Lactate dehydrogenase: a polymorphism of Anoplarchus purpurescens: geographic variation in central California.

Previous studies on the muscle lactate dehydrogenase polymorphism of the stichaeid fish Anoplarchus purpurescens in Puget Sound have demonstrated the existence of a clinal pattern of allele frequency. The LDH-A' allele was observed to increase toward the south, with several environmental factors showing correlation with this change in allele frequency. Populations from California were sampled in the present study to determine whether or not gene frequencies along an independent transect near the southern end of the species distribution are consistent with the interpretation that the geographic patterns reflect the influence of environmental factors. In California, the LDH-A' allele decreases in frequency to the south. This observation necessitates the reevaluation of possible environmental influences on the LDH polymorphism. Only one of several proposed hypotheses is completely consistent with the geographic patterns observed along both the Washington and California transects. However, the genetic differentiation along the California coast cannot be unequivically ascribed to the influence of environmental factors; current morphological data indicate the possibility of historical influences on the population genetic structure of California A. purpurescens.


[An experimental study on various internal fixations in fracture of a long bone (author's transl)].

In the operative treatment of a long bone fracture, the most important point is to secure the bone healing and to strengthen the bone after removal of internal fixation materials. In this regards, the author has analyzed the mechanical strength of various internal fixation methods (a plate, a medullary nail, screws and encircling wires) on the bone by using acrylics models. Experimental studies of their influences on the bone have also been performed especially investigating the decrease in the bone strength in rabbits. All of internal fixation materials are made of 316L stainless steel. Recently, there has been a tendency to use larger materials for internal fixations such as an AO compression plate or a Küntscher type medullary nail. However, it was found that the rigid plate fixation greatly affects the bone strength. A medullary nail produced less impairment to the bone. But this method is restricted in its application because of the weak fixability of the torsional load. On the other hand, the internal fixations with screws or encircling wires are weaker than the other methods especially against the bending load. Therefore the commencement of postoperative treatment will be delayed. But, these two methods have little influence on the bone during fixation.


[Effect of D-penicillamine on vitamine B6 and collagen metabolism (author's transl)].

Although D-Penicillamine (D-PeA) administration is getting popular in the treatment of rheumatoid arthritis (RA), the mechanism by which D-PeA produced therapeutic effect has not been fully elucidated. D-PeA had been shown to exert an antivitamine B6 effect. However, it has not been precisely confirmed if clinical dose of D-PeA induces vitamine B6 (VB6) deficiency. In order to clarify these questions, biochemical analyses of bone and skin collagens and determination of VB6 content in soft tissues have been performed in the rats administrated therapeutic dose of D-PeA. VB6 deficiency was not observed in the brain and skin from rats fed on normal diet containing D-PeA (13.0--33.5 mg/kg wt). There were no significant changes in the stability of collagen from bone and skin. On the other hand, significant VB6 deficiency and reduced stability of collagen were observed in rats fed on VB6 deficient diet containing the same amount of D-PeA. Aldehyde formation of collagen molecule and cross-link formation of collagen were also found to be suppressed. The same results were obtained from analyses in rats fed on VB6 deficient diet without D-PeA administration. These data indicate that D-PeA is not capable of producing VB6 deficiency in the dosage employed in patients. However, in the treatment for patients who are not taking enough nutrition, the possibility of VB6 deficiency can not be neglected. Once VB6 deficiency is induced by D-PeA administration, severe connective tissue disorder may be produced, since VB6 is required for enzymic activity of lysyl oxidase. It is unlikely that the therapeutic effects of D-PeA in the treatment of RA are produced the the disturbance of collagen cross-link formation as discussed before. Immunologic reactions of D-PeA may play more important role in the improvement of clinical symptoms of this disease.


[Biochemical studies on collagen and connectin from human skeletal muscle: age-related changes in the properties of elasticity (author's transl)].

Collagen and connectin, an intracellular elastic protein, play important roles in structural maintenance and mechanical continuity of skeletal muscle. The author has investigated age-related changes in these proteins from human skeletal muscles ranged from 6 lunar month to 79 years of age. The total content of collagen in skeletal muscle at 6 lunar month was 1.7% of wet weight of the tissue. This value was found to decrease to 0.8% by 5 years of age, and no significant change in this value was observed after 5 years of age. Collagen in skeletal muscle tissue was found to consist of 80% of Type I collagen, 19% of Type III collagen and 1% of Type IV collagen. The proportion of these genetically distinct types of collagen was constant throughout the whole life-span. The amount of soluble collagen and formation of reducible cross-links of collagen were found to decrease with age. Although the content of connection in skeletal muscle from human embryo was low, 0.9-1.1% of wet weight of the tissue, it gradually increased to 2.9% at 79 years of age. Following NaB3H4 reduction, connectin was found to contain the reducible cross-links derived from lysine- and hydroxylysine-aldehydes; two of them were identified as lysinonorleucine and histidino-hydroxymerodesmosine, and additional three reducible compounds were eluted between elution positions of dihydroxylysinonorleucine and lysinonorleucine from ion exchange chromatography. These findings strongly indicate that connectin and connective tissue proteins, collagen and elastin, share common features of cross-linking. Furthermore, these reducible cross-links were found to decrease with age. Thus, maturations of both connectin and collagen are apparently due to qualitative changes in their reducible cross-links.


[The effect of calcitonin on contractile function of skeletal muscles (author's transl)].

The analgesic effect of calcitonin in osteoporosis has been considered to originate from its actions on bone metabolism. However, the author assumed a possible presence of other mechanism, since the analgesic effect of calcitonin manifests in an extremely early phase in which an increase in bone mass is hardly conceivable. Namely, the author postulated that its analgesic effect is due to its actions on body trunk muscles, and investigated experimentally the effect of calcitonin on skeletal muscles. The following results were obtained. 1) Recovery from decreased twitch contraction of M. triceps surae was shown in vivo in rats treated with calcitonin, with dose-response relationship. 2) Calcitonin exerted no effect on partial blockade by dTc, in neuro-muscular junction. Therefore, the neuro-muscular junction is probably not the site of the actions of calcitonin. 3. In an in vitro study on isolated M. soleus, the decrease contraction was recovered after treatment with calcitonin. A correlation was found between this recovery and the dose of calcitonin. 4) In the calcitonin treated muscle, a pronounced persistence of normal contraction was demonstrated in contrast to the control group. 5) Calcitonin appears to facilitate Ca release through exerting actions on Ca transport system in the sarcoplasmic reticulum. From these results, it was shown that calcitonin appears to possess an activity to elevate contractile ability of skeletal muscles. This activity is considered to be derived from its effect on sarcoplasmic reticulum. This activity of calcitonin on contractile function of skeletal muscles indicates the presence of a mechanism relating to skeletal muscles in the analgesic effect on low back pain in osteoporosis.


[The effect of hypophysectomy on the epiphyseal cartilage plate of the rat tibia--electron microscopy and histochemistry of the epiphyseal proliferative zone (author's transl)].

It is a well-known fact that longitudinal bone growth is affected especially by hypophysis among other various endocrine organs. Using young rats, changes in body weight and in length of the tibia were studied after removal of hypophysis, and alterations occurring in the proximal epiphyseal cartilage plate of the tibia playing an important role in longitudinal bone growth were examined under light and electron microscopes, with special emphasis on the proliferative zone. Alterations of ATP-ase activity of ruthenium red affinity were also examined electron microscopically. Further, quantitative analyses of the alterations of cell organelles were performed using low power electron micrographs. 1) Following hypophysectomy, immediate suppression in weight gain occured, and little or no gain was seen from 14 to 28 days after removal of the gland with plateau in body weight. Longitudinal bone growth of tibia was also suppressed, and little or no growth was seen from the 14th day afterward as was the case for body weight. 2) Changes revealed by light microscopic examination included reduced width of epiphyseal cartilage plate, decreased number and disturbed arrangement of chondrocytes, rapid transition from proliferative zone to degenerative zone, and disturbed formation of the subchondral trabecula. 3) Electron microscopic examination revealed poor development of rough surfaced endoplasmic reticulum in the cell of proliferative zone, Golgi apparatus ocnsisting of lamellae and a relatively large numbers of vesicles and pronounced decrease in vacuoles. In addition, accumulation of lipid droplets and glycogen granules were seen together with mitochondria exhibited swelling and elevation of electron density in their matrices. ATP-ase activity was decreased. In the cartilage matrix of the proliferative zone, collagen fibrils and ruthenium red positive granules were decreased in number. 4) Rough surfaced endoplasmic reticulum, Golgi apparatus, and cytoplasmic vacuoles were treated quantitatively by dividing the proliferative zone into two parts of upper and lower layers. The data showed marked decrease in the every item examined after hypophysectomy. 5) These results indicate that hypophysectomy causes a decrease in intracellular metabolism of chondrocytes in the proliferative zone with a reduced function of matrix formation. The suppression of longitudinal bone growth after hypophysectomy appears to occur under an intimate correlation with a decrease in matrix formation by the chondrocytes of proliferative zone and inhibition of proliferation of the cells in this zone.


Clinical results of the triangular external fixation device in serious lesions of the lower extremity.

Several types of external fixation devices exist among which those of Judet, Hoffmann, Wagner and Müller can be picked out, each of which has definite applications. Confronted with difficulty in the use and the defect of mechanical rigidity, we have been led to design a new type of the triangular external fixation device. As open fractures of the limbs in stage II and IV of Duparc and Cauchoix, and pseudoarthrosis infected need a considerable stability in addition to careful surgical treatment, so after a comparative mechanical study, and after codifying the most rigid installation, we have used it on several traffic accident victims.


Cell cycle synchronization of the mouse S-180 tumor following alternating period of hydroxyurea-blockade and release.

