Observations with cytochemistry and ultracryotomy on the fine structure of the expanding walls in actively elongating plant cells. Ultracryotomy with negative staining and cytochemistry (periodic acid - thiocarbohydrazide - silver proteinate test for polysaccharides, in conjunction with mild extractions) were used to study the architecture of the cell wall and its modifications during expansion. Those techniques were applied to the study in situ of the walls of actively elongating parenchyma of mung bean (Phaseolus aureus), and pea (Pisum sativum) root and of collenchyma of celery (Apium graveolens) petioles. These complementary techniques provide information on the 3-dimensional disposition and fine structure of the subunits of the wall. In all the examples examined, the bulk of growing primary wall appears well-ordered and no progressive evolution from a transverse texture near the plasmalemma to a scattered texture near the middle lamella was observed. It seems unlikely that the development of the wall structure in relation to growth could be explained mechanically by a passive shift of the fibrillar elements in response to cellular stress. There is no evidence for an inert change in fibrillar orientation in the major part of the wall. If such occurs the process is limited to the outermost and senescent part of the wall. Thus, the texture observed does not agree with the classical multinet growth hypothesis but rather with the idea of an ordered structure of the primary wall. With the latter, the components should be able to respond in different ways to specific growth regulators and other environmental signals and thus exert a more positive control over the processes of oriented cell growth.


Supercoils in human DNA.

Supercoils in human DNA. The three-dimensional structure of a double-stranded DNA molecule may be described by distinguishing the helical turns of the DNA duplex from any superhelical turns that might be superimposed upon the duplex turns. There are characteristic changes in the hydrodynamic properties of superhelical DNA molecules when they interact with intercalating agents. The hydrodynamic properties of nuclear structures released by gently lysing human cells are changed by intercalating agents in this characteristic manner. The characteristic changes are abolished by irradiating the cells with gamma-rays but may be restored by incubating the cells at 37 degrees C after irradiation. These results are interpreted as showing that human DNA is supercoiled. A model for the structure of the chromosome is suggested.


Gas chromatographic resolution of enantiomeric amphetamines and related amines. II. Effects of cyclic structures on diastereomer and enantiomer resolution. Proline and other cyclic amino acids were used as acylated acid chlorides for the resolution of enantiomers of amphentamine and related amines as diastereomers by gas chromatography. Variation of ring size or incorporation of a heteroatom into the ring of the cyclic resolving agent changed retention times and separation factors, depending on the racemic amine derivatized. Separations were achieved on a short, packed Carbowax 20M column. Because N-trifluoroacetyl L-prolyl chloride has proved especially effective for derivatization of amine enantiomers to give diastereomers which often may be resolved by gas chromatography, the proline ring was incorporated into a new optically active stationary phase. For the enantiomeric derivatives examined, the new proline ester phase gave separations essentially equivalent to those obtained on the commercially available phase, carbonyl bis-(L-valine isopropyl ester). The fact that resolution was achieved on the new phase is evidence that, as has been previously suggested, the ester carbonyls of this type of phase are the significant sites of interaction with the antipodes undergoing separation.


Separation of thiazide diuretics and antihypertensive drugs by thin-layer chromatography. A procedure is reported for the thin-layer chromatographic (TLC) separation and identification of thiazide diuretics and other antihypertensive drugs. Several new solvent systems and a variety of possible detection reagents were examined. Twenty thiazides used routinely in therapy were successfully separated and identified. Use of the TLC systems and combinations of the detecting methods described should be useful for the identification of these drugs in biological fluids and in various dosage forms.


Electron-capture gas chromatography of barbituric acids and diphenylhydantoin after pentafluorobenzylation. Alkylation of barbituric acids and diphenylhydantoin with pentafluorobenzyl bromide is described; the reaction is quantitative in the presence of excess of triethylamine. The electron-capture detector response of the derivatives is high, ranging from 2 to 8 x 10(-17) moles/sec. The derivatives demonstrate excellent peak symmetry and are well suited to quantitative analysis. The structures of the derivatives have been confirmed by mass spectrometry.


Isolation and gas chromatographic characterization of some toxaphene components. Column chromatography of technical toxaphene on activated alumina reproducibly yields eight major fractions from which 2,2,5-endo,6-exo,8,9,10-heptachlorobornane and 2,5,6-exo,8,8,9,10-heptachlorodihydrocamphene may be readily isolated by preparative gas--liquid chromatogrpahy. These and some other reported toxaphene components were characterized by gas--liquid chromatographic retentions relative to aldrin on packed columns of OV-101, OV-17, and QF-1, and on a capillary open-tubular column of OV-101. Structural assignments were revised for some components on the basis of retentions. The fractionation and isolation procedure may have general utility for separating toxaphene components, and the retention data form a convenient basis for component comparison.


Thin-layer chromatographic analysis of cocaine and benzoylecgonine in urine. The sensitivity achieved by the described thin-layer chromatographic (TLC) method greatly exceeds that of previously published TLC methods for the determination of cocaine and its principal metabolite, benzoylecgonine, in urine. Sensitivity for cocaine and benzoylecgonine approaches 0.1 and 0.25 mug/ml, respectively, for a 5.0-ml specimen. A simple extraction with a mixed organic solvent provides the basic mechanism for isolating the drugs from biologic specimens. Cocaine and its metabolites are stable in sulfuric acid solutions but labile in aqueous media containing certain other inorganic and organic acids; therefore, an emphasis on the utilization of sulfuric acid solutions is employed throughout the procedure. An evaluation of sensitivities achieved for cocaine and benzoylecgonine by various detection reagents is presented. The technique is applicable to drug screening programs.


Evaluation and selection of optimal solvents and solvent combinations in thin-layer chromatography. Application of the method to basic drugs. A series of simple mathematical techniques for the evaluation of solvents and solvent combinations in thin-layer chromatography have been investigated. A strategy for the rapid selection of the optimum combination is proposed. It uses classification procedures based on calculation of the similarity between systems. The classification is carried out using a simple graph-theoretical procedure (Kruskal's algorithm) or numerical taxonomy. The selection of optimal sets from the clusters which appear in the classification is based on the information content as derived from Shannon's equation. The method has been applied to an RF data set for basic drugs. It is concluded that these methods indeed allow the selection of optimal systems or combination of systems.


The analysis of paraquat in urine by high-speed liquid chromatography. The paraquat content of urine can be directly determined by high-speed liquid chromatography using ultraviolet spectrophotometric detection. The method separates paraquat (and diquat) from the ultraviolet-absorbing components of urine and no extraction or pre-treatment of the sample is required prior to analysis. Concentrations down to 100 mug/1 of paraquat in urine were determined. Quantitative results are in good agreement with those obtained by a colorimetric method. Diquat does not interfere with the analysis of paraquat, and it would also be possible to analyse diquat in paraquat-containing urine.


Behaviour of cardiac glycosides and cardenolides related to digitoxigenin on sephadex LH-20. The behaviour of six cardenolides and eight cardiac glycosides related to digitoxigenin during column chromatography on Sephadex LH-20 gel has been investigated. Complete resolution was obtained for mixtures of digitoxigenin, gitoxigenin and digoxigenin, but not for those of the 3-epimeric cardenolides. It was possible to achieve a group separation of cardenolides and their glycosides of the digitoxigenin series from those of the digoxigenin or gitoxigenin series.


Thin-layer chromatographic assays of histamine and its metabolites in urine of man and dog. A method for the extraction and quantitation of histamine and its metabolites from relatively small volumes of urine is described. It employs primarily ion-exchange and thin-layer chromatography and allows for quantitation in the mug range. Studies of atopic man and dog that employed this procedure yielded values comparable to those reported with gas chromatographic methods.


Sterols of scallop. I. Application of hydrophobic sephadex derivatives to the resolution of a complex mixture of marine sterols. Column chromatography on a hydroxyalkoxypropyl derivative of Sephadex LH-20 and on Anasil B has been applied to the resolution of complex marine sterol mixture in combination with argentation thin-layer chromatography and gas chromatography. This approach permits isolation in quantity of individual sterols from a complex mixture and separation of sterol mixtures that were not resolved without the modified Sephadex step. Seventeen sterols were detected in the scallop Placopecten magellanicus. 24-Methyl-cholesterol, 24-ethyl-cholesterol, 24-methyl-22-dehydrocholesterol and 24-ethyl-22-dehydrocholesterol, i.e. sterols whose configuration at C-24 had not been definitively established, were isolated in sufficient quantities for further study by nuclear magnetic resonance spectroscopy.


Gas-liquid chromatographic studies of reactions and structural relationships of steroids. IV. Substitution in the pregnane side-chain. Qualitative and quantitative effects of classical reactions on steroids observed by gas-liquid chromatography (GLC) under standardized conditions, including the double internal standard technique are reported. Simple procedures applicable to nanogram amounts of reactants are described. Reactions studied include the conversion of keto groups to hydroxyl groups by NaBH4, and to dioxolone derivatives by 1,2-diethanol; 17 alpha-hydroxylation of C20-ketosteroids; the conversion of hydroxyl groups to trimethylsilyl (TMS) ethers by hexamethyldisilazane; the hydrolysis of dioxolone and TMS derivatives by H+. Effects of Wolff-Kishner reagents, and CrO3 were also studied. GLC chromatograms of reaction mixtures of single- and multistep reactions readily provide information on effects on functional groups at positions 3, 17, 20, and 21 in the pregnane series, and the retention times of many steroids unavailable from commercial and other sources. GLC data analysis provides relationships between steroid structure and retention time from which methods for the computation of retention times and for steroid identification are designed. The accuracy of the computation methods is demonstrated.


Application of over-run thin-layer and gas-liquid chromatography in the separation of closely related C19O2 steroids. An improved method for the separation of epimeric C19O2 steroids and their related allylic alcohols is described. In this method, the steroids are first separated by over-run thin-layer chromatography, and the unresolved groups are further analysed as free or as trimethylsilyl ether derivatives by gas-liquid chromatography. The behaviour of twenty-one C19O2 steroids was investigated by thin-layer chromatography in four systems and by gas-liquid chromatography in four liquid phases. All steroid pairs of similar polarity were resolved by the combination of these two fractionation procedures.


