced a sharp decrease in the colour intensity of bands B-E when stained with Amido black. After 21 days of castration, bands D and E were undetectable, bands B and C were severely diminished and band A was more intense. Seven days of replacement with testosterone (1 mg/day) induced a return towards a normal pattern. The degree of restoration was inversely proportional to the duration of castration. Quantitation by densitometry showed that the relative contributions of bands B-E to the region A-E were 61% in the control rat, only 27% after 21 days of castration and 35% when testosterone was given between days 14 and 21 of castration. The components of bands A-E are presumed to be proteins since the electrophoretic pattern was altered by digestion with pronase but not by ribonuclease, phospholipase C or neuraminidase. Epididymides from castrated and androgen-treated castrated rats were incubated with 14C- and 3H-labelled mixed amino acids respectively. After co-electrophoresis the ratio 3H: 14C rose from a baseline of 2-5 in band B, 32 in band C and 7 in bands D and E. Molecular weights were estimated as 27900 for B, 23100 for C and 34400 for D. Band A had the same electrophoretic mobility as serum albumin. Bands B and C were also present in testicular cytosol. Bands D and E were only found in the epididymis, localized mainly within the lumen of the tubules. Bands B-E increased with age during sexual maturation, bands D and E became detectable in the 20-day-old rats. Preliminary evidence indicates that the proteins in bands C, D and E can be removed from caput spermatozoa by washing.


Effects of androgens, oestrogens and deoxycorticosterone acetate on plasma concentrations of luteinizing hormone in laying hens. Testosterone, androstenedione, oestrone, oestradiol-17beta or deoxycorticosterone acetate (DOCA) were injected intramuscularly at several dose-levels and at various stages of the ovulatory cycle, and subsequent changes in plasma LH concentration were measured by radioimmunoassay. In 19 out of 24 hens, injection of 0.1, 0.5 or 1.0 mg DOCA/kg resulted in a mean maximal increase in plasma LH concentration of between 0.47 and 2.10 ng/ml. The magnitude of this response was not related to either the dose or the stage of the cycle at which the DOCA was injected. In the remaining five hens DOCA failed to stimulate LH secretion. Injection of either androstenedione, oestrone or oestradiol did not result in any increase in LH level in the circulation. In contrast, injection of 0.5, 1.0 or 2.0 mg testosterone/kg between 22 and 26 h after the terminal ovulation of a sequence resulted in mean maximal incremental changes in plasma LH level of 1.98 +/- 0.17, 2.17 +/- 0.21 and 2.41 +/- 0.31 (S.E.M.) ng/ml from pre-injection values of 1.38 +/- 0.16, 1.58 +/- 0.30 and 1.43 +/- 0.39 ng/ml (n=7, 6 and 5, respectively). The interval between the injection and the resulting rise in LH level was inversely proportional to the dose. The same doses of testosterone injected between 0 and 8 h after ovulation failed to stimulate LH secretion. There was also no significant increase in LH levels after injection of 0.5 and 1.0 mg testosterone/kg between 8 and 9 h after ovulation. However, injection of 2 mg testosterone/kg at this time resulted in a small but significant (P is less than 0.05) increase in LH levels. Since the largest ovarian follicle is more mature at 22-26 h after ovulation than at 0-9 h after ovulation, the ability of testosterone to cause the release of LH therefore appears to depend upon the degree of maturation of the ovarian follicle next due to ovulate.


Effects of postnatal thyroxine administration on brain development, response to postnatal androgen and thyroid regulation in female rats. Some developmental and functional manifestations of thyroxine (T4) administered on the first 2 days of postnatal life were studied in the female rat. Brain myelinogenesis estimated by brain esterified cholesterol concentration, and brain myelin age estimated by brain total cholesterol concentration, were subsequently determined. Thyroxine treatment resulted in a greater concentration of esterified cholesterol in the brain that saline treatment, but the latter appeared to delay the normal increase shown by non-injected controls. Thyroxine treatment resulted in total and free cholesterol levels similar to those of non-injected controls, these again being greater than those in saline-treated rats. Cholesterol concentrations in liver and serum were not affected by T4 or saline treatment. Administration of T4 to female rats before administration of 1-25 mg testosterone propionate on day 7 resulted in an ovarian and uterine weight response to human chorionic gonadotrophin (HCG, 1 i.u./day on days 23-26) on day 27 that was greater than that in litter-mates given saline at birth before testosterone propionate and HCG treatment. Postnatal T4 treatment alone in the female was also associated with a reduced thyroid and pituitary gland enlargement after 7 days of propylthiouracil feeding (0-015% in tap water, days 24-31 of life) when compared with either saline or non-injected controls.


Effects of sexual activity on luteinizing hormone and testosterone levels in the adult male rabbit. Sexually mature New Zealand White male rabbits were subjected to various sexual stimulation procedures. Plasma samples were obtained through an indwelling catheter in the central ear artery and analysed for LH and testosterone using specific radioimmunoassays. Coitus and exposure to females occasionally led to increases in testosterone levels which were usually preceded by a rise in LH. Increases in hormone concentration were not significantly different from those of rabbits which did not mate or which were isolated from females. These results suggest that coitus in the male rabbit does not cause the massive increase in LH concentration which is known to occur in the female.


Plasma luteinizing hormone and progesterone in the adult female pig during the oestrous cycles, late pregnancy and lactation, and after ovariectomy and pentobarbitone treatment. In a series of experiments on female miniature pigs, the pattern of plasma LH and progesterone levels during the oestrous cycle, late pregnancy and lactation and after ovariectomy were characterized, and the effect of pentobarbitone treatment was tested. The preovulatory surge of LH occurred in seven out of eight animals between 00.00 and 12.0 h on day 0 of the oestrous cycle (day 1 of standing heat). Plasma progesterone strated to decline 8 days before oestrus and reached its lowest value 5 days before the preovulatory LH peak. Increases in progesteron concentration were already noticeable 48 h after the LH surge. During late pregnancy, parturition and lactation, plasma LH was low and showed only minor fluctuations, while plasma progesterone declined 4 to 5 days before parturition. Both hormones remained at low levels throughout lactation. Three weeks before parturition increases in LH were always followed by an increase in progesterone. This dependency was greatly diminished immediately before delivery. Four to 12 days after weaning the animals came into oestrus which was followed by an increase in LH and later an increase in progesterone concentrations. Ovariectomy during dioestrus resulted in a steady increase in plasma LH levels of 35-39 days. Ovariectomy caused abortion if performed on day 100 of pregnancy. It was followed by a rapid increase of plasma LH concentration. Normal parturition (around day 115) and lactation took place when animals were spayed on day 112 of pregnancy. In this case, plasma LH levels remained even lower than before ovariectomy as long as lactation was maintained. Immediately after weaning a rapid increase in the normal postovariectomy pattern of LH secretion was observed. Pentobarbitone anaesthesia (30-35 mg/kg body wt, initial dose), during pro-oestrusoestrus, for less than 5 h had no effect on the preovulatory LH increase. However, pentobarbitone anaesthesia for more than 6 h inhibitied the LH peak and ovulation if the animal was under deep anaesthesia before 24.00 h on the day before oestrus. Pentobarbitone treatment of ovariectomized pigs resulted in a clear decrease in LH levels 40 min after a single i.v. dose.


Comparison of the redox bioassay with other assays for luteinizing hormone. The cytochemical (redox) bioassay for LH has been compared with established LH assays. Measurements made by redox bioassays were considerably lower than those made by radioimmunoassay in human female plasma samples obtained at mid-cycle. There was no apparent relationship between measurements on incubation media from cultures of sheep pituitary glands made by redox bioassay and the ovarian ascorbic acid depletion (OAAD) assay. After polyacrylamide gel electrophoresis of a crude extract of a human pituitary gland, redox LH measurements were lower than those of the OAAD assay and radioimmunoassay in the cathodal segments of the gel. By contrast, there was reasonable agreement between LH measurements made by radioimmunoassay and redox assay in cathodal fractions from gel electrophroesis of a purified pituitary LH preparation. Follicle-stimulating hormone, and the alpha- and beta-subunits of LH depressed the response of intact LH in the redox assay; this might explain the relatively low levels of LH measured by redox assay in some of the experiments described. Which type of assay best reflects the biological activity of LH in man remains to be determined.


Seasonal variation in the episodic secretion of luteinizing hormone and testosterone in the ram. Rams of an ancient breed of domestic sheep (Soay) were housed under artificial lighting conditions to study the way in which the secretion of LH and testosterone changes in relation to the mating season. Conspicuous changes were found in the short-term fluctuations in plasma LH concentrations related to the cycle of testis growth and regression; serial blood samples collected at short intervals revealed episodic peaks in plasma LH at all times, but there were changes in the frequency (lowest when the testes were regressed and highest when fully active), amplitude (lowest at the peak of testis activity, and highest during the developing phase), and duration of the peaks (shortest when the testes were regressed). In addition, the basal levels changed from being lowest in the regressed phase of the testis cycle, and highest when the gonads were most active. Plasma testosterone concentrations changed in parallel with the cycle of testis size and were correlated with the fluctuating levels of LH. Each episodic peak in plasma LH was associated with an increase in the levels of testosterone, beginning after 0-30 min and rising to a peak at 60-90 min; the speed and magnitude of the response being greatest when the testes were largest, but was not correlated with the magnitude of the LH change. Injections of LH releasing hormone (5 mug) stimulated an increase in plasma LH and testosterone proportional to the endogenous fluctuations in the hormones at the various stages of the seasonal cycle; LH concentrations were raised to supra-physiological levels after the injections, while testosterone concentrations seldom exceeded the normal peak values at any stage. These observations are used to discuss the role of the hypothalamus in the control of male seasonality with emphasis on the dynamic interplay between the hypothalamus, pituitary and testis.


