Identification of human luteinizing hormone, follicle-stimulating hormone, luteinizing hormone beta-subunit and gonadotrophin alpha-subunit in foetal and adult pituitary glands. Specific radioimmunoassays were used to assess the content of LH, FSH, the gonadotrophin alpha-subunit and the LH beta-subunit in four adult, 19 normal foetal pituitary glands (9-5--32 weeks of gestation) and a pituitary extract from an anencephalic foetus (36 weeks). The hormones and subunits were further identified by column chromatography on Sephadex G-100. All pituitary glands contained free alpha-subunit and intact LH but the alpha-subunit:LH ratio was significantly higher in the early foetal pituitaries (9-5--16 weeks) than in the four adult pituitaries. Only small or undetectable amounts of LH beta-subunit and 'undetectable' FSH were found in these early foetal pituitaries (9-5--11-5 weeks). The concentration of intact hormones or subunits in the pituitaries showed no significant sex difference in any of the groups. In contrast to these results, only alpha-subunit was detectable in the pituitary of the anencephalic foetus. For 14 early foetuses (age of gestation 10--16 weeks) the serum levels of LH-HCG, FSH, and alpha-subunit in the circulation were significantly higher than in 26 foetuses at term (37--41 weeks). On the basis of these results a theory for the development of the gonadotrophin secretion from the foetal pituitary gland is outlined.


Changes in plasma concentrations of luteinizing hormone after injection of progesterone at various times during the ovulatory cycle of the domestic hen (Gallus domesticus). Changes in plasma LH concentrations after i.m. injections of 0-5 mg progesterone/kg at various stages of the ovulatory cycle were measured by radioimmunoassay. Four types of response were observed. (1) When the steroid was injected between 4 h after and 12 h before an ovulation, LH levels started to rise after 15--45 min and reached peak values within 90--120 min. The mean maximal incremental change in the level of LH was 1-58 +/- 0-10(S.E.M.) ng/ml (n = 37). (2) In contrast, when progesterone was injected 12--8 h before ovulation, i.e. immediately before a spontaneous pre-ovulatory LH surge, the resulting mean maximal incremental change in LH level, 0-79 +/- 0-12 ng/ml (n = 9), was significantly smaller (P less than 0-001). (3) If progesterone was injected 8--4 h before ovulation, i.e. when pre-ovulatory LH levels were rising, they immediately started to rise more rapidly and reached peak values within 45 min. The maximal incremental change in the level of LH under these circumstances, 2-34 +/- 0-20 ng/ml (n = 12), was significantly greater (P less than 0-001) in both cases) than the changes observed in the responses 1 and 2 described above. (4) Levels of LH generally showed no incremental change in response to injections of progesterone given 4--0 h before ovulation, i.e. when pre-ovulatory LH levels were falling. It was concluded that the type of change in plasma LH levels induced by progesterone depended upon the stage of the ovulatory cycle at which the steroid was injected.


Effects of testosterone mediated or modulated by pituitary factors. Adult rats of both sexes were either gonadectomized or hypophysectomized and gonadectomized. Three to eight weeks later they were treated for 14 consecutive days with oil or with 75 or 200 mug testosterone propionate (TP) per 100 g body weight. The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3alpha-hydroxy-steroid dehydrogenases (3alpha-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned. For two of the latter, i.e. the relative kidney and prostatic weights, no significant differences were found. Transcortin levels, relative adrenal weights and renal NADPH-dependent 3alpha-HSD activities were higher in oil-treated gonadectomized animals than in oil-treated hypophysectomized-gonadectomized animals. The opposite was found for the relative weights of uterus and seminal vesicles and renal NADH-dependent 3alpha-HSD activities. These differences between gonadectomized and hypophysectomized-gonadectomized animals disappeared after TP treatment as far as transcortin levels were concerned but remained for the five other parameters. After gonadectomy sexual differences subsisted for all parameters studied. But whereas intact male rats had higher NADH-dependent 3alpha-HSD activities than female rats the opposite was found after gonadectomy. After gonadectomy plus hypophysectomy the between sex differences disappeared as far as transcortin levels were concerned but remained in the other parameters studied.


Increased concentrations of 17alpha, 20alpha-dihydroxypregn-4-en-3-one in maternal and foetal plasma near parturition in sheep. Using specific radioimmunoassays, 17alpha,20alpha-dihydroxypregn-4-en-3-one and progesterone were measured in maternal utero-ovarian venous plasma from four sheep during parturition induced with dexamethasone and two sheep at spontaneous delivery. 17alpha,20alpha-Dihydroxypregn-4-en-3-one was also measured in maternal jugular venous and foetal posterior vena caval plasma from one dexamethasone-induced animal over the same period. Basal utero-ovarian venous levels of 17alpha,20alpha-dihydroxypregn-4-en-3-one were in the range 3-7 ng/ml; at the time of the pre-labour fall in maternal progesterone, the concentration of 17alpha-20alpha-dihydroxypregn-4-en-3-one increased, reaching 17-76 ng/ml at delivery. Maternal levels fell rapidly after delivery. In contrast to foetal progesterone concentrations, which are low, foetal 17alpha,20alpha-dihydroxypregn-4-en-3-one levels were approximately the same as those in the maternal utero-ovarian vein. Maternal jugular venous levels in one animal were 50-80% of those in the utero-ovarian vein. These findings confirm earlier results obtained in vitro which indicated that exposure to glucocorticoid results in increased activity of a steroid 17alpha-hydroxylase in the ovine foetal placenta.


Differential reinforcement and signal detection. Reinforcement was introduced for responses normally treated as errors in signal-detection procedures. The first experiment used a standard two-response discrete-trial procedure with no reinforcement for errors. Results showed that rats altered their response biases but maintained constant sensitivity to visual signals when reinforcement probabilities varied, and that their sensitivity depended on the physical difference between signals, in accordance with the predictions of signal-detection theory. Experiment II, with rats, and Experiment III, with pigeons, demonstrated that sensitivity decreased in this procedure when reinforcement was scheduled for errors with the signals held constant, despite independence of overall number of reinforcers and sensitivity. Experiment IV, with rats, replicated the decrease in sensitivity in a continuous procedure employing only one response. The decrements in sensitivity were similar across Experiments II, III, and IV, and accorded well with earlier research. Thus, contrary to a fundamental assumption of signal-detection theory, estimates of sensitivity are not always invariant with respect to the outcomes of responding, but depend on relative reinforcement of correct responses.


The RNA polymerase activity of the preimplantation mouse embryo. The activation of the mouse embryo genome has been studied during early cleavage, in vivo. Individual embryos, prepared as whole mounts, were assayed for endogenous RNA polymerase activity. RNA synthesis was detected by autoradiography as the incorporation of [3H]UMP into an acid-insoluble product. No RNA polymerase activity could be detected in the pronuclei of one-cell embryos. Radioactive incorporation was first evident in the nuclei of two-cell embryos. This appeared to be confined to the nucleoplasm and could be abolished by alpha-amanitin but not by low concentrations of actinomycin D. Polymerase activity which was not affected by alpha-amanitin was first detected in the four-cell embryo, predominantly at the peripheries of the nucleoli. Nucleolar labelling increased markedly between subsequent cleavages, reaching a peak in early morulae. In one- and two-cell embryos, label incorporation could be found in the nucleus of the persisting polar body.


Neuroectodermal origin of avian hypothalamo-hypophyseal complex: the role of the ventral neural ridge. Embryonic discs from White Leghorn chick embryos (presomite to 12-omite stages) were examined in serial transverse and longitudinal sections. Later stages, up to 21 days, were also examined. The following observations were made: (1) Lateral folding rather than head folding is the mechanism by which the avian embryo is delimited. The process takes place at two terminal points, one cephalic the other caudal. (2) Thickening of the ventral ectoderm around the tip of the presumptive anterior neuropore, beginning at the 4-somite stage, subsequently extends the dorsal neural ridge to form a ventral neural ridge. (3) The cephalic portion of the ventral neural ridge, extending from anterior neuropore to optic chiasma, is mainly incorporated into the alar plates of the diencephalon. (4) The caudal portion, extending from optic chiasma to the stomodeum, gives rise to Rathke's pouch and thus to the adenohypophysis. We conclude that the latter is to be regarded as of neuroectodermal rather than ectodermal (stomodeal) origin, and that some or all of the neuroendocrine nuclei of the hypothalamus are similarly derived from the neuroectoderm of the neural ridge. The hypothalamo-hypophyseal complex is thus to be regarded as a single rather than a composite entity.


Electron microscopic studies on chick limb cartilage differentiated in tissue culture. The hind limb-bud mesenchyme of chick embryos 4-4 1/2 days old was cultured in Eagle's Minimum Essential Medium supplemented with both horse serum and fresh chick embryo extract. Whereas no differences are seen at the light-microscope level, at the electron-microscope level the chondroblasts differentiated in tissue culture are noticeably different from those differentiated in vivo, particularly in the possession of some cytoplasmic fibrils and vacuoles. It is proposed that the secretion of the extracellular matrix alone is not sufficient to account for the pattern of cellular arrangement in a cartilaginous condensation.