[Separation of the four diastereoisomers of 6-hydroxy-5, 6-dihydrothymidine formed by gama-radiolysis of thymidine in deaerateed aqueous solution (author's transl)]. The compounds produced by gamma irradiation of deaerated aqueous solutions of thymidine have been isolated by thin-layer chromatography. The separation of (+) and (-) trans and cis diastereoisomers of thymidine "hydrates" has been carried out. Correlations between conformations given by nuclear magnetic resonance spectra and RF values are discussed.


Analysis and purification of 2-hydroxyethyl methacrylate by means of thin-layer chromatography. Poly(2-hydroxyethyl methacrylate) is nowadays accepted as a biocompatible, safe and stable hydrogel for medical use. In this paper, the use of thin-layer chromatography for the analysis and small-scale preparation of the initial monomer, 2-hydroxyethyl methacrylate, is described. Development on silica gel, with n-hexane-diethyl ether (1:1, v/v) and/or n-hexane-isobutyl methyl ketone-n-octanol (9:2:1, v/v; saturated with 25% nitric acid) is recommended for qualitative analysis. Preparative-scale work is preferably carried out on sulphuric acid-impregnated silica gel, with n-hexane-diethyl ether (1:1, v/v) as mobile phase. Inhibitors are detected by thin-layer chromatography and a drop-test procedure with diazotised sulphanilic acid. The nature of the contaminants present in several commercial samples of 2-hydroxyethyl methacrylate is discussed. n20D values are reported for the system 2-hydroxyethyl methacrylate-water.


Gas chromatography of alpha-keto acids as their O-trimethyl silylquinoxalinol derivatives. The O-trimethylsilyl (TMS) quinoxalinols are very useful derivatives for the gas chromatography of alpha-keto acids because of their high stability and the absence of stereoisomerism and because of the presence of specific, common and abundant fragments in electron impact mass spectra, which allows the low-level detection of whole groups of keto acids by single-ion detection. In this paper, the chromatographic properties of eleven O-TMS-quinoxalinols on OV-1, OV-17 and Dexsil 300 are reported in terms of methylene units. Also by use of methylene units, the chromatographic isotope effect is analyzed in detail for nine perdeutero-TMS derivatives. The effect is explained by the diminished interaction of the deuterated compounds with the unlabelled liquid phase.


Identification of carcinogenic acetates of fluorenylhydroxamic acids by high-pressure liquid chromatography. A method for the identification and quantitation of carcinogeniic O-acetates of fluorenylhydroxamic acids by high-pressure liquid chromatography is described. The adsorbent is Corasil II and a mixture of ethyl acetate-n-hexane (1:1) is used as the solvent. N-Acetoxy-2-fluorenylacetamide or N-acetoxy-3-fluorenylacetamide are separable as single peaks from N-acetoxy-4-fluorenylacetamide and from N-acetoxy-2-fluorenylbenzamide. The peak height traced by the recorder is linearly proportional to the amount of compound in the effluent. The method can be utilized for the detection of 0.1-1.0 mug of compound. The method has been used to identify the products of the decomposition of N-acetoxy-2-fluorenylacetamide in aqueous media.


The determination of hydralazine in plasma by gas-liquid chromatography. A description is given of a gas chromatographic method for the determination of hydralazine in plasma. On treatment with nitrous acid, hydralazine is converted into tetrazolo[1,5-a]phthalazine, a stable compound that can be extracted from biological material with organic solvent and determined quantitiatively by gas-liquid chromatography. The 4-methyl analogue of hydralazine serves as internal standard for derivatization, extraction and gas chromatography. The sensitivity (10 ng per ml of plasma) is sufficient to monitor plasma levels in man after administration of single oral doses of 50 mg of Apresoline¿. The known metabolites do not interfere.


Evidence for two different modes of tripeptide disappearance in human intestine. Uptake by peptide carrier systems and hydrolysis by peptide hydrolases. The intestinal fate of two tripeptides (triglycine and trileucine), which differ markedly in solubility and molecular weight, have been investigated by jejunal perfusion in healthy human volunteers. Rates of glycine or leucine uptake from test solutions containing triglycine or trileucine were greater than from test solutions containing corresponding amounts of free glycine or free leucine, respectively. The rate of glycine uptake from a 100 mM triglycine solution was greater than that from a 150 mM diglycine solution. At each infused load of triglycine (e.g., 1,000 mumol/min) the rates (micromoles/minutes per 30 cm) of either triglycine disappearance (810 +/- 40) or glycine absorption (2,208 +/- 122) were markedly greater than the luminal accumulation rates of either diglycine (56 +/- 10) or free glycine (110 +/- 18). The luminal accumulation rate of free leucine during infusion of a 5 mM trileucine solution was over threefold greater than that of free glycine during the infusion of a 5 mM triglycine solution. Luminal fluid exhibited no hydrolytic activity against triglycine, but contained some activity against trileucine. Saturation of free amino acid carrier system with a large load of leucine did not affect glycine absorption rate from a triglycine test solution, but isoleucine markedly inhibited the uptake from a trileucine solution. When the carrier system for dipeptides was saturated with a large amount of glycylleucine, the disappearance rate of triglycine was considerably reduced while that of trileucine remained unaffected. After addition of glycylleucine to tripeptide solutions, there was a minimal increase in the luminal accumulation of diglycine, while dileucine accumulation was incresed by 62-fold.


Metabolism of prostaglandins A1 and E1 in man. To investigate the in vivo whole blood metabolic clearance rates and sites of metabolism of prostaglandins A1 and E1 in man, constant infusions of the tritiated compounds were administered to normal subjects and to patients undergoing cardiac catheterization. The whole blood metabolic clearance rate of [3H]prostaglandin A1 in eight men was 5,003 +/- 864 liters/day (SD) or 2,546 +/- 513 liters/day per m2 (SD). Nonradioactive prostaglandin A1 was similarly infused in two subjects, and the metabolic clearance rates were determined, utilizing a specific radioimmunoassay. The clearance rates with this method correlated closely with those determined by the isotope infusions. Extraction studies of prostaglandin A1 showed that pulmonary, splanchnic, renal, and extremity perfusions resulted in 8.1 +/- 4.1, 56.1 +/- 10.1, 50.3 +/- 3.4, and 34.4 +/- 5.9% (SEM) removal, respectively. With [3H]=prostaglandin E1, the whole blood metabolic clearance rate was determined from the pulmonary artery concentration in three patients and averaged 4,832 +/- 1,518 liters/day (SD) or 2,686 +/- 654 liters/day per m2 (SD). Pulmonary extraction was 67.8 +/- 6.8% (SEM) and extremity removal averaged 6.6 +/- 4.9% (SEM). These results indicate that A prostaglandins are metabolized by several organs, such as the liver and kidney, and possibly by intravascular pathways as well. In man, the E prostaglandins are primarily metabolized by the lung, but extraction is not complete and approximately one-third may escape lung metabolism. Thus, these findings suggest that both E and A prostaglandins in the venous circulation may reach the systemic circulation in man.


The relationship between regional myocardial perfusion at rest and arteriographic lesions in patients with coronary atherosclerosis. Measurements of mean left ventricular (LV) and regional myocardial blood flow rates were made at rest in 161 patients with 133Xe and a multiplecrystal scintillation camera. Myocardial perfusion rates were correlated with assessments of the degree of coronary artery disease made from the arteriograms obtained during the same studies. In patients with normal coronary arteries without heart failure, the presence of hypertension, aortic stenosis, or aortic insufficiency was not associated with changes in mean LV perfusion from the control value of 61+/-7 ml/100 g-min. However, mean LV perfusion was significantly reduced in patients with normal coronary arteries who had cariomyopathy and impaired ventricular performance. Mean LV perfusion was not significantly different from control values in patients with "mild" coronary artery disease (less than 50% obstruction) or in patients with significant isolated disease (greater than 50% obstruction) of the left anterior descending (lad) artery. Significant reductions in mean LV perfusion were found in patients with greater than 50% obstruction of two coronary arteries (LAD + right or LAD + circumflex) and in patients with triple-vessel disease. The average perfusion rate for regions distal to LAD obstructions in patients with isolated LAD disease was not lower than the LAD perfusion in control patients, but was significantly reduced in patients with LAD + right coronary artery disease (43+/-14 ml/100 g-min). In the latter group average perfusion distal to the LAD lesion was significantly lower than the average regional perfusion rate for the remainder of the LV. However, the mean blood flow rate for the remainder of the LV was also significantly lower than control values despite the lack of significant circumflex disease. The data demonstrate that the presence of radiographically "mild" or significant isolated LAD coronary disease is not associated with reductions in mean LV perfusion at rest, but that mean LV perfusion is reduced in the presence of significant disease of two or three coronary artieries. None of the patients experienced angina during the resting studies and most had clinical evidence of ventricular failure. The observation of depressed LV perfusion in this group, as in the patients with cardiomyopathy, raises the possibility that a lowered resting blood supply may be adequate for a reduced level of performance of a diseased ventricle. The lack of selective reductions of regional perfusion at rest in the majority of the patients with LAD lesions suggests that regional myocardial blood flow must be measured during an intervention which increases myocardial oxygen consumption in order to assess the physiological significance of lesions which are observed at coronary arteriography.


The purification and partial characterization of an insulin-like protein from human serum. A preparative scheme has been developed for the purification of a trace protein in human serum exhibiting nonsuppressible insulin-like activity (NSILA). This scheme consisted of (a) adsorption chromatography of serum utilizing the sulfonic acid polystyrene resin, Dowex 50, at pH 6.8; (b) (200 gel filtration at pH 8.9; and (c) acrylamide gel electrophoresis in a discontinuous preparative system. Throughout all procedures, NSILA fractionated as a single molecular species approximating 90,000 mol wt. The purified protein exhibited a single band by disk gel electrophoresis, an isoelectric pH approximating 6.2, doublet bands of 90,000 mol mt by analytical sodium dodecyl sulfate gel electrophoresis, and a biologic specific activity approximating 50 mU/mg. Serum somatomedin (sulfation factor) activtiy did not fractionate with NSILA in this scheme, and partially purified NSILA did not stimulate radiosulfate uptake into hypophysectomized rat costal cartilage. This protein appears to represent the major constituent of serum NSILA: its purification and partial characterization provides the first step towards elucidation of its metabolic role.