Activity of steroid C-17,20 lyase in the ovine placenta: effect of exposure to foetal glucocorticoid. Microsomal fractions isolated from post-partum ovine placentae catalysed the synthesis of [3H]oestrone and [3H]oestradiol from [3H]17alpha-hydroxyprogesterone and NADPH; oestrone and oestradiol were formed in a ratio of approximately 50:1. The expected intermediate, [3H]androstenedione, did not accumulate during these incubations but was shown by trapping experiments to be the intermediate involved. Mean (+/- s.d.) uields of [3H]oestrone (% conversion of substrate) during incubation for 1 h of placentae from five animals in late pregnancy before the onset of labour, from five animals which delivered spontaneously at term and from four animals in which labour was induced by administration dexamethasone to the foetus were: in tissue obtained before labour, 3-2+/-0-44; in tissue obtained after the spontaneous onset of labour, 20-6+/-10-2 (P less than 0-01) and in tissue obtained after dexamethasone-induced labour, 24-4+/-2-13 (P less than 0-0001). This increase in oestrone synthesis suggests activation of steroid C-17,20 lyase, since this is the step limiting the rate of synthesis of oestrone in vitro. The enzyme is probably activated by foetal glucocorticoid. The findings are discussed in relation to the site of synthesis of oestrogens which in the sheep increase in concentration in the peripheral circulation at term, and with reference to a possible mechanism by which foetal glucocorticoid may control the onset of labour in this species.


Effects of ferrous ions on preoptic area neurones and luteinizing hormone secretion in the rat. Ferrous ions (Fe2+) were applied by microiontophoresis of 29 neurones recordid from the forebrain of ten pro-oestrous rats. The spontaneous activity of 24 cells was reduced by Fe2+ and five units did not respond. No excitations were observed. Reproducible responses could not be obtained with ferric ions (Fe3+). Microinjection of 1 mul 200 mM-Fe2+ into the preoptic area of eight pro-oestrous rats produced a sharp increase in plasma LH levels. Similar treatment with saline was without effect. Rats anaesthetized with sodium pentobarbitone during the early afternoon of pro-oestrus ovulated overnight when injected with both Fe2+ and Fe3+. The experiments do not confirm the widely held belief that raised plasma LH levels following deposition of iron in the rostral hypothalamus result from increased firing of nerve cells.


Purification and properties of the subunits of human pituitary follicle-stimulating hormone. Highly purified human pituitary FSH was partially dissociated by treatment with 8M-urea, and alpha- and beta-subunits were isolated by ion-exchange chromatography and gel filtration. Tests of biological activity by in-vivo assays and in-vitro radioreceptor assays were in good agreement and showed that preparations of isolated alpha-subunit had less than 1%, and beta-subunit from 2 to 10% of the FSH activity of the intact hormone. In contrast to results reported elsewhere, most of the subunit preparations reassociated with counterpart subunit to regain biological activity equal to that of intact FSH (around 160 mg NIH-FSH-S1/mg). The intact FSH recovered as a by-product after isolation of subunits was of high biological activity, and its LH contamination was reduced by more than 90% when compared with thepurified FSH starting material. The subunits are relatively inactive in a radioimmunoassay specific for intact FSH. Sialic acid and tryptophan determinations indicated that both subunits contain sialic acid and that tryptophan is present only in the beta-subunit.


Facilitation of human tobacco self-administration by ethanol: a behavioral analysis. The effect of ethanol on the cigarette smoking of alcoholic subjects was studied in a residential laboratory. During daily 6-hr sessions, cigarettes were obtained either by request to the ward staff or by operation of a lever (fixed-ratio 5 or 10). In a mixed sequence across days, sessions involved ingestion of either vehicle (orange juice or vehicle plus ethanol (133.7 g). During ethanol sessions, the rate of cigarette smoking increased from 26% to 117% of vehicle levels. A series of control studies eliminated a number of potential behavorial mechanisms for the observed effect and indicated that the ethanol-induced increase in cigarette smoking occurred under a variety of experimental conditions: (1) when smoking could not occur concurrently with ethanol or vehicle consumption; (2) when subjects were not allowed to socialize; (3) when ingestion of ethanol or vehicle was scheduled for a number of consecutive days; (4) when various doses of ethanol were administered under blind conditions. In control experiments, weighing unsmoked tobacco and counting the number of puffs per cigarette indicated the effect was not due to smoking less of each cigarette. The effect was not limited to the experimental sessions alone, since total daily smoking was higher on ethanol days than vehicle days.


Some effects of delta-amphetamine and pentobarbital on performance under a long fixed-interval schedule. The effects of delta-amphetamine and pentobarbital were studied on performance during 3-hr sessions under fixed-interval 60-min schedules of food presentation. Low doses of delta-amphetamine increased rates of responding and higher doses decreased rates of responding, both during the entire 3-hr session and during each of the individual fixed intervals. Pentobarbital produced little effect on rates of responding averaged over the 3-r session, but it decreased rates during the first fixed interval and increased them during the second and third fixed intervals. The effects of delta-amphetamine were shown to be dependent on the control rate of responding, as has been shown with shorter fixed-interval values. Analysis of delta-amphetamine effects in terms of the point at which the probability of responding is greater than zero was not descriptive of overall fixed-interval performance.


Abnormalities in the differentiation and cellular properties of hyperplastic lens epithelium from strains of chickens selected for high growth rate. Similar morphological abnormalities of the lens of the eye of two unrelated strains of chicks, both of which had been selected for high growth rate, were found to be associated with epithelial cells showing marked deviations from the normal in cell surface properties, mitotic rate, capacity for differentiation, and in DNA, RNA and protein metabolism. The relationship between these modified properties and the observed morphology is discussed.


Embryogenesis of an insect nervous system. I. A map of the thoracic and abdominal neuroblasts in Locusta migratoria. Maps of the thoracic and abdominal neuroblasts have been prepared by reconstruction from serial sections of timed Locusta migratoria embryos. The maps are bilaterally symmetrical, periodic and consistent for embryos of the same age, with a fundamental arrangement of 7 rows of 4-10 cells plus 1 median neuroblast per segment. A map of 60 + 1 cells is repeated in each of the three thoracic segments, with an additional median cell developing late at the anterior end of the prothorax. The arrangement in the abdomen is similar, with 56 + 1 cells per segment. Neuroblasts differentiate and subsequently degenerate in an antero-posterior sequence, but construction of the thoracic ganglia involves a delayed degeneration of part of the original set in these segments. The maps show that the neuroblasts are as reliable in their number and arrangement as the adult cells they produce. The number of neuroblasts used in constructing the relatively complex thoracic ganglia is  similar to that which produces the simpler abdominal ganglia. Some motorneurons have the same parent neuroblast. The maps are intended as a first step in an analysis of the relation between the progeny of different neuroblasts and the family of neurons which each neuroblast produces.


The formation of the gonadal ridge in Xenopus laevis. I. A light and transmission electron microscope study. In Xenopus laevis tadpoles, between stages 44 and 49 (Nieuwkoop & Faber, 1956), the primordial germ cells (PGCs) migrate from the dorsal mesentery of the gut to the site of the presumptive GD gonadal ridge. This paper describes the process at the light- and electronmicroscope levels. The PGCs in the mesentery, which at first are very large and yolk-laden, seem to lie entirely within the cellular matrix of the mesentery, although this is not obvious in light micrographs. Where the PGCs bulge out into the coelomic cavity, they stretch the somatic cell covering to a thin, cytoplasmic layer. The somatic cells of the mesentery are held together around them at this stage by well-differentiated desmosomes. At this, and subsequent stages, the PGCs have cytoplasmic processes, roughly the size of microvilli, which are irregularly distributed over their surfaces, and which are inserted between surrounding somatic cells. Whether these processes play any role in locomotion or exploration of the substrate is uncertain. As the PGCs move laterally from the root of the mesentery to the presumptive gonadal ridge, the coelomic lining cells which cover them, initially with a very thin squamous layer, differentiate to form the cuboidal cells of the germinal epithelium. Several interesting ultrastructural features of these cells, and the PGCs, are described, particularly in the light of their surface interaction. In the light of the morphological data presented here, particularly of the cell surfaces involved, we conclude that both active locomotion by the PGCs and passive movement by the morphogenetic movements of the cells around them contribute to the establishment of the early gonadal ridge.


The formation of the gonadal ridge in Xenopus laevis. II. A scanning electron microscope study. This paper studies the surface morphology of the developing gonadal ridge in X. laevis between stages 44 and 49 (Nieuwkoop & Faber, 1956). During this period the primordial germ cells (PGCs) move laterally from the dorsal mesentery of the gut to the position of the presumptive gonadal ridge. As they do so the coelomic lining cells lateral to the mesentery differentiate into a specialized, longitudinally orientated band, stretching nearly the full length of the dorsal mesentery on each side. The PGCs migrate beneath this band of cells, which thus becomes the germinal epithelium of the gonadal ridge. We have demonstrated by irradiation experiments that this specialized band of cells can differentiate independently, in the absence of the PGCs.


The effect of 5-bromodeoxyuridine on cell division and differentiation of preimplantation mouse embryos. Mouse embryos exposed to concentrations of 5-bromodeoxyuridine (BUdR) ranging from 0-01 to 1-0 mug/ml in vitro for two days from the 8-cell stage exhibit a concentration-dependent decrease in the frequency of normal blastocysts and decrease in average cell number per embryo. A 20-h exposure was adequate to achieve the full BUdR response. Both effects were eliminated in the presence of excess thymidine. Autoradiographs demonstrated that BUdR[3H] was incorporated into DNA during the first and second day of culture. Thus, BUdR appears to act through incorporation into DNA; and, in this system, cell division is at least as sensitive to BUdR as is differentiation.


Complete preimplantation development in culture of parthenogenetic mouse embryos. The present experiments were undertaken to determine whether, in parthenogenesis, heterozygous embryos develop better than homozygous embryos. Such experiments may provide an approach to elucidating whether fertilized embryos develop better than parthenogenetic ones because of heterozygosity, or if the sperm provides another contribution necessary for complete embryonic development. The parthenogenetic embryos studied included uniform haploids after extrusion of the second polar body, mosaic haploids in which each blastomere contained a genetically different haploid nucleus, and heterozygous diploid mouse embryos. Eggs were activated and cultured in a chemically defined medium. About three times as many mosaic haploid or heterozygous diploid eggs developed beyond the 4-cell stage after 98-100 h and to the blastocyst stage after 120 h in culture, than uniform haploid eggs. This indicates that the development of parthenogenetic embryos is probably under genetic control and that there was a better development of the heterozygous embryos. Mosaic haploid embryos showed the same high frequency of development as heterozygous diploids. The results therefore indicate that heterozygosity provided a developmental advantage even when distributed between two genetically different clones of cells in the same embryo.


