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Previous reports have noted a constant association between the Carpenter syndrome (acrocephalopolysyndactyly, type II) and mental retardation. We report two patients with this condition with normal intelligence. These observations indicate that mental deficiency is not necessarily a component of the Carpenter syndrome and that early surgical correction of the craniosynostoses may improve the chances of normal mentality. | US |
The "idiopathic" Fanconi syndrome occurs mostly sporadically, occasionally as an autosomal recessive trait. However, few instances of autosomal dominant inheritance have been reported. We described a father and son with the Fanconi syndrome, ie, with renal glycosuria, generalized aminoaciduria, phosphaturia, metabolic acidosis, and bone disease. No other causes of the Fanconi syndrome were found. Both father and son developed end stage renal disease. Aminoaciduria in excess of that seen in renal insufficiency is shown by comparison with published data for amino acid excretion in uremia. Renal transplantation in the father has improved kidney function with no evidence of Fanconi syndrome. This family is unique in that there are no other reports of autosomal dominant Fanconi syndrome with progression to early renal failure. | US |
In the KOP translocation, t(X;14)(q13;q32), virtually the entire long arm of the X has been translocated to the end of the long arm of chromosome 14. Meiotic secondary nondisjunction in a female balanced carrier of the translocation has led to a son with two der(14) or 14-X chromosomes. The normal X chromosome is late replicating in the mother. One of the two 14-X chromosomes is late replicating in the son, with heavy terminal labeling of all but the centromeric end of the chromosome. This suggests that genetic inactivation has spread from the Xq segment of the translocation chromosome to at least two thirds of the segment derived from chromosome 14, and that the remaining proximal segment of chromosome 14 is possibly still genetically active. These findings provide an explanation for the phenotype: Klinefelter syndrome plus a few mild malformations that are sometimes seen in this syndrome but are also seen in duplication of the proximal portion of chromosome 14. Although the proband has a duplication of virtually an entire chromosome 14, 14(pter leads to q32), the phenotypic effect of the autosomal duplication has been mostly nullified by the spread of inactivation. | US |
We report the anatomical variations of the limbs in eight infants with the trisomy-18 syndrome that were dissected and studied in detail. In each case, the upper limbs showed defects which further define the specific influence of this aneuploidy on the development of its preaxial (radial) component, and the tendency towards reduction defects. Abnormalities included muscle variations concentrated along the radial margin of the forearm and hand, the absence of the definitive musculocutaneous nerve in all of the limbs, and reductions of the radial artery in four of the bodies. Pathogenetic mechanisms explaining the observed defects are discussed, and include: 1) a defect in peripheral nerve development; or 2) tissue necrosis. The characteristic flexion deformities of the fingers seem to be due to a displacement of the tendons of extensors digitorum and digiti minimi. The lower limbs did not show a consistent pattern of defects, except for the absence of some muscles (psoas minor, the tendon of flexor digitorum brevis to digit V), and the presence of several supernumerary muscles. These variations are discussed as possible nonspecific effects of 18-trisomy on development. The additional anatomical data from this and the first paper in this series [Bersu and Ramirez-Castro, 1977] provide a more detailed picture of the trisomy-18 phenotype which may be useful in corroborating an unconfirmed clinical diagnosis of the syndrome. | US |
Fourteen patients with hypodontia and the ocular features of the Rieger syndrome were examined for the presence of systemic anomalies. A periumbilical defect that consisted of failure of the periumbilical skin to involute was seen in ten of the thirteen evaluated for the defect. Three others had scars over the umbilical area and had a history of surgery for herniation. In addition, four males in one family and one male from another family had hypospadias. None of several other anomalies reported to be components of the Rieger syndrome by other authors was detected in the fourteen patients. The mode of inheritance in the familial cases studied was compatible with autosomal dominance. The results of this study indicate that the Rieger syndrome is an autosomal dominant syndrome whose cardinal features are hypodontia, goniodysgenesis, and failure of the periumbilical skin to involute properly. | US |
Eighty normal Caucasians were studied by CBG technique for estimation of size and inversion heteromorphisms of chromosomes 1, 9, and 16. Size heteromorphisms were classified into one of five sizes using 16p as a reference standard: very small, small, intermediate, large, and very large. Inversion heteromorphisms were also classified into 5 categories - eg, no inversion; partial inversion - minor; half inversion; partial inversion - major; and complete inversion. The frequencies of size heteromorphisms for chromosomes 1, 9, and 16 were 11.3%, 47.5%, and 7.5%, respectively. Thirty-four chromosomes were found to have inversions. Of these, 16 were in chromosome 1, and 18 were in chromosome 9. No inversions were found in chromosome 16. An increase in the size of the h region was more frequently associated with inversion, suggesting that there is a possible relationship between size and inversion. For example, there were 118 chromosomes that were classified as "intermediate" by size; 23 (19.5%) had inversions. In contrast, there were 225 that were "small" in size, and only 10 (4.4%) had inversions. There was no significant difference between males and females for size and position heteromorphisms. | US |
The transfer and metabolism of cortisol and cortisone and the effect of protein binding on these processes have been investigated in vitro in the perfused human placenta. The clearance of cortisol in buffer, expressed as a fraction of the antipyrine transfer rate (clearance index), was 0.50 +/- 0.05 SEM in either direction. Extensive conversion to cortisone (85%) occurred during transfer. Addition of corticosteroid-binding globulin (CBG) in amounts sufficient to bind 50% of the cortisol reduced the clearance (0.40 +/- .026) insignificantly, whereas human serum albumin (HSA) in amounts sufficient to bind 50% of the cortisol reduced the clearance to 0.28 +/- 0.012 (P less than 0.001) even though the association constant for albumin is approximately 1000-fold less. The percent of conversion to cortisone did not change significantly with protein binding. The clearance index of cortisone from a protein-free perfusate was 0.74. With CBG and albumin in the same concentrations as used in the cortisol experiments, the binding of cortisone to CBG was 23% and its clearance was 0.70; with albumin, the binding was 45% and the clearance index was 0.45. The addition of albumin and CBG to the same perfusate resulted in a cortisol clearance equal to that obtained with perfusate containing only albumin. Binding to albumin may be more significant than binding to CBG in controlling the transfer rate of cortisol to the fetus. | US |
We have demonstrated that in patients given a single iv injection of T3, rT3, or, to a lesser extent, T4, all labeled with 125I in the outer or phenolic ring, chromatography of serum on columns of Sephadex G-25 superfine revealed the presence of a labeled material, separate from the administered hormone and from both iodide and iodoprotein. This peak has been termed pre-T3 because it elutes just before the T3 peak. Identification of the various compounds in pre-T3 was carried out by cation exchange chromatography. Pre-T3 generated from [125I]T3 consistently contained labeled compounds with the chromatographic behavior of 3,3'-diiodothyronine and 3'-monoiodothyronine, while pre-T3 generated from [125I]rT3 contained labeled products with the chromatographic mobility of 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine. In addition, pre-T3 also contained the glucuro- and sulfoconjugates of these several labeled products. These studies demonstrate that T3 and rT3 undergo progressive and probably sequential deiodination in the peripheral tissues, resulting in the formation of a variety of diiodothyronines and monoiodothyronine, as well as their glucuro- and sulfoconjugates. | US |
Chromatography of serum on columns of Sephadex G-25 superfine after the iv administration of 125I-labeled T4 consistently yielded labeled iodide, iodoprotein, T3, and a labeled peak that eluted from the column before the T3, termed "pre-T3." Much larger quantities of pre-T3 were generated after the iv administration of 125I-labeled T3 and rT3. The ratio of [125I]pre T3:[125I]T3 and [125I]pre T3:[125I]rT3 plateaued at approximately 10 h and 2 h, respectively, after the iv administration of the labeled hormone, and averaged approximately 15% in euthyroid subjects. As pre-T3 behaves like its precursors in the TCA precipitation-ethanol extraction or anion exchange chromatographic procedures used to separate labeled iodide and iodoprotein from administered labeled T3 and rT3, concentrations of labeled hormone measured by these techniques will be in error, because pre-T3 will be included. Thus, the MCR of labeled T3 and rT3 measured by Sephadex chromatography will always be higher than values obtained by the other two separative techniques and the magnitude of change will be similar to the ratio of pre-T3 to precursor T3 or rT3. The Sephadex chromatographic technique is laborious, but appears to be the method of choice where greatest accuracy of measurement is required. As the generation of pre-T3 from labeled T4 is sufficiently slow, the present chromatographic technique is not necessary in studying peripheral T4 turnover. | US |
As part of a study on the physiological role of hCG in the human fetus, the hCG concentrations in homogenates of various fetal tissues were measured using a hCG beta subunit RIA. The mean concentrations (picograms of hCG per mg wet tissue +/- SEM; n greater than 10, unless otherwise indicated) found in human fetuses of 12-20 weeks were: ovary, 46.9 +/- 4.3; testis, 8.2 +/- 1.7; kidney, 20.3 +/- 2.8; thymus, 11.5 +/- 1.2; adrenal, 2.6 +/- 0.4; lung, 3.4 +/- 0.7; liver, 1.8 +/- 0.2; spleen, 1.4 +/- 0.4 (n = 5); muscle, 2.4 +/- 0.8 (n = 6); and meconium, 356 +/- 104. That the immunoreactive material measured behaved like hCG was determined by RIA of the supernatants. Parallelism was demonstrated between dilution curves for the tissue homogenates and the hCG standard for all tissues except meconium. A rat Leydig cell in vitro bioassay was used to demonstrate that there was hCG biological activity in the supernatants in ovarian, thymic, and renal tissues. The mean ratios of biological to immunological activities were 5.3 in kidney (n = 4), 1.6 in thymus (n = 3), and 1.3 in ovary (n = 2). Blood content of the tissues was determined from measurements of hemoglobin levels and it was found that for the ovary, testis, kidney, and thymus, hCG concentrations were higher than could be explained by the presence of circulating hCG in the tissues. These results, together with our previous results of the binding and effects of hCG in the human fetal testis, support the fact that the fetal testis is a target organ for hCG in the stimulation of steroidogenesis. The presence of high levels of hCG in the ovary, thymus, kidney, and meconium poses questions for further study of the possible physiological role of hCG. | US |
An investigation into the feasibility of using X-ray computed tomography (CT) to measure disease induced changes in bone mineral content of the human spine is described. A theoretical study of this type of measurement has been made using a mathematical model of osteomalacia. The measured EMI number changes linearly with the mineral content, and the sensitivity is shown to be 1.2 EMI units (EU: 500 scale)/1% change in mineral content in vertebral bone. The physical sensitivity to an equal mineral change in cortical bone is found to be 8.6 times greater. The mineral selectivity of the CT method is such that only about half the change in the EMI number arising from progressive osteomalacia reflects change in actual mineral content, while half is due merely to changes in bone density that accompany demineralization. In addition, the perturbing effects of beam hardening on measurement accuracy are evaluated and shown to be significant. Finally, an experimental measurement indicates that in practice the reproducibility of such measurements would be about 1 EU, and it is shown that the measured parameter correlates well with the calculated total linear attenuation coefficients. | US |