An attempt at synchronization was carried out by intravenous administration of hydroxyurea (HU) into mice bearing the S-180 solid tumor. Following HU blockade for 6.0 hrs equal to (Tc-Ts) period, 65% of all tumor cells were in S-phase. After 2 cycle blockade; HU blockade for 6 hrs, released for 7.5 hrs and reestablished for 6 hrs, 84% of tumor cells were gathered in S-phase with a sharp peak at G1-S junction. Appropriate cycles of HU infusion and release will synchronize significant increments of S-phase or mitotic cells in the S-180 tumor during predictable time intervals.


Crystallographic study of rhinoliths.

Five nasal stones were extracted from five patients. The etiology and clinical picture have been discussed. The stones were analysed by a crystallographic method, using an X-ray diffraction technique. Their composition was identified as calcium phosphate.


Goldenhar's syndrome associated with anomalous internal auditory meatus.

A case of Goldenhar's syndrome associated with fifth, seventh, and eighth nerve involvement is described. Tomographic examination of the temporal bones showed evidence of an abnormal internal auditory meatus. Otoneurological examination suggested that involvement of the seventh and eighth nerves was closely related to the abnormality in the internal auditory meatus.


Congenital choanal atresia and nerve deafness.

Four cases of bilateral congenital choanal atresia are presented. Three of them (75 per cent) were shown by Electric Response Audiometry (ERA) tests to have, in addition, congenital nerve deafness; and two had other congenital anomalies. Thus, congenital nerve deafness should be considered as a possible congenital anomaly associated with choanal atresia. Early diagnosis and treatment of congenital choanal atresia can prevent death from asphyxia during the neonatal period, but after surgical correction of the atresia the possible existence of additional anomalies has to be determined and treated. By the use of electric response audiometry we are able to detect sensorineural hearing loss during the neonatal period and can plan the rehabilitation of deaf infants.


Surgical findings and results of stapedectomy in patients with osteogenesis imperfecta.

Nine patients with osteogenesis imperfecta tarda and stapedial fixation (12 ears) are presented. Surgical findings as well as the immediate and long-term results of stapedectomy are described and compared with the results of previous authors. We found firmly fixed footplates in all 12 ears. Only 2 ears had thick and soft footplates. In 10 ears the stapes crura were abnormally slender and brittle, but only 1 had fractured. In 4 ears a troublesome bleeding tendency occurred during the operation. Both the immediate and the long-term hearing results were in general satisfactory.


Extramedullary plasmacytoma.

Extramedullary plasmacytomas of the head and neck are very uncommon tumours. Three rare cases of extramedullary plasmacytoma are presented-one each in the nose, larynx and maxilla.


Effect of L-thyroxine treatment on the levels of various hepatic metabolites in rats.

The effects of L-thyroxine (T4) treatment upon hepatic metabolism of control and T4 treated rats was studied. Livers were excised and freeze-clamped rapidly. The levels of adenine nucleotides and glycolytic and TCA cycle metabolites were determined. The redox ratios of free pyridine nucleotides of cytoplasm and mitochondria were calculated from selected substrate concentrations. T4 treatment resulted in lower phosphorylation states and caused reduction in ratios of cytoplasmic NAD and NADP and reduction in the ratio of mitochondrial NAD. T4 treatment changed the redox state of NADP to a greater degree than that of NAD, implying disequilibrium of the transhydrogenase reaction. Changes in glycolytic intermediates were minimal and did not indicate significant "crossover points" of enzymatic change. The most striking changes in metabolites caused by T4 were: increase in citrate, increase in ketones, and decrease in alpha-ketoglutarate. The metabolic consequences of changes in metabolites and of redox states of NAD and NADP were discussed. The equilibrium of reactions interrelating the phosphorylation potential and redox state of cytoplasmic NAD was not altered by T4 treatment. Reduction of cytoplasmic and mitochondrial NAD suggests a greater effect of T4 upon the transport of reducing equivalents into mitochondria than upon enhancement of oxidative capacity.


Effects of outboard motor exhaust emissions on goldfish (Carassius auratus).

Goldfish (Carassius auratus) were exposed to outboard exhaust products in water or to toluene (a constituent of outboard motor exhaust water) via a continuous flow bioassay dosing apparatus. Various physiologic and pathologic changes were noted. In the blood a consistent decrease (p less than 0.05) in the partial pressure of oxygen, a significant increase (p less than 0.05) in the partial pressures of carbon dioxide, and significant decreases (p less than 0.05) in pH and oxygen saturation were found in many of the blood gas experiments. Laboratory experiments also indicated that these fish are capable of metabolizing toluene to hippuric acid (p less than 0.05). Exposure up to 30 days to these exhaust products produced gross and microscopic lesions in the high-, intermediate-, and low-dose fish. Grossly, livers were smaller and pale; intestines were empty of ingesta and feces; and gills were coated excessively with mucus. Microscopically, the livers of the exposed fish had a decreased cytoplasmic:nuclear ratio, gill filaments were fused, and some kidneys had tubular vacuolization.


Evaluation of dimethoate (Cygon 4E) for teratogenic activity in the cat.

A commercial formulation (Cygon 4E), containing 47.3 percent dimethoate and 52.7 percent of unknown ingredients, was administered orally in single daily doses of time-mated cats between the 14th and 22nd day of pregnancy. The cats were necropsied on the 43rd day of pregnancy. Fetal values for survival, body weight, and skeletal and visceral anomalies were obtained following conventional methods. The highest dose, 12 mg/kg, was associated with polydactyl in eight of the 39 fetuses, whereas the 6 and 3 mg/kg doses produced no evidence of teratogenicity or embryotoxicity.


Statistical design of toxicity assays: role of genetic structure of test animal population.

This paper considers certain statistical aspects of the problem of among-strain differences in cancer susceptibilities and how these differences may affect the design of toxicity assays. First, in order to investigate the magnitude of within-study, between-strain differences in tumor induction, the data of Innes et al. (1969) were examined. It was found that although there was a very high overall association between mouse strains with respect to the induction of hepatomas, several compounds showed evidence of strain-to-strain variability. Next, a number of long-term carcinogenicity studies with DDT were considered, and among-strain differences in cancer susceptibility for this compound were noted. Finally, it was shown that if susceptible subgroups do exist and certain simplifying assumptions are made, then in many cases tumor increases can be detected more readily by using several inbred mouse strains for study rather than a single outbread stock.


The distribution and pharmacokinetics of styrene monomer in rats by the pulmonary route.

Exposures (5 hr) of individual rats to atmospheres having styrene concentrations of from 50 to 2,000 ppm yield uptake blood profiles which show a continued and increasing absorption of styrene, proportional to the styrene atmospheric concentration, over the entire absorption period. Post-exposure elimination follows a dose-dependent two compartment model, similar to that observed after I.V. administration, although the initial stage of the elimination is more rapid and the terminal stage much slower than is observed in the I.V. case. A two-compartment pharmacokinetic model, with zeroth-order input, is proposed to interpret the uptake kinetics. Tissue concentrations of styrene in the heart, liver, lung, kidney, spleen, brain and perirenal fat show a different pattern of distribution as the dose increases. At all exposure concentrations the concentration of styrene in the perirenal fat is ten times that in any organ. At the lowest exposure concentration the kidney registered the highest concentration while a higher level of styrene is found in the liver, brain and kidney as the exposure level increases and for these tissues the concentration of styrene is always greater than that in the blood.


Effect of chronic inhalation of sulfuric acid mist upon mucociliary clearance from the lungs of donkeys.

The effect of chronic inhalation exposures to sulfuric acid mist upon mucociliary clearance from the lungs was studied, using the donkey as an analogue for man. Four animals were exposed 1 hr/day, 5 days/week, for 6 months. The mean mass concentration of acid mist was 102 microgram/m3 for two animals, and 106 microgram/m3 for the other two. The mass median aerodynamic diameter was approximately 0.5 micrometer. Clearance was monitored by serial, external in vivo measurements of the retention of an insoluble, radioactively tagged ferric oxide aerosol which was inhaled following exposure to the acid mist. Bronchial clearance became erratic within the first week of exposure; rates were significantly different, usually slower than control on many test days, although the degree of response varied among the four animals. Two animals exhibited a sustained impairment of clearance towards the end of the 6-month exposure period and continued to have erratic clearance during a 3-month follow-up period. No changes in the regional deposition of the ferric oxide occurred during the course of the study in any of the animals. It is proposed that alterations in bronchial mucociliary clearance may be an early, if not the first, physiologic effect resulting from the inhalation of sulfuric acid mist, and this may be a factor in the pathogenesis of chronic bronchitis in populations exposed to the sulfur oxide-particulate-complex in the ambient air, which often includes sulfuric acid.


In vitro biological effects of glass fibers.

Two glass fiber samples, which had previously been tested for their ability to induce mesotheliomata in rats, were subjected to size fractionation and the respirable fibers from each were collected. The sizes of the fibers in the total and respirable fractions were measured and all four materials were tested in vitro for their cytotoxic activities against V79-4 cells, A549 cells, and mouse peritoneal macrophages. The respirable fraction from the coarser material had considerably enhanced activity (on a mass basis) compared with its parent (total) material. The respirable fraction of the other fiber was only slightly more active than the corresponding total sample. The fiber size distributions are discussed in relation to the observed biological activity of all four samples, and it is concluded that the cytotoxic activity of fibrous glass is determined by the number of fibers within certain size ranges. It is likely that in the systems used in this present paper, fibers less than 10 micrometer long are inactive. The relationship between these observations and those obtained with fibrous glass in vivo by Stanton et al. (1977) are discussed.


Health aspects of radio and microwave radiation.

Recent publications are selectively reviewed to indicate the characteristics of radio and microwave interaction with biological systems. The emphasis is on low-level effects that occur at or below the currently accepted safety standard. This information is then used to examine the adequacy of existing emission and exposure standards for controlling the environmental levels of radio and microwave radiation, and safeguarding the general population from the deleterious effects resulting from typically encountered exposure in the United States.