Effects of formamide on neuroepithelial cells and on interkinetic nuclear migration in the chick embryo. Young chicken embryos were incubated on media containing formamide at concentrations of 0-1, 0-25, 0-31, 0-37, 0-43 and 0-5 M. In the neuroepithelium of these embryos we found that (1) the 0-1 M concentration  had no detectable effect, (2) the 0-25 M concentration only affected mitosis which was blocked in metaphase so that mitotic figures accumulated near the neurocoele, (3) 0-31 M formamide totally inhibited interkinetic nuclear migration and affected only slightly the cell asymmetry, (4) the 0-37 M concentration considerably reduced the amount of cytoplasmic microtubules and that the cells became round, (5) at 0-43 M formamide, all microtubules had  disappeared and all cells were spherical, (6) 0-5 M formamide all cells were spherical, detached from one another and the epithelium had lost its usual characteristics. Our results on exposure of the cells to low temperature (2 degrees C) suggest that formamide directly affects microtubules. All the effects observed at concentrations up to 0-43 M formamide are reversible.


The teratogenic effects of hydrocortisone on palatal development in the hamster. The effect of different doses of hydrocortisone, administered at various times during gestation, on the fetal hamster and its palatal development was studied. Both the frequency of cleft palate and that of resorption depended upon the dose of hydrocortisone and the time of its administration. Two peaks in the incidence of cleft palate were observed, which appeared to be due to inhibition of different events. Incidence of morphologically different types of cleft palate was related to the doses and gestational time of hydrocortisone treatment. A close association was observed between the frequency of cleft palate and fetal growth retardation and between the latter and the dose and time of drug administration. It was suggested that maternal physiology and the placental barrier may  play a crucial role in cleft palate induction.


Reorganization of retinotectal projection of compound eyes after various tectal lesions in Xenopus. The retinotectal connexions of double nasal (NN), double temporal (TT) and double ventral (VV) eyes in juvenile Xenopus were mapped after post-metamorphic removal of the rostral, caudal, medial or lateral tectal halves with the subsequent cutting of the optic nerve of the operated eye. A whole visual field projection occurred from NN  eyes on to residual caudal tectum, from TT eyes on to residual rostral tectum and from VV eyes on to residual medial tectum. When optic fibres from NN, TT or VV eyes grew into inappropriate rostral, caudal or lateral tectal halves respectively, there was a projection deficit in the nasal and temporal or in the dorsal and ventral poles of the visual field. The persisting scotomas in the visual field indicated that only the optic fibres of the central retinal fundus had succeeded in connecting with an inappropriate tectal half whereas the peripheral optic fibres had not. The incongruous results of optic nerve regeneration obtained in the various recombinations may be taken to indicate that the assumption of early embryonic pattern regulation is inadequate to explain the findings in this experimental situation.


The distribution of melanocytes in the dorsal coats of a series of chimaeric mice. Chimaeras, made by aggregating two embryos from the randomly-bred Q-strain, and X-inactivation mosaics both have similar, balanced distributions of pigmentation in the dorsal coat, while (C57BL X C3H) F1 reversible Recessive chimaeras tend to have an unbalanced pigment distribution, with a higher proportion of F1 pigmentation in the posterior than in the anterior part of the coat. This observation can be explained if differences in the timing of the migration of the  two melanocyte populations from the neural crest cause anterior-posterior differences in selection pressures.


Energetics of swimming of a sea turtle.

Energetics of swimming of a sea turtle. Young (mean mass 735 g) green turtles (Chelonia mydas) were able to swim in a water channel at sustained speeds between 0-14 and 0-35 m.s-1. Oxygen consumption at rest was was 0-07 l.kg-1.h-1; at maximum swimming speed oxygen consumption was 3-4 times greater than at rest for a given individual. In comparison with other animals of the same body mass the cost of transport for the green turtle (0.186lO2.kg-1.km-1) is less than that for flying birds but greater than that for fish. From drag measurements it was calculated that the aerobic efficiency of swimming was between 1 and 10%; the higher efficiencies were found at the higher swimming speeds. Based upon the drag calculations for young turtles, it is estimated that adult turtles making the round-trip breeding migration between Brazil and Ascension Island (4800 km) would require the equivalent of about 21% of their body mass in fat stores to account for the energetic cost of swimming.


Insect blood-brain barrier: an electrophysiological investigation of its permeability to the aliphatic alcohols. The anaesthetic effects of the aliphatic alcohols were used to measure their concentration at the neuronal surfaces of the cockroach central nervous system. The results were in most cases fairly closely described by first-order kinetics. The exchange half-times of the lower alcohols were only a few seconds, being little affected by the removal of the nerve sheath. The half-times for the higher alcohols were somewhat longer, and were more significantly reduced by desheathing; these observations were interpreted in terms of a reservoir effect resulting from their higher liposolubility. It was shown that the ionic diffusion barrier in intact nerve cords remained undamaged in the presence of the alcohols.


Insect blood-brain barrier: a radioisotope study of the kinetics of exchange of a liposoluble molecule (n-butanol). About 90% of the butanol uptake by the cockroach abdominal nerve cord washed out with half-times of a few seconds, in good agreement with an electrophysiological estimate, and the temperature sensitivity suggested an activation energy of 3 Kcal mole-1. The remaining activity washed out far more slowly, with a similar time course to that observed in a previous investigation which had not detected the fast fraction. Its size was similar to the non-volatile uptake, and was considerably affected by the butanol concentration and incubation period. It apparently consisted of butanol metabolites, which could be detected by chromatography.


The action of the excretory apparatus of Calliphora vomitoria in handling injected sugar solution. Recent evidence suggests that the isolated Malpighian tubules of Calliphora possess mechanisms which restrict the loss of glucose and trehalose from the insect. This report establishes that the intact, diuresing fly does not excrete glucose or trehalose when solutions of these sugars are injected. When solutions of non-metabolized sugars such as sorbose and xylose are injected into the fly, these sugars are rapidly excreted. High concentrations of sorbose and xylose are found in the urine, suggesting that rapid reabsorption of fluid occurs in the excretory apparatus even during the diuresis which the injections provoke. However, injected sucrose is apparently not excreted in large amounts and it is possible that the Malpighian tubules when functioning in vivo are impermeable to disaccharides.


The regulation of haemolymph calcium concentration of the crab Carcinus maenas (L.). After acclimation, Carcinus can maintain calcium balance in dilute (35-100%) but not in low calcium sea water. 71% of total haemolymph calcium (9-54 +/- 0-42 mM) was in ionic form as compared with 90-9%(9-9mM) in sea water. On acclimation to dilute sea water the calcium activity of the haemolymph was greater than that of the medium, the difference being maintained by active calcium uptake. Carcinus is highly permeable to Ca2+, influx from sea water being 0-513 +/- 0-07 mumoles g-1 h-1 and the time constant for calcium influx 4-3 +/- 0-48 h. Calcium space represented ca. 25% wet body weight independent of body size or salinity of acclimation medium.


Form of developing bends in reactivated sperm flagella. 1. Dark-field, multiple-exposure photographs of reactivated tritonated sea urchin sperm flagella swimming under a variety of conditions were analysed. 2. The length, radius and subtended angle of bends increased during bend development. The pattern of development was essentially the same under all conditions observed. 3. The angles of the two bends nearest the base tend to increase at the same rate, cancelling one another, so that the development of new bends causes little if any net microtubular sliding. 4. The direction of microtubular sliding within a bend is initially in the same direction as that within the preceding bend, and reverses as the bend develops.


The receptive fields of Daphnia ommatidia. 1. The focal length and positions of the principal planes of an isolated Daphnia lens were determined, and the refractive index of the rhabdom was measured. 2. The lens can form an image, but this always lies well behind the rhabdom. This was confirmed by direct observation of images inside a clear-eye mutant Daphnia eye. 3. The rhabdom was shown to be unlikely to function as a waveguide, and a ray optics model is proposed to enable the prediction of ommatidial receptive fields from the lens data. 4. The predicted receptive fields have wide plateaus and steep sides, and there are virtually no totally blind gaps between neighbouring ommatidia.


Sodium extrusion by the sea-water-acclimated fiddler crab Uca pugilator: comparison with other marine crustacea and marine teleost fish. 1. Measurements of the blood Na concentration and transepithelial electrical potential (T.E.P.) across Uca pugilator acclimated to sea water indicate that Na is maintained out of electrochemical equilibrium with sea water. The resulting net Na influx as well as the sodium gain due to ingestion of the medium must be balanced by extrarenal Na extrusion. 2. The small T.E.P. (-0.7 mV) and the 'transport numbers' of Na and Cl indicate that the permeability to these ions is equivalent. 3. Removal of external K results in a significant stimulation of unidirectional Na efflux that is dependent upon external Na but is not inhibited by ouabain. 4. Transfer of Uca to K and Na-free sea water results in a 54% decline in unidirectional efflux, which is not due to T.E.P. changes. Readdition of 25mM-K stimulates Na efflux much more than can be accounted for by changes in the T.E.P. Readdition of 25mM-Na to potassium-free sea water does not change the Na efflux. 5. The results indicate that Na extrusion by Uca is via a Na/K exchange mechanism which partially inhibits Na/Na exchange. Cessation of Na/K exchange (in K-free sea water) removes this inhibition and allows rapid Na/Na exchange. It is not known whether Na/K and Na/Na exchange are via the same or parallel carrier systems.


The effects of hypophysectomy, prolactin therapy and environmental calcium on electrolyte balance of the brown trout Salmo trutta, L. Adaptation of the brown trout to fresh water containing increasing concentrations of calcium resulted in a decrease in plasma electrolyte level and total electrolyte excretion. The electrolyte excretion rate was higher at the beginning than at the end of the urine collection periods. Hypophysectomized fish had a lower plasma electrolyte concentration than the controls. This deficiency was partially corrected by polactin therapy. High environmental calcium was only effective to a limited extent. There was no difference in the normal renal sodium output between hypophysectomized and intact fish in fresh water. Environmental calcium did not have any significant effect on renal electrolyte output of hypophysectomized fish.