The effects of intraventricular cycloheximide (CHX) pretreatment were examined on the ability of rats to recall a light position discrimination task. The CHX pretreatment used inhibited brain protein synthesis at the time of training by 71%. Following treatment with CHX the animals demonstrated no retention of the task 18 hr later. Free feeding for 24 hr prior to treatment with cerebro-spinal-like fluid (CSF) produced similar effects as CHX. It is proposed that the amnesic effect of CHX in this behavioral paradigm may be a nonspecific action resulting from decreased motivation. Both the CHX-treated and satiated animals exhibited low responding levels during training, despite comparable behavioral activity levels for the CHX- and CSF-treated groups. | US |
In a shock escape T-maze task, rats were trained to turn right following one drug treatment and left following a second drug treatment. The specific drug and dose conditions were the only discriminative cues available to the animals. The number of training sessions before criterion performance indicated the discriminability of the two training conditions. Drug vs no drug training showed that discriminability was proportional to dosage for low doses, but was constant over a range of higher doses. Such an asymptote of discriminability was observed with scopolamine, atropine, benactyzine and Ditran (JB 329), and was shown not to result from tolerance. High dose vs low dose discriminations involving scopolamine were learned very slowly if both doses were within the asymptotic range; this indicates that similar discriminable effects were produced by high and low doses. To compare various drugs, substitution tests were administered to trained rats. The four antimuscarinic drugs generally substituted for one another but did not mimic and were not mimicked by drugs in other pharmacological classes. Some exceptions to this pattern were noted. The discriminable effects of scopolamine were partially antagonized by physostigmine. The results indicate that the antimuscarinic drugs share discriminable actions probably produced by their anticholinergic actions. The asymptote of action at high doses appears genuine, possibly reflecting receptor saturation. | US |
As time increased between drug administration and the start of experimental sessions, effects of drugs on food-maintained responding in rhesus monkeys increased to a maximum and then decreased. d-Amphetamine, ethanol, and alpha-l-acetylmethadol (LAAM) generally decreased high response rates in one component of a chain schedule, while very low response rates in another component were increased reliably only by ethanol. The time of peak LAAM and ethanol concentrations in blood or plasma corresponded with or overlapped the time of maximal behavioral effect, while the time of maximal behavioral effect with d-amphetamine occurred somewhat prior to the time of peak plasma-amphetamine concentration. With d-amphetamine and perhaps with ethanol, effects on operant responding were greater after 30-min pretreatment intervals than after six-hr pretreatment intervals despite higher plasma or blood concentrations at six hours than at 30 min. | US |
Slow potentials were recorded from the anterior cortex of rats during discrimination conditioning and the effects of various doses of d-amphetamine on these responses were examined. In the discrimination paradigm one tone (Sd) was followed at three see after the onset by food reinforcement while another tone (S delta) indicated that no reinforcement would follow. Slow potential (SP) responses were measured during the three-sec period following onset of the stimulus. For the first several training sessions the SP responses demonstrated a phase of generalization during which responses were the same to both stimuli. Thereafter, the responses to Sd were significantly greater than responses to S delta. d-Amphetamine produced a dose-related depression of SP responses to the reinforced stimulus in doses of 0.25 to 2.0 mg/kg. The effect of amphetamine on SP responses to S delta was biphasic; the lower doses (0.25 and 0.5 mg/kg) enhanced responses, no change was seen after 1.0 mg/kg and the high dose (2.0 mg/kg) depressed responses. This study demonstrates that the rat develops differential slow potential responses to reinforced and nonreinforced stimuli in a discrimination paradigm and that d-amphetamine produces a differential and dose-related alteration of these SP responses. It is suggested that the actions of amphetamine may be produced through interference with mechanisms of discrimination, by an effect on subcortical activating systems involving norepinephrine, and/or by activation of inhibitory dopamine receptors on cortical neurons. | US |
The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationships, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases. | US |
A new test of goodness of fit for the polygenic threshold model is proposed. This test, when applied to disorders showing different incidence rates in males and females, is designed to account for ascertainment in more detail than previously done by other investigators. This is accomplished by computing the expected distribution of nuclear families with more than one affected sib conditioned on several family-dependent variables, including whether each family was ascertained via only affected boys or via at least one affected girl. A direct measure of the probability of observing a data set is thereby derived. The test, when applied to data on pyloric stenosis, exposes the critical nature of the ascertainment procedures. Different levels of statistical significance are obtained when mode of ascertainment is taken into account than when the mode of ascertainment is ignored. | US |
Synthetic filaments prepared from column-purified rabbit skeletal myosin by slow dialysis exhibit characteristic bipolar organization and 14-nm axial subunit spacing. Backbone substructure can be discerned in high resolution micrographs in the form of striations of 3--4-nm width and slight angular tilt from the direction of the filament axis. Filament backbone diameters vary over the population, although remaining relatively constant for a single filament. Approximately 25% of the filaments appear poorly stained and frayed, which may be due to collapse on the electron microscope grid. Optical diffraction studies reveal a 43-nm axial repeat as well as the 14.3-nm subunit repeat, indicating a structural homology with natural filaments. A model for synthetic filament aggregation is presented that is consistent with observations of backbone diameter variation, absence of bare zones, and the presence of fraying filaments. | US |
The effect of 6-mercaptopurine on the development and expression of delayed hypersensitivity was studied in the guinea pig. Results indicated that 6-MP produced its suppressive effects primarily by action on cells of the monocyte-macrophage series. Suppression could occur under conditions of both developing and pre-established delayed hypersensitivity. The defect primarily involved newly synthesized, bone marrow-derived monocytes. Marked alterations in monocyte macrophage generation and distribution, especially the T1/2 of circulating monocytes were demonstrated. Suppressive effects were associated with the appearance of a unique morphologic microscopy. Finally, the in vivo expression of delayed hypersensitivity correlated better with a variety of parameters relating to qualitative macrophage function and distribution rather than those relating to quantitative macrophage levels. | US |
Multivariate behavioral genetic analyses may employ either genetic and environmental correlations or phenotypically standardized covariances to assess the structure of genetic and environmental influences. Correlations and phenotypically standardized covariances answer different questions--correlations are appropriate for understanding the nature of genetic and environmental influences, whereas covariances are appropriate for determining the etiology of phenotypic correlations. The ratio of the genetic and environmental covariances to the phenotypic correlation yields estimates of bivariate heritability and environmentality, measures of the extent to which observed phenotypic covariance is due to genetic and environmental influences. Multivariate analyses of genetic and environmental correlations and covariances are illustrated with twin data on scholastic abilities. Factor analyses of correlations suggest that the same set of genes affects the major areas of academic achievement and that the environmental influences are similarly structured. Analyses of phenotypically standardized covariances indicate that the structures of genetic and environmental influences as they contribute to phenotypic resemblance among scholastic abilities are both similar and simple: there are one general genetic factor and one general environmental factor. Bivariate heritabilities and environmentalities are similar in magnitude, indicating that the strong phenotypic relationship among scholastic abilities is due roughly equally o genetic and environmental influences. | US |
Since Galton's time, critics of the twin method have rejected the evidence of genetic differences in human behavior, because the twin method assumes that identical and fraternal pairs have equally similar environments. Twins whose genetic similarity is misperceived by themselves and others provide a critical test of the adequacy of this assumption. The relative effects of perceived and actual genetic similarity on cotwin differences in cognitive, personality, and physical development were assessed in a sample of young, adolescent twins whose genetic similarity was often misperceived. Twins' responses to questions about their own and others' judgments about their zygosity and physical similarity, and the ratings of similarity by eight judges, were used to estimate the perceived similarity of the twins. Actual zygosity was established by matching cotwins on 12 or more blood group loci. Perceived zygosity and perceived similarity by self and others were found to be insignificant biases in the twin study method. | US |
The present study investigated whether maternal aggression has shown a correlated response in a program of artificial selection for isolation-induced interfemale aggression in housemice. Females from the first replicate of lines (H1, C1, L1) and the second replicate of lines (H2, C2, L2) from generation S5 were given daily aggression tests for 20 consecutive days following the birth of their first litter. Evidence of a correlated response was found for replicate 2, but results for replicate 1 provided no evidence of a correlated response. In generation S10, when better separation of the lines on isolation-induced aggression had occurred, the study was repeated. In S10 there was clear evidence of a correlated response in both of the replicates. | US |
Circulating thymic hormone activity and thymic histology were studied in patients undergoing open heart surgery. Plasma thymic hormone activity was measured using a bioassay based upon thymocyte antigen induction on null mouse lymphocytes. Activity was highest at 15-30 yr of age and declined thereafter, being negligible after the sixth age decade. The age-related decline of circulating thymic hormone activity correlated, in general, with progressive thymic involution. However, hormone activity was detected in plasma from some cases with advanced involution, suggesting that the normal young thymus may have considerable functional reserve. | US |
The concentrations of immunoreactive somatomedin-C (Sm-C) in the sera of women with uncomplicated pregnancies were found to be progressively higher as the duration of gestation increased. Between 19 and 42 weeks of gestation, there was a significant correlation between serum Sm-C concentration and duration of gestation. A striking decline in Sm-C was observed following delivery. While the data are too preliminary to elucide the mechanisms for the raised Sm-C, the concurrent increase in Sm-C and human placental lactogen (hPL) raises the possibility that hPL may mediate the increment in Sm-C. | US |