Iron incorporation and haemoglobin synthesis in erythropoietic cells during the ontogenesis of the mouse. Iron incorporation (59Fe) into erythropoietic cells from adult and foetal (11- to 15-day) peripheral blood and from foetal (12- to 15-day) livers has been investigated. Ion-exchange chromatography of haemolysates from such cells revealed two groups of 59Fe-containing proteins. The first group (X-fraction) was eluted from CMC-columns in the void volume and was highest in lysates of immature erythropoietic cells. This fraction contained a radiolabelled haemprotein of high molecular weight as well as other 59Fe-containing proteins. The haemprotein does not appear to be related to haemoglobin. The second group consisted of haemoglobins. One major (A1) and two minor (A2 and A3) haemoglobins were found in adult peripheral blood. In foetal liver lysates two major (F1 and A1) and two minor (F2 and A3) haemoglobins were present. The relative proportion of the major haemoglobins changed during development. Haemoglobin F1 was highest in the more mature livers. F1 proved to be different from A1 by chromatographic behaviour, in polypeptide chain composition and in fingerprints. A unique foetal polypeptide chain, intermediate in electrophoretic behaviour between the adult alpha- and beta-chain, was identified. In young foetal peripheral blood (11-day), in which 95% of the cells are of yolk-sac origin, one major (E1), two intermediate (E2 and E3) and one minor (F1) haemoglobin were demonstrable. Haemolysates of the peripheral blood of older embryos contain haemoglobins from erythroid cells of both yolk-sac and foetal liver origin. The haemoglobin pattern of such lysates is explicable in terms of the decreasing amount of embryonic haemoglobins (E1, E2 and E3) and the increasing amount of foetal haemoglobins (F1 and A1). Since A1 and E1 are the most prominent haemoglobins of livers from young embryos and yolk-sac erythrocytes respectively, and since they are very similar in chromatographic behaviour, foetal peripheral blood at all stages contain one dominant haemoglobin peak in the A1-E1 region. Most authors have neglected the relatively slight elevation of the foetal haemoglobin peak (F1) in front of A1-E1, the more because the F1-A1 region has been suspected sometimes to contain artificial haemoglobin components (Riggs, 1965). This probably explains why no foetal haemoglobin (F1) has been reported previously in the peripheral blood of foetal mice.


Activities of haem synthetic enzymes in blood cells of pre-natal flexed-tailed (f/f) anaemic mice. Levels of activity of beta-aminolaevulinate synthetase, delta-aminolaevulinate dehydratase, porphyrinogen synthetase and haem synthetase in circulating reticulocytes of pre-natal FL4/Re +/+ and congenitally anaemic FL1/Re f/f mice have been determined. The activities of delta-aminolaevulinate synthetase and delta-aminolaevulinate dehydratase were found to be decreased in proportion to the hypochromia observed in mature liver-derived erythrocytes in neonatal f/f mice, but activities of enzymes later in the haem synthetic pathway were relatively undisturbed. No significant differences were found in levels of haem synthetic enzymes in foetal livers of +/+ and f/f mice. These results indicate that the severe anaemia of late prenatal and neonatal f/f mice is due both to reduction in haem synthesis expressed at the reticulocyte stage of erythroid differentiation and to restricted production of erythroid progenitor cells. Retarded foetal growth and skeletal abnormalities, both characteristic of the pre-natal expression of the f/f gene complement, can also be related to reduced levels of haem synthesis, but the abnormal distribution of pigment cells seen in f/f animals appears to be a secondary effect of reduced tissue oxygenation resulting from pre-natal anaemia.


Development of parthenogenetic and fertilized mouse embryos in the uterus and in extra-uterine sites. Mouse eggs were activated with hyaluronidase in vitro and subsequently transferred to the oviduct. In the female reproductive tract they formed morulae and blastocysts which died soon after implantation. Haploid blastocysts were transferred beneath the kidney capsule and here some formed disorganized egg-cylinder structures in a week. Morulae and blastocysts from haploid and diploid parthenogenones were also transferred beneath the testis capsule. Two to four months later the growths which had formed were sectioned. They contained neural tissue, pigment, keratinized epithelium, glandular epithelium, ciliated epithelium, cartilage, bone, muscle, adipose tissue, and haemopoietic tissue. The range of cell types was similar to that produced by fertilized control blastocysts except that the parthenogenones did not form identifiable yolk-sac carcinoma or embryonal carcinoma cells. The growths from haploid and diploid parthenogenones in the testis were stained with Feulgen and their DNA content measured. Growths from diploid embryos contained the normal diploid amount of DNA while growths from haploid embryos contained less than this amount. Cell cultures were prepared from the growths. The cells which were investigated contained no Y chromosome, suggesting that they were derived from the embryonic cells rather than the cells of the male host. These cells contained a near diploid chromosome number, although some of them were originally derived from haploid embryos.


[The first stages of genesis of the pelvic fin analage in the trout (Salmo fario and Salmo gairdneri). III. Regulation capacities (author's transl)]. In S. fario and S. gairdneri, microsurgical excisions of parts of pelvic fin-buds showed the important regulation capacities of the fin anlage. At the stages studied, a complete unilateral excision is generally not followed by a regulatory response. On the contrary, a unilateral partial excision performed at the same developmental stages is followed by a regulatory response. Bilateral excision of the fin-buds, performed at earlier developmental stages than unilateral ones (and at a slightly different level for mesoderm) are followed by regulation. The results are discussed in this article. It appears that the mesoderm is a determining factor in the development of the fin-buds; the epidermis does not appear influential - at least in the first stages of regulation. We noticed a higer percentage of regulation in S. gairdneri than in S. fario; the results obtained are analysed with regard to histoenzymological data.


The development of embryos in the uteri of mice treated with actinomycin D before implantation. This investigation follows the development of embryos in the uteri of mice in which the differentiation of the implantation chamber has been retarded by the administration of actinomycin D before implantation. For the first 48 h after the induction of implantation both embryonic and extra-embryonic parts of the blastocyst develop, but after 72 h the embryonic parts cease to grow and die. The giant cells and other extra-embryonic tissues, on the other hand, continue to develop for a much longer period, up to 288 h. It is suggested that the actinomycin D, by delaying the formation of the implantation chamber in the endometrium, interferes with the formation of a proper functional connection between the trophoblast and endometrium with the result that the embryo receives insufficient nutrition for its development.


Progesterone-induced in vitro maturation in oocytes of Notophthalmus viridescens (Amphibia Urodela) and some observations on cytological aspects of maturation. Maturation in vitro of oocytes of the newt, Notophthalmus viridescens, is inducible with progesterone after in vivo treatment of females with gonadotropin; few oocytes mature in vitro in the absence of such gonadotropin treatment. Chromosomes of most large oocytes of animals not receiving gonadotropin are still in the lampbrush condition; chromosomes from gonadotropin-treated animals are shorter and the lateral loops are less profuse and somewhat retracted. The chromosome condition, then, can be correlated with susceptibility to progesterone induction of maturation in vitro. As maturation progresses, the germinal vesicle moves toward the surface and decreases in size, with an apparent loss of nuclear material from the centripetal end. Although lateral loops of most chromosomes disappear during the changes in the germinal vesicle, profuse loops develop during this period at the sphere loci, which were previously devoid of loops.


Cell cycle parameters in dedifferentiating iris epithelial cells. After lentectomy of the adult newt eye, non-dividing iris epithelial cells re-enter the cell cycle. Some of the iris epithelial cells become completely depigmented while they are in the cell cycle, and then differentiate into lens cells. The remaining iris epithelial cells become partially depigmented in the induced cell cycle, but resynthesize melanosomes and recover the normal state of iris epithelial cells. The two groups of cells are spatially separated within the iris epithelium. The cell cycle parameters of both groups of iris epithelial cells were estimated by a mathematical procedure on a computerized programme from the percentage of labelled mitotic cells as a function of time after peritoneal injection of [3H]methyl-thymidine on day 6 after lentectomy. The total cell cycle time was found significantly shorter in the cell population with complete depigmentation as compared with that with partial depigmentation. Based on these results the possible role of differential cell cycle time in the control of dedifferentiation was discussed. Grafting of unlabelled iris into the optic cavity of host animals injected 6 h beforehand with [3H]methyl-thymidine, followed by a study of radioactivity of iris epithelial cells of the graft demonstrated incorporation at a low level during the whole period of experiment in which the cell cycle parameters were estimated. The data used for the estimation were corrected for the delayed incorporation.


[Morphogenesis of the chick embryo foot]. Observations were made on chick embryo feet between 6 and 12 1/2 days of incubation in order to (a) give a precise description of programmed cell death in the interdigital membranes; (b) correlate the evolution of interdigital necrosis with the differentiation of the cartilaginous phalangeal skeleton; (c) measure the relative growth rates of digits and interdigits. The programme of interdigital cell death proceeds in three phages which comprise the appearance, the extension and the disappearance of necrotic areas. Fourteen distinct stages are described. The evolution of programmed cell death can be strictly correlated to the chondrogenesis of successive phalanges, in the sense that each stage of necrosis (except two of them) differs from the preceding one by the differentiation of an additional phalanx. Shaping of the foot results from differential growth rates and proceeds in three phases, the second of which is characterized, between days 8 and 10 of incubation, by the actual shortening (decrease of absolute length) of the interdigital membranes. These observations are compared to those that were previously made on other avian and mammalian species and the morphogenetic role of programmed cell death is discussed in the light of that comparison.


Interactions of C-reactive protein with the complement system. III. Complement-dependent passive hemolysis initiated by CRP. Interactions of CRP with various substrates in the presence of human serum have been shown to result in efficient activation of C components C1-C5. We now report the ability of CRP to initiate C-dependent hemolysis. For this purpose CRP was isolated by affinity chromatography using pneumococcal CPS and gel filtration; its purity was established by several criteria. Erythrocytes were coated with CPS (E-CPS) and passively sensitized with CRP. C-dependent lysis of these cells was observed upon the addition of suitably absorbed human serum, and the efficiency of hemolysis compared favorably with that initiated by rabbit IgG anti-CPS antibody. CRP also sensitized E-CPS for lysis by guinea pig C; partial lysis was seen when C4-deficient guinea pig serum was used, suggesting that CRP also shares with antibody the ability of CRP to fully activate the C system and provide further evidence for a role for CRP similar to that of antibody in the initiation and modulation of inflammatory reactions via the complete system.


Frequency and avidity of specific antigen-binding cells in developing mice. In order to analyze the development of antibody diversity in which the genes coding for the antigen-specific cells we have compared the binding of diverse antigens by cells in the fetal, neonatal, and adult mouse. Although the numbers of antigen-binding cells present in fetuses and young animals were smaller than in adults, no restriction could be detected in the varity of specificities expressed in the fetuses, either with respect to the kinds of antigens bound, or to the range of avidities of binding. Cells specific for each of the 11 antigens tested could be detected in the fetus only in the last 4 days before birth, at which time they appeared both in the liver and in the spleen. In all cases, these cells disappeared both in the liver and in the spleen. In all cases, these cells disappeared from the liver within a day of birth, but continued to increase in number in the spleen until adulthood...