Properties of the trochanteral hair plate and its function in the control of walking in the cockroach. 1. The physiological properties of the group of long hair sensilla of the trochanteral hair plate in the cockroach metathoracic leg were studied. The sensilla were divided into type I and type II according to their responses to imposed displacements. 2. Type I hair sensilla responded to dynamic displacements whereas type II hair sensilla responded to both dynamic and static displacements. The hair sensilla are normally excited by phasic flexion movements of the femur near the end of leg protraction. 3. Activity in the trochanteral hair plate afferents had a short latency excitatory effect on the motoneurone producing slow extension movements of the femur and an inhibitory effect on the femur flexor motoneurones. 4. Removal of the trochanteral hair plate in one leg caused overstepping of that leg in a walking animal due to exaggerated flexion of the femur. This change in leg movement can be explained by the removal of the inhibitory influence from the hair plate afferents to the femur flexor motoneurones. 5. We conclude that one function of the trochanteral hair plate is to limit femur flexion during a step cycle.


Printed circuit microelectrodes and their application to honeybee brain. The application of printed circuit technology to the production of a new type of multi-channel microelectrode is described. 2. Recordings have been obtained from the the protocerebrum of the honeybee Apis mellifera L. using printed circuit microelectrodes in both restrained and free-moving preparations. 3. These recordings are compared with those previously obtained from conventional probe microelectrodes and are found to have similar characteristics of transient voltage changes superimposed on an undifferentiated high frequency background. 4. A wide range of development possibilities for the printed circuit microelectrode are discussed.


Carbon dioxide combining properties of the blood of the shore crab Carcinus maenas (L): carbon dioxide solubility coefficient and carbonic acid dissociation constants. The carbon dioxide solubility coefficient, alphaCO2, and the apparent carbonic acid dissociation constants, K'1 and K'2 were estimated in the serum of the crab Carcinus maenas at various temperatures and ionic strengths. At 15 degrees C, the indirectly determined alphaCO2 value is 0-0499 m-mole l-1 torr-1 for crabs living in normal sea water (salinity ca. 35 percent). It is apparently independent of the serum protein concentration and of the stage of the moulting cycle. For crabs living in undiluted sea water, the mean pK'1 value, determined either gasometrically or titrimetrically, is 6-027 at 15 degrees C. At the same temperature, pK'2=9-29. These values approximate to those of sea water at 35 percent salinity. pK'1 drops as temperature rises; the measured deltapK'1/deltat is -0-0053 pH unit degrees C-1 between 10 and 30 degrees C. PK'1 rises as the ionic strength is lowered. Alignment nomograms have been constructed for the determination of alphaCO2, pK'1 and pK'2 values in relation to various conditions of temperature and salinity.


Contribution of an electrogenic pump to the resting membrane polarization in a crustacean heart. 1. In the neurogenic heart of the isopod crustacean Porcellio dilatatus, external K+ removal depolarized the membrane (K0 effect) whereas subsequent restoration of K+ resulted in a rapid hyperpolarization (K1 effect). 2. The amplitude of the K1 effect depended on the duration of the prior K+ deprivation and on the subsequent K+ concentration. 3. The membrane resistance slightly increased during the K0 effect; during the K1 effect, it only returned to its control value. 4. Ouabain, cooling and replacement of external Na+ by Li+ also produced depolarization. 5. The K1 effect was suppressed by ouabain and markedly depressed by lowering the temperature to 4-6 degrees C. It was abolished if Li+ replaced Na+ during the prior privation of K+; moreover Li+ was unable to act as a substitute for external K+ in generating the K1 effect if used at equivalent concentration, but enhanced the effect at high concentration. 6. The findings are consistent with the presence of an electrogenic sodium pump in the myocardium of Porcellio contributing to the resting membrane potential. 7. Changes in the spontaneous rhythm observed during K0 and K1 are further suggestive of the presence of an electrogenic Na+ pump in the pacemaker neurons of the cardiac ganglion. Another explanation is also proposed. 8. The magnitude of the spontaneous contractions of the heart was increased during the K0 effect and markedly decreased during the K1 effect. An indirect effect of the changes in internal Na+ concentration on the contractile processes is suggested.


Unidirectional ion movements in the hindgut of larval Sarcophaga bullata (Diptera: Sarcophagidae). 1. Unidirectional Na+, K+, and Cl- fluxes were measured across the isolated hindgut of larval Sarcophaga bullata. 2. Both K+ and Cl- are actively secreted into the hindgut lumen, whereas Na+ is distributed passively. 3. The movements of K+ and Cl- are not entirely independent of each other, and the movement of one ion influences the flux of the co-ion. 4. The NH4+ ion is secreted into the hindgut by a mechanism separate from K+ secretion.


Effect of recent antigen priming on adoptive immune responses. IV. Antigen-induced selective recruitment of recirculating lymphocytes to the spleen demonstrable with a microculture system. When thoracic duct lymphocytes (TDL) from mice given sheep erythrocytes (SRC) 1 day previously (1-day-primed TDL) were placed in microcultures with antigen for 5-6 days, the cells failed to produce antibody to SRC, but responded well to horse erythrocytes (HRC); reciprocal results were obtained with TDL from HRC-injected mice. The specific unresponsiveness of the TDL was observed despite the presence of an allogeneic factor in the cultures; this factor exerted not only a macrophage-like effect (TDL from normal mice failed to respond in the absence of this factor) but also a T-cell-replacing function. It was concluded therefore that the unresponsiveness of the TDL was the result of selective recruitment of specific B lymphocyte precursors from the recirculating lymphocyte pool to the lymphoid tissues; whether there was also recruitment of specific T lymphocytes was not investigated. Since addition of 1-day-primed TDL to cultures of normal TDL did not inhibit the response of the latter, there was no evidence that active suppression accounted for the unresponsiveness. The spleen appeared to be the main site for recruitment since 1-day-primed spleen cells placed in microcultures contained above normal numbers of specifically-reactive precursors. This was in striking contrast to the effect of transferring 1-day-primed spleen cells in vivo where, as previously reported, the cells fail to respond to the injected antigen within 1 wk of transfer. An explanation for this paradox is discussed.


Collagen-and collagen peptide-induced chemotaxis of human blood monocytes. The ability of collagen and collagen-derived peptides to act as chemotactic stimuli was investigated by in vitro chemotaxis assays. Native human and chick skin collagen (type I) and alpha-chains obtained from purified chick skin collagen were each chemotactic for human peripheral blood monocytes. In addition, smaller peptides obtained either by digesting native collagen with bacterial collagenase or by degrading purified alpha-chains with cyanogen bromide or pepsin were also chemotactic for monocytes. In contrast, native collagen, alpha-chains, and smaller collagen-derived peptides were not chemotactic for human neutrophils. Since collagen is degraded at sites of tissue damage and inflammation, our findings suggest the possibility that such collagen-derived degradation products might directly serve as chemotactic stimuli for human peripheral blood monocytes in vivo.


Successful treatment of enterovirus-infected mice by 2-(alpha-hydroxybenzyl)-benzimidazole and guanidine. Echo virus 9- or Coxsackie A 9-infected newborn mice are protected from paralysis and death by combined treatment with nontoxic concentrations of HBB plus guanidine. HBB alone also protects Coxsackie A 9, but not echo virus 9-infected animals, whereas guanidine alone is ineffective in either case. Protection is due to inhibition of virus multiplication via the antiviral activity of these selective inhibitors. Treatment must be begun at the latest 48 h after virus inoculation. 3 days of treatment are sufficient if started at the time of virus inoculation. Failure of protection after treatment with one compound alone is not due to rapid development of drug-resistant virus mutants. Infected, successfully treated mice may develop a solid immunity.


Introduction of B-chain-inactivated ricin into mouse macrophages and rat Kupffer cells via their membrane Fc receptors. Experiments have been made to test whether the toxic lectin ricin can be bound to and introduced into cells by some other mechanism than via its B chain, the natural binding moiety of the toxin, without its toxic effect being neutralized. Complexes consisting of ricin and antibodies specifically directed against ricin B chain were incubated with mouse peritoneal macrophages and rat Kupffer cells, which are known to possess surface receptors for the Fc portion of the immunoglobulin molecule. After incubation for 26 h, cellular protein synthesis, as measured by incorporation of labeled leucine into acid-insoluble material, was completely inhibited. HeLa cells, which do not possess Fc receptors, were unaffected by the complex. The effect of the complex on protein synthesis of macrophages was prevented by soluble antigen-antibody complexes, but not by the presence of lactose which prevents attachment of the ricin B chain to the cell membrane. The [ricin-antiricin B] complex was attached to red cells, and the resulting complex was incubated with rat Kupffer cells. Cellular protein synthesis ceased after 6 h, and phase contrast microscopy studies showed that the complexes were taken up by the Kupffer cells. The data indicate that ricin, when present in the complex with antiricin B, can be introduced into cells through cell membrane receptors other than the B chain receptor, in this case the Fc receptor, and that the internalized toxin retains a least part of its activity.


Simultaneous and backward fear conditioning as a function of number of CS-UCS pairings. Four experiments examined the possibility that the outcome of simultaneous and backward fear conditioning procedures might depend upon the number of CS-UCS pairings. A punishment procedure will rats as subjects and shock as the UCS was used; the amount of suppression produced by response-contingent CS presentations indexed the strength of acquired fear. Experiments 1, 3, and 4 examined the suppressive tendencies of simultaneous-and backward-trained CSs after 0, 10, 20, 40, 80, and 160 pairings. The pattern of data suggested that initial pairings have the effect of increasing suppressive tendencies of the CS, while subsequent pairings decrease them. In addition, evidence of fear inhibition was found after 160 pairings in the case of the backward paradigm. Experiment 2 examined several nonassociative accounts based upon differential shock exposure. Groups given 10 pairings or 80 pairings were compared to ggroups given 10 pairings plus 70 shock-alone presentations. The results indicated that number of pairings, rather than number of UCS occurrences, is the important factor in decreasing the initial suppression. The evidence for eventual inhibition in the backward paradigm suggests that this occurs through the acquisition of inhibitory tendencies which are antagonistic to the previously conditioned excitation.