DDT administration: haematological effects observed in the crowned guinea-fowl (Numida meleagris).

The continued use of chlorinated hydrocarbons as pesticides prompted an investigation into the effects of DDT (dichlorodiphenyltrichloroethane) on the blood of the crowned guinea-fowl (Numida meleagris). Birds were acclimated for 10 weeks, and haematological data obtained after this period served as baseline values. DDT was then administered per os at 75 ppm/kg body mass. This treatment was continued daily for 5 days. Subsequent blood analyses illustrated significant effects on several of the test parameters.


Renal function impairment in secondary lead smelter workers: correlations with zinc protoporphyrin and blood lead levels.

Potential kidney function decrement with long-term lead exposure is important in the overall assessment of adverse health effects of lead in industrial workers or other exposed groups. Two clinical field studies of secondary lead smelter workers have shown that a significant proportion of workers had slightly to moderately elevated BUN and creatinine levels; the prevalence was higher in those with longer lead exposure. Since a decrement of kidney function with age has been documented, and, since duration of lead exposure may also be strongly related to age, it was necessary to assess the age dependent renal function decrement in a control (non-lead-exposed) population. BUN and creatinine levels in the lead-exposed workers showed a much more significant correlation with age than that which was found in the non-exposed population; the correlations between the indicators of renal function, BUN and creatinine, and duration of lead exposure remained statistically significant after removing the age-dependent decrement derived from the control population. Moreover, a highly significant correlation between BUN and zinc protoporphyrin levels was found. The results indicate a sizeable and significant decrement in kidney function in the secondary lead smelter workers studied; this effect was found to be lead-induced, by removing its age-dependency.


Oxidative damage to the erythrocyte induced by sodium chlorite, in vivo.

Sodium chlorite in drinking water was found to produce a slight but compensated anemia in rats after exposure to up to 500 ppm for 90 days. Decreases in hemoglobin, red cell count, and packed cell volume seen after 30 days exposure had substantially recovered by 90 days of treatment. Signs of adaptation remained in that 2,3-diphosphoglyceric acid concentrations in the red cell remained elevated after 90 days exposure to 50 and 100 ppm CIO2-. However, dose-related decreases in erythrocyte glutathione levels, detected at chlorite levels as low as 50 ppm, remained decreased after 90 days exposure. While no other signs of overt toxicity were observed, the fact that hemolytic anemia was involved was confirmed by an increased turnover of red cells in cats exposed to CIO2-. Chlorite-induced decreases in glutathione in vivo were demonstrated to enhance formation of hydrogen peroxide when treated further with chlorite in vitro. Consequently, before a comprehensive determination of the hazards of chlorite in water can b: made, particular attention must be paid to individuals sensitive to hemolytic anemia.


Fate maps and cell differentiation in the amphibian embryo--an experimental study.

The aim of this paper is to test two different fate maps for the amphibian blastula with respect to their predictions concerning the process of cell differentiation. The first of these fate maps is the one proposed by Vogt, according to which all three germ layers can be projected on to the surface of the embryo. The second is a revision which claims that only endoderm and ectoderm are located in the surface, while the mesoderm is represented by free cells in the interior of the embryo. The testing has been performed by observing the differentiation of small explants of cells taken from various regions of the embryo. It was found that the spontaneous cell differentiation comprises three patterns: undifferentiated cells (free interior cells and circumpolar endodermal cells), fibroblast-like cells (the remaining endodermal cells) and epidermis (ectodermal cells). Further differentiation occurs only through induction, exerted either by the fibroblast-like endodermal cells or by heparan sulphate. When induced, the equatorial ectodermal cells give rise to swollen, hyaline cells (chordocytes), while the remaining ectodermal cells form a sequence of cell differentiation patterns, mesenchyme cells, nerve cells, melanophores and xanthophores. The free interior cells differentiate into striated muscle cells and elongated collagen-producing fibroblasts. Our results thus confirm the revised fate map, and they also give an insight into the mechanisms of the initial cell differentiations in the amphibian embryo.


Induction of renal cancers in rats by intrarenal injection of nickel subsulfide.

The carcinogenicity of nickel subsulfide (alpha Ni3S2) was studied following intrarenal (i.r.) injection in rats. Within 100 weeks after i.r. injection of 5 mg of alpha Ni3S2, renal cancers were found in 64 percent of Wistar-Lewis rats, 50 percent of NIH Black rats, 28 percent of Fischer rats and 0 percent of Long-Evans rats. These findings demonstrate significant differences in susceptibilities of the four rat strains to alpha Ni3S2-induction of renal cancers. No renal cancers were found in male Fischer rats that received i.r. injection of alpha Ni3S2 in dosages of 0.6, 1.2 or 2.5 mg. In male Fischer rats that received i.r. injection of alpha Ni3S2 in dosages of 5 or 10 mg, the incidences of renal cancers were 28 percent and 75 percent, respectively. These findings demonstrate a dose response relationship for alpha Ni3S2-induction of renal cancers. In male Fischer rats that received i.r. injection of 10 mg of alpha Ni3S2 combined with 6.9 mg of Mn dust, the incidence of renal cancers was 32 percent, which differed significantly from the corresponding incidences of 75 percent and 0 percent in rats that received i.r. injections of only alpha Ni3S2 (10 mg) or Mn dust (6.9 mg). These findings demonstrate that alpha Ni3S2-induction of renal cancers is inhibited by simultaneous administration of manganese dust. The 54 renal tumors that were found in this study were all malignant, and distant metastases were present in 69 percent of tumor-bearing rats. The histogenesis of alpha Ni3S2-induced renal tumors from epithelial or mesenchymal progenitor cells could not be definitely established.


On the 'clock' mechanism determining the time of tissue-specific enzyme development during ascidian embryogenesis. I. Acetylcholinesterase development in cleavage-arrested embryos.

During ascidian embryogenesis a tissue-specific enzyme, muscle acetylcholinesterase (AChE) may first be detected histochemically in the presumptive muscle cells of the neurula. In order to investigate the 'clock' or counting mechanism that is determining the time when AChE first appears, Whittaker's experiment (1973) has been repeated using eggs of the ascidian, Halocynthia roretzi. Embryos that had been permanently cleavage-arrested with cytochalasin B were able to differentiate AChE in their muscle lineage blastomeres. The time of first AChE occurrence in embryos that had been cleavage-arrested in the 32-cell stage with cytochalasin B was about the same as in normal embryos. This result indicates that the clock is not apparently regulated by the events of cytokinesis. The early gastrulae which had been arrested with colchicine or with colcemid could develop AChE activity, although no histochemically detectable AChE activity was observed in the cleavage-stage embryos that had been arrested with either drug. Therefore the clock does not seem to be controlled by the mitotic cycle of the nucleus. It is suggested that the cycle of DNA replication may be related to the regulation of the clock that is determining the time of development of histospecific protein.


Toxicity of chelated mercury.

The oral and iv acute toxicities of several mercury chelates were determined in mice in a search for relationships bearing on the effectiveness of various chelating agents in therapy. It was found that the toxicity was independent of the stability constant for the mercury chelate when the toxicity was expressed on a molar basis. For the mercury chelates of sulfhydryl containing chelating agents, the oral toxicity was unexpectedly low, presumably due to the poor absortion of these materials from the G.I. tract. The results suggest that the toxicities of mercury complexes are independent of the stability constant of the complex over the range of stability constant from 10(23) on down, provided chelation does not drastically alter the distribution of the complex in the body.


Segmental innervation of the chick forelimb following embryonic manipulation.

A number of studies have shown that the segmental innervation of some muscles in the developing limb undergoes some modification during the earliest stages of ontogeny. These observations can be interpreted in support of the hypothesis that the motor axons and muscles are matched during this period of development. As a further test of this suggestion we have made a quantitative examination of the motor innervation of the chick forelimb under conditions of controlled abnormal development. Embryos were surgically manipulated at stages before the motor axons invade the limb. The operations were controlled such that forelimbs were induced with segments deleted or reduplicated or simply that a segment of the spinal cord had been deleted. In preparations with abnormal limbs the motor innervation of the muscles present was the same as for those muscles in the normal limb. Where a spinal segment had been deleted the limbs developed normally and their innervation was completed by the remaining brachial segments. These results suggest that any particular matching property of a developing muscle does not develop as a consequence of its position in the limb relative to those segments of the limb proximal to it. Furthermore, that some muscles which are normally innervated by two spinal segments can be completely innervated by one of those spinal segments, in the absence of the other, suggests that any matching between growing axons and developing muscle cells is hierarchical rather than strictly all-or-nothing.


Comparison of the clastogenic and carcinogenic effects of intravenous beta-propiolactone and benzo(a)pyrene in rats.

Scored at 24 hours, the LD-50 of a solution of beta-propiolactone administered intravenously to young rats was 225 +/- 55 mg/kg. Twenty-four hours after a single intravenous injection (100 mg/kg = 1.4 m mole/kg) of beta-propiolactone into male and female rats of both the Long-Evans and Sprague-Dawley strains, the incidence of breaks found in the chromosomes of metaphase marrow cells was low (8.8 percent vs. 5.0 percent in controls). The s5 chromosomes were preferentially damaged. A 200 mg/kg dose increased the incidence modestly to 11.3 percent. In comparison, a single intravenous dose of benzo(a)pyrene (40 mg/kg = 0.16 m mole/kg) produced a break incidence of 19 percent. In long-term experiments multiple (five) intravenous injections (100 mg/kg each) of beta-propiolactone given in a 6 week period elicited only two neoplasms (a chloro-leukemia and a mammary fibroadenoma) among 37 animals during the following 12-13 months. In contrast, four injections of benzo(a)pyrene (40 mg/kg) produced a 14-times greater mammary tumor incidence in the Sprague-Dawley female rat than did beta-propiolactone. Marrow cell chromosome examination indicated no significant chromosomal changes due to the earlier beta-propiolactone treatment except for one animal with a consistent 43-chromosome karyotype resulting from S1 trisomy; no neoplasm was evident in that animal. Earlier treatment with benzo(a)pyrene produced a persistent and significant elevation in break incidence. Both the carcinogenic and clastogenic effects of intravenous beta-propiolactone are low in rats and are not comparable in magnitude to those produced by benzo(a)pyrene.