Humoral immunostimulation. V. Selection of variant cell lines. A permanent L-cell variant cell line (LC1) was isolated by the growth of the parent L-cell line (L) in the presence of a cytostimulatory dose (1:200) of rabbit anti-L-cell antiserum (AL) for 9 mo. LC1 differed from L in many aspects: (a) it was larger (1,533 mm3 vs. 1,284 mm3), (b) it grew faster (1.5- to 2-fold), (c) it grew in aggregated fashion, (d) its growth was no longer stimulated by AL, (e) it was almost completely resistant to high concentrations of AL in the presence of complement (C), (f) its original membrane antigens (immunogenic for AL) were redistributed in sparse and patchy clumps as noted by fluorescence microscopy, (g) it contained about 65% of the total original 125I-AL membrane-binding sites (1.4 X 10(7)/cell vs. 2.2 X 10(7)/cell), (h) its AL-binding sites displayed a lower average affinity constant (K = 0.9 X 10(5) M-1 vs. 2.8 X 10(5) M-1), (i) it contained a smaller proportion of high affinity (K greater than 10(6) M-1) binding sites (13% vs 21%), and (j) LC1 was fully immunogenic in that it was readily killed by homologous antiserum (ALC1) and C, whereas L was not similarly affected by ALC1 indicating that LC1 contained new membrane antigens not present on L. Another variant (LC2) was produced by growth of LC1 in a 10-fold higher dose (1:20) of AL (cytotoxic for L) for 1 mo. LC2 was even more resistant to AL in the presence of C, contained 0.84 X 10(7) AL-binding sites/cell with an average affinity constant of 1 X 10(5) M-1 (unchanged from LC1), and was less susceptible than LC1 to lysis in the presence of ALC1 and C. These findings confirm and extend our previous in vitro and in vivo observations dealing with the direct stimulation effects of antibody on tumor cell metabolism and suggest that immunostimulation may be a mechanism of tumor escape from immune control in vivo possibly by immunoselection and antigenic modulation as proposed by other investigators.


Proliferative characteristics of monoblasts grown in vitro. In a previous study also done with a liquid culture technique, the monoblast was identified and characterized as the most immature cell of the mononuclear phagocyte cell line recognized so far. The present study concerned the proliferative behavior of the monoblast and promonocyte in colonies. The cell-cycle times of both cell types were determined on the basis of four independent methods. The resulting values all show excellent agreement: for the monoblast 11.0-11.9 h, and for the promonocyte 11.4-12.8 h. The DNA-synthesis time found for the two cell types amounted to 5.7 h for the monoblast and 5.5 h for the promonocyte. The duration of the other phages of the cell cycle of the proliferating mononuclear phagocytes proved to be: G2 phase, 0.6 h; mitosis phage, 1.8 h; and G1 phase, 3.5-3.8 h. The individual colonies showed a biphasic pattern of colony growth, an initial phase of rapid proliferation being followed by a stage wtih a markedly decreased growth rate. In the initial stage only monoblasts are present in the colony; when the growth rate slows down promonocytes and macrophages appear. These observations support the earlier conclusion that the monoblast is without doubt the precursor of the promonycyte. Colony size was found to vary widely. The main factor underlying this variation proved to be the lag time between the start of the culture and the time point at which the colony-forming cells begin to divide. Mathematical analysis showed that the variation in colony size probably does not arise from heterogeneity of the population of colony-forming cells. A mathematical approach was used to determine the proportion of self-replicating and differentiating cells among the dividing monoblasts and promonocytes in the colony. The results indicate that initially in vitro the majority of the cells of both types are self-replicating cells, but later an increasing proportion of the dividing cells give rise to another, more mature type of cell. On the basis of the conclusion that the monoblast initiates the mononuclear phagocyte colony, the number of monoblasts (2.5 X 10(5)) present in vivo was estimated to be half the number of the promonocytes. In view of this ratio the mostly likely pattern for the proliferation of mononuclear phagocytes in the bone marrow is that a monoblast divides once, giving rise to two promonocytes which in their turn divide once and form two nonproliferating monocytes.


Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particle-bound ligands to specific receptors on the macrophage plasma membrane. These experiments were designed to evaluate the role of macrophage plasma membrane receptors for the third component of complement (C) and for the Fc portion of IgG in the ingestion phase of phagocytosis. Sheep erythrocyte (E) were coated with anti-E IgG [E(IgG)]; these E(IgG) were then attached to cultivated monolayers of mouse peritoneal macrophages under conditions which reversibly inhibit ingestion of E(IgG). The E(IgG)-macrophage complexes were further incubated under similar conditions with an antimacrophage IgG fraction which blocks Fc receptor-mediated ingestion but has no effect upon ingestion mediated by other phagocytic receptors. When these cultures were subsequently incubated under conditions optimal for particle ingestion, phagocytosis of the IgG-coated erythrocytes did not occur; the erythrocytes remained bound to the Fc receptors of the macrophage plasma membrane. To determine whether ligands must cover the entire surface of an attached particle to permit ingestion of that particle, C-coated E [E(IgM)C] were bound to the C receptors of thioglycollate-induced (activated) macrophages at 4 degrees C. E(IgM)C-macrophage complexes were then trypsinized at 4 degrees C, a procedure which resulted in cleavage of erythrocyte-bound C3b molecules to a form of C3 not recognized by the macrophage receptors for C3b. Under the conditions used, trypsin did not affect the attachment of E(IgM)C to the macrophage surface or the macrophage receptors for C3b. When these trypsin treated E(IgM)C-macrophage complexes were incubated at 37 degrees C, the bound E(IgM)C were not ingested; the erythrocytes remained attached to the macrophage plasma membrane via the macrophage's C receptors. These results indicate that attachment of a particle to specific receptors on the macrophage plasma membrane is not sufficient to trigger ingestion of that particle. Rather, ingestion requires the sequential, circumferential interaction of particle-bound ligands with specific plasma membrane receptors not involved in the initial attachment process.


C1 fixation and classical complement pathway activation by a fragment of the Cmu4 domain of IgM. A 56 residue fragment derived from a Waldenströme IgM protein and consisting of 24 residues of the amino-terminal portion of the Cmu4 domain disulfide bonded to 32 residues of the carboxy-terminal region of the loop has been shown to fix active C1 (C1) in a C1-fixation assay. Cleavage of the disulfide bond within the CH4 fragment resulted in a marked decrease of C1-fixing ability, although the isolated A and B fragments did retain a limited ability to fix C1. Upon incubation with normal human serum the intact CH4 fragment and equal molar amounts of the isolated A and B peptides consumed C4 suggesting that the C1-activating determinant of IgM remains intact in these three fragments. Furthermore, on a molar basis the intact or the reduced CH4 fragment consumed C4 as effectively as each of its component chains suggesting that transient binding of C1 by the individual A and B peptide chains is sufficient to activate C1. On the basis of these observations it is proposed that a classical complement fixation function, i.e. C1 binding and activation, can be localized within a region of the IgM molecule corresponding to the Cmu4 domain.


Antigenic properties of cultured tumor cell lines derived from spleens of Friend virus-infected BALB/c and BALB/c-H-2b mice. BALB/c-H-2b (BALB.B) mice are less susceptible to the Friend virus (FV) disease syndrome than congenic BALB/c (H-2d) mice, and spleen cells from FV-infected BALB.B mice are markedly less tumorigenic on transplantation to syngeneic hosts than those from FV-infected BALB/c mice. For these reasons we investigated the expression of FV-associated cell surface antigens on cultured, FV-trnasformed cell lines of BALB.B and BALB/c origin. Both cell lines induced transplantation immunity in syngeneic hosts toward further implantations of the same tumor, BALB.B cells being significantly more potent in this respect than BALB/c cells. BALB.B tumor cells, which produce complete, infectious FV, expressed both the cell surface antigen, FMR (corresponding to the cytotoxic antibodies in anti-FV antisera), and virus envelope antigen (VEA, corresponding to the virus-neutralizing antibodies in the anti-FV antisera). BALB/c tumor cells, on the other hand, which are FV-nonproducers, expressed no FMR antigen, but did express VEA on their surfaces for at least 100 passages in culture. These cells could induce FV-neutralizing but not cytotoxic anti-FMR antibodies when used to immunize syngeneic hosts. The absence of FMR antigen may be the basis for the reduced capacity of BALB/c tumor cells, by comparison with BALB.B tumor cells, to induce transplantation immunity. After about the 125th serial transfer in culture, BALB/c tumor cells spontaneously ceased to express VEA and simultaneously became very weak inducers of transplantation immunity in BALB/c hosts. This loss of VEA did not stem from the loss of either the spleen focus-forming virus or the helper virus genomes from these cells, since both viruses could still be recovered from the cell line.


Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT). Several inbred as well as congenic resistant strains of mice, which fail to respond to the random copolymer of L-glutamic acid50-L-tyrosine50 (GT), were shown to develop specific PFC responses when stimulated by GT complexed to an immunogenic carrier such as methylated bovine serum albumin (MBSA). In these studies we have found that GT preimmunization has a tolerogenic effect on the response to GT-MBSA in some mouse strains; whereas in other strains of mice, GT fails to inhibit the GT-MBSA response. We may, therefore, conclude that immune suppression cannot account for nonresponsiveness in all cases. The development of specific immune suppression in response to GT was shown to be inherited as a dominant trait in F1 hybrids resulting from the mating of suppressor with nonsuppressor strains. This trait is, therefore, under the control of a gene or genes that we have designated as specific immune suppression gene(s) Is genes. The strain distribution of GT induced suppression demonstrates that Is genes are coded for in the H-2 complex. Furthermore, immune suppression by the two related copolymers, GT and GAT, are distinct in different strains of mice. The significance of these data for our understanding of the regulation of the immune response is discussed.