Unconditional stimulus characteristics in rabbit eyelid conditioning. Three experiments employed aversive or positive subcortical electrical stimulation in an unconditional stimulus (US) role in rabbit eyelid conditioning. Conditional response (CR) development to a tonal conditional stimulus (CS) was examined when the intracranial stimulation was combined with a conventional cheek-shock US (Experiment 1) or with a lightflash US (Experiment 2). Our findings were consistent with previus observations that the affective impact of the US is important in the development of an overt motor CR. The complex pattern of our results, however, implies that intracranial stimulation has multiple effects on conditioning and argues against any unidimensional interpretation of these outcomes. Our analysis of CR-contingent intracranial stimulation presentation in Experiment 3 indicated that such stimulation does not act as a Thorndikian reward or punishment in rabbit eyelid conditioning.


The reliability of a mechanized procedure (Perkin-Elmer C4) for the Enzymatic determination of uric acid according to Kageyama. The enzymatic determination of the uric acie concentration in urine and serum according to Kageyama ((1971), Clin. Chim. Acta 31, 421--426), which excludes the deproteinization of samples, was adapted to the C4 automatic analyzer (Perkin-Elmer). The reliability of this procedure and its correlation with an UV-method were investigated. The interaction from-sample-to-sample was considerable, but this could be reduced by the addition of Brij-35. The recovery of uric acid added to protein-containing samples (about 96%) was better than with the UV-method. Novaminsulfone was the only substance tested which interfered significantly.


The influence of D-penicillamine on enzymatic activities: glucose-6-phosphate dehydrogenase. Correlation with serum levels measured in humans. The influence of D-penicillamine on glucose-6-phosphate dehydrogenase of yeast (pure enzyme), human hemolysate, and human skin homogenate were determined. In high concentrations, D-penicillamine inhibits glucose-6-phosphate dehydrogenase activity (concentrations above 6.7 mmol/l, i. e. l g/l). In low concentrations, D-penicilliamine exerts an indirect influence by removing some inhibiting metal ions, such as zinc. In human skin homogenates, an activating action of D-penicillamine on glucose-6-phosphate dehydrogenase activity occurs due to the chelation of metal ions.


[Determination of lead in beard hair by atomic absorption spectrometry (author's transl)]. The lead content of hair from the electric razor can be determined by atomic absorption spectrometry, using the micro-sampling technique of Delves. 1--5 mg of the washed and dried hair are partially oxidized with hydrogen peroxide prior to analysis. The method is simple and quick and therefore suited for the serial investigation of persons exposed to lead.


[Protection of erythrocytes in D2O against damage by hyperthermy and freezing (author's transl)]. The haemolysis of erythrocytes after heating to 55 degrees C, after freezing and after osmotic damage was studied in normal water and in heavy water (D2O). Haemolysis in all cases was lower in the presence of D2O. The greatest increase in stability was observed between 5--20% D2O. The practical consequences of this protective effect for the preservation of blood are discussed.


[Micromethod for the determination of glucose with glucose dehydrogenase in the autoanalyzer (author's transl)]. A new AutoAnalyzer method is described for the determination of glucose in 20 mul of haemolysate, urine, or cerebrospinal fluid, using glucose dehydrogenase. Without loss of precision, accuracy, sensitivity, or linearity, 900 samples may be analyzed, using the same volume of reagents normally required for the manual analysis of 75 samples. A comparison with the hexokinase method yields a correlation of 0.9978. A haemolysing solution compatible with the reagents used is described.


Are more items identified than can be reported? Subjects are typically able to report only about four items from a many-item array presented tachistoscopically (full-report span). Current models of visual information processing disagree as to whether the limiting process is best represented as identification or as short-term memory. Estes and Taylor have argued that the number of items identified is up to twice the full-report span and, hence, that memory limits report. Experiment 1 here used a memory-probe method which showed that when no position report is required the large number of items that were identified in the Estes and Taylor paradigm is not greater than the number in a posticonic memory. Experiment 2 indicated that when position report is required the number of items identified (with correct position) does not exceed the number which can be reproduced in full report. These results support models in which memory is entailed by identification either as an aspect of the identification process or as a separate stage.


Spatial probability learning by alcoholic Korsakoff patients. Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups.


When preparation fails: disruptive effects of prior information on perceptual recognition. There is a conflict in the literature on selective attention. Suppose a subject is briefly presented an item followed by a multiple-alternative recognition test. If the items are pictures, the subject's performance is facilitated by presenting the alternatives beforehand (a before facilitation), but when the items are letters the subjects' performance is disrupted by presenting the alternatives beforehand (a before disruption). Five experiments were conducted to resolve this conflict, and all involved a comparison of tachistoscopic recognition when alternatives were either presented beforehand or not. The first two studies showed that the before disruption with letters was not due to certain task parameters. Experiments 3-5 demonstrated that this effect was due to masking conditions. Experiments 3 and 4 revealed that the disruption occurred only when a mask is used, while the last experiment indicated the disruption effect was sensitive to the type of mask employed. Preseumably, the before disrption arises because a subject erroneously considers the features of a mask along with those of the test item in arriving at a perceptual decision.


U-shaped backward contour masking during stroboscopic motion. Two stationary and spatially separated visual stimuli, presented briefly and successively in time, are known to produce stroboscopic motion whose vividness is a U-shaped function of the stimulus onset asynchrony. Contour masking is also known to occur under such stimulus conditions. The findings show that the contour masking is confined to only the first stimulus and that it, like metacontrast, is a backward U-shaped function of the stimulus onset asynchrony. A simple model, based on known psychophysical and neurophysiological properties, is proposed to explain these results.


Conflicting motion perspective simulating sinultaneous clockwise and counterclockwise rotation in depth. Motion projections (pictures) simulating a horizontal array of vertical lines rotating in depth about its central vertical line were observed by 24 college students who rotated a crank handle in the direction of apparent rotation. All displays incorporated contradictory motion perspective: Whereas the perspective transformation in the vertical (y) dimension stimulated one direction of rotation, the transformation in the horizontal (x) dimension simulated the opposite direction. The amount of perspective in each dimension was varied independently of the other by varying the projection ratio used for each dimension. We used the same five ratios for each dimension, combining them factorially to generate the 25 displays. Analysis of variance of the duration of crank turning which agreed with y-axis information yielded main effects of both x and y projection ratios but no interaction, revealing that x- and y-axis motion perspectives mediate kinetic depth effects which are functionally independent.


Further evidence for two components in visual persistence. The phenomenal durations of tachistoscopically presented letter arrays at five levels of redundancy were measured using a subtractive reaction-time technique. Phenomenal duration was inversely related to redundancy only when report of the letters was required. The duration of functional availability of stimulus information for stimuli at the five levels of redundancy was determined in a backward masking paradigm. The measurements of the duration of functional availability and phenomenal presence were convergent, indicating that one process is responsible for both the phenomenal and functional duration of a persisting representation of a visual stimulus. The results are interpreted as providing further evidence for two components in visual persistence: a physical component whose duration is unrelated to stimulus parameters and an informational component whose duration is inversely related to the efficiency of encoding stimulus information.


Effects of concurrent verbal memory on recognition of stimuli from the left and right visual fields. Two experiments examined the effect of concurrently holding 0, 2, 4, or 6 nouns in memory on the recognition of visual stimuli briefly presented to the left or right visual fields. When stimuli to be visually recognized were complex visuospatial forms it was found that a relatively easy memroy load of 2 or 4 nouns improved visual recognition accuracy on right visual field (left-hemisphere) trials relative to the no-memory condition; however, a more difficult memory load of 6 nouns decreased visual recognition accuracy to a level slightly below the no-memory condition. There were no effects of concurrent verbal memroy on visual form recognition on left visual field (right-hemisphere) trials. When the stimuli to be visually recognized were words it was found that a relatively easy memroy load of 2 or 4 nouns improved visual recognition accuracy and a more difficult load of 6 nouns decreased visual recognition accuracy on both left and right visual field trials. The complete pattern of results indicates that several factors including cerebral hemisphere specialization, stimulus codability, selective perceptual orientation, and selective cerebral hemisphere interference interact in systematic ways to produce overall visual laterality effects.


Detection errors on the word the: evidence for reading units larger than letters. In four experiments, subjects read 100-word passages and circled instances of the letter t. Subjects missed a disproportionate number of ts in the word the. Evidence was provided against explanations of this effect involving the location and pronunciation of the t in the and against an explanation in terms of the redundancy of the. Rather the high frequency of the appeared to be critical, and it was suggested that high-frequency words are read in terms of units larger than the letter.


Lexical ambiguity, semantic context, and visual word recognition. Some alternative hypotheses about the recognition of ambiguous words are considered. According to the selective-access hypothesis, prior semantic context biases people to access one meaning of an ambiguous word rather than another in lexical memory during recognition. In contrast, the nonselectiveaccess hypothesis states that all meanings of the word are accessed regardless of the context. We tested certain versions of these hypotheses by having students decide whether selected strings of letters were English words. The stimuli included test sequnces of three words in which the second word had two distinct possible meanings, whereas the first and third words were related to these meanings in various ways. When the first and third words were related to the same meaning of the ambiguous second word (e.g., SAVE-BANK-MONEY), the reaction time to recognize the third word decreased. But when the first and third words were related to different meanings of the second word (e.g., RIVER-BANK-MONEY), the reaction time for the third word was not reliably different from a control sequence with unrelated words. These and other data favor the selective-access hypothesis. Selective access to lexical memory is discussed in relation to models of word recognition.


Processing two dimensions of nonspeech stimuli: the auditory-phonetic distinction reconsidered. Nonspeech stimuli were varied along two dimensions--intensity and rise time. In a series of speeded classification tasks, subjected were asked to identify the stimuli in terms of one of these dimensions. Identification time for the dimension of rise time increased when there was irrelevant variation in intensity; however, identification of intensity was unaffected by irrelevant variation in rise time. When the two dimensions varied redundantly, identification time decreased. This pattern of results is virtually identical to that obtained previously for stimuli that vary along a linguistic and a nonlinguistic dimension. The present data, taken together with those from other  studies using the same stimuli, suggest that the mechanisms underlying the auditory-phonetic distinction should be reconsidered. The results are also discussed in terms of general models of multidimensional information processing.