Development of the tibiotarsus in the chick embryo: biosynthetic activities of histologically distinct regions.

The dynamics of the histological changes which occur in the distal half of the tibial portion of the embryonic chick tibiotarsus from day 8 to day 18 of incubation are correlated with the capacities of histologically distinct zones to incorporate isotopic precursors into mucopolysaccharides and collagen. At the distal end of the tibia, which abuts the suture line formed by the fusion of the two tarsals with the tibia, there persists throughout embryonic development a narrow band of small, round or oval, rapidly dividing chondrocytes which synthesize chondroitin SO4 and collagen at low rates. Just proximal to this zone is a broader zone of flattened, disc-shaped chondrocytes which divide more slowly and are extremely active in chondroitin SO4 and collagen synthesis. Proximal to the zone of flattened chondrocytes is a zone of non-dividing, hypertrophied chondrocytes which are large and round and increase continually in size going from the distal to the proximal end of the zone. The biosynthetic activities of the cells in this zone fall sharply with their distance from the zone of flattened chondrocytes. Finally, there is a fourth zone, the marrow cavity, formed by a proximal to distal disintegration of the hypertrophied chondrocytes, starting at mid-diaphysis. The marrow cavity is surrounded by a shell of periosteal and intra-membranous bone which extends to the distal end of the zone of hypertrophied chondrocytes. Our data suggest that as the tibiotarsus grows in length the small, round rapidly dividing cells of the tibia differentiate first to flattened chondrocytes which synthesize matrix at a high rate and ultimately to low activity, hypertrophying chondrocytes. This sequence proceeds in a linear fashion.


Oxidative damage to the erythrocyte induced by sodium chlorite, in vitro.

The ability of sodium chlorite to react with constituents of the erythrocyte, in vitro, was examined and compared to that of nitrite. The oxidative damage resulting from chlorite is fundamentally different from that of nitrite. Nitrite is slightly more potent as an oxidant of hemoglobin, while chlorite appears to be less specific in its oxidation of cellular constituents. Unlike nitrite, chlorite was found to deplete erythrocyte glutathione, which was accompanied by an increase in hydrogen peroxide generation. Chlorite also produced substantial changes in erythrocyte membrane morphology. These effects of chlorite are characteristic of compounds that produce oxidant-induced hemolytic anemia in vivo.


Effect of oxygen concentration on morphogenesis of cranial neural folds and neural crest in cultured rat embryos.

Rat embryos, 9 1/2 days old, cultured with a 5% or 10% O2 gas phase underwent normal or near-normal cranial neurulation; however, culture at 20% or 40% O2 resulted in abnormal morphogenesis of the cranial neural folds from the 9-somite stage onwards, and the brain tube frequently failed to close. Normal morphogenesis was characterized by a narrowing V-shaped profile, development of a slightly concave neuroepithelial surface, and formation of a sharp mediad curvature of the most lateral region prior to midline apposition and fusion. These morphogenetic events were related to cellular changes within the neuroepithelium, namely cell death, onset of neural crest cell migration, and loss of apical microfilament bundles from the most lateral cells. In 20% and 40% O2-cultured embryos, failure of curvature of the neuroepithelium was associated with failure or retardation of the related cellular changes; it may therefore have been due to the maintenance of an excessive rigidity which opposed the forces involved in bringing about the final stage of brain-tube formation. Mitochondria in normal (low O2 and in vivo) embryos were of the anaerobic type, having few cristae; in high O2-cultured embryos they were of the characteristic aerobic type, indicating an adaptation to the abnormal environment.


Cell contact and positional communication in hydra.

Positional communication and the functional coupling of muscular reflexes were examined in grafted hydra. A head and distal gastric region inhibited head regeneration by a host sub-hypostome within 4--5 h of grafting. Functionally coupled pathways which indicated the presence of gap junctions also formed between graft and host during this time. It is suggested that gap junctions provide a channel for positional communication.


In vitro studies on skeletogenic potential of membrane bone periosteal cells.

In the avian embryo ectomesenchyme cells, derived from the mesencephalic level of the cranial neural crest, migrate into the presumptive maxillary region and subsequently differentiate into the membrane bones and associated secondary cartilage of the upper jaw skeleton. The cartilage arises secondarily within the periosteum at points of articulation between membrane bones and provides an embryonic articulating surface. The stimulus for the differentiation of secondary cartilage is believed to be intermittent pressure and shear created at the developing embryonic movement. The development of one such system--the quadratojugal, has been analysed using organ and explant culture techniques and studied with particular reference to the differentiation of periosteal cells into secondary cartilage. A number of conclusions were reached. (1) Normally only cells at discrete loci express a chondrogenic potential in vivo: the periosteal cells at these sites of future articulation become committed to chondrogenesis during stage 35, more than 24 h before cartilage is identifiable in vivo. (2) However, cells with a 'latent' chondrogenic potential are widespread in membrane bone periosteum and occur over most, if not all, of the surface area of the bone. This potential is expressed in the 'permissive' environment created by submersion of the tissue in explant culture or in submerged organ culture. (3) This chondrogenic potential exists long before the time at which commitment of cartilage-forming cells occurs and even presumptive maxillary ectomesenchyme at stage 29 has a limited ability to form cartilage in vitro. It is suggested that spatial position is a principal factor controlling the differentiation of secondary cartilage. Ectomesenchyme cells with the potential to form secondary cartilage are widespread but it is only those cells whose migration from the neural crest positions them and their progeny at the site of a presumptive joint which subsequently express this potential. This epigenetic interpretation is discussed in the general context of development mechanisms underlying the spatial and temporal patterns in which neural crest-derived cells differentiate to produce bone and cartilage during the formation of the head skeleton.


Muscle-forming potential of the non-somitic cells of the early avian limb bud.

It has recently been shown that the musculature of the chick wing arises by migration of cells from the somites, and that on morphological grounds this process begins at about stage 14. We have carried out grafts of wing anlagen separate from the somites from quail donors to the extra-embryonic coelom of chicks, and find that anlagen from as early as stage 10 (11 pairs of somites) can give rise to muscle. We discuss the possible reasons for this finding, and conclude that in the absence of the cells normally giving rise to the musculature, mesodermal cells themselves can give rise to muscle.


Development of retinal synaptic arrays in the inner plexiform layer of dark-reared mice.

In the central area of the retina of mouse the rate of synaptogenesis in the inner plexiform layer (IPL) drops precipitously at about the time the eyes open. To determine if the visual input at eye opening provides a signal for the neurons to stop adding synapses, mice were raised in darkness during the period of maximal synaptogenesis and through eye opening. Retinal synaptic arrays of dark-reared and normally reared animals were compared quantitatively. The rate of synaptogenesis after eye opening in dark-reared mice indicated that the onset of visual stimulation was not the cue to stop synaptogenesis. However, the synaptic arrays of the IPL of dark-reared mice consistently had more conventional synapses than those of normally reared mice. It is concluded that the number of conventional synapses in the central retina was increased by dark-rearing.


Elevation of lesioned palatal shelves in vitro.

Fetuses were obtained from CD-1 mice at a time estimated to be 12 h prior to vivo secondary palate closure. One of the palatal shelves of each partially dissected fetal head was lesioned in one of five ways, the other left intact to serve as control. Single transverse cuts extending the width of the shelf were made at one of three positions along the longitudinal axis of the shelf: one-third, one-half or two-thirds the shelf length estimated from the rostral edge. Some specimens were cut in two places, dividing the shelf into three equal segments. Another group received a lesion which separated the caudal third of the shelf from its maxillary connections. All specimens were cultured for 18 h. At the end of the culture period the heads were fixed, examined and the degree of elevation of each shelf piece assessed. Intact, control shelves of all preparations were elevated in the rostral two-thirds of the shelf, while the caudal third was partially elevated. Results seen in lesioned shelves depended upon both the size of the segment and the region of the shelf contained in the segment. The rostral two-thirds of the shelf, the presumptive hard palate, whether intact or in segments elevated without physical connections to neighboring shelf tissue. Thus, it is unlikely that this elevation requires a wave of contraction be transmitted from the caudal soft palate region. In contrast, the presumptive soft palate requires continuity with the rostral portions of the shelf both to maintain structural stability and to elevate.


The effect of prolonged decompaction on the development of the preimplantation mouse embryo.

A rabbit antiserum to a mouse embryonal carcinoma cell line blocks compaction of cleaving mouse embryos. Cell division is not affected up to the 32-cell stage but intracellular junctions fail to develop. Removal of the antibody at this stage permits compaction to occur and a normal blastocyst develops. Prolonged decompaction beyond the 32-cell embryo results in an increasing proportion of malformed blastocysts in which trophectodermal cells predominate and functional inner cell mass (ICM) cells are reduced or absent. The relationship of compaction to the generation of ICM and trophectoderm lineages in the intact embryo is discussed.


Metabolic co-operation between embryonic and embryonal carcinoma cells of the mouse.