Dominant nonresponsiveness in the induction of autoimmunity to liver-specific F antigen. The liver-specific F antigen, although not an autoimmunogen, can induce the production of autoantibodies in responder strains. The ability to respond is under the control of two genes, one linked to the H-2 locus of mice, the other not. Responders possessing both genes produce high anti-F titers, while the H-2-linked gene alone permits a significant but low antibody response. (Responder X nonresponder) F1 hybrids derived from parents possessing identical F molecules are nonresponders, in contrast with the dominance of responsiveness in Ir gene systems. The presence of the H-2 locus from nonresponders appears involved in the inability to respond. This is discussed in terms of self-tolerance and suppression.


Binding of monomeric immunoglobulins to Fc receptors of mouse macrophages. The binding properties of surface receptors of immunoglobulins on mouse macrophages were studied with mouse myeloma proteins and normal peritoneal macrophages, thioglycollate-stimulated macrophages, and a macrophage cell line, P388D1. Primary cultures of mouse embryo fibroblasts served as controls. IgG2a proteins were bound strongly;IgG2b was bound weakly (one-twentieth as well as IgG2a);IgM, IgA, and IgG1 were not bound significantly. The number of binding sites per cell for IgG2a was 4 X 10(5) for thioglycollate-stimulated cells and 1 X 10(5) for normal and P388D1 cells. Binding was exothermal: with decreasing temperature the equilibrium (association) constants increased and dissociation rate constants decreased (at 37degreesC the respective values were 2 X 10(7) M-1 and 0.26 min-1, the latter value corresponds to a half time for dissociation of 2.6 min). From the rapidity of association and dissociation, it appears that the surface of the macrophage is in a dynamic equilibrium with IgG2a molecules in the cell's immediate microenvironment. The receptors for IgG2a are clearly specific for determinants in the immunoglobulin constant domain: two IgG2a proteins with greatly different isoelectric points (determined by isoelectric focusing) were bound with the same affinity to the same receptors; moreover, the Fc fragment was bound and Fab fragments were not. The Fc receptors for IgG2a proteins were readily eliminated by exposing macrophages briefly to trypsin. The receptors were regenerated during subsequent cultivation in serum-free medium; regeneration was inhibited totally by cycloheximide and partially by actinomycin D.


Activated macrophages release a factor which lyses malignant cells but not normal cells. When rat macrophages are activated by exposure to bacterial endotoxin they acquire the capacity to lyse sarcoma cells in tissue culture. Although showing no immunological specificity this lytic effect was only detectable on malignant cells; normal cells were unaffected. This tumor-selective lytic effect is mediated by a labile supernatant product.


Hemispheric processing differences revealed by differential conditioning and reaction time performance. Two different experimental procedures were used to examine (a) information-processing differences between two groups of subjects (Cs versus Vs) identified by the form of their conditioned eyeblinks; (b) information-processing differences between the right and left cerebral hemispheres; and (c) parallels between hypothesized C-V differences and right-left hemisphere differences. In the first experiment, the evocative command words BLINK and DON'T BLINK served as positive and negative conditioned stimuli. It was found that Vs gave more conditioned eyeblinks than Cs and that differential eyelid conditioning of Vs more than Cs was influenced by the semantic content of the stimuli. More importantly, the conditioning performance of Cs was more influenced by the semantic attributes of the stimuli when they were presented directly to the right visual field (left hemisphere) than when they were presented directly to the left visual field (right hemisphere). In contrast, the conditioning performance of Vs was equally influenced by the semantic attributes regardless of which hemisphere received direct stimulation. A second experiment was designed to determine whether such hemisphere-of-presentation differences for Cs versus Vs could also be obtained in a very different task. Subjects classified as Cs or Vs during a differential eyelid conditioning task then performed two same-different reaction time (RT) tasks that required discrimination of complex polygons in one case and the names of letters in another. On each RT trial both stimuli of a pair appeared briefly either in the center, left, or right visual field. For both Cs and Vs RTs to complex polygon pairs averaged 20 msec faster on left visual field trials than on right visual field trials, consistent with current hypotheses about right-hemisphere specialization for visuospatial processing. In contrast, the results for letter pairs generally confirmed the C-V differences found in Experiment 1. That is, the right visual field (left-hemisphere) advantage for these verbal stimuli was once again larger for Cs than for Vs. The present results suggest that the two groups of subjects (Cs versus Vs) differ qualitatively in the modes of information processing that they typically employ. The results also suggest that these different modes of processing are related to aspects of cerebral hemisphere organization and that even right-handed individuals may differ from each other in the extent to which each cerebral hemisphere is mobilized for a given experimental task. Such individual differences must be incorporated into both models of classical eyelid conditioning and models of cerebral hemisphere specialization.


Verbal coding and redintegrative memory for shapes. Four experiments examined the effect of label training on redintegrative memory for novel shapes (remembering the whole shape when only a part is presented). Redintegrative memory was markedly better when subjects were trained with names as compared to unnamed control conditions. The first two experiments demonstrated that the effect of labeling was even stronger when subjects were required to use the labels during the transfer test. This result suggests that the naming effect is not due to attentional differences during training. The last two experiments explored the quality of the assigned labels and the relationship of the label to the visual stimulus. There was a slightly greater effect of relevant meaningful labels on redintegrative memory, but in general all types of names (relevant, irrelevant, and paralog) were facilitative. The experiments suggest that a verbal code can exert a strong influence in tasks that require the integration and retrieval of visual information.


Auditory location as an encoding dimension. In two experiments, subjects were given five successive short-term memory tests. In Experiment 1, recall was not significantly facilitated when memory material in the final test was delivered to the ear opposite to the one that received the memory material in the four preceding tests. In Experiment 2, events were presented from two differentially located speakers rather than through headphones. A shift across speakers on the final test did produce proactive interference release. These findings suggest spatial location as a potential encoding dimension of verbal material.


Stimulus structure, discrimination, and interference. Subjects learned lists of consonant trigram word pairs varying in intralist formal stimulus similarity. On test trials, subjects were tested with all but one stimulus, then presented either the missing stimulus or one previously tested. Subjects had to correctly identify this stimulus, then recall its associated word. Both recall and recognition performance varied with the difficulty of discovering and utilizing a discriminated element. However, when subjects were instructed as to list structure, recall was improved without improvement in recognition in one condition, and recognition was improved without recall in another. This indicates that stimulus discrimination is neither necessary nor sufficient to reduce intralist interference.


Classical skin conductance response conditioning: effects of intermittent reinforcement and information about schedule contingencies. Skin conductance responses were differentially conditioned using reinforcement schedules of 25%, 50%, 75%, and 100%, manipulated between subjects. Half of the subjects were informed about schedule contingencies, and half were uninformed. The interstimulus interval was 6 sec. Discrimination of first-interval responses (1.0-3.5 sec after conditioned stimulus [CS] onset) by informed subjects did not vary with the ratio variable, but that by uninformed subjects improved with increasing reinforcement ratio because of diminished response levels to the nonreinforced CS (CS-). Discrimination of second-interval responses (3.6-7.0 sec after CS onset) improved as a function of increasing reinforcement ratio because of elevated response levels to the reinforced CS (CS+), but the effect was not persistent across trials in informed subjects. Performance in the first and second intervals did not reflect sequential increments and decrements as a function of reinforced and nonreinforced trials. Third-interval responses (7.1-9.9 sec after CS on nonreinforced trials) were not affected by schedule manipulations, but unconditioned responses diminished with increasing reinforcement ratio. Information about schedule contingencies led to superior discrimination of first-, second-, and third-interval responses and to suppression of unconditioned responses.


Aspects of phonological fusion.

Aspects of phonological fusion. Phonological fusion occurs when the phonemes of two different speech stimuli are combined into a new percept that is longer and linguistically more complex than either of the two inputs. For example, when PAY is presented to one ear and LAY to the other, the subject often perceives PLAY. The present article is an investigation of the conditions necessary and sufficient for fusion to occur. The rules governing phonological fusion appear to be the same for synthetic and natural speech, but synthetic stimuli fuse more readily. Fusion occurs considerably more often in dichotic stimulus presentation than in binaural presentation. The phenomenon is remarkably tolerant of differences in relative onset time between the to-be-fused stimuli and of relative differences in fundamental frequency, intensity, and vocal tract configuration. Although phonological fusion is insensitive to such nonlinguistic stimulus parameters, it is sensitive to linguistic variations at the semantic, phonemic, and acoustic levels.


Ratio scale measurement of the perceived lengths of lines. In Experiments 1 and 2, magnitude and category estimates of perceived line length difference were used to rank order 36 pairs of lines with respect to the psychological length difference between the lines forming a pair. In Experiment 3 magnitude estimates of line length ratios were used to order the same 36 pairs with respect to the psychological length ratio between the lines comprising a pair. A nonmetric analysis of the rank-order of the difference and ratio judgments was used to construct a ratio scale of perceived line length. Perceived line length was found to be a power function of physical line length with an exponent of .46. In Experiments 4 and 5, magnitude and category estimates of line length similarity were obtained. A nonmetric analysis of these data indicated that similarity judgments were monotonic inverses of judgments of psychological ratios.


Perception of temporal order in vowel sequences with and without formant transitions. Temporal-order perception of phoneme segments in running speech is much superior to temporal-order perception in repeating vowel sequences. The more rapid rates possible in running speech may be due largely to the presence of formant transitions. In a series of five experiments we observed that many temporal-order misjudgements of repeating vowels can be explained in terms of auditory stream segregation, triggered for the most part by discontinuities in first-formant frequencies of adjacent vowels. Streaming, however, can be suppressed by formant transitions appropriate for the perception of stop consonants and by continuous transitions resembling those in coarticulated vowels. At rapid sequence rates, when the constraints of auditory streaming are removed, correct temporal-order identification is limited by linguistic transformations of vowels into other phoneme segments.


Feedback versus motor programming in the control of aimed movements. In the Fitts paradigm the subject moves a stylus to the left or right of an initial rest position to reach targets that vary in size and in distance from the initial position. The classic finding for relatively long movements is that movement time, measured from leaving the initial position until contact with the target, depends on both distance and target size according to a relationship known as "Fitts' law." By contrast, reaction time, measured from the signal to move until the stylus leaves the initial position, is independent of these parameters. While replicating these results for long movements, the present data show a different pattern for very short movements, for which Fitts' law no longer holds and for which reaction time increases as the size of the target is decreased. These findings were interpreted as implying that long movements are under feedback control, whereas short movements are predominately programmed and ballistic. This conclusion was supported by the additional finding that elimination of visual feedback was more disruptive to the long than to the short movements.