Processing interaction between two dimensions of nonphonetic auditory signals. In 1974 Wood proposed a hybrid serial-parallel model to account for the within-stimulus interactions between the acoustic cue of "pitch" and the phonetic cure of "place." Three of the five experiments in this paper replicate the Wood findings with analogous, clearly nonphonetic stimuli and thus refute Wood's implicit assumption of the involvement of any uniquely phonetic processes as factors in his results. The experiments in this paper demonstrate that the patterns of interaction found by Wood are independent of the experience of the subjects, the order of cue presentation, and whether the cues are presented simultaneously or sequentially. We conclude that the given patterns of interaction are general characteristics of the auditory system. These characteristics probably are not related to backward or forward "recognition" masking but may be a function of several other general factors.


Reaction time to temporally-displaced phoneme targets in continuous speech. In seven experiments, reaction time (RT) was recorded to phoneme targets in sentences. By means of tape splicing or other experimental interventions preceding the target, speech information was or was not discarded, and targets were either temporally displaced "early" or "late" or remained on time." RT to displaced targets was slower than to on-time targets, except when the tape-splicing manipulation in effect presented coarticulatory target information in advance, in which case RT was faster than RT to on-time targets. The latter manipulation also produced faster RT than RT to the same targets in the original sentence, that is, that containing no experimental intervention at all. In three of the experiments, half the targets were contained in stressed syllables, half in unstressed syllables. Stressed and unstressed targets were affected differently, depending upon practice and other factors. Results were interpreted in terms of listener expectancies based on timing redundancy in continuous speech. They indicate an interaction between the effects of segmental and suprasegmental cues during ongoing perception.


An experimental test of two mathematical models applied to the size-weight illusion. Two quantitative models, which make different quantitative predictions for the amount of the size-weight illusion, were tested according to the psychophysical methods employed by the respective authors (magnitude estimation versus category ratings). Both models with their corresponding method were supported. This causes uncertainty over Anderson's chaim that the validity of both a model and the applied scale used is sufficiently test by the socalled joint testing procedure.


Extra cytoproct mutant in Paramecium tetraurelia: morphogenetical analysis of proters and opisthes. To account for the differences between proters and opisthes with regard to extra cytoproct morphogenesis in Paramecium tetraurelia, two hypotheses have been proposed and tested. (i) The differences may be a result of different actions of proter-macronucleus and opisthe-macronucleus. This hypothesis has been tested by cytoplasmically connecting the proter with the opisthe in the form of chains, some of which have only one macronucleus per chain. However, the connected proters and opisthes remain different in extra cytoproct morphogenesis, thus arguing against the hypothesis. (ii) The differences may be a result of differences between the proter and the opisthe with regard to the development of their posterior-ventral cortex: proters have a newly-developed posterior-ventral cortex whereas opisthes receive the posterior-ventral cortex from the pre-fission mother animal. This hypothesis has been tested by surgically producing an opisthe with a newly-regenerated posterior cortex. Such opisthes, however, remain different from proters in extra cytoproct morphogenesis. Thus no direct support for the second hypothesis is obtained. Also, proter-opisthe difference in morphogenesis may be understood in terms of Wolpert's positional information hypothesis, by assuming that the anterior and posterior ends of a dividing animal serve as reference points for establishing a gradient and that positional information before separation of the two daughter animals leads to differences in extra cytoproct morphogenesis between them after separation.


Maturation and sperm penetration of canine ovarian oocytes in vitro. Canine ovarian oocytes were cultured in a medium consisting of TC medium 199, fetal calf serum and antibiotics. Ninety-nine percent of the apparently healthy oocytes were in the germinal vesicle (dictyate) stage when recovered from the ovaries; 25% of them reached metaphase I or II by 72 hours of culture. Washed ejaculated spermatozoa were added to BWW medium containing oocytes which had either been removed directly from the follicles or which had been cultured for 24--72 hours. The earliest acrosome reaction and zona penetration by spermatozoa were seen at seven hours after insemination. Seventy-four percent of the oocytes examined between 11 and 24 hours after insemination showed evidence of zona penetration by spermatozoa. Neither the condition of the oocyte vitellus nor the stage of nuclear maturation influenced the incidence of zona penetration. Decondensing sperm nuclei were found in the vitellus of 27% of the oocytes which had not been cultured and in the vitellus of 20% of those which had been cultured for 24--72 hours and were in various stages of maturation. These results indicate that (1) canine ovarian oocytes can be matured in vitro, (2) the spermatozoa require capacitation which takes approximately seven hours in vitro and (3) maturation of the oocytes is not required for sperm passage through the zona pellucida or entry into the vitellus nor for sperm nuclear decondensation.


Changes in the tail of Ambystoma maculatum at different stages of metamorphosis: observations on tissue remodeling and its relationship to hydrolytic enzymes. A system for staging A. maculatum during growth and metamorphosis was devised, based on several parameters of body size; body length, tail length and tail width. Animals at various stages of metamorphosis were employed to study the relationship between specific biochemical and histological changes that occur in the tail of this urodele during metamorphosis. The specific and total activity of two hydrolytic enzymes, acid phosphatase and beta-N-acetyl-glucosaminidase, were measured in tail tissues at progressive stages of development. The activities of these enzymes increased in both the fins and muscular portion of the tail during metamorphosis. These activities can be correlated with resorption of the tail fins and the remodeling of tissues in the muscular portion of the tail.


Regenerative abnormalities in Notophthalmus viridescens induced by repeated amputations. The fidelity of the regenerative response in the adult newt, Notophthalmus viridescens, was examined following repeated amputations at the level of the distal one-third of humerus. Three to four months following amputation, all regenerates were scored for gross morphology, reamputated, and stained with methylene blue for skeletal elements. The occurrence of abnormal regeneration with respect both to gross morphology and to skeletal structure was found to increase directly with the number of times the limb stumps were required to initiate dedifferentiation and repair. The initial amputation-regeneration process produced structurally normal replacement limbs in 91% of the cases examined. Reamputations of 4-digit regenerates (3--4 months after the previous transection) resulted in structurally abnormal regenerates in 28% of the cases following two amputations; 50% of the cases following three amputations; 65% of the cases following four amputations; and 81% of the cases following five amputations. The relationships between repeated dedifferentiation, proliferation, and redifferentiation and normal limb development are discussed.


Putative synaptic mechanisms of inhibition in Limulus lateral eye. Serotonin (5-HT) perfusion of a thin section of Limulus lateral eye hyperpolarizes retinular and eccentric cell membrane potential, and blocks spike action potentials fired by the eccenteric cell. The indoleamine does not directly affect retinular cell receptor potential or eccenteric cell generator potential in response to light stimuli. LSD perfusion blocks both this inhibitory action of 5-HT and light-evoked, synaptically mediated, lateral inhibition. Iontophoretic application of 5-HT to the synaptic neuropil produces shorter latency and duration and larger amplitude of inhibition than does the perfusion technique. This inhibition is dose dependent; the accompanying inhibitory postsynaptic potential (IPSP) appears to have an equilibrium potential more hyperpolarized than normal resting potential levels of ca. -50 mV. IPSP amplitude is sensitive to extracellular potassium ion concentration: it increases with decreased [K+]0 and decreases with increased [K+]0. LSD blocks the inhibition produced by iontophoretic application of 5-HT. Interaction between light-evoked, natural synaptic transmitter-mediated IPSP's and 5-HT IPSP's suggests a common postsynaptic receptor or transmitter-receptor-permeability change mechanism.


Nonuniform distribution of sodium in the rat hepatocyte. The volume of the nucleus, endoplasmic reticulum (including Golgi complex), mitochondria, and cytoplasmic ground substance was measured in rat hepatocytes by stereological methods. The Na content was also measured by flame photometry. Variations in Na content correlated significantly with variations in volume of nucleus and endoplasmic reticulum. From the correlation parameters, Na concentrations were estimated as follows: nucleus, 108 mM; endoplasmic reticulum (ER) (including Golgie complex) 27 mM; cytoplasm (including and remaining organelles) 16 mM.


Comparison of the side-dependent effects of Na and K on orthophosphate-, UTP-, and ATP-promoted ouabain binding to reconstituted human red blood cell ghosts. This paper is concerned with analyzing the sidedness of action of various determinants which alter the rate of ouabain binding to human red blood cell ghosts. Thus, ouabain binding promoted by orthophosphate (Pi) and its inhibition by Na are shown to be due to inside Pi and inside Na. External K inhibits Pi-promoted ouabain binding and Nao acts to decrease the effectiveness of Ko. Similarly, inside uridine triphosphate (UTPi) stimulates the rate of ouabain binding which can be antagonized by either Nai or Ko acting alone. The actions of Nai and Ko are different when ouabain binding is promoted by Pi and UTPi compared to inside adenosine triphosphate (ATPi). With ATPi, the ouabain binding rate is only affected when Nai and Ko are both present. Possible differences in the mechanism of action of K and Na on Pi-and UTP-promoted binding are discussed in the light of their sidedness of action.


Effects of Mg and Ca on the side dependencies of Na and K on ouabain binding to red blood cell ghosts and the control of Na transport by internal Mg. The effect of alteration in the concentration of internal Mg on the rate of ouabain binding to reconstituted human red blood cell ghosts has been evaluated as well as the effect of Mgi on Na:Na compared to Na:K exchange. It was found that the dependence of the rate of ATP-promoted ouabain binding on the combined presence of Nai and Ko which occurs at high [Mg]i is lost when the concentration of Mgi is lowered. The sensitivity of the external surface for Ko is also changed since Ko can now inhibit the ouabain binding rate in the absence of Nai; on the other hand Nao at low [Mg]i can stimulate ouabain binding indicating that the relative affinity of the outside surface for Nao has either increased or that for Ko has decreased or both. Thus the effects of changes in [Mg]i result in a change in the side-dependent actions of Na and K and emphasize the possible difficulties of interpreting results obtained on systems lacking sidedness. Mgi was found to be required for Pi-promoted ouabain binding and that the inhibitory action of Nai increased as [Mg]i was increased. In addition, Ca was found to be most effective in inhibiting the rate of ATP-promoted ouabain binding when Na and K were present together than when either was present alone. Na:K exchange was found to be more sensitive to the concentration of Mgi than Na:Na exchange; at low [Mg]i Na:K exchange could be stimulated without changing the extent of Na:Na exchange. These results are consistent with the idea that conformational states of the pump complex are directly influenced by [Mg]i.