Mouse embryonal carcinoma (EC) cells form permeable junctions at their homotypic cell-to-cell contacts which permit intercellular exchange of metabolites (metabolic co-operation). Hooper & Slack (1977) showed how this exchange could be detected by autoradiography as the transfer of [3H]nucleotides between PC13 (a pluripotential EC line) and PC13TG8 (a variant of PC13 which is deficient in hypoxanthine guanine phosphoribosyltransferase). We now show that cells taken from several different tissues of early mouse embryos, that is, from the morula, the inner cell mass of the blastocyst, and the endoderm, mesoderm and embryonic ectoderm of the 8th day egg cylinder, are able to serve as donors of [3H] nucleotides to PC13TG8. In contrast, trophectodermal cells of cultured blastocysts, and the trophectodermal derivatives in the 8th day egg cylinder, that is, extra-embryonic ectoderm and ectoplacental cone cells, showed little or no metabolic co-operation with PC13TG8. With reference to some common properties of EC and embryonic cells, we suggest how our findings may provide insight into cell-to-cell interactions in the early mouse embryo.


Growth and differentiation of an embryonal carcinoma cell line (C145b).

Several cell and tumour lines were isolated from a single-embryo-derived teratocarcinoma and their karyotypes and differentiation in adult hosts recorded. The majority of cells contained normal karyotypes by banding. The cells were injected into blastocysts and although they sometimes colonized the yolk sac, they never colonized the embryo. Thus the possession of a normal karyotype is not a sufficient condition for embryo colonization. The loss of growth capacity was investigated by studying differentiation and tumourigenicity in a variety of circumstances. The change in appearance from an EC cell morphology to a big flat cell in culture leads to retardation of growth in adult hosts. When EC cells are injected into a blastocyst, the ability to grow progressively both in culture and in adult hosts is lost.


The differentiation and proliferation of follicle cells during oocyte growth in Lacerta sicula.

The follicular epithelium of the lizard oocytes undergoes structural and morphological modifications throughout oocyte growth. During this process the number of follicle cells increases and the epithelium acquires a multilayered and polymorphic organization which is characterized by the appearance of large follicle cells (intermediate and pyriform cells). The number of large cells also increases during oocyte growth and this increase parallels that of small cells. However, only the small cells become labelled one hour after [3H-]thymidine administration. Large cells have been found labelled after a longer period of time, i.e. 4--5 months after isotope injection. All these results together indicate that large follicle cells arise from the differentiation of small cells.


The role of extracellular matrix in the formation of the sclerotome.

The development of the sclerotome is considered as a model for the formation of mesenchyme from an epithelium. In early epithelial somites, transmission and scanning electron microscopy indicate considerable ultrastructural similarity between the future sclerotome and dermamyotomal regions. Subsequently, these two regions diverge in their development. In the forming dermamyotome, junctional complexes become more extensive and the cells become elongated, closely applied to each other, and have angular surface contours. In the forming sclerotome, there is an early reduction in apical junctions. The cells elongate, keeping their original polarity, and acquire numerous filopodia which contain punctate junctions at sites of cell-to-cell contact. Associated with cellular extension is an expansion of the intercellular spaces which do not contain any ultrastructurally recognizable material. Evidence for a role of hyaluronic acid in the expansion of the intercellular spaces is presented. As identified by the susceptibility of cetylpyridinium chloride precipitates to Streptomyces hyaluronidase and chromatographic separation of chondroitinase ABC digestion products, as much as 64--68% of the [3H]glucosamine-labeled glycosaminoglycans synthesized by explanted somites is hyaluronic acid. In addition, hyaluronidase-sensitive label is localized in the intercellular spaces of the sclerotome, as demonstrated by autoradiography. When Streptomyces hyaluronidase is injected in ovo into living embryos, the sclerotomal mesenchyme differentiates morphologically, but intercellular spaces are drastically reduced. It is hypothesized that the sclerotomal cells produce a hyaluronate-enriched extracellular matrix which is inflated by hydration to mediate the expansion of the sclerotomal mass towards the notochord.


The formation of muscles in regenerating limbs of the newt after denervation of the blastema.

The purpose of this experiment was to examine the relationship, if any, between nerve fibers and the formation of muscle pattern in the regenerating amphibian limb. During embryogenesis, nerve fibers grow into the limb bud at the time when the common muscle blastemas subdivide into individual muscle primordia, whereas in regeneration nerve fibers are always present. In order to learn whether or not the muscle pattern could be laid down in the absence of nerves we amputated 58 limbs of newts (Notophthalmus viridescens) at the mid humeral level and allowed them to regenerate to the medium-bud or late-bud stage. The limbs were then denervated. The majority of limbs denervated at the medium-bud stage either regressed or failed to regenerate further. Regeneration after denervation failed in 9 of 25 limbs denervated at the late-bud stages. In those limbs that continued to regenerate after denervation, the formation of individual muscle primordia did occur, following the same sequence with respect to the gross stage of regeneration as innervated regenerates. In comparing these results with our previous results on the development of muscular pattern in aneurogenic limbs of the axolotl, we conclude that in neither the embryonic nor the regenerating amphibian limb are nerve fibers directly involved in the subdivision of common muscle blastemas into the primordia of individual muscles.


Associative transfer and stimulus selection in classical conditioning of the rabbit's nictitating membrane response to serial compound CSs.

Four experiments were conducted to determine whether in conditioning to a serial compound, CS1-CS2-UCS, there are (a) associative mechanisms operating to extend conditioning beyond the bounds of a CS-UCS contiguity gradient and (b) stimulus selection processes acting to attenuate the potency of CS-UCS contiguity. In Experiments 1 and 2, the CS2-UCS interval was held at .35 sec while the CS1-UCS interval was varied across groups from .75 to 2.75 sec. CS1 test trials revealed substantial CR acquisition at all CS1-UCS intervals. Moreover, Experiment 2 indicated that when the contribution of cross-modal generalization from CS2 to CS1 was factored out, there still remained a substantial level of conditioning, which Experiment 3 indicated was attributable to an associative mechanism like higher-order or sensory conditioning. The observation of CR acquisition at CS1-UCS intervals of 4.75, 8.75, and 18.75 sec in Experiment 4 suggested that serial compound training yields conditioning to CSs located well beyond the single CS contiguity gradient for the rabbit's nictitating membrane response. Experiments 1 and 2 also indicated the presence of stimulus selection processes because, at the shorter CS1-UCS intervals (.75 and 1.25 sec), the levels of test-trial responding to CS2 fell below those observed to the less contiguous CS1.


Loss of associability by a compound stimulus comprising excitatory and inhibitory elements.

In each of two experiments rats learned a discrimination between a stimulus (A) that signaled shock and a compound stimulus (AB) that signaled no shock. In Experiment 1 it was found that the AB compound acquired excitatory strength only slowly when, in a second phase of training, it was made to signal the occurrence of shock. In Experiment 2 the acquisition of inhibitory strength by the compound was similarly found to be retarded. This second experiment also replicated the results of Experiment 1. The relevance of these results to current theories of latent inhibition and attention is discussed.


Latent inhibition of a CS during CS-US pairings.

In each of three experiments rats were trained by the conditioned-emotional-response technique with a conditioned stimulus (CS) predicting a relatively weak shock, the unconditioned stimulus (US). In the second stage of training the intensity of the shock was increased, and it was found that subjects for whom the same CS was used in both stages acquired further suppression less readily than subjects that experiences a new CS in the second stage. The implication of these results for theories of attention and for theories of habituation is discussed. It is suggested that associations formed by the test CS during the first stage of training reduce the readiness of the stimulus to enter into new associations, either because an association between the stimulus and the context reduces further processing of the stimulus or because the association between the test stimulus and the weak shock attenuates the formation of an association with the stronger shock.


The eye blink as a time-locked response: implications for serial and second-order conditioning.

A series of experiments were conducted to determine what factors control responding to the first element of a two-element serial compound in rabbit eyelid conditioning. An examination of response topography indicated that the eye-blink CR is rigidly timed to occur when the US is expected. This response-system characteristic prevents the occurrence of a CR during the first element of a serial compound or during the second-order CS in second-order conditioning. The comparison of a serial gap procedure with conventional serial and trace conditioning procedures suggested that the associative strength of the first element of a serial CS is not strongly influenced by either a second-order conditioning process or by the variable-reinforcement principle.


Differential effects of two ways of devaluing the unconditioned stimulus after Pavlovian appetitive conditioning.

Three experiments with rat subjects investigated the effects of two methods of devaluing a food unconditioned stimulus (US) after pairings of an auditory conditioned stimulus (CS) with that US. Experiment 1 found no effect of postconditioning pairings of the food US with lithium chloride (LiCl) on general activity to a tone CS, even though those pairings substantially reduced food consumption. Experiments 2 and 3 compared the effects on conditioned responding of postconditioning pairings of food with LiCl and with high-speed rotation. In these experiments the general activity measure was supplemented by a detailed visual analysis of the rats' behavior. Experiment 2 found that food-rotation pairings had larger effects than food-LiCl pairings on general activity responding and on two detailed behavioral measures but that food-LiCl pairings had larger effects on food consumption and on one behavioral measure. Experiment 3 replicated the findings of Experiment 2 and found that the ability of the CS to serve as a reinforcer for second-order conditioning after US devaluation was reduced more by food-LiCl pairings.


Aspects of the reinforcer learned in second-order Pavlovian conditioning.

Four experiments used an autoshaping procedure in pigeons to explore learning about the reinforcer in a second-order conditioning paradigm. Experiment 1 conditioned two visual second-order stimuli (S2), using as reinforcers two visual first-order stimuli (S1), each of which had previously been paired with food. Animals for which the S2 stimuli were each consistently paired with one particular S1 developed second-order responding more rapidly than did animals for which the identity of S1 varied from trial to trial. Moreover, following consistent pairings, extinction of an S1 had a depressive effect upon second-order responding which was peculiar to the S2 with which it had been paired. Both results suggest that in this preparation the organism identifies a particular S1 as the reinforcer for each S2. The remaining experiments examined the details of that identification. A compound S1, itself composed of two separable elements, was used to reinforce an S2. Subsequent extinction of either element of S1 led to a depression in the responding to S2, which indicates that both elements were involved in the second-order conditioning. Moreover, the use of several complex discriminations, which produced different behavior to S1 and to its elements, suggested that the organism had associated the S2 with the compound S1 rather than with its separate elements. However, even complete extinction of the response to S1 left some residual behavior to S2, which indicates that a portion of the second-order conditioning is independent of the current state of the reinforcer. These results demonstrate that in some situations the organism associates a conditioned stimulus with a rich representation of the reinforcer.