Feedback as a source of information and as a source of noise in absolute judgments of loudness. Two experiments investigated the effects of feedback on absolute judgements of loudness. In Experiment 1, subjects received aceurate, unreliable, or no feedback. While feedback improved the information transmitted in judgments, it gave lower d' values than no feedback. These results were not compatible with a signal detection model with a noisy sensory stage and a decision stage with a fixed criterion, but suggested that criteria move in response to feedback and thus contribute judgmental noise to perceptual processes. Further confirmation for a variable criterion was obtained in Experiment 2, where reliability of feedback was held constant, but feedback was biased to favor some response alternatives more than others. Biased feedback shifted the positions of criteria, but also increased the inertia of some criteria in responding to feedback which caused changes in d'.


Tests of the psychological meaning of the power law. The purpose of this study was to establish a theoretical framework for Stevens' empirically derived power law. Three models were proposed to explain the power law. They respectively outline how sensory, stimulus, and response variables determine the judgmental behavior in a psychophysical task. A correlational study on individual differences in exponents was carried out to test the predictions derived from each model. The use of four different sensory continua and four scaling procedures provided the experimental means of manipulating the sensory, stimulus, and response variables in the scaling situation. The results showed that response variables are important determinants of judgmental behavior in psychophysical scaling. These findings suggest that subjects' responses to stimulus intensities in a scaling task are largely cognitive.


Comparative strategies in the investigation of neural networks. Comparative studies on nervous systems, though infrequently undertaken for the purpose of comparison, have yielded some important generalities about the formats of nervous networks, and about the cell biology of certain neural types. In the first category, it is clear that convergent evolutionary processes arrived at very similar networks to accomplish reciprocal and lateral inhibition, and load-compensation in "resistance reflexes." A newer general network format is described, command-derived inhibition, in which the central nervous elements controlling a rapid movement deliver presynaptic inhibition to the terminals of sensory neurons that carry reafferent excitation from the movement. It is argued that such circuits occur in several groups of animals, and that they include as a special class the efferent inhibitory neurons innervating acoustico-lateralis receptors in vertebrates. The properties of circuit elements that now seem to constitute useful generalizations include size principle (the inverse relationship between size and excitability in a variety of neurons), and the late differentiation of sensory neurons, failure to decussate, and their inability to mediate inhibition. Many other generalities have emerged, only to fall; one conclusion from such searches is that many supposedly "basic" properties of cell types or neural circuits are in fact not phylogenetically conservative, however much the physiologist may expect them to be.


Neural factors and evitability in insect behavior. Compared with more complex behavior patterns involving goal selection, evasive behavior of prey animals elicited by the presence of a natural predator is usually considered to be relatively inevitable and stereotyped. Noctuid moths, while flying in the field at night, show two types of evasive response pattern when their tympanic organs detect the ultrasonic cries of marauding insectivorous bats. Since sound is the sole communication channel between prey and predator, this situation invites neurophysiological and behavioral analysis. When, in the course of studying this behavior, moths are removed by stages from the natural circumstances of this interaction their evasion responses become much less invariant; that is, more evitable. The possible survival value of some evitability in this behavior under natural circumstances is discussed. The afferent nerve response of the noctuid auditory organ is highly stable; therefore, the source or sources of this evitability must lie down-stream in the moth central nervous system. Acoustic interneuronal systems within the thoracic ganglia and the brain have been examined for lapses in responsiveness and for other indications of transsynaptic instability that might correlate with the demonstrated behavioral evitability.


The role of sex hormones in the growth of antler bone tissue. I: Endocrine and metabolic effects of antiandrogen therapy. Cyproterone acetate (CA), an antiandrogenic compound, was used in order to investigate the role of testosterone in bone growth processes. The formation of Haversian systems in the growing antlers of white-tailed deer (Odocoileus virginianus) were substantially affected by only 3.5 mg of CA kg/wk. The mineralization processes of the bone matrix were almost completely blocked and the antlers persisted in growing throughout the whole year. Plasma levels of thyroxine, alkaline phosphatase and GH were higher while cortisol and testosterone levels were lower than in controls. No differences were registered in plasma levels of Ca, P or urea nitrogen. Despite hypertrophy of interstitial tissue, spermatogenesis was almost completely blocked. The sexual behaviour and the body appearance of experimental animals was typical for castrates.


The relation of nerves to multiple regeneration in a single newt limb. Three amputation surfaces were formed on the lower arm of a single newt. Growth occurred on all combinations of these surfaces. The proximal surface (the only single surface to form regenerates) produced more regenerates (76% of the cases) than the two more distal surfaces. Blocking the proximal surface with whole skin greatly stimulates the production of accessory structures on the first and/or second more distal surfaces. The mean number of nerve fibers on the proximal surface is considerably higher than the nerve counts of the first more and second most distal surfaces. Limbs possessing a notch or digit(s) on the proximal surface and the absence of growth on the first more and second distal surfaces also show a decrease in nerve number on the first more and second most distal surfaces. An analysis of the mean number of nerve fibers on the blocked (proximal) surface shows a noticeable decrease in comparison with nerve fibers in an equivalent level on normal limbs. Nerve fiber counts on the first more and second most distal surfaces are markedly increased on those limbs where the proximal surface was blocked with whole skin. Threshold experiments suggest that the irregular occurrence of accessory structures on the first more distal and second most distal surfaces may be related to an insufficient number of nerve fibers on these surfaces. Similarly, a possible explanation for the regular occurrence of accessory structures on the proximal surface is that nerve number on this surface is always above threshold.


Structural and functional heterogeneity in an insect muscle. Singing muscles of the katydid, Neoconocephalus robustus (Insecta, Tettigoniidae) are neurogenic, yet perform at contraction-relaxation frequencies as high as 212 Hz (Josephson and Halverson, '71). The mechanical and electrical responses of different bands of one of these muscles (the dorsal longitudinal muscle, DLM) has been examined with respect to ultrastructural features of each part which may be related to muscle performance. The DLM is composed of three bands and is innervated by four motoneurones. The cell bodies of three of these motoneurones occur ipsilaterally in the prothroracic ganglion; the cell body of the other motoneurone is contralateral in the mesothoracic ganglion. Three of the motoneurones (as yet unidentified fast axons) initiate extraordinarily fast twitches (rise time equal 7.3 msec, half duration equals 14.3 msec, 25 C), the fourth (an unidentified slower axon) evokes twitches which are considerably slower (rise time equals 18.9 msec, half duration equals 5.10 msec). Whereas the ventral and medial bands of the muscle are innervated only by fast axons (some fibers of the medial band are doubly innervated), the dorsal band is innervated by both a fast axon and the slower axon. A few fibers of the dorsal band are doubly innervated. The structure of fibers from the ventral and medial bands is very similar, with short sarcomeres (4.0 and 4.3 mum, respectively) and thin strap-like myofibrils delineated by well-developed sarcoplasmic reticulum (SR). Twenty-four percent of the volume of ventral band fibers is SR and the diffusion distance from SR to the center of the adjacent myofibril averages 0.083 mum. Twenty percent of the medial band fiber volume is SR, with a diffusion distance of 0.118 mum. Ventral and medial band fibers contain about 40% mitochondria, and 33% myofibrils. The dorsal band fibers have longer sarcomeres (9.5 mum), and only 10% of the fiber volume is SR. The muscle fibrils of the dorsal band are larger and consequently the diffusion distance is greater (0.227 mum) than in the ventral and medial bands. Mitochondria comprise 23% of the volume of dorsal band fibers. Most dorsal band mitochondria are aggregated into distinct clumps. Although some dorsal band fibers are innervated by a fast axon and some by the slower axon, the dorsal band fibers are structurally homogeneous, suggesting that neurotrophic effects are not important in maintaining the structure of dorsal band fibers. The mechanical-electrical performance and ultrastructure of the ventral and medial bands suggest their roll as fast, metabolically active but weak muscles, used in singing; the dorsal band as a slower but stronger muscle, perhaps involved in postural movements of the wing during singing.


Disruption of normal forelimb regeneration in adult Notophthalmus viridescens by sublethal concentrations of trypan blue. The effects of the vital dye trypan blue (TpB) on the regeneration of amputated newt forelimbs were examined. Administration of the dye (10 mug/g body weight) via IP injection during the early wound healing and dedifferentiation phases of regeneration inhibited the normal regenerative response. The accumulation phases of regeneration are similarly halted but only by greater concentrations of TpB (50 mug/g body weight) while redifferentiation and morphogenesis are only affected by still greater concentrations of the dye (100 mug/g body weight). In addition to abolishing the regenerative response, low levels of TpB were also capable of inducing skeletal abnormalities in the regenerates as might be expected from previous reports on the teratogenicity of the dye. The in vitro action of newt hyaluronidase (as well as purified testicular hyaluronidase) on hyaluronate was diminished by TpB, with virtually complete inhibition observed at initial reaction mixture concentrations of 100 mug/ml. The results of this study suggest that TpB acts to disrupt the normal regenerative response by preventing dedifferentiation and remodeling, perhaps by inhibition of various necessary lytic enzyme functions or by interference with normal intercellular communications.


Multienzymic nature of pyruvate kinase during development of Hymenolepis diminuta (Cestoda). H. diminuta at different stages of development contained as many as five pyruvate kinase isozymes. Four of these were unusually sensitive to allosteric activation by fructose-1,6-P2. One isozyme which occurred only in adults or near-adults was insensitive but had a relatively low Km. All were inhibited by ATP and Ca2+, none by alanine, and the pH optimum was unaffected by fructose-1,6-P2. The five isozymes were present in gravid or reproductively active proglottids. Two of them occurred after eight days growth in the rat intestine, and three after four days. These three were also present in the immature, anterior proglottids of adult parasites. Hexacanth larvae from gravid proglottids, as well as cysticercoids developing from these larvae in Tenebrio molitor, possessed only two isozymes. It was inferred from information on tissue concentrations of ADP, ATP, phosphoenolypyruvate (PEP) and on K0.5S and Km that competition between pyruvate kinase and PEP carboxykinase is probably controlled by fructose-1,6-P2 concentrations. Since H. diminuta is an obligatory fermenter in which gluconeogenesis is minimal, the probable function of its L-type pyruvate kinases is to control the specific composition of lactic, acetic and succinic acid mixtures that are excreted at different stages of development.