Sodium permeability of dog red blood cell membranes. I. Identification of regulatory sites. Divalent cations and group-specific chemical modifiers were used to modify sodium efflux in order to probe the molecular structure of sodium channels in dog red blood cells. Hg++, Ni++, Co++, and PCMBS (parachloromercuribenzene sulfonic acid), a sulfhydryl reactive reagent, induce large increases in Na+ permeability and their effects can be described by a curve which assumes 2:1 binding with the sodium channel. The sequence of affinities, as measured by the dissociation constants, reflects the reactivity of these divalent cations with sulfhydryl groups. In addition, the effects of Hg++ and PCMBS can be reversed by the addition of dithiothreitol, an SH-containing compound, to the medium. Much smaller increases in Na+ permeability are produced by Zn++ and the amino-specific reagents, TNBS (2,4,6-trinitrobenzene sulfonic acid) and SITS (4-acetamido-4'-isothiocyano-stilbene-2-2'-disulfonic acid). The Zn++ effect can be described by a curve which assumes bimolecular binding with the channel, and its effect on Na+ permeability can be reversed by the addition of glycine to the medium. The effects of Ni++ and SITS can be completely reversed by washing the cells in 0.16 M NaCl while TNBS binding is partially irreversible. Measurements of mean cell volumes (MCV) indicate that the modifier-induced increases in Na+ permeability are not caused by shrinkage of the cells. It is concluded that the movement of sodium ions through ionic channels in dog red blood cells can be enhanced by modification of amino and sulfhydryl groups. Zn++, TNBS, and SITS increase Na+ permeability by modifying amino groups in the channel while Hg++, Ni++, Co++, and PCMBS act on sulfhydryl groups.


Ion transport studies and determination of the cell wall elastic modulus in the marine alga Halicystis parvula. Using cultured cells of the marine alga, Halicystis parvula, we measured the concentrations of 11 inorganic ions in the vacuolar sap and the electrical potential difference (PD) between the vacuole and the external solution. In normal cells under steady-state conditions a comparison of the electrochemical equilibrium (Nernst) potential for each ion with the PD of -82 mV (inside negative) indicates that Na+ and K+ are actively transported out of the vacuole whereas all anions are pumped into the cell. Although the [K+] in the vacuole is only 9 mM, the cytoplasmic [K+] is about 420 mM, which suggests that the outwardly directed pump is at the tonoplast. Using large Halicystis cells we perfused the vacuole with an artificial seawater and conducted a short-circuit analysis of ion transport. The short-circuit current (SCC) of 299 peq - cm-2-s-1 is not significantly different from the net influx of Cl-. There is a small, but statistically significant net efflux of K+ (less than 1 pmol-cm-2.-1), while the influx and efflux of Na+ are not significantly different. Therefore, the SCC is a good measure of the activity of the Cl- pump. Finally, we measured the volumetric elastic modulus (epsilon) of the cell wall by measuring the change in cell volume when the internal hydrostatic pressure was altered. The value of epsilon at applied pressures between 0 and 0.4 atm is about 0.6 atm, which is at least 100-fold lower than the values of epsilon for all other algae which have been studied.


Control of action potential duration by calcium ions in cardiac Purkinje fibers. It is well known that cardiac action potentials are shortened by increasing the external calcium concentration (Cao). The shortening is puzzling since Ca ions are thought to carry inward current during the plateau. We therefore studied the effects of Cao on action potentials and membrane currents in short Purkinje fiber preparations. Two factors favor the earlier repolarization. First, calcium-rich solutions generally raise the plateau voltage; in turn, the higher plateau level accelerates time- and voltage-dependent current changes which trigger repolarization. Increases in plateau height imposed by depolarizing current consistently produced shortening of the action potential. The second factor in the action of Ca ions involves iK1, the background K current (inward rectifier). Raising Cao enhances iK1 and thus favors faster repolarization. The Ca-sensitive current change was identified as an increase in iK1 by virtue of its dependence on membrane potential and Ko. A possible third factor was considered and ruled out: unlike epinephrine, calcium-rich solutions do not enhance slow outward plateau current, ikappa. These results are surprising in showing that calcium ions and epinephrine act quite differently on repolarizing currents, even though they share similar effects on the height and duration of the action potential.


Adult "failure-to-thrive" syndrome.

Adult "failure-to-thrive" syndrome. The analogy between the "failure-to-thrive" syndrome of childhood and a symptom complex seen in adult neurology is described. Adults presenting with a variety of central nervous system diseases occasionally seem to follow an unusual stereotyped course resulting in intractable weight loss, wide variations in temperature, and a tendency to intractable decubitus ulcerations in a setting of decreased levels of consciousness. Sudden death occurs unexpectedly. This syndrome can be observed following cerebral thrombosis, traumatic encephalopathy, degenerative central nervous system disorders, and encephalitis. The pathophysiology is thought to result from the random aggregate of lesions rather than a verifiable discrete hypothalamic deficit.


The development and validation of a measure of the psychiatrist's authoritative domain. In order to examine issues relevant to the authority which patients bestow upon psychiatrists the present authors constructed the Psychiatrist's Sphere of Influence Scale (PSIS). The PSIS is a 68-item Likert-type questionnaire which asks patients to specify the skills which they believe belong to the psychiatrist's authoritative domain. Patients being treated in day hospital (N=82), inpatient (N=113), and outpatient (N=121) settings were individually administered the PSIS along with various discriminant and construct validity measures. The findings indicated that the PSIS is an internally consistent, factorially complex, relatively stable measure of the roles which are ascribed to psychiatrists. Neither the social desirability nor the agreement response set represents important contaminants of the PSIS. Moreover, individual differences on the PSIS appear to be predictable, within broad limits, from patients' positions in the social structure, their preferred styles of help seeking in hospital and therapy settings, and their generalized orientations toward power and authority. A tendency to blur the boundaries between "psychiatric" and "nonpsychiatric" roles appears to be concentrated among patients who are middle-aged or older, minimally educated, of lower socioeconomic status, inclined toward an authoritarian conception of the good patient and the good hospital, and who endorse traditional family role relationships. The implications of these findings for the manner in which psychiatrists exercise their authority were discussed.


Forensic psychiatry: diagnosis and criminal responsibility. An examination of the primary and secondary diagnoses of 1195 defendants admitted to an urban forensic service was carried out. This indicated that personality disorders dominated the referral patterns from the court. Of those conditions which could produce thought disorders, schizophrenia dominated. An analysis of the prevalence of schizophrenia among defendants charged with homicide in St. Louis revealed a rate of schizophrenia similar to that found in the general population. Organic brain syndromes resulted in a large proportion of assaultive behavior, and these cases also involved a large number of secondary diagnoses. Alcohol and drug abuse were the most common secondary diagnoses. In general, no correlation between psychiatric diagnosis and types of criminal activity was found.


Therapeutic implications of tricyclic antidepressant plasma levels. Methodological advances in drug assay techniques and their increasing availability have made the measurement of tricyclic antidepressant plasma levels more frequent and even fashionable. Plasma levels of tricyclics have been correlated with diagnosis, prognosis, clinical response, and side effects. But even in the area most extensively examined, the correlation between plasma level and clinical response, the results have been conflicting. Different studies have suggested that there is no relationship between plasma level and clinical response, as well as positive and negative correlations, and even a curvilinear relationship. On the basis of available evidence, it is impossible to define a therapeutic range of plasma levels that will be applicable to depressed patients as a group. For the moment, the problem of finding a suitable therapeutic dose for the individual patient remains of paramount importance. Studies to date suggest the need to take into consideration genetic factors, previous and present use of other drugs, the possibility that therapeutic failure might be a result of too high as well as too low a dose, as well as the possible relationship between high plasma levels and side effects. Also, since for the specific individual, the metabolism of different tricyclic antidepressants is similar, it may be useful to adjust dosages until a therapeutic one is obtained instead of immediately switching to another medication. Finally, although the usefulness of routine plasma level determination remains to be established, this technique may be indicated in cases of intractable depression and remains an important research tool.


Gammahydroxy butyric acid: cardiovascular effects in the rat. Gammahydroxybutyric acid (GHBA) 1 g/kg i.p. induced a marked and sustained increase in heart frequency and blood pressure in the rats. These effects of GHBA were abolished by a high spinal transection. In biochemical experiments GHBA in the same dose increased the turnover of brain noradrenaline but decreased the turnover of dopamine. The cardiovascular effects of GHBA are suggested to be of central origin, and possibly involve central noradrenergic mechanisms.


Quantitative changes in number of "synaptic" ribbons in rat pinealocytes after orchidectomy and in organ culture. A quantitative study of "synaptic" ribbons in rat pinealocytes was performed after orchidectomy and in organ culture. Both orchidectomy and culturing the pineal organ caused an increase in number and size of these structures. Present study indicate that microtubular sheaves and/or microtubules may represent precursors of "synaptic" ribbons. It is suggested that "synaptic" ribbons of rat pinealocytes, far from being phylogenetic relics of no functional significance play a role in the function of the pineal organ. An exact functional interpretation of the "synaptic" ribbons, however, is still a matter of conjecture.


Differential drug effects on dopamine concentrations and rates of turnover in the median eminence, olfactory tubercle and corpus striatum. Dopamine synthesis rates were determined in terminals of tuberoinfundibular, mesolimbic and nigrostriatal neuronal systems by observing the decline of dopamine contents in the median eminence, olfactory tubercle and corpus striatum after administration of alpha-methyltyrosine. In control (no drug treatment) animals the rate of synthesis of dopamine was greater in the median eminence than in the other two brain regions. Haloperidol increased and piribedil decreased dopamine turnover in the corpus striatum and olfactory tubercle, but not in the median eminence. Gamma-Butyrolactone increased dopamine concentrations in the olfactory tubercle and striatum without altering the concentration in the median eminence. Thus, the regulatory mechanisms governing the activity of central dopaminergic neurons in the tuberoinfundibular system appear to differ from those in the mesolimbic and nigrostriatal systems.