The placental membrane radioreceptor assay was used to measure the levels of somatomedin (SM) peptides in plasma. Displacement of both [125I]somatomedin A ([125I]SM-A) and [125I]somatomedin C ([125I]SM-C) by normal whole plasma, the peptide fraction of acid-chromatographed plasma, and a partially purified, insulin-free SM preparation were compared. The peptide fraction of plasma was isolated by acid chromatography over Sephadex G-50 in 0.25 M formic acid with a yield of greater than or equal to 90%, as determined by bioassay and [125I]SM. In the case of [125I]SM-A, the dose-response curves for whole plasma, acid-chromatographed plasma, and the standard SM preparation were parallel (P less than 0.2). In contrast, for [125I]SM-C, the dose-response curves for acid-chromatographed plasma and the purified SM preparation were parallel (P less than 0.2), but both differed significantly from that of whole plasma (P less than 0.001). In addition, there was less variability in the assay of acid-chromatographed plasma compared to whole plasma. The results indicate that radioreceptor assay of unextracted normal plasma using [125I]SM-A is a valid measure of SM peptide concentration, while radioreceptor assay of unextracted normal plasma using [125I]SM-C, in our hands, is not. Acid chromatography of plasma before its assay is an uncomplicated procedure which allows valid and precise measurement of SM peptide content using either [125I]SM-A or [125I]SM-C. | US |
Neuroendocrine function in two women with galactorrhea-amenorrhea arising from abnormalities in the PRL reflex arc was compared to that of normal women. Basal gonadotropins were lower than normal, and one patient lacked episodic secretion of LH; however, the serum gonadotropin rise after iv LRH was in the normal range in both patients. Mean basal PRL levels were slightly elevated in one patient and were normal in the other, and the PRL levels after TRH, chlorpromazine, and levodopa testing were similar to those seen in normal women. Breast stimulation did not increase PRL levels in either patient. PRL levels fell with bromergocryptine therapy, galactorrhea ceased, and normal menses resumed. These studies indicate that chronic afferent impulses originating in the PRL reflex arc can result in galactorrhea and amenorrhea and that bromergocryptine therapy in such patients can restore normal menses. | US |
Fat excretion and absorption in 38 healthy S-f-D born infants fed on 4 kinds of diet, differentiated with regard to fat quantity and quality as well as protein quality, were examined by means of three 24 hour fat balances. Higher fat intake, higher fat excretion in feces and lower index of its absorption, typical of these infants, were observed. Differences in relation to the infants born with normal body-weight were particularly distinct in the first six months of life. It was noted that the quantity of fat excretion in feces was influenced by the degree of fetal malnutrition. An advantageous influence of fat modification, which consisted in partial replacement of cow-milk fat with vegetable oil (soya oil) on fat excretion and absorption, was shown. Feeding higher fat formulas--3 g/100 ml and modified protein were also considered advantageous. It was noted that S-f-D infants, even in cases of feeding with modified fat formulas, at the end of the first year of life did not reach such values of the absorption index as infants born with normal body-weight. The conception that the triglyceride structure differing from that in the breast milk is the factor deteriorating cow-milk fat absorption in the infants was suggested and discussed. | US |
The interaction of a class of oxonol dyes with sonicated phospholipid vesicles was followed optically. The spectra of vesicle-associated dyes resemble those found for the dyes in organic solvents, indicating that the oxonols occupy a hydrophobic region of the membrane. At equilibrium the affinity of the oxonols for the vesicles depends on the structure of the dye, the physical and chemical composition of the vesicles, and the ionic strength of the medium. The oxonols occupy soybean lipid vesicles to a level of 147.9 +/- 17.1 nmol/mg lipid with a dye membrane dissociation constant of 3.33 +/- 0.54 muM. The interaction of the oxonols with soybean lipid vesicles is biphasic. The fast phase has a second order rate constant of 9.04 +/- 0.36 x 10(6)M(-1) s(-1) and the number of "fast" binding sites, 68 +/- 8 nmol/mg lipid, was determined from the ratio of the second order rate constants obtained with lipid and with dye in excess. The dissociation of oxonols from soybean lipid vesicles is also biphasic, and the fast process has a rate constant of 17 +/- 2 s(-1), yielding a dissociation constant for the fast sites (k(-1)/k(2)) of 1.88 +/- 0.15 muM. The slow phases of oxonol association with, and release from, soybean lipid vesicles are not second order and have half times of between 0.2 and 5 min, depending on the physical and chemical composition of the membrane lipids. The amplitudes of the slow phases are sensitive to the composition of the aqueous media on each side of the vesicle membranes, which suggests that the slow processes represent the permeation of the membrane by the oxonols. The importance of the properties of the oxonol dyes in the interpretation of their behavior in natural membranes is discussed. | US |
We have found that herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has the ability to increase the rate of transport of positive ions of several kinds, and to inhibit transport of negatively charged tetraphenylborate ions in lipid bilayer membranes. It has been found that only the neutral form of 2,4-D is transport active, whereas the ionized from of 2,4-D does not modify transport of ions, and does not by itself permeate through lipid membranes. The results suggest that the enhancement of transport of positively charged ions such as tetraphenylarsonium + and nonactin-K+ is dominated by the increase of the ion translocation rate constant. It has been shown that the enhancement of nonactin-mediated transport of K+ by 2,4-D can be accounted for by a simple carrier model. We have observed that a 2,4-D concentration above 3 X 10(-4) M the potassium ion transport in phosphatidylcholine-cholesterol as well as in cholesterol-free glycerolmonooleate membranes is enhanced to such a degree that, depending upon the concentration of potassium ions, it becomes limited by the rate of recombination of K+ with nonactin, and/or by backdiffusion of unloaded nonactin molecules. Furthermore, the effect of 2,4-D is enhanced by ionic strength of aqueous solution. From the changes of kinetic parameters of nonactin-K+ transport, as well as from the changes of membranes conductance due to tetraphenylarsonium + ions, we have estimated the changes of the electrical potential of the membrane interior. We have found that the potential of the interior of the membrane becomes more negative in the presence of 2,4-D, and that its change is proportional to the aqueous concentration of 2,4-D. The effect of 2,4-D on ion transport has been attributed to a layer of 2,4-D molecules absorbed within the interfacial region, and having a dipole moment directed toward the aqueous medium. The results of kinetic studied of nonactin-K+ transport suggest that this layer is located on the hydrocarbon side of the interface. | US |
The orientation of an amphipathic, long acyl chain fluorescent carbocyanine dye [diI-C18-(3)] in a biological membrane is examined by steady-state fluorescence polarization microscopy on portions of single erythrocyte ghosts. The thermodynamically plausible orientation model most consistent with the experimental data is one in which the diI-C18-(3) conjugated bridge chromophore is parallel to the surface of the cell and the acyl chains are imbedded in the bilayer parallel to the phospholipid acyl chains. Comparison of the predictions of this model with the experimental data yields information on the intramolecular orientations of the dye's transition dipoles and on the dye's rate of rotation in the membrane around an axis normal to the membrane. To interpret the experimental data, formulae are derived to account for the effect of high aperture observation on fluorescence polarization ratios. These formulae are generally applicable to any high aperture polarization studied on microscopic samples, such as portions of single cells. | US |
The alignment of dilauryl-, dimyristoyl-, and dipalmitoylphosphatidylcholine at various water concentrations into large oriented monodomain multilayers by annealing at elevated temperatures (Powers and Clark, 1975, Proc. Natl. Acad. Sci. U.S.A. 72:840; Powers and Pershan. 1977. Biophys. J. 20:137) is accompanied by the formation and subsequent dissolution of various defect structures. Some of these defects appear similar to those observed in thermotropic and other lyotropic liquid crystals, reflecting the lamellar structure of these materials. The formation and evolution of defects during the alignment of the lipids into the defect-free, monodomain, multilamellar geometry is studied using polarized microscopy. A combination of polarized and dark-field microscopy facilitated characterization of the defects; specific structural models are proposed. A new alignment technique involving compression and dilation of the lipid, which effects sample alignment at temperatures that are lower than those required by the Powers technique, is described. Lower temperature alignment avoids thermal decomposition that will sometimes occur if the lipid is maintained at elevated temperatures for prolonged periods. With this technique, samples (80 micrometer thick) of dilaurylphosphatidylcholine with 20% water by weight were aligned at room temperature. | US |
In the absence of C-protein, synthetic filaments prepared from column-purified myosin exhibit the following features: individual filament diameters are uniform over a long length, but a wide distribution of diameters is apparent over the population; approximately 25% of the filaments have a frayed appearance and take up stain poorly, whereas the remaining 75% are well-stained; optical diffraction of well-stained filaments reveals a 14.3-nm subunit period and a 43-nm axial period (Koretz, 1978; Koretz, 1979). Addition of C-protein to myosin before filament formation affects all of these features in a manner related to C-protein concentration. At the physiological ratio of C-protein to myosin in the banded region of the natural thick filament, synthetic aggregates are uniform in diameter over the population and show less than 10% frays. Whereas the subunit period remains unchanged, the axial period has increased to 114.4 nm, or eight times the subunit repeat. Above and below the physiological ratio, disorder of a specific nature is apparent. Addition of C-protein after filament formation appears to coat the aggregates so that elements of backbone ultrastructure are obscured, and some evidence of axial period change is visible in diffraction patterns. A model is presented for the binding of C-protein to myosin, and its observed effects on filament structure are explained in terms of this model. | US |
The effect of the small anesthetic molecule, benzyl alcohol, on the structure of various bilayer system has been studied by optical, electrical, and x-ray diffraction techniques. We find that the modifications in bilayer thickness caused by benzyl alcohol differ dramatically for planar (or black lipid) bilayers containing solvent, planar bilayers containing little or no solvent, and vesicular bilayers. Benzyl alcohol increases the thickness of planar bilayers containing n-alkane solvents, yet decreases the thickness of "solvent-free" planar bilayers. The effect of benzyl alcohol on vesicular bilayers below the phase transition temperature also depends on whether solvent is present in the bilayers. Without solvent, gel-state bilayers are reduced in thickness by benzyl alcohol, whereas in the presence of solvent, the thickness is unchanged. Above the phase transition temperature, benzyl alcohol has no measurable effect on vesicular bilayer thickness, whether solvent is present or not. These results indicate that different model membrane systems respond quite differently to a particular anesthetic. | US |
An order parameter-based interpretation is applied to the temperature dependence of the deuterium magnetic resonance splittings and the anisotropic contribution to the chemical shift for 31P from the head groups of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). It is shown that the rotational motion of the molecule about its long axis is not a free rotational motion as normally assumed, but instead a biased one. Changes in the degree of biasing appear to be primarily responsible for the variation of the NMR spectra with temperature. The degree of biasing is described by orientational order parameters. With the use of these order parameters, it is shown that the temperature dependence of the anisotropic contribution to the chemical shift for 31P can be predicted from that of the deuterium quadrupole splittings. | US |