Activities of potassium and sodium ions in rabbit heart muscle. Activities (a) of intracellular K and Na in rabbit ventricular papillary muslces were determined with cation-selectivve glass microelectrodes and concentrations (C) were estimated with flame photometry. The CK and aK of the muscles were 134.9 +/- 3.1 mM (mean value +/- SE) and 82.6 mM, respectively, at 25 degrees C. The corresponding CNa and aNa were 32.7 +/- 2.7 and 5.7, respectively. The apparent intracellular activity coefficients for K (gammaK) and Na (gammaNa) were 0.612 and 0.175, respectively. Similar results were obtained at 35 +/- 1 degree C. gammaK was substantially lower than the activity coefficient (0.745) of extracellular fluid (Tyrode's solution), which might be expected on the basis of a different intracellular ionic strength. gammaNa was much lower than that of extracellular fluid, and suggest that much of the Na was compartmentalized or sequestered. For external K concentrations greater than 5 mM, the resting membrane potentials agreed well with the potential differences calculated from the K activity gradients across the cell membrane as a potassium electrode. These results emphasize that potassium equilibrium potentials in heart muscle should be calculated by activities rather than concentrations.


Conductance increases produced by bath application of cholinergic agonists to Electrophorus electroplaques. When solutions containing agonists are applied to the innervated face of an Electrophorus electroplaque, the membrane's conductance increases. The agonist-induced conductance is increased at more negative membrane potentials. The "instantaneous" current-voltage curve for agonist-induced currents is linear and shows a reversal potential near zero mV; chord conductances, calculated on the basis of this reversal potential, change epsilon-fold for every 62-mV change in potential when the conductance is small. Conductance depends non-linearly on small agonist concentrations; at all potentials, the dose-response curve has a Hill coefficient of 1.45 for decamethonium (Deca) and 1.90 for carbamylcholine (Carb). With agonist concentrations greater than 10(-4) M Carb or 10(-%) M Deca, the conductance rises to a peak 0.5-1.5 min after introduction of agonist, then declines with time; this effect resembles the "desensitization" reported for myoneural junctions. Elapid alpha-toxin, tubocurarine, and desensitization reduce the conductance without changing the effects of potential; the apparent dissociation constant for tubocurarine is 2 X 10(-7) M. By contrast, procaine effects a greater fractional inhibition of the conductance at high negative potentials.


Ionic selectivity, saturation, and block in sodium channels. A four-barrier model. Ionic fluxes in Na channels of myelinated axons show ionic competition, block, and deviations from simple flux independence. These phenomena are particularly evident when external Na+ ions are replaced by other permeant or impermeant ions. The observed currents require new flux equations not based on the concepts of free diffusion. A specific permeability model for the Na channel is developed from Eyring rate theory applied to a chain of saturable binding sites. There are four energy barriers in the pore and only one ion is allowed inside at a time. Deviations from independence arise from saturation. The model shows that ionic permeability ratios measured from zero-current potentials can differ from those measured from relative current amplitudes or conductances. The model can be fitted to experiments with various external sodium substitutes by varying only two parameters: For each ion the height of the major energy barrier (the selectivity filter) determines the biionic zero-current potential and the depth of the energy well (binding site) just external to that barrier then determines the current amplitudes. Voltage clamp measurements with myelinated nerve fibers are given showing numerous examples of deviations from independence in ionic fluxes. Strong blocks of ionic currents by guanidinium compounds and Tl+ ions are fitted by binding within the channel with apparent dissociation constants in the range 50-122 mM. A small block with high Na+ concentrations can be fitted by Na+ ion binding with a dissociation constant of 368 mM. The barrier model is given a molecular interpretation that includes stepwise dehydration of the permeating ion as it interacts with an ionized carboxylic acid.


Intracellular recordings from gecko photoreceptors during light and dark adaptation. Intracellular recordings were obtained from rods in the Gekko gekko retina and the adaptation characteristics of their responses studied during light and dark adaptation. Steady background illumination induced graded and sustained hyperpolarizing potentials and compressed the incremental voltage range of the receptor. Steady backgrounds also shifted the receptor's voltage-intensity curve along the intensity axis, and bright backgrounds lowered the saturation potential of the receptor. Increment thresholds of single receptors followed Weber's law over a range of about 3.5 log units and then saturated. Most of the receptor sensitivity change in light derived from the shift of the voltage-intensity curve, only little from the voltage compression. Treatment of the eyecup with sodium aspartate at concentrations sufficient to eliminate the beta-wave of the electroretinogram (ERG) abolished initial transients in the receptor response, possibly indicating the removal of horizontal cell feedback. Aspartate treatment, however, did not significantly alter the adaptation characteristics of receptor responses, indicating that they derive from processes intrinsic to the receptors. Dark adaptation after a strongly adapting stimulus was similarly associated with temporary elevation of membrane potential, initial lowering of the saturation potential, and shift of the voltage-intensity curve. Under all conditions of adaptation studied, small amplitude responses were linear with light intensity. Further, there was no unique relation between sensitivity and membrane potential suggesting that receptor sensitivity is controlled at least in part by a step of visual transduction preceding the generation of membrane voltage change.


Repetitive spikes in photoreceptor axons of the scorpion eye. Invertebrate eye structure and tetrodotoxin. A graded depolarization accompanied by nerve impulses can be recorded from the scorpion lateral and median eyes in response to light. Electron microscopy shows that axons forming the optic nerve arise directly from the photoreceptors. Thus, photoreceptors must respond both by the generation of a slow receptor potential and the initiation of spikes. The latency of the first spike, and the maximal and mean discharge frequencies were a function of light intensity. Spikes were abolished by tetrodotoxin. Repetitive firing to light therefore appears to be a normal response of scorpion photoreceptors and is the result of regenerative Na influx in the cell membrane.


Selective modification of sodium channel gating in lobster axons by 2, 4, 6-trinitrophenol: Evidence for two inactivation mechanisms. Trinitrophernol (TNP) selectively alters the sodium conductance system of lobster giant axons as measured in current clamp and voltage clamp experiments using the double sucrose gap technique. TNP has no measurable effect on potassium currents but reversibly prolongs the time-course of sodium currents during maintained depolarizations over the full voltage range of observable currents. Action potential durations are increased also. Tm of the Hodgkin-Huxley model is not markedly altered during activation of the sodium conductance but is prolonged during removal of activation by repolarization, as observed in sodium tail experiments. The sodium inactivation versus voltage curve is shifted in the hyperpolarizing direction as is the inactivation time constant curve, measured with conditioning voltage steps. This shift speeds the kinetics of inactivation over part of the same voltage range in which sodium currents are prolonged, a contradiction incompatible with the Hodgkin-Huxley model. These results are interpreted as support for a hypothesis of two inactivation processes, one proceeding directly from the resting state and the other coupled to the active state of sodium conductance.


Local adaptation in the ventral photoreceptors of Limulus. Local adaptation was demonstrated in the ventral photoreceptors of Lumulus using either flashes or continuous illumination. Spots of light locally desensitized the region of the photoreceptor on which they were focused. In dark-adapted photoreceptors where "quantum bumps" were clearly discernible, local adaptation of the quantum bumps was observed. Local adaptation could induce differences of threshold of 1 decade over distances of 50-80 mum. With continuous local illumination these gradients could be maintained from 2 s to 30 min. In addition, the decrease in time scale associated with light adaptation was also found to be localized to the region of illumination.


Factors influencing the formation and stability of D-glucoside 3-dehydrogenase activity in cultures of Agrobacterium tumefaciens. D-glucoside 3-dehydrogenase specific activity in Agrobacterium tumefaciens was maximal towards the end of the exponential growth phase of batch cultures; over 90% of the activity disappeared within the next 15 h. Manganese ions, although essential for growth of the organism, strongly repressed D-glucoside 3-dehydrogenase synthesis in sucrose medium but had little effect when the carbon source was methyl alpha-D-glucoside. D-Glucoside 3-dehydrogenase activity increased linearly with increasing specific growth rate in chemostat cultures limited by carbon, nitrogen, phosphate or manganese when methyl alpha-D-glucoside was the carbon source. High enzyme activity was found with sucrose as carbon source only when the growth medium was manganese-limited. D-Glucoside 3-dehydrogenase activity disappeared from A. tumefaciens incubated in carbon- and nitrogen-free medium or in nitrogen-free medium containing succinate, but on continued incubation the activity returned and was then stable. The recovery of activity could be prevented by chloramphenicol or erythromycin. Bacteria containing the recovered dehydrogenase activity could not convert sucrose to 3-ketosucrose when oxygen acted as the terminal electron acceptor, but produced 3-ketosucrose at the normal rate in the presence of ferricyanide. D-Glucoside 3-dehydrogenase activity disappeared irreversibly from bacteria incubated in nitrogen-free medium containing sucrose. Loss of activity followed first order kinetics in bacteria taken from nitrogen-, phosphate- or manganese-limited chemostat steady states; an accelerating rate of decay occurred in cells grown under carbon-limitation. 8-Hydroxyquinoline, chloramphenicol, erythromycin, 2,4-dinitrophenol and manganese ions could reduce the rate of decay.