Effects of denervation and colchicine treatment on the chloride conductance of rat skeletal muscle fibers. Membrane potentials, cable parameters, and component resting conductances were measured in extensor digitorum longus (EDL) muscle fibers from adult rats in vitro at 24 degrees C, after 15 to 18 days of denervation by nerve section, and at seven to ten days following epineural injection of 100 to 450 mug of colchicine in the peroneal nerve. The denervated muscles were paralyzed throughout the experimental period, whereas the colchicine-treated preparations showed no clinical paralysis except for the first day or two. The EDL from the untreated side served as a control. Both the denervated and colchicine-treated fibers were depolarized, showed signs of fibrillation, had tetrodotoxin-resistant potentials, and membrane resistance was increased two- to sevenfold. In the denervated fibers, mean chloride conductance GC1 dropped from a control value of 3196 to 596 mumhos/cm2 while mean potassium conductance GK showed a tendency to rise from 260 to 332 muhos/cm2. Colchicine-treated fibers while showing a similar fall in mean GC1 from 2993 to 1066 mumhos/cm2, also showed a significant fall in mean GK from 213 to 116 mumhos/cm2. It was concluded that factors transported by the microtubular system are important for the maintenance of the high resting GC1 of mammalian skeletal muscle fibers.


Chloride conductance of denervated gastrocnemius fibers from normal goats. Membrane potentials, cable parameters, and component resting ionic conductances of gastrocnemius fibers from normal goats were measured in vitro at six to 32 days following denervation by section of the tibial nerve. Denervated fibers were depolarized an average of 11.6 +/- 1.5 mV (six preparations) from the control mean of 62.1 +/- 1.0 mV (124 fibers) over the period studied. Fibrillation, tetrodotoxin-resistant action potentials, and anode-break excitation were present in the denervated preparations after 13 days. The control cable parameters from 124 fibers (13 preparations) were membrane resistance, 1052 +/- 70 omega-cm2 and membrane capacitance, 6.2 muF/cm2. In denervated fibers membrane resistance increased two to three times in the 13 to 32 day period; membrane capacitance increased about 50% in normal solution at eight to nine, 27-28, and 32 days. Myoplasmic resistivity was assumed to be 112 omega-cm. Measurements were made at 38 degrees C. Component resting conductances were determined from the cable parameters in normal and chloride-free solution. Mean chloride conducantance GC1 and mean potassium conductance GK of control fibers were 776 +/- 49 mumhos/cm2 and 175 +/- 15 mumhos/cm2 (92 fibers), respectively. Following denervation GC1 increased slightly at six to nine days then fell to low values at 16 to 32 days that were close to or indistinguishable from zero. GK increased significantly to 372 +/- 40 mumhos/cm2 and 499 +/- 90 mumhos/cm2 at 16 to 20 and 32 days, respectively. It was concluded from these findings that GC1 and GK of mammalian skeletal muscle are controlled by factors from the nerve and/or muscle action potentials. Goat muscle is different from frog muscle in which GC1 does not change and GK decreases during denervation.


Anatomical basis for an apparent paradox concerning conduction velocities of two identified axons in Aplysia. Larger axons usually have faster conduction velocities, lower thresholds, and larger extracellular action potentials than smaller axons. However, it has been shown that the largest fiber, R2, in the right pleurovisceral connective of the marine mollusc, Aplysia, has a higher threshold and a slower conduction velocity than does the smaller axon of cell RI, even though the amplitude of R2's spike is larger than R1's spike. One explanation of this apparent parodox is that the two axons have different "intrinsic membrane and axoplasmic constants" (Goldman, L. (1961), J. Cell Comp. Physiol. 57: 185-191). However, the deep infolding of R2's axonal membrane suggested that differences in the shape of the two axons might also account for the paradox. Accordingly, we measured the conduction velocities of the two axons and then examined the same axons in the electron microscope in order to measure their volumes and surface areas. Our morphological observations indicate that the extensive infolding of surface membrane causes R2 to have a smaller volume to surface area ratio than R1. Thus, since conduction velocity is proportional to the square root of the volume to surface area ratio (Hodgkin, A.L. (1954), J. Physiol. 125: 221-224), it is predictable that the smaller axon would have a faster conduction velocity. The results suggest that the paradoxical conduction velocities can be explained largely as resulting from differences in the shapes of the two axons. However, certain discrepancies between the measured and the predicted values suggest that other factors are contributing as well.


Cytophotometric identification of tetraploid Purkinje cells in young and aged rats. DNA content of cerebellar basket and Purkinje cells of four month, one year, and two year old albino rats was determined by Feulgen cytophotometry. DNA content per nucleus remained essentially constant during aging although there was a slight shift to lower Feulgen-DNA values occurring in the one year age group. Purkinje cells of all three age groups were found to contain tetraploid amounts of DNA as compared to diploid basket cells.


Electrical properties and structure of the frog arachnoid membrane. We have used an in vitro preparation of the frog arachnoid membrane to study the role of this membrane in the maintenance of the "blood-cerebrospinal fluid (csf) barrier". Electron microscopy showed that the membrane was made up of 10-15 layers of flat epithelial cells joined together by numerous cell junctions. The electrical resistance of the preparation was about 2000 ohms cm2. The steady-state transmural potential difference (pd) ranged up to 45 mV, csf positive, and this eliminated by either the addition of ouabain to the csf, or by replacing the NaC1 with TEA C1. The pd across the membrane increased when bicarbonate was added to the external bathing solutions. We conclude that this pd is due to the active transport of sodium from the subural fluid to the csf. In some preparations the transmural pd was reversed, i.e., csf negative, and this was also abolished by the addition of ouabain to the csf, or by replacing chloride with isethionate. We conclude that this pd is related to active chloride transport. These, and other experiments, lead us to the conclusion that the arachnois membrane is involved in the production of the cerebrospinal fluid and the maintenance of the blood-cerebrospinal fluid barrier.


A long-lasting birefringence change recorded from a tetanically stimulated squid giant axon. A long-lasting birefringence change (the delayed response) was found to be produced in a tetanically stimulated squid giant axon. The change was independent of the concurrent membrane potential change, summated on repetitive stimulation, and always had a sign representing a decrease in resting birefringence. The axons was placed between a polarizer and an analyzer with their polarizing axes crossed, making an angle of 45 degrees with the longitudinal direction of the axon. The light beam that passed through the axon and the other optical elements was received by a photodiode. The change in light intensity evoked by repetitive stimulation was composed of brief initial responses, which took place in response to individual stimuli, and a delayed response, which developed gradually and lasted for several hundred msec. It was necessary to differentiate the effect of birefringence change from that of turbidity change. Formulas were derived on the assumption that the optical properties of the axon could be represented by a model of a uniaxial crystal that was not only birefringent but also dichroic, its extinction coefficients and the angle of retardation being changed independently on excitation. Calculations with them yielded the resting retardation, which agreed well with those obtained by the Senarmont's method, and the change in birefringence, which agreed well with the other calculated value derived from experiments using a quarter-wave plate. The results of the calculation confirmed the existence of the long-lasting birefringence change in the tetanically stimulated axon.


Subarachnoid block and enlargement of the spinal canal in hypertrophic neuritis. A case of Dejerine-Sottas hypertrophic neuritis is reported. The patient, a 45-year-old male, suffered from chronic hypertrophic polyneuropathy, abnormal pupils, fasciculations, tremor, back pain, impotence, sphincter disorders, cramps, and lightning pains in the lower extremities. Besides extensive subarachnoid block, there was X-ray evidence of enlargement of the bony spinal canal with scalloping of the lumbar vertebrae. Surgical exploration showed these abnormalities to be due to extreme hypertrophy of the cauda equina. Histologic findings in peripheral nerve and lumbar root biopsies were typical of hypertrophic neuropathy of the onion bulb type. Vertebral changes secondary to hypertrophied nerve roots appear not to have been described before in hypertrophic neuritis; however, knowledge of their possible occurrence may be of practical importance in the management of similar future cases. A simple way of visualizing enlarged peripheral nerves is briefly described.


[Hereditary spongiform dystrophy in young children (Canavan: van Bogaert-Bertrand)]. Hereditary spongiform dystrophy in young children is characterised by macrocephaly with spasticity, convulsions and ultimately a decerebrate state and diffuse electroencephalographic changes. Histological examination of the brain remains essential for its diagnosis. A review of the ultrastructural studies reported by various authors complements the findings obtained by conventional histology. We have thus endeavoured to determine whether van Bogaert-Bertrand's disease is to be considered as congenital or acquired. The anatomical findings in 3 cases together with the descriptions of other authors lead us to the following conclusions: -that the spongiform changes may be due to an osmolar disequilibrium in which the ATPase-Na/K relation with mitochondrial abnormalities is yet unclear. -that the constant finding of Alzheimer type II cells is certainly an indication of intra-astrocytic malfunction. -that the oedema blocks both myelin synthesis and its coiling into lamellae. Case 1, which showed a long survival compared to others described (about 4 years), enabled us to study terminal lesions. Sub-cortical zones, in both cerebrum and cerebellum, contained neither myelin nor spongiform cavities, but, on the other hand, showed a compact glio-fibrillosis with large vesicles and oligodendroglia of increased density. We have interpreted these lesions, progressively replaced by spongiosis deeper in the cortex, as evidence of retracted scar tissue. Differences found between cerebral weights seem to confirm this hypothesis.


The neuropathic factor in the aetiology of diabetic foot ulcers. The nature and severity of changes due to peripheral neuropathy has been assessed clinically and electrophysiologically in 39 diabetic patients, 23 of whom had penetrating ulcers on the sole of the foot. Patients suffering from diabetic foot ulcers were found to have sensory loss to pin prick in the feet more frequently than "controls". The electrophysiological measurements confirmed the severity of the neuropathy with absent sural nerve action potentials in 95% of the ulcer patients and inexcitability of small foot muscles in 40%. Weakness of small foot muscles due to neuropathy is thought to underlie the foot deformity that leads to maldistribution of weight bearing, and subsequent pressure necrosis of analgesic skin.