The synthesis of very high specific activity 25-OH-vitamin D3 (78 Ci/mmol) has made possible the study of the metabolism and plasma disappearance of 3H after a single dose of 3H-1,25-(OH)2-D3 in quantities that are only 10-20% of the endogenous plasma pool. We studied seven healthy adults who were given doses of 1,25-(OH)2-D3 ranging from 30-2300 pmol. Plasma disappearance was rapid with only 14 +/- 2% of administered 3H remaining in the plasma pool 4 h after labeling. Plasma metabolite profiles during the first 4 h showed only 1,25-(OH)2-D3. Thereafter, significant amounts of other metabolites were detected. The 6-day cumulative excretion of 3H in urine and feces (virtually all associated with metabolites of 1,25-(OH)2-D3) averaged 16 +/- 3% and 49 +/- 11% of the dose, respectively. Compartmental analysis of the isotope data for two subjects who received the smallest doses of 1,25-(OH)2-D3 indicated that endogenous renal 1,25-(OH)2-D3 synthesis rates approximate 0.8-2.4 nmol/day (0.3-1.0 microgram/day). | US |
A simple, reproducible, and highly specific RIA has been developed for measurement of 3',5'-diiodothyronine ((3',5'-T2) in unextracted serum. Interference in binding of radioactive 3',5'-T2 to anti-3',5'-T2 by serum proteins was minimized by using 0.4 M phosphate buffer (pH 6.2) and merthiolate. The detection threshold of the RIA was 2.5 ng/100 ml. Recovery of nonradioactive 3',5'-T2 added to serum averaged 99%. T4, T3, and rT3 cross-reacted with 3',5'-T2-binding sites on anti-3',5'-T2 antibody only to the extent of 0.0025, less than 0.0004, and 0.22%, respectively. 3'-Monoiodothyronine cross-reacted 1.7%. Serum 3',5'-T2 concentrations were (mean +/- SD) 6.4 +/- 2.4 ng/100 ml in 53 normal subjects, 4.2 +/- 3.5 ng/100 ml in 7 hypothyroid patients, 14.9 +/- 7.7 ng/ml in 25 patients with hepatic cirrhosis, and 14.3 +/- 5.3 ng/100 ml in 31 newborns' cord blood sera. The values in each of the latter four groups were significantly different from normal. The mean serum 3',5'-T2 concentration of 7.7 +/- 2.5 ng/ml in eight subjects in the third trimester of pregnancy did not differ significantly from normal at a time when serum T4 and T3 were clearly elevated. Oral administration of 300 microgram rT3 to 9 normal subjects led to a mean maximal increase in serum 3',5'-T2 concentration of 45% at 1 h. Total fasting in 3 obese subjects was associated with a significant increase in serum 3',5'-T2 from 8.6 to 16.3 ng/100 ml at 6-8 days; serum rT3 increased similarly, while serum T3 decreased and T4 did not change. Administration of dexamethasone (2 mg also associated with nearly parallel increases in serum 3',5'-T2 and rT3 and a decrease in serum T3. 3',5'-T2 concentrations were also measured in amniotic fluids at different stages of gestation; the mean value of 15.2 ng/100 ml at 15-20 weeks gestation was significantly higher than that of 5.8 ng/ml at 33-40 weeks gestation. Pronase hydrolysates of 9 autopsy specimens of normal thyroid glands contained (mean +/- SD) 350 +/- 144 microgram T4 and 0.24 +/- 0.15 microgram 3',5'-T2/g wet wt. On the basis of these data and those available for MCRs of 3',5'-T2 and T4, it was estimated that thyroidal secretion contributes less than 1% of 3',5'-T2 measured in serum of normal man. The various data suggest that: 1) 3',5'-T2 is a normal component of human serum; 2) almost all 3',5'-T2 in human serum derives from extrathyroidal sources; and 3) changes in serum 3',5'-2 generally parallel those in rT3. | US |
This report describes the effect of administration of repeated doses of ipodate (Oragrafin; 3 g orally every third day for five doses) in six hyperthyroid patients. Baseline serum concentrations of immunoassayable T3, rT3, and T4, were 926 +/- 206 ng/100 ml, 165 +/- 31 ng/100 ml and 21 +/- 2.7 micrograms/100 ml (mean +/- SEM), respectively. Within 24 h after the first dose of ipodate, serum T3 fell by 54% and it remained between 66-77% below baseline until the third day after the fifth dose; subsequently, there was a gradual recovery from the effect of ipodate. Serum T4 also decreased after ipodate administration; it was 23-31% lower than baseline from the second day after the third dose to the sixth day after the fifth dose. Serum rT3 increased after each dose of ipodate; peak values of 97%-203% above baseline value were observed at 24-48 h after each dose. There was a subjective improvement in clinical symptoms of hyperthyroidism in all cases. Resting pulse rate and pulse pressure dropped significantly (P less than 0.02) by the ninth day of study and remained so thereafter. Body weight increased significantly by the ninth day of the study. The various data suggest that ipodate may serve as a useful adjunct in the early treatment of hyperthyroidism. | US |
Fetal rat bones in organ culture constitute a sensitive system for assay of the vitamin D metabolite, 1 alpha,25-dihydroxyvitamin D3. Significant bone resorption is obtained with as little as 2 pg 1,25-dihydroxyvitamin D3 after 48 h of culture and with 1 pg after 64 h of culture. In the current study, organ cultures of fetal rat bone are used as a bioassay for 1,25-dihydroxyvitamin D i normal human plasma, which was prepared for assay by extraction with dichloromethane, chromatography on Sephadex LH-20, and purification on silicic acid by high pressure liquid chromatography. The concentration of 1 alpha,25-dihydroxyvitamin D3 in normal adult human plasma was 24.8 +/- 2.0 pg/ml (n = 19) by this assay. | US |
To evaluate the interactions of the renal prostaglandin and kallikrein-kinin systems during mineralocorticoid escape, we administered desoxycorticosterone acetate (DOCA; 20 mg im daily for 10 days) to five normal men and then repeated the study 2-16 weeks later with simultaneous indomethacin (200 mg/day) or ibuprofen (1600 mg/day) for prostaglandin inhibition (PI). Plasma aldosterone, PRA, and urinary prostaglandin E (PGE) were measured by immunoassay; urinary kallikrein activity was measured by esterase activity. With DOCA, subjects gained 2.0 +/- 0.1 (SE) kg and retained 485 +/- 125 milliequivalents (meg) sodium; serum potassium fell from 4.6 +/- 0.2 to 3.2 +/- 0.1 meq/liter, aldosterone fell from 3.8 to 2.2 ng/dl, and PRA fell from 0.9 to 0.1 ng/ml . h (all P less than 0.05). Kallikrein increased from 6.4 +/- 1.6 to 65.3 +/- 18.8 esterase U (P less than 0.01), but PGE (820 +/- 110 vs. 780 +/- 80 ng/day) did not change. With DOCA and PI, PGE fell by 80%. Subjects again gained 2.0 kg and retained 530 +/- 106 meq sodium; aldosterone fell to 1.1, PRA fell to 0.2, and potassium fell to 3.3 (all P less than 0.05 from basal, but P less than 0.4 from DOCA alone). Kallikrein again rose to 56.0 +/- 19.2 (P less than 0.01). However, the rate of sodium retention was enhanced slightly but significantly. These studies demonstrate that with DOCA, urinary kallikrein activity increases but PGE is unaltered. The minimal effects of prostaglandin inhibition and the lack of change in PGE excretion suggest that prostaglandins do not play an important role in mineralocorticoid escape. There is no apparent interaction of prostaglandins with the kallikrein system in this model; however, the kallikrein-kinin system may still play a direct role in the escape phenomena. | US |
This report presents the results of interviews with 16 Mexican-American folk healers (curanderos and curanderas) in San Antonio, Tex. Curanderismo was found to be alive and well in San Antonio, though its practitioners tend to be older and its future unclear. Several salient characteristics of the practitioners were clarified such as the process of becoming a healer, referral practices, types of disorders treated, and treatment of the traditional folk illnesses. We take a basically conservative position on whether curanderos can ever be incorporated into the health care delivery system. However, this study confirms that the practitioners and their clients simultaneously utilize the folk medical system and the scientific medical system. | US |
This report describes a study of subject refusal as a source of bias limiting the generality of psychiatric research results. Fifty psychiatric patients who refused to participate in a battery of research interviews and psychological tests were compared with 50 participant patients. Between-group comparisons were made on an extensive and detailed set of clinical, treatment, and demographic data. Results revealed a remarkable lack of difference between the participant and refusal groups in demographic features, type or duration of hospitalization, and type or degree of pathology as defined by symptoms, prognostic measures, and diagnoses. These results and a review of related studies suggest that sample bias in psychiatric research resulting from loss of eligible subjects by refusal depends on the amount of institutional contact and the severity of disorder in the sample studied. | US |
We compare the effects of chlordiazepoxide, oxazepam, and placebo on hostility, as both an inner motivational or potential state and verbal interpersonal behavior. This article reports the findings relevant to the latter dimension of hostility and integrates them with those findings, presented in an initial report, relevant to hostility as an inner motivational state. The verbal data again support the hypothesis that chlordiazepoxide-induced increases in verbal interpersonal hostility, following frustration, are greater than those associated with placebo. With regard to oxazepam, the verbal hostility data were consonant with the motivational data that suggested that oxazepam does not substantially disinhibit hostility but did not as consistently differentiate oxazepam and chlordiazepoxide at the level of overt hostile behavior. | US |
Fifty preterm children who had experienced a range of biological hazards were divided into two competence groups on the basis of their receptive language development at 24 months. The groups were then compared in terms of the kinds of caregiver-child interactions the children and their primary caregivers engaged in three months earlier in a laboratory assessment. The two language skill groups did not differ on perinatal factors such as birth weight and gestational age, or on length of hospitalization, but did differ in social transactions. The more competent group as compared to the less competent group had caregivers who were more stimulating, the children themselves emitted more vocalization, and the caregivers and children engaged in more reciprocal social transactions. | US |
Rhabdomyosarcoma of the head and neck often presents with vague symptoms which mimic other disease conditions. These factors lead to undue delay in the establishment of the correct diagnosis and the delivery of acceptable therapy, including surgery, radiation therapy, and chemotherapy. There is, however, evidence of improved results of treatment of these tumors since the addition of multiple drug chemotherapy to surgery and radiotherapy. | US |
The experience of three institutions in the management of atrial flutter in infants under 2 years of age without associated heart disease is reviewed. Five babies with neonatal onset were treated with digoxin and had uncomplicated resolution of their arrhythmia, although one continued to have episodes of paroxysmal supraventricular tachycardia for six years. Two of the three older infants required DC cardioversion for complications after quinidine was substituted for digoxin therapy. Digoxin continues to be the preferred initial therapy for non-acutely ill patients; those showing signs of cardiac decompensation should be converted with DC countershock. | US |
To assess the possibility that non-aminoglycoside antibiotics may adversely affect the nephrotoxicity of the new semisynthetic aminoglycoside netilmicin, we gave ampicillin, carbenicillin, methicillin, cefamandole, and clindamycin, either singly or in combination with netilmicin, at two dose concentrations in rats. Results were compared as to the effect of netilmicin given singly and to saline-injected and noninjected controls. Antibiotic combinations resulted in no greater nephrotoxicity than did netilmicin alone. Netilmicin concentrations in renal tissue were high, and these levels were not consistently affected by the other drugs. The data suggest that in rats the nephrotoxicity of netilmicin is not affected adversely by the presence of non-aminoglycoside antibiotics. | US |
The vehicle of miconazole inhibited adherence and leukotaxis, but did not affect nitroblue tetrazolium reduction and trypan blue exclusion by granulocytes at 0.33% concentration and above. | US |
By in vitro methods, five aminoglycoside antibiotics (amikacin, kanamycin, gentamicin, tobramycin, and netilmicin) were shown to produce modest changes in granulocyte adherence (increase) and migration (decrease) and no change in phagocytosis or nitroblue tetrazolium reduction. | US |
Fifteen children with scleroderma have been presented. All had characteristic cutaneous abnormalities at onset and during the course of disease. All were girls. All had visceral involvement, primarily of the gastrointestinal tract, heart, and lungs. The presence of visceral disease might have been missed without specific and extensive diagnostic procedures, including gastrointestinal barium studies, esophageal motility, pulmonary function and carbon monoxide diffusing capacity, and plethysmography. Raynaud's phenomenon was frequent and accompanied by evidence of occlusive vascular disease. Contractures around joints were readily evident and arthralgias were common, but evidence of objective arthritis was absent. Sixty percent of the patients in this series had ANA. Overlap syndromes with myositis and SLE were present in 7 patients. Three of 15 children died 6-10 years after onset of disease. | US |