Molar growth yields, respiration and cytochrome patterns of Beneckea natriegens when grown at different medium dissolved-oxygen tensions. The effect of medium dissolved-oxygen tension on the molar growth yield, respiration and cytochrome content of Beneckea natriegens in chemostat culture (D 0-37 H-1) was examined. The molar growth yield (Y), the specific rate of oxygen (qo2) and glucose consumption, and the specific rate of carbon dioxide evolution were independent of the dissolved-oxygen tension above a critical value (greatest than 2 mmHg). However, the potential respiration rate increased with reduction in the dissolved-oxygen tension at values of the dissolved-oxygen tension well above the critical value. Changes in the cytochrome content occurred at dissolved-oxygen tensions well above the critical value. An increase in cytochrome c relative to cytochrome b was observed as the dissolved-oxygen tension was decreased. Reduction of the dissolved-oxygen tension to less than I mmHg caused a switch to fermentative metabolism shown by the apparent rise in YO2 and decrease in the molar growth yield from glucose. At this point the potential respiration rate (qO2) increased to its highest value, while the cytochrome pattern reverted to that observed at dissolved-oxygen tensions above 96 mmHg. There appeared to be no correlation between cytochrome content, potential qO2, in situ qO2, and cyanide sensitivity of the organism at various dissolved-oxygen tensions.


Keto acid metabolism in Desulfovibrio.

Keto acid metabolism in Desulfovibrio. Four strains of Desulfovibrio each excreted pyruvate to a constant level during growth; it was re-absorbed when the substrate (lactate) was exhausted. Malate, succinate, fumarate and malonate also accumulated during growth. One of the strains (Hildenborough) excreted alpha-ketoglutarate as well as pyruvate when incubated in nitrogen-free medium; the former was re-absorbed on addition of NH4Cl. In a low-lactate nitrogen-free medium, strain Hildenborough rapidly re-absorbed the pyruvate initially excreted, but did not re-absorb the alpha-ketoglutarate. Arsenite (I mM) prevented the accumulation of alpha-ketoglutarate; I mM-malonate did not affect the accumulation of keto acids. Isocitrate dehydrogenase activity (NAD-specific) in all strains was lower than NADP-specific glutamate dehydrogenase activity. Alpha-Ketoglutarate dehydrogenase could not be detected in any strain. NADPH oxidase activity was demonstrated. This and previous work indicate that a tricarboxylic acid pathway from citrate to alpha-ketoglutarate exists in Desulfovibrio spp., and that succinate can be synthesized via malate and fumarate; however, an intact tricarboxylic acid cycle is evidently not present. The findings are compared with observations on biosynthetic pathways in clostridia, obligate lithotrophs, phototrophs, and methylotrophs, and various facultative bacteria.


Potassium fluxes in Neocosmospora vasinfecta. The unidirectional K+ fluxes across the mycelial surface of Neocosmospora vasinfecta were determined using 42K. Influx was mediated by at least two kinetically distinct systems, one having an apparent Km of 6-5 mu-equiv. K+/l and the other of about 1-0 m-equiv. K+/l. The VMAX for both systems was in the range 18 to 22 mu-equiv. K+/100 mg mycelial dry matter/h (1-0 to 1-2 m-equiv. K+/l cell-water/min). Influx was strongly inhibited by 2,4-dinitrophenol, sodium azide, sodium arsenate and anaerobiosis. K+ efflux was dependent on the external K+ concentration and ranged from 3 to 10% of mycelial K+/h. The maximum efflux rate was always considerably less than the initial influx rate for the K+ concentrations examined. During incubation in dilute KCl solutions, K+ influx decreased to a value approaching the K+ efflux rate. It is considered that equilibrium with external K+ is attained primarily by the regulation of K+ influx, and that this may be the principal mechanism controlling cytoplasmic K+ levels. Adsorption of K+ was also observed throughout the K+ concentration range examined and can be attributed to two distinct K+-binding entities at the mycelial surface, half-saturating at approximately O-I mM-and 4-4 mM-KCl respectively.


A plasmid involved in chloramphenicol production in Streptomyces venezuelae: evidence from genetic mapping. To test the hypothesis that chloramphenicol production in Streptomyces venezuelae depends on the presence of a plasmid, mapping analysis was carried out by using eight markers in addition to chloramphenicol production and melanoid pigment formation. The sequence of the eight markers was determined on a circular linkage map as follows: -his-ade-str-leu-lys-met-ilv-pro-(his-). This sequence resulted in the frequency of quadruple crossover (q.c.o.) recombinants having the lowest value, 3-2 to 4-9%. However, the character of chloramphenicol non-production, which was obtained by incubating mycelia with acriflavin, was not required to explain the results. From these results and other tests, it is concluded that chloramphenicol production is controlled by a plasmid. This plasmid appeared to be non-transferable in conjugation.


Self-parental alientation and locus of control in delinquent girls. Social maladjustment has been related to an external locus of control orientation. It was hypothesized, therefore, that delinquent females would be more external than a control sample. Further, since alienation from others is also associated with maladjustment, it was expected that the delinquents would also prefer greater distance from others. These hypotheses were confirmed with discussion being in terms of implication for rehabilitation of delinquents.


Recognition of inverted photographs of faces by children and adults. Inverted black-white photographs of the faces of highly familiar peers (classmates, fraternity brothers, etc.) were presented to 350 Ss ranging from 3 to 20 years of age. In an untimed test session, S tried to identify the person in the inverted photograph. Success in this task was positively correlated with age up to approximately 14 years, but performance deteriorated after this age; college-age Ss and preschool Ss' performances were approximately equal. This finding contrasts with the current view that the effects of disorientation on perception becomes less potent with age. A cognitive explanation is offered for the early rise in the performance curve; the subsequent reduction in level of performance is attributed to rigidity of the perceptual mechanism as a function of overlearning of a mono-oriented configuration.


The relationship between perceptual egocentrism and field-dependence in early childhood. Fifty-three kindergarten children were administered tests of inductive reasoning and field-dependence and a series of perceptual egocentrism tasks. The principal expectation of the study, that field-dependence would relate positively to perceptual egocentrism, was confirmed. Perceptual egocentrism was found to be independent of induction for the age range studied; however the relatively low correlations obtained between the field-dependence measures and their common relationship with induction led to the questioning of the validity of the field-dependence construct in early childhood.


Affective relationship, locus of control, and imitative behavior. The effects of the affective relationship between the model and the observer and locus of control on imitative behavior were investigated by exposing 28 boys to their most liked peer and least liked peer on a simple imitative task. Locus of control was determined by the Nowicki-Strickland (6) Locus of Control Scale for Children. More imitative responses were exhibited to the most liked peer than to the least liked peer, and a positive correlation between number of imitative responses and internal locus of control was found. Results were interpreted as indicating the need to control the affective relationship between the model and observer and as supporting Bandura (1) in the imitative behavior is primarily under self-reinforcement control.


Sex differences in the activity level of preschool children as a possible precursor of hyperactivity. The major objective of the present study was to determine whether or not preschool age boys had a higher activity level than girls. While it is a widely known fact that more boys than girls are referred to specialists for being hyperactive, the question of whether a sex-linked pattern of hyperactivity is observable in the general population remains unanswered. To investigate this issue, the activity levels of preschool children from a "normal" sample were measured randomly by an observation technique as they took part in a nursery school program. The results not only indicated that boys were more active than girls, but that the boy's behavioral activity was manifested in patterns that were similar in nature to those often included as part of the various definitions of hyperactivity. The implication of the results were discussed, and future research needs were delineated.


Drive and reward in an acquired-fear paradigm. Either five minutes or 48 hours following classical fear conditioning (CS paired with inescapable shock) four groups of rats were trained to jump a hurdle from the conditioning box into an adjoining box. During hurdle jumping one-half of the Ss in each delay condition had the CS present in both boxes, while for the remaining Ss it was absent (NCS). CS Ss performed better than NCSSs (p less than or equal to .005) and five-minute Ss performed better than 48-hour Ss (p less than or equal to .001). The results suggest (a) that there is a need for a drive concept in behavior theory, (b) that drive and reward combine additively, and (c) that there is a loss over 48 hours of fear conditioned to apparatus cues, but not of fear conditioned to the CS.


Cognitive and nonverbal perceptual processing in dyslexics. A sample of 33 dyslexic and 33 control children were compared on tasks involving visual matching with spatial transformation (VMST), tactual serial matching (TSM), visual sequential memory (VSM), and auditory sequential memory (ASM). Contrary to expectation, the dyslexics performed at the same level as controls on VMST. This result was not explicable as a floor or ceiling effect and was considered evidence that dyslexics do not suffer impairment in visual spatial transformation ability per se. Dyslexics were not significantly different on TSM, but were inferior to controls on VSM and ASM.


Measurements of a single galvanic skin response based upon its rate topography. Methods for the identification of the points of transition among three states (nonresponse, response, and recovery) of a single GSR are described. It is proposed that the topography of the rate of change of the skin resistance provides a basis for both the identification of the initiation and termination of a simple GSR and the estimation of the GSR magnitude. Data selected from a study in differential GSR conditioning suggest, for the present purposes, the desirability of a trichotomous classification of GSRs depending upon the response rates which typify the nonresponse state of a particular S under a particular set of conditions. Comparisons among estimates of the time of GSR initiation and termination and of the GSR magnitude by three different methods are made for each of the three proposed method of estimating the GSR magnitude, latency, and recruitment--may increasingly misestimate their values as the preresponse or nonresponse rate departs from zero and as the duration of the response increases.


Apparent reversals seen by three types of perceiver of the Ames trapezoid illusion. Three groups of subjects (three right-handed, right-eye-dominant men in each group), differing in the overall extent to which they perceived illusory oscillation with Ames's rotating trapezoidal window, were tested for their susceptibility to parameters of the illusion previously shown relevant in unselected samples. Differential response of these three perceiver groups to variations in viewing distance and target form was demonstrated; but target pattern produced no significant effects. It was concluded that consideration should be given to the distribution of these perceiver "types" in samples taken to study illusions of oscillatory motion.


An auditory analog of the Stroop Test.

An auditory analog of the Stroop Test. With use of a tape-recorded auditory method of stimulus presentation, 112 undergraduates were required to identify the tonal concepts of high and low when these concepts were symbolically coded both in terms of high and low pitches of voice and by the spoken words "high" and "low." Trials consisted of 44-item sequential identifications of the concepts. Results were consistent with those in other realms. With use of a speeded accuracy criterion, findings were that Ss could identify the concepts faster from word symbols than from pitch symbols and faster from the two types of symbol information correctly matched than from either component type alone. More interference was produced when half of the symbols on a trial were mismatched and the other half matched than when all of the symbols were mismatched. Interference effects in both directions were found, but there was a larger interference of words on pitch than of pitch on words.