Effect of dexamethasone on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes. We have studied the in vitro effects of dexamethasone on isolated rat adipocytes at concentrations of dexamethasone therapeutically achieved in man. Glucose oxidation, glucose transport, and insulin binding were assessed. In dexamethasone-treated cells, glucose oxidation was decreased by 30-40% both in the absence of insulin (basal state) and at low insulin levels (less than 25 mu/ML). At maximally effective insulin levels (over 100 muU/ml) no differences existed between control and treated cells. If glucose transport were the rate-limiting step for glucose oxidation in the basal state and at low (submaximal) insulin levels, but not at maximally effective insulin concentrations, then these data could be explained by postulating that dexamethasone has a direct affect on glucose transport and does not affect intracellular oxidative pathways. We tested this hypothesis by directly assessing glucose transport in dexamethasone-treated cells. Glucose transport was assessed by measuring the uptake of [14C]2-deoxy glucose. These studies demonstrated a 30-40% decrease in 2-deoxy glucose uptake by treated cells both in the basal state and at all insulin concentrations. Thus, a direct glucocorticoid effect on the glucose transport system seems to account for the decreased ability of dexamethasone-treated cells to oxidize glucose. Since dexamethasone treatment leads to decreased insulin binding to adipocytes in vivo, we examined the possibility that the in vitro decreases in insulin-mediated glucose transport could be due to decreased insulin receptors. Insulin binding to control and treated adipocytes was measured, and no differences were found. Therefore, in cntrast to previously reported in vivo studies, adipocytes treated in vitro with dexamethasone retain a normal ability to bind insulin. Thus, these studies suggest that all of the in vitro effects of dexamethasone on glucose oxidation are due to direct inhibition of the glucose transport system.


Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. I. Different rates of disappearance of protoporphyrin from the erythrocytes, both in vivo and in vitro. In lead intoxication photosensitivity is usually absent, despite concentrations of protoporphyrin in the erythrocytes equal to or greater than in erythropoietic protoporphyria. Profound differences in the distribution of protoporphyrin in aging erythrocytes were demonstrated by age-dependent fractionation of cells on discontinuous density gradients. In erythropoietic protoporphyria the concentration of protoporphyrin declined extremely rapidly with erythrocyte age; the bulk of the protoporphyrin was lost in less than 3 days and the concentration of fluorescent erythrocytes in the gradient paralleled the decline of protoporphyrin. In lead intoxication the protoporphyrin concentration declined only slightly with cell aging and erythrocytes of all ages fluoresced. In the bone marrow from a patient with erythropoietic protoporphyria all reticulocytes, but only occasional late normoblasts, fluoresced, suggesting a single population. Sterile incubation in plasma (pH 7.5) demonstrated rapid diffusion of protoporphyrin from the erythrocytes in erythropoietic protoporphyria, but not in lead intoxication. Plasma protoporphyrin was elevated in erythropoietic protoporphyria, but not in lead intoxication. Estimates of the daily loss of protoporphyrin from erythropoietic tissue in erythropoietic proporphyria suggested an order of magnitude similar to the total blood protoporphyrin. Therefore, it is not necessary to postulate a preponderant extraerythropoietic source to explain the amount of fecal excretion. A significant amount of the diffused protoporphyrin probably reaches the skin with resulting photosensitivity. In contrast, in lead intoxication protoporphyrin remains within the erythrocyte throughout its life span ; there is no diffusion into the plasma and hence no photosensitivity.


Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. II. Different binding of erythrocyte protoporphyrin to hemoglobin. Acidic solvents extract the same porphyrin-protoporphyrin-from the erythrocytes of patients with either erythropoietic protoporphyria or lead intoxication. However, extractable protoporphyrin disappears rapidly, both in vivo and in vitro, from erythrocytes in erythropoietic protoporphyria but slowly, if at all, in lead intoxication. Consistent with these observations, fluorescence spectroscopy revealed that the intracellular state of the erythrocyte protoporphyrin is different in the two diseases. Spectrofluorometric measurements coupled with fractionations and biochemical syntheses showed that in erythropoietic protoporphyria the protoporphyrin is bound as the free base to hemoglobin molecules at sites other than the heme binding sites. In lead intoxication the fluorescent porphyrin is also bound to hemoglobin but is present as zinc protoporphyrin. The data suggest that the zinc protoporphyrin is bound at heme binding sites. Acidic extraction solvents remove the chelated zinc, but zinc protoporphyrin may be extracted intact from erythrocytes with acetone, ethanol, or the detergent Ammonyx-LO.


Clinical evaluation of group A and group C meningococcal polysaccharide vaccines in infants. Group A and group C meningoccal polysaccharide vaccines were evaluated in infants. No significant local or systemic reactions were observed with 908 doses of vaccine given to 396 infants between 3 and 12 mo of age. The antibody response varied with the age of the infant, vaccine dose, molecular weight of vaccine, prior immunization with vaccine, and prior exposure to naturally occurring cross-reactive antigens. Only 7% of 3-mo-old infants had detectable antibody responses to primary immunization with 5-200 mug of A vaccine, presumably because of suppressive effects of high concentrations of maternal anti-A. More than 90% of 7- and 12-mo-old infants responded to A vaccine, achieving geometric mean anti-A concentrations of 0.38 and 0.98 mug/ml, respectively. The dose-response curve was flat between 10 and 200 mug of A vaccine. Geometric mean anti-A concentrations of 2.51 and 4.00 mug/ml were induced in 7- and 12-mo-old infants by booster injections of A vaccine. Approximately 90% of 3-mo-old infants had detectable antibody responses to primary immunization with C vaccine. The 100-mug dose appeared to be optimal, resulting in geometric mean anti-C concentrations of 0.49, 1.55, and 2.64 mug/ml in 3-, 7-, and 12-mo-old infants, respectively. Significant booster responses were not observed with C vaccine. Indeed, except for the 10-mug dose, booster injections of C vaccine in 7- and 12-mo-old infants resulted in lower anti-C concentrations than did primary immunizations.


Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome. Serum glucocorticoid levels were determined in 20 mothers and 43 premature infants who received prenatal betamethasone therapy for prevention of respiratory distress syndrome (RDS). Maternal betamethasone peaked at 75 microg cortisol equivalents per 100 ml 1 h after injection of 12 mg steroid and declined to half by 6 h. Betamethasone in cord blood was 14.3 microg cortisol equivalents per 100 ml at 1 h, decreased to a level of 4.7 at 20 h, and was not detected 2 days after a second dose at 24 h. After the second dose, the mean level of cortisol in cord blood was 5.9 microg per 100 ml compared with 13.05 microg per 100 ml (p less than 0.001) in untreated premature infants. The unbound glucocorticoid activity in treated infants delivered 1-10 h after the second dose (mean, 8.4 microg per 100 ml) is similar to the unbound cortisol level after birth in untreated premature infants who develop RDS. These findings indicate that (a) serum glucocorticoid levels in the physiologic stress range can induce lung maturation in the human and (b) antenatal treatment with this dose of betamethasone does not expose the human fetus to potentially harmful pharmacologic levels of steroid.


Peripheral metabolism of insulin, proinsulin, and C-peptide in the pregnant rat. To clarify alterations in carbohydrate metabolism which occur in pregnancy, metabolic clearance rates of insulin, proinsulin, and C-peptide were measured by the constant infusion technique in term-pregnant rats and in virgin littermates. In addition, placental permeability to these peptides was evaluated by simultaneous determination of their concentration in fetal blood, amniotic fluid, and maternal arterial blood and the renal extraction and excretion of insulin and C-peptide were determined during simultaneous studies of renal hemodynamics. The metabolic clearance rate (MCR) of insulin was higher (P less than 0.005) in pregnant animals (61.5+/-1.7 ml/min per kg nonconceptus body weight) than in virgin littermates (51.5+/-2.2 ml/min per kg). Insulin disappearance from the circulation after both single injection and discontinuance of a constant infusion was also faster in gravid animals. In contrast, the MCR of proinsulin and C-peptide, and the disappearance of C-peptide from the circulation were similar in pregnant and control rats. The placenta was virtually impermeable to each of the three polypeptides since their mean levels in both fetal blood and amniotic fluid did not exceed 2.5 ng/ml and were only minimally influenced by pharmacological concentrations as high as 60 ng/ml in the maternal circulation. The renal clearance of insulin (renal arteriovenous insulin difference X renal plasma flow) was lower, and its contribution to insulin MCR was less in pregnant animals than in controls (19.4+/-1.5% vs. 28.7+/-3.7%, P less than 0.05), whereas the renal clearance and renal clearance/MCR of C-peptide were similar in pregnant rats and virgin littermates. These results indicate that the peripheral metabolism of insulin is accelerated in pregnancy, while that of pro-insulin and C-peptide is unaffected. Since transplacental passage of insulin is negligible and its renal clearance is not increased, the enhanced MCR of insulin in pregnancy is due to increased metabolism at an extrarenal site probably within the placenta itself.


Serum calcitonin-lowering effect of magnesium in patients with medullary carcinoma of the thyroid. The effect of magnesium chloride or magnesium sulfate infusion on circulating levels of immunoreactive calcitonin (iCT) was evaluated on nine occasions in three patients with metastatic medullary carcinoma of the thyroid. One patient was normocalcemic and had normal circulating levels of immunoreactive parathyroid hormone (iPTH), one patient was hypocalcemic and had surgical hypoparathyroidism, and one patient had mild to moderate hypercalcemia associated with bone metastases. The basal serum iPTH levels were undetectable in the latter two patients. In every instance magnesium administration produced a rapid and striking fall in circulating iCT and usually a detectable fall in serum calcium. During the hypermagnesemic state, serum iPTH fell from normal to undetectable in the patient with normal parathyroid function, while serum iPTH levels remained undetectable in the hypoparathyroid patient and in the patient with hypercalcemia associated with bone metastases. The results of these studies indicate that: (a) contrary to what has been reported in normal experimental animals, magnesium administration lowers circulating iCT in human subjects with thyroid medullary carcinoma and (b) the calcium-lowering effect produced by magnesium in patients with medullary carcinoma may, in part at least, be due to a redistribution of body calcium that is not mediated by the actions of either parathyroid hormone or clacitonin.