Seven girls and 3 boys with MCTD have been described. As a group their clinical characteristics and serological findings are similar to those reported in adults, with several important differences. Children with MCTD may have marked thrombocytopenia and more frequently they have RF. Significant cardiac and renal involvement are more common in children, may lead to longer and higher dose corticosteroid therapy, and may contribute to a less optimistic prognosis than that described in adults. | US |
A synthetic polycarbonate (PC) membrane supplied by C.R. Bard Inc. was assessed as to its clinical usefulness and suitability to regular use with artificial kidney. The permeability of the PC membrane to 11 solutes of increasing molecular volumes (Na+, Ca++, K+, Cl-, HPO4-, urea, creatinine, uric acid, glucose, BSP, cyanocobalamine) was measured in vitro by rotating dialysis cells, as compared to that of Cuprophan PT 150. The evaluation of the PC membrane in vivo was carried out during a regular hemodialytic treatment in 5 patients using a Kiil dialyzer. The dialysance of 6 solutes (HPO4-, urea, creatinine, uric acid, hypaque, cyanocobalamine) across the PC membrane was measured at 200 ml/min blood flow rate. Both in vitro and in vivo the PC membrane showed permeability and dialysance coefficients to small molecules approximately the same than standard PT 150; the ultrafiltration rate of the PC membrane was also superimposable to that of PT 150. On the contrary, larger molecules were removed much more efficiently by the polycarbonate membrane than by PT 150. These data suggest that the membrane evaluated in this study possesses some peculiar features which could possibly result in an improvement of the quality of regular hemodialysis. | US |
Let me summarize. I distinguish between two major different relationships between transference and resistance. One is resistance to awareness of the transference and the other is resistance to resolution of the transference. I argue that the bulk of the analytic work should take place in the transference in the here and now. I detailed Freud's view that the transference should be encouraged to expand within the analytic situation. I suggested that the main technique for doing so, in addition to the analytic setup itself, is the interpretation of resistance to the awareness of transference by searching for the allusions to the transference in the associations not manifestly about the transference; that in making such interpretations one is guided by the connection to the actual analytic situation which every transference includes; that the major work in resolving the transference takes place in the here and now, both by way of examining the relation between the transference and the actuality of the analytic situation from which it takes its point of departure and the new experience which the analysis of the transference inevitably includes; and that, while genetic transference interpretations play a role in resolving the transference, genetic material is likely to appear spontaneously and with relative ease after the resistances have been overcome in the transference in the here and now. Working through remains important, and it, too, takes place primarily in the transference in the here and now. | US |
A specially designed silicone balloon, expanded in vivo with normal saline, was tested for possible use as a retinal tamponade in desperate cases of rhegmatogenous retinal detachment. In six pigmented rabbits there were extensive postoperative complications, but in eight owl monkeys results were noticeably better. When the seam of the balloon was in contact with the retina there were adverse effects; seamless areas of the balloon did not appear to disturb the retina. Histopathologic studies indicated that excessive expansion of the balloon can cause significant damage, but that carefully controlled expansion can probably minimize complications. The presence of the balloon appears to alter electroretinographic response, but without necessarily causing histopathologic changes. Balloons of this type have been used in treatment of a small number of otherwise inoperable cases of retinal detachment with promising results. | US |
The osteoplastic flap technique for treating frontal sinus mucoceles is described. This procedure has the advantages of: being a direct approach, which allows exposure of the entire sinus, provides complete obliteration of the sinus to prevent recurrence of the sinus disease, and prevents blind curettage of any exposed dura mater; leaving no facial deformity after the operation; being a relatively atraumatic procedure with low morbidity and minimum postoperative care; and allowing simultaneous surgery on both frontal sinuses when indicated. | US |
Some aspects of the surgical, radiotherapeutic, chemotherapeutic, cryosurgical, and immunological aspects of eyelid and adnexal malignancy have been discussed. Possibilities for future developments have been mentioned and even rationalized. Oncology is a constantly changing field. It is important for the oculoplastic surgeon to keep abreast of the changes. It is also important for him to be innovative and progressive in the area of possible improvements. It is not for those of us in the rank and file of ophthalmology to try all possibilities, but at least we should be aware of the new techniques and should support their trial. | US |
Experimental evaluation of Wikler's interoceptive conditioning hypothesis of relapse to opioid use in ex-addicts requires a preliminary study of the degree of physical dependence produced by two methods of drug administration. Wistar rats were made physically dependent on morphine by single daily intravenous injections or by a continuous i.v. infusion. Rats received the same total daily dose regardless of administration schedule. The initial daily morphine dose was 20 mg/kg, and was increased every fourth day by 20 mg/kg, until a dose of 200 mg/kg per day was reached. The rats were maintained at the highest dose level for 18 days, at which time morphine was discontinued. Body weight and water intake were the primary variables measured during addiction, maintenance, and abstinence phases of the study. Equivalent and parallel changes in mean weight and water intake in injection and infusion rats indicate equivalent degrees of physical dependence were developed. This finding allows separation of the contribution of conditioning factors and of protracted abstinence in facilitating opioid self-administration in formerly-dependent organisms. | US |
Sequential dependencies were examined as a function of learning, masking, and subject factors in a two-stage differential eyelid conditioning experiment. In Stage 1, all subjects were differentially conditioned to two Vanderplas and Garvin (1959) forms. In Stage 2, the conditional stimuli (CSs) were one of eight words, four reinforced (CS+) and four unreinforced (CS-), with taxonomic category (animals vs. musical instruments) as the discriminandum, and different subjects were given semantic, physical, or no additional CS processing tasks. The results showed sizeable and highly significant sequential dependencies in the form of greater conditional response probabilities when CS+ as opposed to CS- trials were recently experienced. These effects decreased over trials, were greater in the groups given additional processing loads, and were in some cases greater in C-form responders than in V-form responders and greater in subjects who were unable to verbalize the differential contingencies. It was concluded that the magnitude of sequential dependencies was inversely related to the subject's awareness of the differential contingencies and/or ability to use the contingency information to respond appropriately to the CS cues. | US |
The basic findings of these two studies are as follows: a failure of orientating and conditioning of viscero-autonomic responses, but essentially normal orienting and conditioning of a temporal muscle response in amygdalectomized animals. Small procedural differences exist between the two studies,and a possible order effect exists as a result of the use of the same subjects consecutively. However, we fell that the difference between the responses of the viscero-autonomic system and the skeletal system would still be found were all of the measures gathered simultaneously in an optimal conditioning situation. The definitive study--simultaneous viscero-autonomic and skeletal (behavioral) recording--remains to be done. Trial-by-trial analysis of the correlations or lack of correlations between these responses in such a study should be highly informative. These two studies offer substantial information relevant to the original questions. When behavior is modified by simple repetition of experience the effect of amygdalectomy is restricted to the viscero-autonomic components of orienting and classical conditioning, not to the entire spectrum of responses. The issue raised, therefore, is the significance of the viscero-autonomic components of orienting and classical conditioning. The suggestion has been proposed (Pribram, 1969) that these components serve as mechanisms of internal rehearsal necessary to the registration (as novel or familiar) of the orienting and conditioning experience. This proposal requires further testing. | US |
Experiments were carried out on cats fitted with a gastric fistula. In one group of 6 cats basal gastric secretion, and in another group of 7 cats pentagastrin induced gastric secretion was collected two or three times a week during a 2 hr session. The sessions were conducted either in a "harness" situation where the cat's movements were restricted, or in a "cage" situation where the cat was unrestricted and could move freely. It was found that in four of 6 cats in the basal secretion group and in five of 7 cats in the pentagastrin induced secretion group, gastric acid output was significantly higher in sessions in harness than in sessions in cage. These differences in acid output were due to acidity rather than volume of secretion. It was hypothesized that restriction of the animal's movements in the harness could evoke a "reflex of freedom" which, however, could not be accomplished because of the confinement. This could evoke a neural conflict eventually leading to functional disturbances in the autonomic system. This, in turn, resulted in changes in gastric acid secretion. | US |
An epidemiologic investigation of the mental needs and services of 1645 respondents, aged 17 to 92 years and living in a representative southeastern county in Florida, revealed that 7.8% of the sample lived in crowded conditions. The crowded respondents scored significantly higher than did the uncrowded on both a depression scale and on the Health Opinion Survey. Associations between crowding and high scores on both scales were strongest among: respondents in the childrearing and middle years of life, blacks at all income levels, whites in the intermediate annual family income range of $6000 to $9999, and especially, females rather than males. Consistently, the crowded black population, and particularly, crowded white women, had much higher scores than did the uncrowded women. A multiple regression analysis showed that three variables--being a female, having a lower income, and crowding--accounted for 16.5% of the variance. The discussion emphasizes that the relationship between crowding and higher scores on indices of emotional distress is quite complicated. In crowded situations, depression may be a costly, semi-adaptive reaction to excessive interpersonal stimulation. Women living in crowded situations appear to be at high risk for depressive illness; their plight brings to mind the classic animal experiments which showed that the maternal behavior of females deteriorated in crowded situations. | US |
A retrospective review of 500 patients with primary hyperparathyroidism seen from 1951 to 1975 was conducted; the effect of routine screening of calcium and phosphate levels (initiated in 1968) on the incidence and spectrum of the disease was analyzed. The majority of the patients (77%) were diagnosed in the eight-year period after routine biochemical screening was instituted. Comparing the group of patients diagnosed before the advent of biochemical screening and those diagnosed since screening was instituted, we found: (1) a small but significant increase in the number of asymptomatic patients diagnosed (from 2% to 12%); (2) no change in the incidence of related medical disorders, i.e., nephrocalcinosis and hypertension; (3) no change in the incidence of primary hyperplasia and adenoma; and (4) no change in the mean serum calcium level, the mean age at diagnosis, or the number or location of the involved parathyroid glands. Although routine calcium screening has identified significantly more cases of primary hyperparathyroidism, screening apparently does not enable diagnosis at an earlier stage. | US |