A clinical application of subliminal psychodynamic activation. On the stimulation of symbiotic fantasies as an adjunct in the treatment of hospitalized schizophrenics. This study attempted to utilize the subliminal psychodynamic activation method as an aid in the treatment of hospitalized schizophrenics. More specifically, we inbestigated whether the subliminal activation of a fantasy of symbiotic gratification would produce an increment in the degree of improvement that schizophrenics manifested as a result of hospitalization. Forty male patients were seen individually for three weekly sessions over a 6-week period for a fantasy expression task carried out by a psychology graduate student. Both at the beginning and at the end of each session and whenever during the session anxiety was in evidence, the patient was exposed to subliminal stimulation. The patients were divided into two groups equated for intelligence, pathology level, and other pertinent variables. For one group, the tachistoscopically presented stimulus consisted of MOMMY AND I ARE ONE, a verbal message which, in several prior studies, produced a significant reduction in ego impairment within a laboratory session. The other group served as a control, and their stimulus was PEOPLE ARE WALKING. The subjects in each group were subdivided in order to investigate the effects of two other interventions in addition to the subliminal symbiotic stimulation. One of these was aggressive expression consisting of an attempt to elicit specifically aggressive fantasies in the fantasy expression task. The other was self-focuing, designed to strengthen self-boundaries. All patients were blindly assessed for seven measures of ego impairment before and after the intervention period and for the number of rehospitalizations over a 9-month follow-up period. Of the three types of interventions impairment measures. For on of the variables, the symbiotic group showed significantly more improvement than the control group, while for two others the results approached significance. In addition, on an overall measure of ego impairment, there was significantly mor improvement for the symbiotic group than for the control patients.


Cerebral localization and the psi syndrome. On trying to correlate the psi syndrome with a neural substrate, it is necessary to distinguish between spontaneous, "macropsychological" and experimenta, "micropsychological" incidents of the card-calling type. On comparing telepathic drawings with drawings made by brain-injured patients suffering from optical agnosia, the identical tendency to distortion and disorganization of the target materials can be discerned. It suggests that the telepathic subject is "agnostic" in relation to psi impressions, and that his central processing takes place in the right rather than the left hemisphere. The capricious nature of extrasensory perception (ESP) responses of the card-calling type points to fluctuations in the reticular and limbic midbrain system in warding off the intrusion into awareness are subliminal or irrelevant perceptions from the outside world.


Hypohedonia in schizophrenia.

Hypohedonia in schizophrenia. The affective disorder in schizophrenia is an important manifestation of the schizophrenic illness. Such clinical features of joylessness, interpersonal aversion, and affective blunting have been considered by Rado and Meehl to represent a neurophysiological deficit in pleasure capacity which they termed anhedonia, but is more aptly characterized by the term hypohedonia. A free-recall task employing 24 affectively laden words presented in random order over nine trials was given to a carefully selected group of nonpsychotic hospitalized schizophrenics, hospitalized nonschizophrenics, and normals. The results of the study demonstrate that normals remember pleasant words to a significantly greater extent than upleasant words. This Pollyanna tendency or the tendency to utilize pleasant words over upleasant words has been described by Osgood as a stable cross-cultural phenomenon. By contrast, the schizophrenics show a significantly lower recall of pleasant words when compared with normals, although they remember unpleasant words to a comparable degree as normals. These findings provide experimental support for the hypohedonia hypothesis in schizophrenia. The nonshcizophrenic patients recall pleasant and unpleasant words to a significantly greater degree than neutral words. They are thus affectively governed in the free-recall task and seem equally sensitized to both pleasant and unpleasant affect in their mnemonic processing.


Depressive symptoms and the glucose tolerance test and insulin tolerance test. Patients with severe depression have been observed previously to have a reduced rate of glucose utilization accompanied by elevated serum insulin levels during the intravenous glucose tolerance test (GTT) and a reduced metabolic responsiveness to exogenous insulin during the insulin tolerance test (ITT). These abnormalities were less obvious in patients with neurotic depression as compared to patients with severe endogenous or "psychotic" depression. To evaluate more fully the relationships of depressive symptomatology to these metabolic abnormalities, patients were rated by nursing staff on a short clinical rating scale (SCRS) and by a psychiatrist on the Brief Psychiatric Rating Scale (BPRS) at the time the metabolic measurements were made. Patients were given the GTT and the ITT once when they were off medication and symptomatic and then again 3 to 8 weeks later when symptoms had decreased following amitriptyline treatment. Fasting serum-free fatty acid levels (FFA) had a significant positive correlation to rating of anxiety. Fasting levels of glucose, insulin, and human growth hormone (HGH) did not significantly correlate to any of the ratings. A decreased rate of glucose utilization (k) correlated significantly with increased ratings of motor retardation, emotional withdrawal, and blunt affects, but not to other depressive symptoms. The responsiveness of FFA and HGH during the ITT was significantly less in patients with more severe symptomatology; responsiveness improved when those patients improved. Neither incorrelated to the ratings. These data suggest that within the sydrome of depression, increased FFA is realated to anxiety, decreased glucose utilization is related to motor retardation, emotional withdrawal, and blunt affect, and that decreased FFA and HGH responsiveness to insulin is a nonspecific correlate of the general depressive syndrome.


Experimental necrosis and arrest of proliferation of Schwann cells by cytosine arabinoside. In developing rat cervical sympathetic trunks, Schwann cells proliferate intensely during the first week after birth but axonal populations do not increase. Thus, experimental inhibition of DNA synthesis should affect Schwann cells and spare axons whose cell bodies are not dividing. The present investigation was aimed at determining the effects of an inhibitor of DNA synthesis-cytosine arabinoside (ara-C)--on axons and Schwann cells in developing nerves. Ara-C (60 mg kg(-1) body weight) was injected subcutaneously to newborn rats every six hours for 36 hours. At intervals from 2--4 days of age, animals were given tritiated thymidine (4 muCi per gram body weight) to label Schwann cells in synthesis phase. One hour later rats were killed by systemic perfusion of phosphate buffered glutaraldehyde. Cervical sympathetic trunks (CST's) and sciatic nerves were removed and processed for radioautography and electron microscopy (EM). Labelled and unlabelled Schwann cell nuclei were counted to determine the labelling index (LI%) for each nerve. By the end of ara-C treatment there was almost complete absence of labelling but LI's rose sharply 24 hours after discontinuing ara-C. By EM axons appeared normal; Schwann cells, however, showed prominent nuclear and cytoplasmic changes consisting of nuclear degeneration, dilatation of rough endoplasmic reticulum and increased cytoplasmic density. Ara-C, by suppressing proliferation and causing necrosis of Schwann cells but sparing axons, results in a developmental alteration of axon-Schwann cell relationships. It is suggested that the pathogenetic mechanism involves an inbalance in DNA/RNA synthesis metabolism.


Synaptic membrane structure in Torpedo electric organ. The innervated and noninnervated membranes of Torpedo electrocytes have been examined by electron microscopy of thin-sectioned and freeze-fractured specimens. The ventral innervated membrane is approximately 120 A thick and is characterized by an unusually broad outer dense lamina (approximately 60 A) in which a granular substructure can be resolved. The granules are approximately 70 A in diameter and are spaced irregularly. The same membrane specialization was noted in a previous study of amphibian myoneural junctions, and it was proposed then that the granular elements represent ACh receptor molecules. The morphologically equivalent structures presumably have the same significance in the Torpedo electric organ. However, in this case the specialized membrane covers the entire innervated surface, leading to the conclusion that high concentrations of receptors occur normally in extrajunctional as well as post-junctional regions of the innervated membrane of the electrocyte. In replicas of freeze-fractured specimens, the A face of this membrane is covered with large particles having the same distribution and approximate concentration as the granules visible in thin sections, indicating that the granules visible at the outer surface of the membrane extend at least into the hydrophobic middle layer of the membrane. The cytoplasmic surface of this membrane has an amorphous coating into which 'decorated' cytoplasmic filaments insert. Synaptic vesicle and axon terminal membranes also contain granules visible in thin sections but with a much sparser distribution. These probably correspond to the intramembranous particles seen in freeze-fractured specimens. Vesicles are occasionally attached to the axolemma by thin linear strands.


Electron microscopy of synaptic structures in olfactory cortex of early postnatal rats. Layer 1 of the rat olfactory cortex has been studied with the electron microscope at birth and at several consecutive postnatal days up to 14 days of age. Special attention was directed towards synaptic structures and axons of the lateral olfactory tract (LOT). Numerous mature synapses are seen at birth and estimates were made of their subsequent increase in number. In addition, immature synapses are seen and mature postsynaptic sites occur with atypical, partial, multiple or no contact. The findings suggest: (1) considerable prenatal synaptogenesis in contrast to other cortical systems; (2) the maturation of the postsynaptic site may precede that of the presynaptic contact and vesicle accumulation; (3) there may be competition by more than one process for one postsynaptic specialization; (4) the non-innervated sites may result from deafferentation caused by prenatal cell death, although no degeneration was seen, and the atypical contacts may be a stage in the reinnervation of these sites; (5) the LOT develops in parallel with the synaptic neuropil and (6) by 14 days of age the area closely resembles adult tissue.


The "future trends" in neurosurgery are here. The 1975 AANS presidential address. The President of The American Association of Neurological Surgeons discusses the three major problems of his year in office -- medical education, neurosurgical manpower, and professional medical liability -- and the attempts that are being made to solve them.


Cerebral hemorrhage following heart surgery. The authors report a study of the problem of intracranial hemorrhage in 16 children following cardiac surgery, four studied clinically, and 12 by postmortem pathological review. Eleven children sustained subdural hematomas of varying sizes, one had a massive extradural clot, and four had intracerebral clots. The pre-, intra-, and postoperative data of these 16 patients are presented, but the specific factors causing the intracranial hemorrhage remain unexplained. The neurological course was similar to that of patients with an intracranial space-occupying lesion, and fundamental neurosurgical management principles for the treatment of this potentially reversible process should be observed.