Cytochemical localization of lysosomal enzymes in rat megakaryocytes and platelets. Platelets secrete lysosmal enzymes during the "platelet release reaction" early in clot formation. This study was undertaken to identify primary lysosomes of platelets and to detemine their origin in megakaryocytes. Using electron microscopy and cytochemistry, we localized two lysosomal enzymes, arylsulfatase and acid phosphatase, in megakaryocytes and platelets of normal and thrombocytopenic rats. In platelets and mature megakaryocytes, reaction product for both enzymes is confined to vesicles measuring 175-250 nm. These vesicles, which are primary lysosmes, first appear in the earliest recognizable megakaryocytes and increase in number during cellular maturation. In immature and maturing megakaryocytes, arylsulfatase and acid phosphatase can also be demonstrated in an organell similar to GERL (Golgi-endoplasmic reticulumlysosome), i.e., single smooth-surfaced cisternal with associated vesicles near the stacked Golgi cisternae. Scant reaction product for acid phosphatase is also sometimes seen in Golgi cisternae and endoplasmic reticulum. No reaction product was found in alpha-granules at any stage of megakaryocyte maturation, nor in alpha- or serotonin granules of platelets. Thus, our findings indicate that the primay lysosomes of megakaryocytes and platelets are small vesicles derived from GERL early in megakaryocyte differentiation. They can be indentified only after cytochemical staining and are distinct from both alpha- and serotonin granules.


Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways. An asymptomatic woman (Ms. Williams) was found to have a severe abnormality in the surface-activated intrinsic coagulation, fibrinolytic, and kinin-generating pathways. Assays for known coagulation factors were nromal while Fletcher factor (pre-kallikrein) was 45%, insufficient to account for the observed markedly prolonged partial thromboplastin time. Plasminogen proactivator was present at 20% of normal levels and addition of highly purified plasminogen proactivator containing 10% plasminogen activator partially corrected the coagulation and fibrinolytic abnormalities but not the kinin-generating defect. This effect was due to its plasminogen activator content. In addition, Williams trait plasma failed to convert prekallilrein to lakkilrein or release kinin upon incubation with kaolin. Kininogen antigen was undetectable. When normal plasma was fractionated to identify the factor that corrects all the abnormalities in Williams trait plasma, the Williams factor was identified as a form of kininogen by its behavior on ion exchange chromatography, gel filtration, disc gel electrophoresis, and elution from an anti-low molecular weight kininogen immunoadsorbent. High molecular weight kininogen as well as a subfraction of low molecular weight kininogen, possessed this corrective activity while the bulk of low molecular weight kininogen functioned only as a kallikrein substrate. Kininogen therefore is a critical factor required for the functioning of Hageman factor-dependent coagulation and fibrinolysis and for the activation of prekallikrein.


Effects of hippocampal stimulation on acquisition, extinction and generalization of conditioned suppression in the rat. Rats implanted with electrodes in the dorsal or ventral hippocampus received posttrial stimulation in training sessions with footshock reinforcement. Afterdischarges without overt seizures were consistently without effect on the rate of acquisition of suppression of licking during an auditory conditioned stimulus (CS), although conditioning was retarded by the delivery of distracting stimuli following footshock. The rate of conditioning remained insensitive to elicitation of dorsal hippocampal afterdischarges (DHAD) despite subsequent alterations of session length, intertrial interval and preexposure to the CS. However, faster extinction of suppression occurred following DHAD, suggesting a limited but essential role of the hippocampus in addressing stored information.


Active avoidance behavior following archistriatal lesions in pigeons. Experiment 1 examined the performance of 10 pigeons, 5 with bilateral medial archistriatal lesions and 5 sham-operated controls, in the acquisition and maintnenance of a discrete-press avoidance response. The archistriatal subjects had longer response latencies and never attained the level of performance achieved by the controls. In Experiment 2 eight pigeons learned a treadle-press response to avoid or escape shock on a signaled free-operant schedule. After 17 daily sessions four subjects received bilateral lesions in the medial archistriatum, and four received control lesions in the neostriatum. After recovery from surgery, all subjects were returned to the experimental procedure. Avoidance of those subjects with archistriatal lesions was impaired relative to the postoperative level while that of the control group was unchanged. These results are interpreted in the light of earlier experiments showing reduced escape and avoidance behavior both in order avian species and in mammals with lesions in the amygdala, to which the archistriatum is considered homologous.


Form preferences in successive discrimination learning of young chicks. In four experiments the effects of form and orientation pecking preferences of 1- and 3-day old Vantress X Arbor Acre chicks on successive discrimination learning were determined, using heat reinforcement. Major findings were as follows: (a) The young chick has both circle and verticle orientation pecking preferences that are present during at least the first 3 days after hatching; (b) when either of these preferred cues is the nonreinforced cue, the young chick has difficulty in learning not to respond to it but learns quickly not to respond to an unpreferred cue (e.g., triangle and horizontal oriented dots or bar); and (c) these pecking preferences can be modified by heat reinforcement, and the effects of this conditioning is evidenct in subsequent extinction and retention tests. The main conclusion from these experiments is that form and orientation preferences, like brightness and color preferences, are important developmental constraints on conditioning of the young chick.


Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following dorsal hippocampal ablation. Rabbits received  0 to 450 exposures of a tone conditioned stimulus (CS) prior to classical defensive conditioning of the nicitating membrane response based on an infraorbital eye shock unconditioned stimulus. Tone preexposure resulted in retarded conditioning in normal rabbits. This latent inhibition effect was not present in animals with bilateral dorsal hippocampectomy produced by aspiration. Control animals with bilateral neocortical and callosal aspiration lesions demonstrated a latent inhibition effect similar to that shown by normal nonoperated animals. The failure of CS preexposure to retard conditioning in hippocampal rabbits was not due to differences in threshold of the conditioned response to the CS or to differences in response mechanisms as determined by tests of habituation and dishabituation of the unconditioned response. A subsequent experiment employed combined-cue summation tests to confirm the fact that preexposure did not endow the tone with conditioned as well as latent inhibitiory properties. Finally, tests of stimulus generalization along the auditory frequency dimension indicated flatter relative gradients for hippocampals than for nonoperated controls, with cortical controls in between. These findings were discussed in terms of Douglas' model of hippocampal function.


Effects of early exposure to ventral gland odor on physical and behavioral development and adult social behavior in Mongolian gerbils. Comparisons were made between male and female gerbils reared by ventral gland-excised and intact patents. Repeated measurements before and after puberty failed to reveal an effect of gland odor exposure on body weight, ventral gland size, open-field defecation, and time of vaginal opening. Exposed animals were more attracted than nonexposed animals to a strange male's gland odor during preference tests involving "marked" and "unmarked" paper strips. Opposite-sex pairs of exposed animals engaged in more social behavior than did nonexposed pairs, but there was no difference in fighting frequency or, during extended cohabiitation, in fecundity. While early exposure to gland odor apparently does not affect physical maturation, it may enhance later responsiveness to stimuli (gland odors) that are useful in locating conspecifics and that facilitate social interactions between previously unacquainted gerbils.


Effects of obesity and set point on taste responsiveness and ingestion in humans. Two experiments investigated the relationships among degree of obesity, nearness to set point for adipose tissue mass, and responsiveness to taste. In Experiment 1, subjects rated milkshakes varying in sweetness intensity. Overweight and normal weight subjects did not have significantly different detection thresholds or preference ratings. However, overweight subjects worked longer than normals to obtain their most preferred substance. Experiment 2 varied the ease of tasting the milkshake. Preference and food intake of moderately overweight subjects were significantly more influenced by tastes that they found positive and negative than was the preference of normal weight or obese subjects. The ease of ingesting the taste substance also significantly influenced preference and food intake of the moderately obese only. Nearness to set point, operationally defined as weight stability for 2 years, had no significant effects.


Mathematical analysis of energy regulatory pattens of normal and diabetic rats. Analysis of feeding patterns indicated that diabetic (alloxan) hyperphagia is characterized by doubling of meal sizes with no change in feeding frequency. Correlation of meal sizes and intermeal intervals did not provide any systematic relationships for either normal or diabetic rats. When equations of the general form Y = A + Bcos (X) were fit to successive satiety ratios (postmeal interval/meal size), the diabetic rats showed significantly lower A coefficients, reflecting a lower average level of satiety, as well as significantly lower B coefficients, reflecting less systematic variability in the satiating value of food around the average level. It is concluded that the major regulatory deficit in diabetic animals is a chronic reduction in the long-term signal of body nutrient repletion.


Effects of d- versus l-amphetamine, food deprivation, and current intensity on self-stimulation of the lateral hypothalamus, substantia nigra, and medial frontal cortex of the rat. Intracranial sefl-stimulation (ICSS) was studied in rats with chronically implanted lateral hypothalamic, substantia nigra, or medial frontal cortex bipolar electrodes. A comparison of the effects of d- and l-amphetamine on ICSS response rate indicated that the d isomer had a greater facilitatory effect than the l isomer at lateral hypothalamic and substantia nigra electrode sites but that neither isomer significantly affected medial frontal cortex ICSS. d-Amphetamine resulted in a dose-related increase in motor activity, but the same doses of the l isomer resulted in decreased motor activity. Only lateral hypothalamic ICSS response rates increased significantly in response to food deprivation. Increases in current intensity above the level used for amphetamine and food-deprivation testing facilitated lateral hypothalamic and substantia nigra ICSS response rates but did not significantly affect medial frontal cortex response rates. The responsiveness of ICSS at each electrode site appeared to be correlated with the fiber- and cell-body densities of catecholaminergic systems in the brain.