Eleven of 12 patients treated for invasive melanomas of the conjunctiva at the UCLA Hospitals from 1955 to 1976 revealed data sufficient for evaluation. Of these 11 cases, 4 died from 3 to 13 years after treatment as a result of the disease. The plan presented for surgical management of melanosis is based on histologic criteria and on the anatomic location of the tumor. In this series, such management ranged from local excision of noninvasive melanotic lesions to orbital exenteration with parotidectomy and radical neck dissection for invasive melanomas that involved the palpebral conjunctiva or caruncle. Extended follow-up is needed in all patients. | US |
Here we describe the change in thick filament length in striated muscle of Limulus, the horseshoe crab. Long thick filaments (4.0 microns) are isolated from living, unstimulated Limulus striated muscle while those isolated from either electrically or K+-stimulated fibers are significantly shorter (3.1 microns) (P less than 0.001). Filaments isolated from muscle glycerinated at long sarcomere lengths are long (4.4 microns) while those isolated from muscle glycerinated at short sarcomere lengths are short (2.9 microns) and the difference is significant (P less than 0.001). Thin filaments are 2.4 microns in length. The shortening of thick filaments is related to the wide range of sarcomere lengths exhibited by Limulus telson striated muscle. | US |
The vitelline layers (VLs) of unfertilized sea urchin eggs were isolated by homogenization in a hypotonic medium containing Triton X-100 and EDTA. The surface topography of the VL is not changed by isolation. The thickness of the isolated VLs (300-400 A) is greater than that reported for VLs on intact eggs (100-200 A). Sperm adhere to the isolated VLs. When both internal and external VL surfaces are accessible to sperm, the sperm attach only to the external surface, suggesting that the external surface may carry sperm receptor proteins not present on the internal surface. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis shows that isolated VLs are composed of numerous proteins ranging from greater than 213,000 to 25,000 daltons. Lactoperoxidase-catalyzed 125I-iodination of unfertilized eggs labels two high molecular weight bands that stain faintly for carbohydrate. VLs are 90% protein and 3.5% carbohydrate. No predominance of a single amino acid or class of amino acids was found. Carbohydrate analysis yields fucose, mannose, galactose, glucose, xylose, glucosamine, galactosamine, and sialic acid. Controls for purity indicate that isolated VLs contain 2% protein of cytoplasmic origin and no more than 2.5% egg jelly. | US |
Histogenesis of thyroid follicles in the chick embryo begins with a penetration by cells of the mesenchymal capsule into a solid epithelial primordium. Before penetration occurs, slits containing fibrillar material form between the epithelial cells. The fibrillar material is an epithelial cell product as shown by its formation within channels that form in cultures of isolated epithelial primordia. The drugs L-azetidine-2-carboxylic acid (LACA) and alpha, alpha'-dipyridyl, which interfere with collagen synthesis, prevent the formation of fibrils in cultured epithelial primordia and in cultures of whole thyroids. Furthermore, mesenchymal cells do not invade when whole thyroid primordia are cultured in the presence of either drug. The effects of alpha, alpha'-dipyridyl are reversed by washing out the drug; the effects of LACA are reversed by incubation with equimolar or greater amounts of L-proline added to the medium along with the drug. The results are interpreted to mean that the fibrillar material is collagen of epithelial origin, that the collagen in some way plays a role in mesenchymal penetration of the epithelial primordium, and that the epithelium is responsible for the pattern of lobulation within the developing gland. | US |
The rate of disk addition to rod outer segments (ROS) varies widely in Xenopus laevis tadpoles kept in cyclic light (12L:12D). When measured as radioactive band (3H-band) displacement during the 2nd day after injection of [3H]leucine, 75% of the daily increment of displacement occurred during the first 8 h of light. During the same interval, the number of open disks at the ROS base increased more than threefold. During the last 8 h of darkness, 3H-band displacement was undetectable and the number of open disks was reduced. These observations suggest the possibility that disk addition may occur discontinuously. During the 3rd and 4th days after injection of [3H]leucine, maximal displacement of the 3H-band occurred later in the day than on the 2nd day, its movement no longer corresponding to the increase in open disks. This delay in 3H-band displacement may reflect a time delay as a result of propagation of compressive stress in an elastic ROS system. Maximal disk loss from ROS as reflected in counts of phagosomes in the pigment epithelium occurred within 1 h of light exposure, and phagosome counts remained high for 4 h before declining to a low level in darkness. Modified lighting regimes affected the daily rhythms of shedding and disk addition differently, suggesting that control mechanisms for the two processes are not directly coupled. During 3 days in darkness, disk addition was reduced 50% compared to controls (12L:12D), whereas shedding was reduced by about 40%. Although reduced in level, shedding occurred as a free-running circadian rhythm. There was no evidence of rhythmicity of disk addition in darkness. In constant light, the rate of disk addition was not different from controls, but shedding was reduced by about 80% after the 1st day. This resulted in a 21% increase in ROS length. Among animals kept on a 2.5L:21.5D cycle, the rate of disk addition was reduced by 40% while shedding was maintained near control levels, resulting in a slight decrease in ROS length. These observations indicate that normal shedding requires alternating light and darkness, and that the daily rhythm of disk addition is due primarily to daily stimulation by light. | US |
Pigment migration in cultured erythrophores of the squirrel fish Holocentrus ascensionis, after manipulation with K+, epinephrine, 3',5'-dibutyryl cyclic adenosine monophosphate, theophylline, and caffeine, is essentially identical to that observed in this chromatophore in situ. For such observations, the erythrophores are dissociated from the scales with hyaluronidase and collagenase, and allowed to spread on an amorphous collagen substrate, where they resemble the discoid erythrophore in situ. In this state, they are readily fixed by glutaraldehyde and osmium tetroxide, and are then critical-point dried for whole-cell viewing in the high voltage electron microscope. The organization and fine structure of the erythrophore cytoplast was stereoscopically examined after fixation of the pigment granules in four experimental states: pigment dispersed, pigment aggregated, pigment aggregating, and pigment dispersing. In the dispersed cell, granules are contained in an extensive three-dimensional lattice composed of radially oriented microtubules and a network of fine filaments 3-6 nm in diameter (microtrabeculae), whereas in the aggregated cell, the microtrabecular system is absent, and the majority of the microtubules appear displaced into the cortices on the cytoplasmic surface of the plasma membrane. In cells fixed while aggregating, few microtrabeculae are observed, although formless thickenings are observed in the cortices, on granules, and between clumped granules. In dispersing cells, the microtrabecular system is reformed from material stored in the cortices and with the granules in the centrosphere. These observations suggest that the granules are suspended in a dynamic microtrabecular system that withdraws during pigment aggregation and is restructured during pigment dispersion. The microtubules guide linear granule motion not by defining physical channels, but by a recognizable affinity of microtubules, microtrabeculae, and granules for one another. | US |
To determine whether microtubules are linked to intracellular transport in absorptive cells of the proximal intestine, quantitative ultrastructural studies were carried out in which microtubule distribution and content were determined in cells from fasting and fed animals. Rats were given a 1-h meal of standard chow, and tissue was taken from the mid-jejunum before, 1/2 h, and 6 h after the meal. The microtubule content of apical, Golgi, and basal regions of cells was quantitated by point-counting stereology. The results show) that microtubules are localized in intracellular regions of enterocytes (apical and Golgi areas) previously shown to be associated with lipid transport, and that the microtubule content within apical and Golgi regions is significantly (P less than 0.01) reduced during transport of foodstuffs. To determine the effect of inhibition of microtubule assembly on transport, colchicine or vinblastine sulfate was administered to postabsorptive rats, and the lipid and microtubule content of enterocytes determined 1 and 3 h later. After treatment with these agents, lipid was found to accumulate in apical regions of the cells; this event was associated with a significant reduction in microtubule content. In conclusion, the regional distribution of microtubules in enterocytes, the decrease in assembled microtubules after a fat-containing meal, and the accumulation of lipid after the administration of antimicrotubule agents suggest that microtubules are related to lipid transport in enterocytes. | US |
Renal corpuscles from the juxtamedullary and subcapsular regions of the renal cortex were morphometrically analyzed in young rats and in adult rats that had been unilaterally nephrectomized or sham-operated at an early age. Mean corpuscular volumes increased 4.5-fold during normal development, and 7.7-fold as a result of compensatory hypertrophy in both cortical regions. Relative and absolute volumes were determined for Bowman's space, the glomerular tuft, and five glomerular components: epithelial, endothelial, and mesangial cells, capillaries, and the filtration membrane. Normal and hypertrophic enlargement of Bowman's space was slightly greater than glomerular growth, and the growth response of subcapsular glomeruli was greater than that of juxtamedullary glomeruli. The ratio of mean glomerular volumes between outer and inner glomeruli was 1:2 in both adult groups. Both adult groups also developed nearly identical proportions of all glomerular component structures, representing a relative decrease of epithelial cells and increase of capillaries compared to the young animals. Normal and hypertrophic maturation involved absolute increases in all glomerular cell populations, the length of capillary loops and the surface area of the filtration membrane, all nearly in proportion to the respective four- and seven-fold increases in glomerular volume. Changes in the filtration surface area are consistent with published data for glomerular filtration rates in normal and hypertrophied kidneys. The mean cell size in epithelial and mesangial populations doubled during growth, but was not greater than normal in mononephrectomized rats. Hyperplasia among all populations of glomerular cells is indicated in normal growth, and to a greater extent in compensatory renal hypertrophy. | US |
An examination was made of the services received by Chicano and Native American clients in 17 community mental health facilities. Although these minority clients differed from Anglos in demographic variables, there was no evidence that they were rendered inferior or discriminatory services. However, failure to return for therapy was much higher among minority clients. Possible reasons for this failure to return are discussed. It is suggested that for ethnic group clients, equality of services may not mean responsive services. | US |