Acquisition, generalization, and discrimination reversal of a natural concept.

Pigeons rapidly acquired a discrimination between 40 pictures containing trees and 40 not containing trees. Differential reinforcement did not affect the discriminability of individual instances of trees. Generalization to new instances of tree pictures was better than to new instances of non-tree pictures. The level of discrimination did not depend on whether trees constituted the reinforced or the unreinforced category.


Effect of posttrial episodes on conditioning in compound conditioned stimuli.

The effect of signaled and nonsignaled posttrial episodes (PTEs) on conditioning to the target CS of a preceding compound CS-US trial was examined in two conditioned emotional response (CER) experiments with rats. Experiment 1 revealed that a nonsignaled PTE, a second shock US, interfered with conditioning to the preceding target CS and that the interference effect of the PTE was greater when it occurred 5 sec as opposed to 1,800 sec after the preceding compound CS-US trial. Experiment 2 revealed that if the shock PTE was signaled by a CS, its ability to interfere with conditioning was reduced. This second study also revealed that omission of an "expected" US interfered with conditioning to the target CS. The implications of these data for information processing models of Pavlovian conditioning are discussed.


Ontogeny of second-order odor-aversion conditioning in neonatal rats.

In Experimental 1, rat pups 1, 3, 5, or 7 days old received a Phase 1 S1-US (Stimulus 1-unconditioned stimulus) pairing calculated to establish a first-order conditioned aversion to S1 (lemon scent). On the next day each pup received a Phase 2 S2-S1 pairing designed to establish a second-order aversion to S2 (orange scent). Pups at all ages displayed a first-order aversion to S1, but only pups given Phase 2 training when 6 or 8 days old displayed a second-order aversion to S2. Experiment 2 revealed that pups that received the S1-US pairing when 3 days old acquired an aversion to S2 if they were 6 days old when they received the S2-S1 pairing but not if they received the pairing when 4 days old. In Experiment 3, two Phase 2 treatments were compared. One was identical to that employed in Experiments 1 and 2: Pups 4 days old received a sequential exposure to S2 and S1. Another set of pups received a modified treatment: They were exposed first to S2 and then jointly to both S2 and S1. Only pups in the latter set displayed an aversion to S2. It is suggested that these results reflect developmental differences in the memory processes mediating the rat's experience with olfactory stimulation.


Spatial contiguity facilitates Pavlovian second-order conditioning.

Two experiments investigated the effects of spatial contiguity upon the formation of second-order conditioning in pigeon subjects. Experiment 1 used an autoshaping procedure to pair two visual stimuli, S2 and S1, after S1 had previously been paired with food. The resulting second-order conditioning of S2 was superior when both stimuli appeared on the same response key within a trial, compared with their appearing on different keys. Experiment 2 found a similar importance of spatial contiguity between S2 and S1 in a conditioned suppression paradigm. In addition, consistently presenting S2 and S1 in the same spatial location produced superior conditioning compared with varying their spatial relation from trial to trial. The design of these experiments was such as to imply that spatial contiguity facilitates performance by improving the formation of association rather than by promoting stimulus generalization or pseudoconditioning. Moreover, the observation of a facilitative effect of spatial contiguity between S1 and S2 in two different paradigms that use qualitatively different unconditioned stimuli and evoke different responses implies some generality for these findings. Consequently, these results suggest that spatially contiguous stimuli are especially associable in Pavlovian conditioning paradigms.


Differential effects of omission contingencies on various components of Pavlovian appetitive conditioned responding in rats.

Five experiments with rat subjects investigated the effects of omission and partial reinforcement contingencies on five individual behaviors evoked by visual and auditory conditioned stimuli paired with a food unconditioned stimulus. The effects of omission depended on the behavior on which that contingency was placed: One behavior was eliminated, one was unaffected, and three were reduced relative to the performance of yoked controls. Partial reinforcement resulted in lower frequencies of three behaviors and higher frequencies of two behaviors, compared with performance under consistent reinforcement. A partial reinforcement extinction effect was noted with one behavior but not with the others. These results are related to the possible role of instrumental conditioning contingencies in generating conditioned behavior in this appetitive conditioning preparation and to the independence of individual components of a complex conditioned response.


Influence of acoustic experience on the ontogeny of frequency generalization gradients in the chicken.

The role of auditory experience in the ontogeny of perceptual coding was investigated in hatching chickens. In Experiment 1, auditory frequency generalization gradients were determined by using a habituation-generalization paradigm and an orienting response. One-day and 3-4 day chicks were habituated to 800-Hz tones and then tested at five frequencies ranging from 800 to 1,000 Hz. One-day chicks displayed reliably flatter generalization gradients than 3-4-day chicks. In Experiment 2 an auditory deprivation method is described in which an ear impression compound was injected into the external ear. This method (a) is fully calibrated and provides approximately 40 dB of attenuation across a .125- to 4.0-kHz range, (b) appears to be fully reversible, and (c) is applicable prior to normal auditory experience as well as at subsequent stages. In Experiment 3, this method was used to investigate the effects of auditory deprivation on the "perceptual sharpening" described in Experimental 1. Chicks were deprived from Embryonic Day 18 1/2 to 3-4 days posthatch, at which time normal, deprived, and sham-operated chicks were tested as in Experiment 1. The generalization gradients of the deprived chicks were significantly flatter than those of the 3-4 day normal and sham-operated chicks and were similar to those of 1-day chicks. This effect cannot be attributed to (a) operative procedures, (b) changes in auditory thresholds, or (c) changes in response rate with age or condition. Thus the perceptual sharpening normally occurring between 1 and 3-4 days posthatch fails to occur during that time in the absence of a normal acoustic environment.


Effects of the number and form of stimuli on visual search in the pigeon.

Pigeons' pecks at small luminous forms on a large display field were photoelectrically recorded. Pecks to target (S+) forms were reinforced with food; pecks to distractor (S-) forms produced a short time-out. The speed and accuracy of search for a target declined as the number of distractors increased to a maximum of 15. Search was further impaired when the distractors were quite similar to the target. However, search was unaffected by a change in the number of potential targets (memory set size) from one to two, nor was it clearly affected by the use of several different distractor forms instead of a single repeated form. Search was swift over a large (50 degrees) visual field, in the apparent absence of substantial head and eye movements.


Learning when reward is delayed: a marking hypothesis.

Rats were trained on spatial discriminations in which reward was delayed for 1 min. Experiment 1 tested Lett's hypothesis that responses made in the home cage during the delay interval are less likely to interfere with learning than responses made in the maze. Experimental subjects were transferred to their home cages during the delay interval, and control subjects were picked up but then immediately replaced in the maze. Contrary to Lett's hypothesis, both groups learned. Further experiments suggested that handling following a choice response was the crucial variable in producing learning: No learning occurred when handling was delayed (Experiment 2) or omitted (Experiment 3). One possible explanation for the fact that handling facilitated learning is that it served to mark the preceding choice response in memory so that subjects were then more likely to recall it when subsequently reinforced. In accordance with this interpretation, learning was found to be just as strong when the choice response was followed by an intense light or noise as by handling (Experiment 4). The implication of marking for other phenomena such as avoidance, quasi-reinforcement, and the paradoxical effects of punishment is also discussed.


Learned suppression of ingestion: role of discriminative stimuli, ingestive responses, and aversive tastes.

Three experiments were designed to demonstrate that animals learn to suppress contact with aversive-tasting foods and fluids, and to investigate the behavioral mechanisms of this learning. In Experiment 1, domestic chicks (Gallus gallus) rapidly learned to suppress drinking during a visual stimulus (SQ) that signaled ingestion of a quinine solution but drank normally during a second visual stimulus (SW) that signaled water access. In Experiment 2, chicks in Group Con received oral infusions of quinine contingent upon drinking during SQ. Group Non received oral quinine infusions during SQ yoked to those of Group Con and noncontingent upon drinking. Only Group Con suppressed drinking during SQ. The third experiment investigated the contribution of the aversive taste and the postingestive effects into either the beak or the crop following drinking during SQ. Only the orally infused subjects suppressed drinking during SQ. These studies suggest that the relation between the drinking response and the aversive taste of quinine during SQ is crucial to the learned suppression of ingestion produced by the present procedures. The implications of these results for theories of food selection and Batesian mimicry are discussed.


Drug-preexposure effects in flavor-aversion learning: associative interference by conditioned environmental stimuli.

Previous research has documented that exposure to a drug reduces the ability of the drug to support subsequent flavor-aversion learning. The four experiments reported here examined the hypothesis that this drug-preexposure effect is due to associative interference from environmental stimuli associated with the drug effects during preexposure. When distinctive environmental stimuli (confinement in a black compartment) were present during drug preexposure, these stimuli significantly disrupted subsequent flavor-aversion learning. Furthermore, flavor conditioning was not significantly disrupted when drug preexposure occurred in the absence of salient environmental stimuli or when the previously conditioned environmental stimuli were extinguished prior to flavor conditioning. It is significant, and in contrast to other published research, that flavor conditioning was not disrupted when the distinctive cues paired with the drug during preexposure were absent at the time of the flavor-drug pairing. These results are thus consistent with results from conventional studies of stimulus blocking and suggest that associative processes can play a major role in the drug-preexposure effect.


Disrupting the conditioned stimulus preexposure effect in flavor-aversion learning: effects of interoceptive distractor manipulations.