Phenylpropanolamine inhibits feeding, but not drinking, induced by hypothalamic stimulation. In rats bearing lateral hypothalamic electrodes that elicited both feeding and drinking, intraperitoneal injection of the appetite suppressant drug phenylpropanolamine (Propadrine) inhibited only feeding. This occurred whether feeding and drinking were tested simultaneously or separately. Selective inhibition of lateral hypothalamic feeding also followed injection of this drug through lateral, but not medial, hypothalamic electrode cannulas. We conclude that hypothalamically induced feeding is under some of the same pharmacological controls as spontaneous feeding, that this control may be exerted, in part, in or near the lateral hypothalamus, and that the neural systems which induce feeding and drinking during hypothalamic stimulation can be pharmacologically separated.


Cholinergic modulation of tonic immobility in the rabbit (Oryctolagus cuniculus). The present study was performed to determine the effects of the anticholinergic agent scopolamine and the cholinergic agent physostigmine on tonic immobility in rabbits. Recordings of the electroencephalographic (EEG) activity from cortex and hippocampus were also made before, during, and after each test session. Scopolamine significantly prolonged the response and produced large amplitude slow wave activity in the EEG of both cortex and hippocampus. Physostigmine significantly shortened the duration of immobility and increased rhythmic slow activity in the frequency range of 5.5-9.1 Hz in the hippocampus while producing a desynchronized cortical rhythm. It is suggested that the cortex and hippocampus play a role in modulating tonic immobility duration by inhibiting the brain-stem structures thought to control this response.


Telson reflex habituation in Limulus polyphemus. Muscle correlates of reflex telson movement were recorded in intact Limulus (horseshoe crab) preparations with chronically implanted microelectrodes. Muscle activity habituated during repetitive tactile stimulation of the gills with puffs of air. Dishabituation was also observed, as were inverse relationships between the frequency and intensity of stimulation and the rate of response decrement. These findings closely paralleled those obtained during central recordings in acute dissected preparations, as did the demonstration under certain stimulation conditions of an initial incremental phase of responsivity. Although initial levels of responsivity recovered after 1 hr without stimulation, potentiation of habituation was observable after 2 hr. Both of these times greatly exceeded those previously observed in acute preparations. No generalization to a spatial displacement of the stimulus was obtained, although a visually elicited telson reflex had been shown to demonstrate a cross-optic generalization. Aspects of the comparative strategy and the adaptive value of telson reflex habituation in Limulus were briefly considered.


Scotopic sensitivity in coyotes (Canis latrans). The absolute scotopic limen for light intensity was measured for three 10-mo-old female coyotes. The methodology was similar to that used by Blough in determining psychophysical thresholds in pigeons. Three coyotes were operantly conditioned to depress one of two foot treadles, left or right, depending on the condition of the stimulus light. Scotopic adaptation curves for each coyote were generated. Nonlinear regression curves were then fitted to the raw data. The mean scotopic thresholds did not differ significantly. However, time to the curves' asymptotes did differ significantly for one of the coyotes. The adaptation curves showed a distinct rod-cone "break," and retinal histology confirmed that the coyote has a duplex retina with a preponderance of rods. In addition, electroretinographic analysis showed the relative contributions of rods and cones at various light intensities and indicated a rod-cone break at approximately 15 min. Scotopic spectral sensitivity curves were also generated. The coyotes' scotopic visual threshold is exceeded by the natural illumination available under many nocturnal conditions. The results are discussed in relation to the ecology of the species.


The peripheral unconditioned stimulus pathway in a model learning system involving defensively conditioned heart rate change in the pigeon. The peripheral pathway transmitting the unconditioned stimulus information is described in a vertebrate model system for studying learning-visually conditioned heart rate change in the pigeon. In this system footshock serves as the unconditioned stimulus, and it is shown that the effective stimulation field of this stimulus, defined with respect to the unconditioned cardioacceleratory response, includes cutaneous dermatomes 21-25 (L1-Sl). The stimulus information is then transmitted by Group III and IV fibers in portions of the femoral and sciatic nerves which enter the spinal cord over segments 21-25. Further, it is shown that interrupting this pathway by section of dorsal roots 21-25 precludes establishing conditioned heart rate change with footshock as the unconditioned stimulus.


Effect of ventromedial hypothalamic procaine injections on feeding, lever pressing, and other behavior in rats. Rats were given bilateral injections of 1-2 mul procaine HCl solution (50 mug/mul) in the region of the ventromedial hypothalamus. Normal-sized meals occurred reliably with a latency of 16-120 sec, indicating that this region has the function of inhibiting onset of eating, not just the function of stopping a meal. Food-rewarded fixed-ratio-of-one (FR 1; continuous reinforcement) lever pressing was elicited by 2-mul but not by 1-mul procaine. The FR 64 pressing appeared to be disrupted during a period of increased activity following procaine injection, although visual observations indicated that the pressing which did occur was normal in topography and was significantly associated in temporal sequence with approaches of the food magazine.


Peripheral control of drinking: gastrointestinal filling as a negative feedback signal, a theoretical and experimental analysis. The studies described here investigated the hypothesis that the osmotic postingestional satiety signal proposed by McCleary operates through a mechanism related to gut filling rather than by osmotically induced shifts of fluid from osmoreceptors in the brain. A control theory model is presented, which was designed to make quantitatively explicit the hypothesis under question. The results showed that when mannitol, which is not absorbed from the intestine, is added to a highly palatable saccharin-glucose mixture, the amount of fluid consumed decreased in inverse proportion to the mannitol concentration. Mannitol was also shown to block fluid absorption from the intestine at a low concentration (approximately .070 M) and at higher concentrations to lead to a net flux of fluid into the intestinal lumen. It was also shown that mannitol in concentrations that reduced the intake of the palatable solution did not induce thirst when the animals were in water balance. It did induce thirst, however, when the animals were tested in a state of negative water balance. The results of these studies, considered as a whole, support the view that McCleary's osmotic postingestional satiety signal acts as an intestinal distention signal rather than by inducing thirst. The model is found to be reasonably accurate as a first approximation, and suggestions are made for improvements.


Do excoriations in psoriasis delay or prevent the effect of topical treatment? Topical treatment of a number of out-patients with psoriasis vulgaris resulted in reduced induration and diminished thickness of the layer of scales but complete involution was not obtained. A sequential photographic study of the macroscopic appearance of the lesions over a 3-month period of treatment revealed that artificially produced excoriations and a horny layer without scales were prominent features. The view is put forward that the cutaneous reaction to the injury probably elicited by the excoriations, together with an unsatisfactory treatment, may give rise to tissue changes which counteract the effect of topical treatment.


Langerhans cells in actinic reticuloid.

Langerhans cells in actinic reticuloid. Actinic reticuloid was observed in a patient following the development of porphyria cutanea tarda. A cutaneous lymphoma-like infiltrate was found histologically and at the ultrastructural level. In the infiltrate, the main population was histiocytic, with some mast cells and mononuclear cells. Most of the histiocytic cells contained numerous typical Langerhans granules and worm-like structures. Crystalloid cytoplasmic inclusions were occasionally detected.


Regeneration of subcutaneous connective tissue in children. A histological study with application of the CELLSTIC device. Cellular patterns of healing subcutaneous connective tissue were studied histologically in 22 pediatric surgical patients using the CELLSTIC device. This wound drain, specially developed for this purpose, consists of a standardized, viscose cellulose sponge inside a thin silicone rubber tube. When left between the wound edges, wound exudate flows through the drain, allowing its cells to attach themselves to the sponge surface. The sponge serves as a framework within which the cells may migrate, divide and transform. During the first 12 h the cellular pattern in the sponge resembles that of peripheral blood, whereafter the number of polymorphonuclear leukocytes, almost exclusively neutrophils, gradually increases. Later on, monocytes, macrophages and lymphocytes invade. Fibroblasts were usually seen at the end of the third day postoperatively, but in some cases the first fibroblasts appeared even earlier. CELLSTIC neither disturbs normal wound healing nor increases the rate of wound infections. CELLSTIC, as a cell culture in situ, provides a practical way to study human connective tissue regeneration under both physiological and pathological conditions.


Generalized eruptive porokeratosis of Mibelli with associated psoriasis. A case of eruptive porokeratosis of Mibelli with diverse morphologic features, including circinate macular, circinate plaque and verrucous varieties is presented. No matter how variable the clinical presentation may be, the histologic hallmark of porokeratosis, the cornoid lamellae, is always present. The cornoid lamellae vary in height in relation to how prominent the thready ridge of the clinical lesion appears. Our patient also had psoriasis which initially masked the porokeratotic lesions both clinically and histologically. Awareness of the various clinical expressions of porokeratosis of Mibelli would 1) make unnecessary the segregation of certain forms of porokeratosis into separate entities, and 2) help in the recognition of less classical forms of porokeratosis.


Pharmacokinetics of gentamicin in children and adults. Peak concentrations and half-life of gentamicin in serum were measured after 140 intravenous and 13 intramuscular doses in 52 children and 17 adults with normal levels of creatinine in serum. Marked interpatient variation in peak concentrations and half-life of gentamicin was observed, but individual patients tended to have similar values on repeated determinations. Age markedly affected the peak concentrations: a 1-mg/kg dose produced mean peak concentrations of 1.58, 2.03, and 2.81 mug/ml in the one-half to five, five to 10, and greater than 10 year age groups, respectively. This age-related change in dose response was diminished when the dose was calculated on the basis of body surface area. Patients in whom gentamicin had a short half-life, patients with fever, and adults with a high extracellular fluid volume had low peak concentrations. The mean half-life after intravenous administration was 75 min (range, 26-230 min). The mean half-life was 29 min longer after intramuscular dosage (p less than 0.01). A low rate of creatinine clearance was associated with a long half-life; fever and anemia were associated with a short half-life. The dosage of gentamicin necessary to produce mean peak serum concentrations between 4 mug/ml and 6 mug/ml was 60 mg/m2 per dose for all age groups or 2.5 mg/kg per dose for ages one-half to five years, 2.0 mg/kg per dose for ages five to 10 years, and 1.5 mg/kg per dose for ages greater than 10 years.