One hundred and eleven cases of syncope or loss of consciousness are analyzed. Most are of obscure nature while some illustrate features of syncope that deserve further scrutiny. The cases are divided into six groups: Resembling cardiac syncope (30 cases); vasovagal syncope (22 cases); features of both cardiac and vasovagal syncope (12 cases); orthostatic hypotensive (29 cases); akinetic seizure? (12 cases); and miscellaneous (5 cases). Some groups are subdivided according to the circumstances surrounding the spells, for example, seated eating, nocturnal, associated with bowel movement, response to anticonvulsant therapy, etc. The following conclusions seem warranted: The evidence favors the existence of a type of akinetic seizure resembling cardiac syncope; loss of consciousness while seated eating (prandial syncope) may comprise a syndrome; syncope related to bowel movement or abdominal pain is a striking association; sporadic nocturnal syncope due to temporary hyporeactivity of baroreceptors is not sufficiently recognized; alcohol ingestion may precipitate orthostatic hyporeactivity of baroreceptors is not sufficiently recognized; alcohol ingestion may precipitate orthostatic hypotension. Familial syncope, syncope proneness and cold drink syncope are illustrated. | US |
The toxic action of misonidazole towards hypoxic mammalian cells has been shown to be a function of serum concentration, with higher serum concentrations enhancing the toxic effect. Added thiols protect cells against misonidazole toxicity. In addition, the action of misonidazole on hypoxic cells labelled with 5-BUdR has been examined. Cells with incroported 5-BUdR are no more sensitive to misonidazole toxicity than are cells without label. | United Kingdom |
The clinical use of misonidazole as a hypoxic cell radiosensitizer is at present limited by its neurotoxicity at high doses (Urtasun et al., 1977; Dische et al., 1977). An in vivo neurological end point, viz. measurement of nerve conduction velocity, has been developed to examine sensitizer action. Conduction velocity in mice was measured as a function of time after a single dose of misonidazole and as a function of drug dose. Doses greater than 0.33 mg/g produced significant transient reductions in velocity. The time course of the reduction in velocity closely followed the uptake/excretion profile of misonidazole from blood serum. | United Kingdom |
The structure of the staphylococcal nuclease (EC 3.1.4.7)-thymidine 3',5'-bisphosphate-Ca(2+) (enzyme-inhibitor) complex has been extended to 1.5-A resolution by using much additional data and a phase refinement scheme based on an electron-density map modification procedure. By correlating this structure with the known properties of the enzyme, a mechanism of action is proposed that involves nucleophilic attack on phosphorus by a water molecule, which is bound to Glu-43, in line with the 5'-CH(2)O(H) leaving group. The carboxylate of Glu-43 promotes this attack by acting as a general base for the abstraction of a proton from the attacking water molecule. Nucleophilic attack is further facilitated by polarization of the phosphodiester by an ionic interaction between a Ca(2+) ion and a phosphate oxygen atom and by four hydrogen bonds to phosphate oxygen atoms from guanidinium ions of Arg-35 and Arg-87. These interactions may also catalyze the reaction by lowering the energy of a trigonal bipyramidal transition state. The hydrolysis of nucleic acid substrate proceeds by cleavage of the 5'-P-O bond to yield a free 5'-hydroxyl group and a terminal, 3'-phosphate monoester group. In the inhibitor complex the only general acid group found in a position to donate a proton to the leaving 5'-oxygen is the guanidinium ion of Arg-87. Alternative proton donors, presently lacking direct structural support, could be the phenolic hydroxyl group of Tyr-113 or a water molecule. The precision and rigidity of the location of the reactants at the active site and the probable dual binding and catalytic roles of the guanidinium ions of Arg-35 and Arg-87 are especially noteworthy. | US |
Twenty-five patients with symptoms of myofascial pain and abnormal jaw function were treated with use of a full arch maxillary occlusal splint. The level of nocturnal activity of the masseter muscle was monitored as were symptoms before, during, and after occlusal splint therapy. A decreased nocturnal EMG level during treatment was noted for 52% of the patients. A return to pretreatment EMG levels after removal of the splint was noticed in 92% of the patients; in 28% no change was shown and in 20%, an increase was shown in nocturnal EMG levels. The splint was most likely to reduce nocturnal EMG levels in patients with least severe symptoms. | US |
We used a combined behavioral and electrophysiological technique to test the hypothesis that storage of information is impaired in childhood autism. Endogenous event-related potentials associated with the random deletion of stimuli within a regular train of auditory or visual stimuli were examined in three autistic and three normal children. We found that all subjects were able to detect the stimulus deletions, but cortical potentials associated with stimulus omissions were smaller or absent in the autistic subjects. These results are consistent with dysfunction within the system that includes posterior parietal cortex and its connections with the mesolimbic temporal cortex and hippocampus. | US |
Beta-endorphin, morphine, and saline were given intravenously to a single schizophrenic subject on separate occasions in a double-blind design. EEG spectral analyses performed on data collected before and after drug injection demonstrated that beta-endorphin and morphine produced similar increases in alpha power within 5 to 15 minutes after injection. This effect could be distinguished from two placebo (saline) injections. These data suggest that intravenous beta-endorphin can produce changes in the central nervous system in humans. | US |
Interindividual differences in endorphin levels may relate to widespread changes in adaptive processes, and endorphin levels may thus be related to personality traits. In 40 patients with chronic pain syndromes of both psychogenic and organic origin, endorphin levels in cerebrospinal fluid (CSF) were determined, and the patients completed Eysenck's Personality Inventory (EPI) and the Cesarek Marke Personality Scheme. Twenty-seven of the patients also completed the Zuckerman Sensation Seeking Scale (SSS). As a comparison group 30 healthy volunteers completed the personality inventories. The chronic pain patients were characterized by guilt feelings, need for order, low need for autonomy, and low tendency toward sensation seeking. Low levels of endorphins in CSF were found in patients with high scores on all the subscales in the SSS and low scores on the neuroticism subscale in the EPI. | US |
A systematic programme of research on the development of spatial vision (acuity and contrast-sensitivity functions or CSFs) in human and macaque monkey infants (Macaca nemestrina) is described. A forced-choice preferential looking technique has been used to follow the development of acuity in both species. Acuity development is similar across the two species, with the infant monkeys progressing about four times faster than the human infants. Operant conditioning has been used to trace the development of CSFs in monkey infants. Changes in the shape of the CSF are shown for at least 20 postnatal weeks in the macaque infants. Strabismic and meridional amblyopias have also been mimicked in infant monkeys, and the time course of development of strabismic amblyopia in a monkey is described. It is argued that closely parallel behavioural studies, carried out on both species, are important in establishing the monkey as a model for human visual development. | US |
A hand-held stimulator-ophthalmoscope was used to elicit foveal cone electroretinograms (ERGs) from fifteen patients with strabismic amblyopia. The ERGs were in response to a 4 degrees stimulus visualized on the fundus and centred on the fovea throughout testing. Foveal cone ERGs from amblyopic eyes were normal in amplitude and normal in b-wave implicit time. Interocular differences in ERGs in patients with amblyopia were no greater than those in normal subjects. Patients with comparable visual acuity loss due to macular scars or juvenile hereditary macular degeneration had abnormal foveal cone ERGs, while patients with optic atrophy had normal responses. These findings support the idea that the defect in strabismic amblyopia does not involve a functional abnormality in the fovea distal to the ganglion cell layer. | US |
The geniculocortical pathways of many mammals, including primates, are largely comprised of two neuron types. These are known as X and Y cells. Their functional significance in unclear, but the following highly speculative hypothesis is suggested. Y cells, because of their broad sensitivity to the crucial lower spatial frequencies as well as to the higher ones, are involved in a basic analysis of form vision. X cells, because of their fairly selective sensitivity to higher spatial frequencies, add to this certain details (i.e. enhanced acuity, etc.). If an animal develops with ametropia, Y cells should be adequately stimulated and as the lower spatial frequencies remain undistorted many Y cells would develop and reasonable form vision with milk amblyopia would result. Only X cells would be greatly affected by such an environment. However, if the animal develops with cataracts or is reared in an environment which abolishes all spatial frequencies, then neither X nor Y cells will develop. This would result in poor form vision and a deep amblyopia. Many of these phenomena have been observed in experimental studies of cats. The present relevance for clinical problems of this suggested functional dichotomy for X and Y cells is at best tenuous, and it is offered merely as a working hypothesis for future studies. | US |
We have studied the relative importance of visual and nonvisual signals to striate neurons in causing the loss of cortical binocularity that occurs when young kittens are subjected to brief episodes of stabismus. In kittens kept in a normally illuminated colony, the reduction in binocularity was the same whether the strabismic was induced optically or surgically. When surgically strabismic kittens were kept in total darkness, cortical binocularity was unchanged. We conclude that anomalous visual input is both necessary and sufficient to cause loss of binocularity in strabismic kittens and that nonvisual (proprioceptive) input from the orbit has no part in producing this effect. | US |
Studies of the striate cortex of the kitten are reviewed with reference to the effects of very brief periods of uniocular occlusion. It is shown that changes occur in binocular connections within 4 hours after the vision of an eye is blocked. Effects are also found if the occlusion is instituted while an animal is anaesthetized but not if it is paralysed in addition. If 4-hour unilateral 'patching' sessions are given daily, a cumulative uniocular deprivation effect is found if the animals are kept in darkness between the patching sessions. However, the visual cortex is nearly normal if the kittens are allowed binocular vision between patching periods. | US |
Uniocular occlusion (dark patching) of adults for a period of days produces marked reduction in the directional sensitivity of the eye (Stiles-Crawford effect). The effect reaches a maximum 3 to 5 days after the onset of patching. Recovery occurs in a comparable period. The second eye is not affected, and a simple light diffuser fails to produce the same effect. Coupled with alteration in directional sensitivity are an overall increase in sensitivity and modest resolution and perceived colour changes. These findings, with other research, suggest that directional sensitivity is at least partially mediated by light and that orientation of photoreceptors is an active process. | US |
A sensitive period exists in humans and experimental animals during which certain visual functions are modifiable by decreased or abnormal visual stimulation. Experiments in monkeys have shown that, at the beginning of this sensitive period, the manifestations of the visual deprivation syndrome develop more rapidly at the cortical than at the geniculate level. Moreover, a shift of cortical dominance as the result of reverse suturing may occur while the geniculate nucleus still reflects the effects of the original deprivation experiment. At the end of the sensitive period the behavioural, electrophysiological, and histological aspects of the visual deprivation syndrome become less predictable. Cortical physiology remains sensitive to abnormal visual input beyond the first 3 months of life. Clinical examples and animal experiments also suggest that the reversal of the effects of visual deprivation may occur long after maturation of the visual system is completed. These findings support the view that abnormal visual stimulation during visual infancy causes a functional reorganization rather than an arrest of development of anatomical retinocortical connections. | US |
The significance of the distinctive morphological difference between mammalian and non-mammalian vertebrate erythrocytes (disc versus ellipse) is discussed in the light of mammalian erythrocyte rheology. | US |