Rats exposed to a flavor prior to a conditioning trial involving that stimulus learn a significantly diminished flavor aversion relative to nonpreexposed control animals. A series of four experiments investigated the ability of the conditioned stimulus (CS) preexposure effect to be disrupted by the introduction of a distractor flavor stimulus between the preexposure and conditioning episodes. Experiment 1 demonstrated that the preexposure effect could be reduced by a distractor presented immediately following the preexposure. In Experiment 2, it was discovered that a novel distractor was more effective than a familiar distractor, even though both stimuli were sensorily equivalent. Experiment 3 further analyzed the distractor effect and demonstrated that the magnitude of disruption was more pronounced with immediate than with delayed (3 hr) distractor manipulations. Finally, Experiment 4 assessed the effects of the distractor in the absence of CS preexposure. The relation of the results from these experiments to general information theory is discussed.


Control of instrumental behavior by deprivation stimuli.

In Experiment 1, rats were given one trial per day in a straight alley under food deprivation on half of the trials and under water deprivation on the other half. Wet mash was available in the goal box under food deprivation for Group H and under water deprivation for Group T, the other deprivation being nonrewarded for each group. After 15--18 trials both groups ran significantly faster on their rewarded than on their nonrewarded deprivation days. A third group showed that random variation of alley color retarded formation of the discrimination. A fourth group was run in a conditional discrimination in which under food deprivation wet mash was available in a black alley, nonreward in a white alley, and vice versa under water deprivation. This group took 114 trials to begin running significantly faster in their rewarded than in their nonrewarded alley under each deprivation. In Experiment 2, it was shown that prior learning about deprivation cues "blocks" learning about alley color when alley color is subsequently presented in compound with the deprivation cue but that when both alley color and deprivation cues are relevant from the start of training, the rat learns about both cues. It is suggested that previous studies have underestimated the importance of deprivation cues by using conditional discrimination designs, choice measures rather than speeds, and parameters that are not optimal for discrimination learning.


Role of conditioned contextual stimuli in reinstatement of extinguished fear.

If the unconditioned stimulus (US) is presented independently of the conditioned stimulus (CS) following extinction, the conditioned response may be reinstated to the CS. Three experiments are reported that suggest that reinstatement is mediated by conditioning to contextual stimuli that are present during both US presentation and testing. Shocks presented to rats following the extinction of conditioned suppression reliably reinstated suppression to the CS, but only when they were presented in the context in which testing was later to occur. Reinstatement was also reversed by extinguishing fear to the context through nonreinforced exposure to the context between shock presentation and testing. Reinstatement was obtained in these experiments in spite of procedures that have been used in the past to minimize the influence of context conditioning. Moreover, fear of the context was never detected directly by depressed bar-press rates in the absence of the CS. The results do not support the hypothesis that reinstatement results from an increment in the strength of a memory of the US that has been weakened during extinction. Problems inherent in controlling and detecting levels of context conditioning that may influence behavior toward nominal CSs are discussed.


Contrast, component duration, and the following schedule of reinforcement.

Experiment 1 investigated component duration in a four-component multiple schedule designed to separate the effects of the preceding schedule of reinforcement from those of the following schedule of reinforcement. The preceding schedule in the preceding component had no consistent effect regardless of component duration. The following schedule was a powerful determinant of behavior, however, with higher response rates resulting from a following period of extinction. Moreover, the effect of the following schedule was greater with short component durations, which strongly suggests that component-duration effects previously found with multiple schedules are due generally to variation in the degree of control by the following schedule. Experiments 2--4 investigated the basis of the effects of the following schedule. In some situations differential responding in the following component was the controlling variable, but in others it was differential reinforcement in the following component. The results are consistent with the view that response rate during a stimulus is inversely related to the "value" of the following component, where the calculation of value must include both primary and conditioned reinforcement.


Orthographic regularity, positional frequency, and visual processing of letter strings.

Previous research has demonstrated that familiarity with the orthographic structure within a letter string can facilitate the processing of the component letters. The current research was directed at discovering the psychologically relevant properties of this structure. Two fundamental descriptions were independently varied in the construction of six-letter nonword strings. A probabilistic description based on the frequency of occurrence of letters in each position was factorially combined with a rule-governed description defined in terms of graphemic and phonological constraints. College sophomores and sixth-grade readers were asked to indicate whether or not a predesignated target letter was present in these strings. For both groups of readers, orthographic regularity and summed positional frequency were found to have only a small facilitative effect on reaction time (RT). In contrast, RTs to say "no" increased dramatically with increases in the number of letters in the catch string that were physically similar to the target letter. In another experiment, the letter string was presented for a short duration, followed immediately by masking stimulus and then the target letter. College students indicated whether or not the target was present in the test string. Accuracy of performance was critically dependent on the orthographic regularity and summed positional frequencies of the letters in the test string. No effect of letter similarity was observed. The large differences that were observed between these two tasks were accounted for in terms of the stages of processing that are critical for performance in the tasks.


Features versus redundancy: comments on Massaro, Venezky, and Taylor's "Orthographic regularity, positional frequency, and visual processing of letter strings".

Massaro, Venezky, and Taylor (1979) found only a modest effect of familiarity on letter search, apparently because they pitted pseudowords (rather than real words) against nonwords and used lowercase rather than uppercase letters. Precuing the target letter seemed to reduce the familiarity effect they found yet further, but this conclusion is clouded by the fact that reaction time data were compared with accuracy data. Because similarity between target and nontarget letters tended to have more of an effect when familiarity had less of an effect. Massaro et al. proposed a successive model, with features being detected in the first stage and orthographic structure being used in a second stage. However, a concurrent model, with a self-terminating race between lower and higher level processes, can account for the data just as well. Data from Massaro et al. and from Krueger decisively demonstrate that there is a familiarity effect based on sequential redundancy over and above any effect based on spatial redundancy (Mason 1975). The Massaro et al. data also indicate that the relative familiarity effect is constant across various age groups (Krueger, Keen & Rublevich, 1974).


Orthographic regularity, positional frequency, and visual processing of letter strings: a reply to Krueger's comments.

In reply to Krueger, we address the issues of lowercase versus uppercase letter strings, words versus pseudowords, repeated letters in the test string, descriptions of orthographic structure, similarity effects, apples and oranges, and interactions of age with other variables.


Cross-enhancement of the sour taste on single human taste papillae.

The subjective intensity of one taste quality can be increased by prior exposure of the tongue to a different taste quality stimulus. This phenomenon, called cross-enhancement, may be the result of interactions among the physiological mechanisms that code taste quality. Another possible explanation is that the water solvent of the second stimulus acquires a taste after exposure of the tongue to the first stimulus. This water taste could add to the taste of the solute in the second stimulus and result in an increase of its subjective intensity. A third possibility is that taste receptors on the tongue may be sensitized by exposure to a taste stimulus. Using a small number of highly trained subjects, we have demonstrated that sucrose can enhance the intensity of an acid taste on the single papilla. Neither water taste nor sweet taste system activation played any role in the mediation of this enhancement. Through a series of experimentally derived inferential steps, we conclude that this phenomenon depends on the removal of protons from the acid receptors. In addition, we have demonstrated in the single papilla, that suppression of the acid taste when in mixture with sucrose can occur without sweet system activity. We conclude that sugars, through their capacity to bind protons, act to reduce the availability of protons to the acid receptors.


Studies of the cognitive representation of spatial relations: I. Overview.

The present article reviews the major results and conclusions of two experiments on the mapping and planning of actual (campus buildings) and hypothetical (ideal town facilities) items in a two-dimensional space. Direct mapping (planning) techniques are preferred over the method of pair comparisons, especially in the case of the actual environment.


Studies of the cognitive representation of spatial relations: II. A familiar environment.

This experiment tested the ability of people to recall the locations of buildings in a familiar campus setting. Ten graduate students represented the relative locations of buildings by pairwise distance judgments (on a 100-point scale) and by direct mapping of locations on a Tektronix cathode ray terminal. As evaluated by Stevens's power law, both methods led to accurate judgments of relative distance (the average exponent was close to 1). In addition, the pairwise judgments were analyzed by multidimensional scaling (MDS) and the buildings were located in a two-dimensional map. When asked to choose between the MDS representation and the map created directly on the Tektronix, all 10 subjects chose the latter as the more accurate. Moreover, 6 out of 10 subjects thought the direct map was more accurate than the actual map of the building locations. These results suggest that either pairwise judgment or direct mapping yield accurative representations of spatial relations in a familial environment, but that subjects favor the direct map.


Studies of the cognitive representation of spatial relations: III. A hypothetical environment.

This experiment investigated people's preferences for the location of facilities in an ideal town. Ten graduate students represented the relative locations of facilities (such as home, school, factory) by two methods: (a) pairwise ideal distances on a 100-point scale and (b) direct planning of locations on a Tektronix cathode ray screen. The pairwise distances were analyzed by multidimensional scaling (MDS) and the facilities were thus situated in a two-dimensional space. Subjects then expressed a preference between the direct plan and the one created by MDS. In addition, the rank order priorities of the facilities were determined for each subject. The entire procedure was repeated after 4 mo. A common central plan was evident in all cases (and rank order priorities were stable), but there was within-subject variability in the plans for different methods and test occasions. Despite such variability, subjects generally preferred their direct plan over the one created by MDS (based on pair estimates). A second group of subjects showed equal preference (on the average) for both types of town representations created by the first group. Both the pair and direct technique seem appropriate for studying cognitive representations of a hypothetical environment.


Accessing similarity and dimensional relations: effects of integrality and separability on the discovery of complex concepts.