New live attenuated influenza A/England/42/72 (H3N2) vaccine (Alice): reactogenicity,, immunogenicity, and protection efficacy. The Alice strain of influenza A/England/42/72 (H3N2) live attenuated vaccine, when given by the intranasal route to 133 volunteers, was relatively nonreactogenic; only 12% of the vaccinees had upper respiratory tract symptoms after immunization. Seroconversion in 87.2% of subjects whose titers of humoral hemagglutination-inhibiting antibody before immunization were less than 1:8 demonstrated the immunogenicity of the vaccine. The overall seroconversion rate was 66.1% (geometric mean titer of hemagglutination-inhibiting antibody, 1:40.9). Antibody levels were unchanged at six months in 95.5% and at 12 months in 91.7% of the vaccinees. Because of the lack of natural influenza A infection during the season monitored, an experimental challenge study with homotypic virus (influenza A/Udorn/307/72 [H3N2]) was conducted eight months after immunization of a sample population of 22 subjects. Twelve of these subjects were vaccinees whose titers of hemagglutination-inhibiting antibody were greater than or equal to 1:64, and 10 were unimmunized controls whose titers of hemagglutination-inhibiting antibody were less than or equal to 1:8. The group with titers of greater than or equal to 1:64 represented 40.2% of the immunized population. The vaccine was highly effective in this selected group, with a 91% protection efficacy against illness and a 100% rate of protection against illness associated with influenza A infection.


Selective clearance of a benign clone of Venezuelan equine encephalitis virus from hamster plasma by hepatic reticuloendothelial cells. A benign small-plaque clone of Venezuelan equine encephalitis virus was efficiently removed from the blood of inoculated hamsters by adsorption to cells of the hepatic reticuloendothelial system. More than 99% of infectious small-plaque virus, intrinsically labeled with 32P, was cleared from the blood within 30 min of inoculation; 47.6% of the 32P-labeled small-plaque virus inoculum was concentrated in the liver. In contrast, only 0.8% of a virulent large-plaque clone of the virus was cleared from the blood. The affinity of small-plaque virus for liver tissue was confirmed by electron microscopy, since inoculated small-plaque virions were readily visualized in phagocytic vacuoles of hepatic endothelial and Kupffer cells, where they appeared to be undergoing degradation. In contrast, large-plaque virus was not visualized in the liver. A critical determinant of virulence for viruses that do not replicate in hepatic reticuloendothelial cells may be the efficiency with which they are removed from the blood by adsorption to such cells.


Effect of quinidine together with antibiotics on contractility of cat papillary muscle. The extent of depression of myocardial contractility produced by the combination of quinidine and gentamicin, tetracycline, or amphotericin B was found, in an in vitro model, to be no greater than that due to the more active drug alone.


Prebycusis: physiological or pathological. A study was made on human temporal bones to elucidate the effects of aging on the auditory system. Ninety-six ears from 68 individuals, varying in age from infancy to 84 years, served as 'normal ears'. None of these cases had clinical or pathological evidence of specific ear diseases. 'Pathological ears' consisted of 89 ears from 58 individuals which exhibited slowly progressive hearing loss, and which had no specific known cause for the loss. Two aging phenomena were found to affect the human ear. The first is physiological, and has been called 'auditory senility'. It involves all the different parts of the auditory mechanism equally, and is responsible for the rise in auditory thresholds for the high frequencies, commonly seen in elderly people. The second phenomenon is pathological, and was termed 'auditory decay'. It involves only the perceptive system of the ear, and results in different types of clinical presentations, according to the morphological layer involved. Therefore, the recognition of two aging phenomena which affect the human ear may explain the reason for the wide variations in auditory acuity associated with old age.


Triamcinolone acetonide injection for laryngeal stenosis. Three cases with acquired laryngeal stenosis have been presented. They were treated by percutaneous intralesional injection of triamcinolone acetonide using mirror laryngoscopy. The laryngeal airway and the phonation have been satisfactory for a period of two to six years of close follow-up.


Tympanoplasty on only hearing ears.

Tympanoplasty on only hearing ears. The methods, results, and indications for operation on only hearing ears are discussed on the basis of 13 patients operated upon for chronic otitis media and its sequelae. Although good results were obtained, with an air-bone gas closure within 15 dB. in 77 per cent, this should not serve as propaganda for the general use of surgery on only hearing ears. On the other hand, they show that surgery on only hearing ears should not be rejected a priori and that on certain indications and under c ertain circumstanc es it may be carried out with minimal risk of aggravating the hearing loss. In most of the patients the indication for surgery was a progressing cholesteatoma, in some cases the sequelae of otitis, either in the form of myringoplasty or type II tympanoplasty, and one patient had the operation on a vital indication. To avoid postoperative exacerbation of the hearing, the patients must be strictly selected, the ears have to be pretreated conservatively, the Eustachian tube must be passable, the operation must be carried out by the most experienced otosurgeon, and thoroughly tested, very gentle operative methods must be used.


A case of salivary gland choristoma of the middle ear. The authors present a case of tympanic cavity salivary gland adenochoristoma in association with an abnormal course of the facial nerve, absence of the oval and round windows, absence of the stapes, hypoplasia of the long process of the incus, and the existence of a subtympanic bony lamina.


Sudden deafness following chromic acid application to a perforation of the tympanic membrane. It is current practice in the treatment of many ear diseases to instil locally into the ear potentially ototoxic agents. It is now becoming increasingly clear that some of these agents may pass from the middle to the inner ear despite the presence of intact labyrinthine windows and hence produce deafness. This paper reports a case of severe sensorineural deafness which developed following the application of chromic acid to a perforation of the tympanic membrane--a hitherto unrecognized complication. Therefore, the risks outlined above should be carefully considered prior to local therapy with any such agents and they should be applied with extreme caution.


Stimulus change as a factor in response maintenance with free food available. Rats bar pressed for food on a reinforcement schedule in which every response was reinforced, even though a dish of pellets was present. Initially, auditory and visual stimuli accompanied response-produced food presentation. With stimulus feedback as an added consequence of bar pressing, responding was maintained in the presence of free food; without stimulus feedback, responding decreased to a low level. Auditory feedback maintained slightly more responding than did visual feedback, and both together maintained more responding than did either separately. Almost no responding occurred when the only consequence of bar pressing was stimulus feedback. The data indicated conditioned and sensory reinforcement effects of response-produced stimulus feedback.


Evidence for the innate basis of the hue dimension in the duckling. Different groups of ducklings reared under sodium monochromatic light (589 nanometers) and under white light were trained to discriminate between the stimulus correlated with reinforcement (589 nanometers), and the stimulus correlated with extinction, whole value was either 570 or 610 nanometers. The peaks of subsequently obtained gradients of wavelength generalization of both groups were displaced away from the stimulus correlated with extinction. The peaks of the groups trained not to respond to 570 nanometers were located at 600 nanometers. The peaks of the groups trained not to respond to 610 nanometers were located at 580 nanometers. These results (in agreement with earlier data of Rudolph and Honig, 1972) suggest that ducklings have an innate basis for ordering stimuli of different wavelengths along the hue dimension.


Active transport of potassium by the Cecropia midgut; tracer kinetic theory and transport pool size. 1. Tracer influx kinetics have been analysed theoretically to determine the size of the transport pool with no assumptions regarding the transport pathway. 2. For a calculation of the size of the transport pool to be made, the following six conditions are required by the theory: tracer steady state attained, tissue steady state attained, Isc measures next flux, small magnitude and constant time-course of efflux, and correction for decay in pumping rate. 3. The size of the pool, SI, is given by the steady state influx, Finfinity, divided by the mixing-time constant, alpha. 4. Some experimental results are analysed by three different graphical methods, and it is shown that these three methods are equivalent. Specifically, alpha is equal to the reciprocal of the 75% mixing time, t75, divided by 1n 4 and is equal to the reciprocal of the lag time, X. 5. The tracer kinetic theory is applied to active potassium transport across the isolated short-circuited midgut: the transport meets the six conditions required by the theory. 6. The size of the transport pool of potassium in one midgut is calculated to be 80.5 muequiv./g wet weight under high-K steady-state conditions. A value as high as this suggests that the pool is intracellular.


Active transport of magnesium across the isolated midgut of Hyalophora cecropia. 1. The 28Mg-measured net flux of magnesium from lumen-side to haemolymph-side of the isolated and short-circuited midgut was 1.97 +/- 0.28 mu-equiv cm(-2) /(-1) in 8 mM-Mg2+. 2. The magnesium-influx shows a delay before the tracer steady-state is attained, indicating the existence of a magnesium-transport pool equivalent to 6.7 mu-equiv/g wet weight of midgut tissue. 3. Magnesium depresses the short-circuit current produced the midgut but not the potassium transport, the depression being equal to the rate of magnesium transport. 4. Magnesium transport yields a linear Lineweaver-Burk plot with an apparent Km of 34 mM-Mg2+ and an apparent Vmax of 14.9 mu-equiv cm(-1) /(-1). 5. Magnesium is actively transported across the midgut and contributes to the regulation of the haemolymph magnesium concentration in vivo.


Cation distributions across the larval and pupal midgut of the lepidopteran, Hyalophora cecropia, in vivo. 1. The levels of potassium, sodium, magnesium and calcium in leaves, midgut contents, midgut tissue, and blood were analysed in seven developmental stages between feeding, fourth-instar larvae and new pupae of the Cecropia silkworm. 2. Three dramatic changes in cation levels were found: the K level in the contents drops from 284 /+- 51 mEquiv./1 tissue water in the fifth-instar larva to 51 +/- 6 mEquiv./1 in the new pupa; the Mg level in the midgut tissue increases from 28 +/- 3 mEquiv./1 at the time of gut evacuation to 1093 +/- 104 mEquiv./1 in the new pupa; and the Ca level in the contents drops temporarily from 56 +/- 12 mEquiv./1 in the feeding fourth instar larva to 17 +/- 5 mEquiv./1 in the new fifth instar larva. The Na level was nerve higher than 2.8 +/- 0.5 mEquiv./1. 3. The relative levels of the four cations were different for each tissue studied, but each tissue maintained the same relative levels during the developmental stages studied. The sequences are: leaf, Ca greater than K GREATEr than Mg greater than Na; midgut contents, K greater than Ca greater than Mg greater than Na; midgut tissue, K GREATEr than Mg greater than Ca greater than Na; and blood, Mg greater than K greater than Ca greater than Na. 4. There were three large concentration gradients across the midgut; the K level in the midgut contents is approximately 10 times the level in blood; the Mg level in contents is one-half to one-sixth the level in blood; and the Ca level in contents is 3-4 times the level in blood. The K gradient and the Ca gradient are opposed and the Mg gradient is favoured by the electrical gradient across the larval midgut, the contents being 100 mV positive with respect to the blood. The K gradient and the electrical gradient are not present across the pupal midgut while the Mg gradient and the Ca gradient persist. 5. The K gradient is presumably maintained by the midgut K pump, the Mg gradient is aided by the midgut Mg pump, and the Ca gradient suggests that the midgut may possess a Ca pump.