Dynamic aspects of whole body protein (nitrogen) metabolism were explored in healthy young adults and elderly men and women. Measurements were made of the rate of whole body protein breakdown, with the aid of 15N-glycine, and the rate of muscle protein breakdown, as estimated from urinary N tau-methylhistidine excretion. The results also were evaluated in relation to obligatory (endogenous) urinary nitrogen losses, previously determined in this laboratory for the two age groups. Rates of whole body and muscle protein breakdown, per unit body weight, were lower in elderly subjects than in young adults. Muscle accounted for a mean of 27% of whole body protein breakdown in young adults and 20% or less (p less than 0.01) in elderly subjects. Daily obligatory N loss was positively correlated (p less than 0.01) with whole body protein breakdown. It was calculated that muscle contributed less to the obligatory N output in elderly subjects than in young adults. These results indicate a change in the distribution of whole body protein metabolism during aging in human subjects, with muscle making a lower contribution to total body protein metabolism in elderly subjects compared with young adults. | US |
The time required to name four groups of pictures was measured in 83 community dwelling males (18-70 years of age). One group consisted of objects used 50 to 70 years ago (unique dated exemplars), and another consisted of objects unique to contemporary times (unique contemporary exemplars). For comparison, other pictures of contemporary and dated objects commonly used in both periods were employed. There were three major findings. One, the familiarity of the pictured object is the major determinant of the time required to retrieve its name. Older subjects named the dated unique objects that were relatively more familiar to them more rapidly than did younger adults, while the reverse was true for contemporary unique objects. No age difference in the speed of naming common contemporary objects was found. Two, the overall age-related difference in naming latency was attributed to perceptual-motor aspects of the task. Three, the physical features as well as the familiarity of the object contributed to the speed of retrieval of the object's name. | US |
Two experiments were carried out to measure age-related differences in speed of error-free recall by normal adults. The major results were that: (a) the time taken to read a word aloud (retrieval from lexical memory) does not increase appreciably until subjects reach their 60s; (b) the time taken to recall a verbal item just attended to (retrieval from primary memory) increases steadily throughout the adult years, and most markedly between the sixth and seventh decades; and, (c) the time taken to recall recent verbal information outside the span of attention (retrieval from secondary memory) also increases as a function of chronological age, at a relatively rapid rate and most markedly between the fifth and sixth decades. The effects are independent of the number of stimulus-response alternatives. | US |
In a simulation of the "cocktail party" problem, subjects listened to recordings of a target voice, obscured by four background voices from adjacent locations in space. Listening conditions were either dichotic (with interaural directional cues preserved) or diotic (same input to both ears, directional cues removed). Elderly subjects were unable to use binaural directional cues as effectively as young subjects to improve intelligibility of the target voice. The results suggest that there is an age related deficit in the ability to perform the binaural signal analysis necessary to effectively separate speech signals from noise. | US |
This study described several brief behavioral measures which, with further validation, could be useful in predicting the deaths of older adults within a five-year period following testing. Such tests can be used in routine biomedical examinations, alerting the physician to possible problems in the future. The study was based on a battery of 18 tasks as well as 8 measures of health, social activity, and demographic characteristics administered to 380 healthy men and women aged 60 to 89 years. Five years later, the scores of those who had subsequently died (N = 83) were compared with a matched sample of those still living. Thirteen of the 18 task performances significantly distinguished between those still living and those who died. Discriminative analyses were carried out, and the discriminative score cut-offs correctly classified 66% of the subjects as to survival status. | US |
In the present state of science no morphological or chemical changes may be detectable at a time when behavior is profoundly disturbed, as in schizophrenia. Until we are reassured to the contrary, we must assume that exogenetic intoxication can produce changes detectable only as behavioral changes. Therefore behavioral toxicology must be studied. In contrast to toxic manifestations such as lethality or carcinogenicity, which tend to be unequivocal and irreversible, behavioral changes are like physiological changes in that they are quantitative, changing in time, and relate to variables with a considerable range of normal variability. An experiment on behavioral teratology in mice is described and the results used to illustrate the limits of the possible in behavioral toxicology. From reported and observed variability it is surmised that changes that occur in as many as 1 per 100 of the population or average as large as a 10% decrement will still be too small to be detected by direct experiment. Such risks are frequently unacceptable. Reasons are given for hoping that epidemiological studies may be able to supplement experimental toxicological studies to provide a better assessment of risk of small impairments or rare susceptibility. | US |
Two sets of observations are reported as illustrations of problems encountered in behavioral toxicology. First, in an attempt to determine the contribution of methylmercury-induced ataxia to behavioral changes observed on the fixed-consecutive-number schedule, some ancillary control experiments were undertaken. Neither pharmacologically-produced incoordination (ethanol) nor mechanically-produced incoordination (foot taping) led to behavioral changes similar to those seen after exposure to methylmercury. Second, total crop impaction in a pigeon that died during a behavioral experiment on lead suggested some further work. Lead-induced crop stasis in pigeons was measured by x-raying the passage of force-fed stainless steel ball bearings through the crop. This retardation of motility reliably preceded signs of overt toxicity. These results suggest that the behavioral changes in the pigeon noted by us and reported by other investigators cannot be attributed to CNS dysfunction alone, but more likely arise from starvation, or from combined CNS damage and starvation. In addition, these results demonstrate that the appearance of behavioral effects prior to overt toxicity does not necessarily reflect CNS damage. | US |
Behavioral toxicology in the natural environment can be considered a special branch of epidemiology. Behavioral epidemiology, because it typically relies on complex functional criteria, faces all of the problems of behavior measurement posed by uncontrollable variation, and amplified even further by chemical exposure. Many such issues arose in a study of behavioral responses to artificial food colors in children. Difficulties in employing Applied Behavioral Analysis in such a context run the gamut from selection of retrospective criteria to appropriate statistical models. | US |
The analysis of visual toxicity is complicated by the heterogeneity of visual capacities in different regions of the visual field. Since various toxicants may impair different functions allied to localized portions of the visual field, it is important to explore the relationship of field defects to residual visual abilities. We have begun this exploration by studying methylmercury poisoning in macaque monkeys. Extended exposure to this toxicant produces a marked concentric constriction of visual fields, a result similar to that found in human victims. In addition, visual sensitivity is greatly reduced on those tests in which the periphery of the visual field is more sensitive than the center. Our findings suggest simple but reliable clinical tests for screening suspected victims of substances impairing peripheral vision. | US |
Neonatal rats were exposed to lead (Pb) from parturition to weaning via the milk of dams which consumed 0 (tap water), 0.02% or 0.2% PbAc2 solutions. To determine if this regimen altered physiological and neurobehavioral development, responses to a battery of sensory-motor tests were evaluated during maturation and as adults. The tests were: visual evoked responses (VER), temperature regulation, maximal electroshock seizure patterns, reflex patterns, and neuromuscular performance. Overall results revealed that the Pb-exposed group compared to controls exhibited delayed maturation, altered developmental patterns and long-term CNS disturbances. Additionally, low-level strychnine administration during development caused additive interactions with both Pb groups, uncovering subtle effects of toxicant exposure. These sensitive and quantifiable techniques proved useful for assessing CNS functioning following perinatal insult, and except for the VER, are simple to conduct and cost efficient because they require a minimal amount of personnel training, equipment cost and time invested per animal. These screening tests also suggest further areas of study and may indicate the mechanism(s) responsible for the deficit. | US |
Pregnant Sprague-Dawley rats received 25 mg/kg of prochlorperazine, 20 mg/kg of fenfluramine, 75 mg/kg of propoxyphene or 200 mg/kg of diazepam daily between the 7th and 20th days of gestation. Vehicle control groups and a positive control group (vitamin A 40,000 IU/kg/day) were similarly prepared. Observations of reproductive performance were made and the offspring examined in a battery of neurobehavioral tests. Fenfluramine and prochlorperazine produced abnormalities in both the reproductive measures and neurobehavioral testing. Propoxyphene produced developmental delays and other signs of "pure" behavioral teratogenesis in that these effects were not anticipated in any of the observations of reproductive performance. Diazepam appeared to have the mildest effect on all the measurements taken. The test methods used in this study appear to be a reasonable initial approach to the development of neurobehavioral screening procedures which are comprehensive, sensitive, and usable. | US |
Broad agreement on specific approaches or standardized test batteries for assessing behavioral toxicity is unlikely to emerge in the foreseeable future. EPA should reject test standardization in any case, however; standardization stifles progress and, in addition, may bypass unique properties of new types of substances. The optimal strategy is to prescribe a set of functions, such as sensory, motor, and complex performance processes, leaving it to the manufacturer to select adequate tasks. Adequacy would be judged by EPA staff, in consultation with advisory panels, and resolved, in most cases, by a dialogue with the manufacturer. | US |
Behavioral conditioning together with conventional sensory testing methods may be used in the evaluation of toxic effects on sensory systems in experimental animal models. Such procedures yield precise quantitative estimates of impairment in absolute and differential acuity and in sensory perception. Additionally, these behavioral changes can be related to the presence of histopathology in peripheral sensory structures; this orderly relation between structure and function may aid in our understanding of the basis for sensory coding in the normal end organ. | US |
Laboratory procedures have been developed for the experimental analysis of risk-taking and psychophysical functions in dog-faced baboons (Papio anubis). In a procedure analogous to the traffic light situation, animals are rewarded with food pellets for completing a fixed ratio of 100 responses in the presence of a green light. Superimposed upon this baseline performance are 5-second presentations of a yellow warning light terminated by a red light in the presence of which all responses are punished with electric shock. When the yellow light is introduced late in the sequence (e.g., after 93 responses have been completed), response rates increase and the 100-response ratio is completed before the 5-second yellow light times out. When the yellow light appears early in the sequence (e.g., after 73 responses) a marked decrease in response rate is observed with cessation of responding before onset of the red light. The sensitivity of components of this risk-taking performance to pharmacological toxicants is reported and psychophysical assessment of relevant sensory-motor effects described. | US |