A series of studies investigated how stimulus integrality and separability impact the cognitive accessibility of similarity and dimensional relations. A good deal of previous work has established that stimulus integrality and separability differentially determine perception; here, the question is whether they also have differential effects on conception. Are the principles that govern perception also principles that can be readily discovered in concept learning tasks? Is a similarity-based rule especially easy to abstract from integral stimuli and a dimensionally-based rule especially easy to abstract from separable stimuli? In Experiments 1 and 2, we measured the relative ease with which the two types of rules (similarity and dimensional) are discovered by adults with the two types of stimuli (integral and separable). In experiment 1, the two rules were made redundant and we asked which rule the subjects learned. In Experiment 2, one rule was made relevant and the other irrelevant, and we compared relative speeds of learning. The results from the studies led us to conclude (a) that dimensionally based rules are more accessible from separable than from integral stimuli; (b) that similarity-based rules are more accessible from integral than from separable stimul; and (c) that, in general, subjects have a bias to access dimensional relations in this type of task. Experiment 3 pursued an additional suggestion from Experiments 1 and 2 that the dimensional relations within integral stimuli are sometimes accessible, more so when larger interstimulus differences are encountered. In confirmation, Experiment 3 demonstrated that adult subjects are more successful in applying a dimensional rule to pairs of integral stimuli that differ by a small amount if they also have exposure to pairs of integral stimuli that differ by a large amount. In a later discussion, it was argued that such a finding is consistent with the notion that the "dimensions" of integral stimuli are merely arbitrary directions in the integral stimulus space, and some relevant pilot data to that effect were presented. Finally, Experiment 4 took up a developmental issue. Young children have sometimes produced perceptual responses governed by similarity relations when presented with stimuli that are separable for adults. Will they more readily access similarity-based or dimensionally-based relations from such stimuli in the concept learning tasks here? The results showed that both kindergarteners and fifth graders more readily access the dimensional relations. A final discussion integrated the findings from the several experiments, taking up the following issues: (a) the relation between the perception and the conception of stimulus relations and (b) the nonprimacy of the dimensional axes in the integral stimulus space.


Processing determinants of reading speed.

Two groups of university undergraduates differing in reading ability were tested on a number of reaction-time tasks designed to determine the speed of encoding visual information at several different levels. In addition, the subjects were given tests of sensory functions, verbal and quantitative reasoning ability, short-term auditory memory span, and ability to comprehend spoken text. The groups did not differ on the sensory tests. However, the faster reader group had faster reaction times on all of the reaction-time tasks, and the size of the fast-reader advantage increased with the mean reaction time. Faster readers also performed more accurately in verbal and quantitative reasoning, short-term auditory memory, and speech comprehension. Regression analyses suggested that the ability to comprehend spoken material and speed of accessing overlearned memory codes for visually presented letters represented two important independent correlates of reading ability in our sample of subjects. Two variables reflecting these abilities--the percentage of correct answers to a listening comprehension test and the reaction time for correct responses in a letter-matching task--accounted for nearly all of the variance in reading ability tapped by both of our reading tests. In a second experiment, no reaction-time difference was found between fast and average readers in a matching task requiring no long-term memory code access but considerable visual information processing as indexed by overall mean reaction time. The results supported the conclusion that one skill allowing fast readers to capture more information from each reading fixation is faster access to letter codes from print.


Selective inattention to anxiety-linked stimuli.

The term selective inattention as used here subsumes those phenomena whose primary function is the active blocking or attenuation of partially processed contents en route to conscious expression. Examples are anxiety-motivated forgetting or perceptual distortion and hypnotically induced negative hallucinations. Studies in the field of selective attention have typically been designed to explain what takes place in a task in which the subject is first instructed to attend to a particular stimulus and then to consciously execute that instruction as well as he can. The rejection of content in process is examined only sceondarily as a consequence of the acceptance of relevant information. In the present experiments and theorizing, the emphasis instead is on inhibitory operations that take place automatically, without conscious intent, in response to a potential anxiety reaction. Experiment 1 explored the interaction of anxiety-linked inattention with strength of a target stimulus. Three female subjects were programmed under hypnosis to respond posthypnotically in the On condition with prescribed degrees of anxiety when certain Blacky pictures popped into mind later ,t the end of experimental trials; in the Off conditionall pictures were to become neutral. With the three female subjects still under hypnosis, each of the loaded pictures was then paired with a four-letter work relevant to the individual's own version of what was happening in the picture. The waking recognition task, carried out with amnesia for the prior hypnotic programming, consisted of tachistoscopic exposure of loaded words and physically similar filler words at four durations within a baseline range of recognition accuracy from 50%--75% correct. The data yielded a curvilinear relationship in which the recognition of only the loaded words was significnatly lower in the On condition at the 60%--70% range of recognition accuracy but not at shorter or longer stimulus durations. Experiment 2, for which the prior hypnotic programming of the same three subjects was similar to Experiment 1, used an anagram approach to comparable four-letter words, except that pleasure-loaded words were introduced as a control along with filler words. Four durations of tachistoscopic exposure of the anagrams were used with each individual, and the major dependent variable was response latency measured in milliseconds. An independent measure of perceptual discriminability of the scrambled stimulus letters was obtained to isolate perceptual from cognitive aspects of the task. The results indicated that both low perceivability and high solvability increase the likelihood of response delays specifically in the presence of anxiety-linked stimuli. Experiment 3 was a nonhypnotic replication of Experiment 2, using 12 male and 13 female subjects. The potential affective loading of key anxiety and pleasure words was accomplished by structured scenarios for the Blacky pictures in which subjects were asked to place themselves as vividly as possible...


Information processing in the cerebral hemispheres: selective hemispheric activation and capacity limitations.

Several previous experiments have found that concurrently maintaining verbal information in memory influences visual laterality patterns (e.g., Hellige & Cox, 1976; Kinsbourne, 1975). The present article critically reviews existing experiments and reports five additional experiments designed to identify the mechanisms responsible for such effects. Experiment 1 demonstrates that laterality patterns are not influenced by a concurrent memory task that does not require verbal processing. (The verbal nature of the concurrent task was an important aspect of previous experiments.) Experiments 2 and 3 were designed to determined whether concurrent verbal memory primarily influences very early visuospatial processes or later processes such as those involved in visuospatial memory. In Experiment 2, observers indicated whether two simulteneously presented nonsense forms had the same shape. Observers held 0, 2, 4, or 6 words in memory during each shape judgment trial. Responses were faster when the forms were presented to the left visual field--right hemisphere (LVF-RH) than to the right visual field--left hemisphere (RVF-LH). This effect did not interact with memory set size. In Experiment 3, observers indicated whether either of two simultaneously presented forms was identical to a target form held in memory. Observers held 0, 2, or 6 words in memory on each trial. On same-as-target trials, responses were faster on LVF-RH trials than on RVF-LH trials in the no-word memory condition; this difference was reversed in the two-word and six-word conditions. The combined results of Experiments 2 and 3 suggest that concurrent verbal memory influences stages of processing beyond the initial registration of visuospatial information. Experiments 4 and 5 examined the influence of concurrent verbal memory on verbal laterality tasks. Observers indicated whether two simultaneously presented letters of different cases had the same name. In Experiment 4, different groups of observers held 0, 2, 4, or 6 words in memory on each letter-pair trial. In Experiment 5, memory set size was manipulated within subjects. On the same-pair trials of Experiment 4 and the first session of Experiment 5, responses in the no-memory condition were faster on RVF-LH trials than on LVF-RH trials; this difference was reversed in all of the work memory conditions. This shift is opposite to that found when the laterality task does not require verbal processing and further indicates that concurrent verbal memory influences processing stages beyond those that are common to the form-pair and letter-pair tasks. Neither directness-of-pathway nor attention-gradient laterality models can explain the entire pattern of results from the present experiments. Rather, the results suggest that the left hemisphere functions as a typical limited-capacity information processing system that can be influenced somewhat separately from the right hemisphere system.


Contingency contrast effects in discrimination conditioning.

Three experiments observed differential electrodermal responding to signal stimuli (CSs) by contrasting positive, random, and negative contingencies between the signals and strong stimuli (UCSs). Experimentation began as a test of the proposition that electrodermal response to a random signal (or CSR) would lie between the response to a reinforced or excitatory stimulus (CS+) and that to a nonreinforced or inhibitory stimulus (CS- or CSI). A clear intermediate position for CSR did not result. Instead it appeared that CSR was operating as a mildly excitatory signal. This led to a second experiment where response to pairs of stimuli with different contingent relations could be compared in independent samples. The pairs were CS+ and CS-, CS+ and CSR, and CSR and CS-. Differential responding was observed in all pairs and response to CSR was significantly larger in the group receiving CSR with CS- than it was in the group receiving CSR with CS+. A contingency contrast effect was suggested. A third experiment explored the implications of a contingency contrast effect by varying overall UCS density, the duration of "safety intervals," and the presence or absence of instructions about contingencies. The UCS density and instruction variables influenced the differential performance to CSR and CS-, a result that was interpreted as further evidence for a perceptual contingency-contrast effect. Some theoretical implications of such a contrast phenomenon are examined, as they apply to autonomic learning. The CS is interpreted as a signal supplying contingency information that is dependent upon a complex of factors in the stimulation environment.


Comment on "Information processing in the cerebral hemispheres: selective activation and capacity limitations" by Hellige, Cox, and Litvac.

The attentional model of hemisphere differences proposed by Kinsbourne is reviewed, and some of the difficulties inherent in this model are pointed out. In particular, the difficulty of distinguishing shifts in the allocation of attention from changes of strategy is underlined, and the fact that the effect of imposing a concurrent memory load is uncertain, sometimes priming and sometimes depressing the performance of the loaded hemisphere, is seen as seriously limiting the predictive power of the model. Hellige, Cox, and Litvac attempted to clarify several aspects of Kinsbourne's theory. In their studies concurrent verbal loads produced complex and variable changes in the performance of both hemispheres. To explain these, they postulate a dual mechanism whereby general activation primes the performance of both hemispheres while selective activation acts to prime or to depress the performance of the left hemisphere. Although they succeeded in identifying some of the factors that govern the effects of selective activation, the effects of general activation are uncertain, so the overall outcome of concurrent memory loading is still difficult to predict.