The secretion of hyperosmotic fluid by the rectum of a saline-water mosquito larva, Aedes taeniorhynchus. 1. Fourth-instar larvae of the mosquito A. taeniorhynchus (Wiedemann), when living in sea water, drink at a rate of 100 nl h(-1) larva(-1) and maintain ionic and osmotic levels in the haemolymph at about one-third those of the external medium. 2. Hyperosmotic urine is produced in the rectum by secretion of fluid having an osmotic concentration and ionic composition similar to that of sea water, with the exception that potassium levels are elevated 18-fold in the secretion. The average rate of fluid secretion observed was 19 nl h-1) larva(-1) with a maximum of 92 nl h(-1) larva(-1). 3. The concentration and volume of rectal secretion may be too low to account completely for osmotic balance. The possible role of anal papillae is discussed in this regard.


The effects of calcium on water balance of the brown trout Salmo trutta. Water space, tritiated water flux, drinking and urine flow rates of the brown trout were decreased by increasing the environmental calcium concentration. Diffusional and osmotic permeabilities were identical in fresh water. This suggests that water flow across the gill occurs entirely by diffusion. Previous suggestions of a discrepancy between the two permeabilities in freshwater teleosts could have been due to an overestimation of urine flow rate upon which the determination of osmotic permeability coefficient is based. The wide-ranging effects of calcium on hydro-mineral regulation suggests that the ion interacts with the gills.


The effect of hypophysectomy and prolactin therapy on water balance of the brown trout Salmo trutta. A technique for the hypophysectomy of the brown trout is described which might be applicable to other salmonids. Hypophysectomy produced a decrease in water turnover which was corrected by prolactin therapy. Hypophysectomy resulted in a decrease in the next flux of osmotic water. Both osmotic and diffusional water permeabilities were evenly decreased after hypophysectomy, such that the ratio of the osmotic and diffusional permeability coefficients (Pos/Pd) retained a value of approximately unity. The data suggest that calcium and prolactin have opposing actions on water balance and that their modes of action are likely to separate.


A quantitative analysis of ventilation tachycardia and its control in two chelonians, Pseudemys scripta and Testudo graeca. 1. In both the turtle, Pseudemys scripta, and the tortoise, Testudo graeca, lung ventilation is closely accompanied by a tachycardia of predictable magnitude and duration. 2. Efferent vagal activity progressively decreases as heart rate increases with the onset of lung ventilation. Atropine decreases heart rate during apnoea to those levels observed during prolonged breathing series when the development, duration or magnitude of ventilation tachycardia. It is thus concluded that heart rate change during chelonian lung ventilation is mediated solely by alterations in vagal tone. 3. Peripheral sensory reflexes involving pulmonary stretch receptors, arterial chemoreceptors and baroreceptors, and receptors stimulated by water immersion do not affect heart rate during breathing. It is suggested that ventilation tachycardia in these chelonians is the result of the spread of activity between the respiratory and cardiac centres of the medulla.


Diuresis in the tsetse fly Glossina austeni. After taking a blood meal, the tsetse fly Glossina austeni excretes the excess water and salts of the meal in approximately 30 min. During this period a volume of fluid equivalent to 80% of the unfed weight of the fly passes through the haemolymph, whose composition nevertheless remains almost constant. The fluid excreted has a higher sodium and lower potassium concentration than the haemolymph, indicating that sodium may be the prime mover in urine formation in Glossina.


The control of diuresis in the tsetse fly Glossina austeni: a preliminary investigation of the diuretic hormone. The rate of secretion of the Malpighian tubules of Glossina austeni is controlled by a diuretic hormone. This hormone is present in the nervous tissue of the fly together with a degradative enzyme that can be activated by boiling. It is demonstrated that the Malpighian tubules are able to destroy the diuretic hormone; they may therefore participate in the control of diuresis. The diuretic hormone appears to be a heat-stable, non-dialysable, alcohol-soluble molecule, containing amino acid, glucose and sialic acid residues.


Localization and electrical activity of the distance chemoreceptors that mediate predator avoidance behaviour in Acmaea limatula and Acmaea scutum (gastropoda, prosobranchia). 1. The marine gastropods Acmaea (Collisella) limatula and Acmaea (Notoacmea) scutum respond to distant predatory starfish (i.e. to starfish scent) by moving up a vertical surface. 2. The distance chemoreceptors that mediate this avoidance behaviour are located on the mantle margin. Heat cauterization of the limpets' mantle margin eliminates their responsiveness to Pisaster ochraceus scent, while a similar cauterization of the ctenidium and the osphradia does not diminish the avoidance behaviour. 3. Primary afferent electrical activity can be recorded from the chemoreceptors on the mantle margin that are responsive to starfish scent and also from other physiologically distinct receptors that are responsive to contact with starfish tube feet.


The permeability to ions of the neural lamella and the extracellular spaces in the C.N.S. of Anodonta cygnea. Rapid axonal depolarization follows the elevation of [K+]o in the Ringer bathing the surfaces of the connectives of both intact and desheathed cerebrovisceral connectives of Anodonta cygnea. Potassium movements between the blood or medium bathing the surface of the connectives and the axonal membranes can be accounted for in terms of a first-order diffusion process. No visible structural barriers to prevent free movements of materials through the neural lamella and the extracellular spaces can be detected in electron micrographs of the cerebro-visceral connectives. In desheathed preparations fast action potentials are conducted in sodium-free (dextran) Ringer. Mechanisms of axona  .l function and ionic regulation in this and other invertebrate central nervous tissues are discussed in the light of these observations.


Extrinsic modulation of crayfish escape behaviour. Extrinsic systems were shown to control the excitability of the neurones which mediate tail-flip escape in the crayfish. Restraint suppresses the escape mediated by giant fibres and some, but not all, categories of non-giant mediated escape; autotomy of claws increases the excitability of non-giant mediated escape without affecting the lateral giant reflex. The effects of restraint on the lateral giant reflex result from inhibition rather than reduced facilitation. The inhibition descends from thoracic and higher levels, and the lateral giant escape command neurone appears to be its primary target. Inhibition may serve to shift the control of escape behaviour from short latency 'reflex' systems to more flexible 'voluntary' ones which can produce responses at times most opportune for successful escape.


Regeneration of peripheral nerves to supernumerary legs in cockroaches. 1. Clusters of legs were grown from metathoracic coxae of the cockroach. Legs of a cluster had different segmental origins, sizes, and orientations. 2. Regenerating metathoracic nerves tended to enter the nearest leg, and to a lesser extent of the largest leg, but showed no significant tendency to penetrate metathoracic rather than prothoracic legs, or normally oriented rather than abnormally oriented legs. 3. Movements of legs were evoked by nerve stimulation significantly more often in nearest, largest, and normally oriented legs, but were equally frequent in prothoracic and metathoracic legs. 4. Close proximity of peripheral nerves is not required for the differentiation of the legs, since nerves were visible in the legs only at the later stages of their development, and many of the legs were apparently nerve innervated.


Motor innervation within supernumerary legs of cockroaches. 1. Clusters of legs having prothoracic and metathoracic origins were grown from the metathoracic coxa of the cockroach. 2. Or occasionally two, of the three major nerves innervating the cockroach leg. 3. Stimulation of a particular leg nerve (no. 3, 5 or 6) evoked movement at the same joints and in the same directions in a leg having only one nerve as in a normal leg. 4. Stimulation of a particular metathoracic nerve generally produced the same movements in a prothoracic leg transplanted to the metathoracic site as it did in a regenerated or intact metathoracic leg.


Physical and adrenergic factors affecting systemic vascular resistance in the rainbow trout: a comparison with branchial vascular resistance. The passive distensibility and adrenergic reactivity of the systemic vascular resistance (Rs) in Salmogairdneri have been studied using perfused trunk preparations, and the data compared with previous results on the branchial resistance (Rg). At normal levels of efferent blood pressure, Rs is relatively more distensible than Rg in response to afferent pressure increases, but this difference may not be important in vivo. alpha-adrenegic constrictory receptors predominate in Rs, in contrast to beta-adrenergic dilatory receptors in Rg; a significant alpha-adrenergic tone in Rs is lost during perfusion. Rs is far less sensitive than Rg to circulatory catecholamine levels. It is suggested that the sympathetic nervous system, rather than plasma catecholamines, provides the effective adrenergic control of Rs in vivo.


The ontogeny of auditory frequency generalization in the chicken. To determine if there is an ontogenetic change in stimulus coding, chickens between the day of hatching and 9-10 days old were tested using a habituation-generalization paradigm. Experiment 1 indicated that 1 day-old and 3--4-day-old chicks show similar habituation of an eye-opening response to auditory stimuli in the 800--1,200-Hz range. In Experiment 2 the eye-opening response to a 1,000-Hz stimulus was habituated and then immediately tested using stimuli which varied between 800 and 1,200 Hz. Each age-group (1 day, 3--4 days, and 9--10 days) showed a symmetrical stimulus generalization gradient around the 1,000-Hz stimulus and the 1-day-old chicks displayed a reliably flatter gradient than either of the older groups, which did not differ. In a third experiment, the position of the gradients relative to the baseline was shifted without altering the relative shapes. These results allow general arousal, general auditory responsiveness, overall error rate, and metric characteristics of the independent and dependent variables to be eliminated as possible sources of the age differences in gradient shape. The changes in stimulus generalization, therefore, support the view that during normal development there is a sharpening of perceptual coding processes.


Effects of desalivation on schedule-induced polydipsia in the rat. The development and magnitude of schedule-induced polydipisa (SIP) were examined in desalivate and control rats in two experiments. In Experiment 1 animals were placed on a noncontingent fixed time (FT) 60-sec schedule for 24 days. Results indicate speeded development but asymptotically lower levels of SIP in desalivate rats compared to controls. Home cage consumption, however, was elevated in desalivate rats. In Experiment 2 schedule length, pellet size, and the percentage of body weight were manipulated. Desalivate rats consumed less fluid during each schedule condition relative to controls, but the pattern of results across schedules was similar to controls. It was concluded that (a) desalivation attenuates SIP; (b) SIP is a learned phenomenon; (c) dry mouth theories of SIP appear inadequate; and (d) the developmental aspect of the SIP phenomenon deserves additional research attention.


Blocking of conditioned suppression: role of the first compound trial. Four experiments, all employing the conditioned suppression of licking in thirsty rats, examined the extent to which reinforcement of one component, A, of a compound conditioned stimulus, AB, would "block" conditioning to the other element, B, on the first compound trial. Suppression to B was unaffected by prior reinforcement of A; that is, no evidence of blocking was obtained. If additional reinforced trials were given to the AB compound, further conditioning to B was blocked by prior reinforcement of A. Thus blocking appeared to take at least one trial to develop. These results suggest that blocking is not due to any competition between stimuli for association with reinforcement, but is a consequence of the animals' ignoring the added element once they have learned that it is redundant.


The effect of two ways of devaluing the unconditioned stimulus after first- and second-order appetitive conditioning. Rats received first- and second-order conditioning based upon a food unconditioned stimulus (UCS). They then received one of two manipulations designed to reduce the value of that food, satiation, or pairing of food with high-speed rotation. The effects of these manipulations were assessed during extinction tests of the conditioned stimuli (CSs). Compared with controls, both manipulations reduced the activity produced by the first-order CS but did not affect that produced by a second-order CS. The results are interpreted as consistent with those from aversive UCSs in implying the involvement of a UCS representation in first- but not in second-order conditioning. They also suggest that a major effect of satiation is to reduce the value of the UCS.


Stimulus familiarity modifies perceived duration in prerecognition visual processing. Three experiments further explored the Avant, Lyman, and Antes finding that, during prerecognition processing, differences in subjects' familiarity with letters, words, and nonwords generate differences in the apparent duration of tachistoscopic flashes. The results replicate and extend the earlier findings, showing apparent duration differences with a variety of verbal stimuli over a range of tachistoscopic exposure intervals. The results also suggest that exposures of stimuli on early trials of an experiment reduce differences in preexperimental stimulus familiarity such that unfamiliar stimuli come to be processed more nearly like familiar stimuli. Familiarity acquired on early trials appears to accumulate at prerecognition levels of processing and to reduce apparent duration differences among stimuli on later trials.


Visual transformation of size.

Visual transformation of size. To investigate human visual identification of different-sized objects as identically shaped, matching reaction times were measured for pairs of simultaneously presented random figures. In three experiments, reaction time for correct reactions to test pairs of figures of the same shape and orientation consistently increased approximately linearly as a function of the linear size ratio of the figures. In the second experiment, where this ratio was defined for control pairs as well as for test pairs, reaction time for correct reactions to control pairs showed a similar increase as a function of size ratio. The results suggest that the task was performed by a gradual process of mental size transformation of one of the members of each pair of figures to the format of the other one.


Detection of symmetry as a function of angular orientation. Subjects decided as quickly as possible whether dot patterns were or were not symmetrical about a line. Their decision times were shorter when the line was verticle and increased as the angle between the line and the verticle increased. This orientation function was essentially the same whether or not the subjects knew in advance what the orientation of the line would be. When the subjects tilted their heads, the function shifted in the direction of the head tilt, indicating that it was tied more closely to retinal than to gravitational coordinates. These data can be interpreted to mean that people mentally rotate patterns to a vertical orientation before judging their symmetry. This in turn suggests that the "template" for detecting symmetry may itself be embedded symmetrically in the brain.


Information processing analysis of the Chevreul pendulum illusion. An information processing investigation was performed to quantify the Chevreul pendulum effect: the tendency of a small pendulum, when suspended from the hand and imaginatively concentrated on, to oscillate seemingly of its own accord. Using a time exposure photographic measurement technique, electronically automated visual and auditory imaginal prompts were presented to the subject during imaginal processing tasks. It was found that the pendulum effect was enhanced when vision of actual pendulum oscillations was permitted and visual or auditory spatially oscillating stimuli were present. Visual spatially oscillating stimuli were superior to their auditory counterparts. Results were discussed in terms of ideomotor and visual capture interpretations of signal and imaginal processing.


Allocation of attention and the locus of adaptation to displaced vision. Experimental subjects were exposed to prism-induced visual displacement of a target whose location was correctly given by proprioceptive-kinesthetic information. Control subjects were exposed alternately to visual displacement or proprioceptive-kinesthetic location information. During the adaptation period, experimental subjects in the visual attention condition performed a localization task that directed them to attend selectively to the visual modality; experimental subjects in the proprioceptive attention condition attended selectively to the proprioceptive modaltiy; control subjects performed the task on the basis of the available modality. Measures of adaptation and aftereffect were secured separately in each of the two modalities. These confirmed the predictions that the shifts in the experimental conditions would be confirmed to localization tests dependent on the unattended modality and that control subjects would not exhibit adaptation. We proposed that allocation of attention determines situational dominance and that dominance determines the locus of adaptation. The findings were compared to those reported by Canon (1970) and were applied to a reassessment of the "visual capture" phenomenon.


Differential hemispheric mediation of nonverbal visual stimuli. Studies employing schematic faces of three features explored the role of the left hemisphere as an analytic processor in difficult discriminations and the role of the right hemisphere in easy gestalt matches. In a discrimination task, the successively presented members of a stimulus pair differed in all three features. When both stimuli went to the same visual field there was a Visual Field X Judgments interaction; judgments same were processed faster in the left visual field. When a test stimulus differing on all three features from a previously memorized target face was matched to the latter, both judgments same and different were made faster for stimuli in the left visual field. However, when the test stimulus and the memory items differed on only one feature the right field proved superior for both judgments same and different.


Spatial position versus ear of entry as determinant of the auditory laterality effects: a stereophonic test. The study concerned discriminating between ear of entry and apparent spatial position as possible determinants of lateral asymmetries in the recall of simultaneous speech messages. Apparent localization to the left or right of the median plane was created either through a time difference (.7 msec), through intensity differences between presentations of the same verbal message at the two ears, or through dichotic presentations. Right-side advantage was observed with the three types of presentation (Experiments 1, 2, and 3). The finding of right-side advantage with stereophony based on a time difference only, in the absence of intensity difference, cannot be accounted for in terms of an ear advantage and shows that apparent spatial separation of the sources can by itself produce a laterality effect. Differences in the degree of lateral asymmetry between the various conditions were also observed. The findings of Experiments 4 and 5 suggest that these differences are better explained in terms of different impressions of localization of the sound sources than in terms of relative intensity at the "privileged" ear.


Auditory segregation: stream or streams? When auditory material segregates into "streams," is the unattended stream actually organized as an entity? An affirmative answer is suggested by the observation that the organizational structure of the unattended material interacts with the structure of material to which the subject is trying to attend. Specificially, a to-be-rejected stream can, because of its structure, capture from a to-be-judged stream elements that would otherwiise be acceptable members of the to-be-judged stream.


Decision-related cortical potentials during an auditory signal detection task with cued observation intervals. Cortical-evoked potentials were recorded from human subjects performing an auditory detection task with confidence rating responses. Unlike earlier studies that used similar procedures, the observation interval during which the auditory signal could occur was clearly marked by a visual cue light. By precisely defining the observation interval and, hence, syncrhonizing all perceptual decisions to the evoked potential averaging epoch, it was possible to demonstrate that high-confidence false alarms for accompanied by late-positive P3 components equivalent to those for equally confident hits. Moreover the hit and false alarm evoked potentials were found to covary similarily with variations in confidence rating and to have similar amplitude distributions over the scalp. In a second experiment wherein the signal intensity was increased to make signal presence and signal absence clearly discriminable and the a priori probability of signal presentation was varied from .5 to .9, it was demonstrated that correct rejections can be associated with a P3 component larger than that for hits. Thus it was possible to show, within the signal detection paradigm, how the two major factors of decision confidence and expectancy are reflected in the P3 component of the cortical-evoked potential.


Development of locomotor behavior in wild type and spastic (sp/sp) axolotls, Ambystoma mexicanum. The homozygous recessive spastic mutant found in the Mexican axolotl shows violent coiling and thrashing behavior when subjected to strong tactile or electrical stimulation. In order to establish the time of onset of the first behavioral manifestation of the spastic gene, an etiological analysis of the ontogeny of swimming behavior in mutants and wild type siblings was undertaken. The locomotor patterns shown by embryos in response to an electrical stimulus were analyzed quantitatively from the embryonic early flexure stage through the larval early feeding stage. Spastic larvae failed to show dorsal-up swimming frequencies equal to those of sibling controls from day 12 (Harrison stage 40) of development indicating a lack of equilibrium. Both spastics and their siblings showed "sinusoid swimming" and "coiling" behavior in response to an aversive stimulus through day 18 (Harrison state 46, early feeding stage) of development. From day 18, wild type siblings abruptly decreased "coiling" behavior and showed strong "escape swimming" in response to an intense stimulus. Spastics never developed "escape swimming" patterns but retained a mixture of "sinusoid swimming" and "coiling" patterns characteristic of pre-feeding stage larvae.


Dietary tocopherol and sexual reproduction in the rotifers Brachionus calyciflorus and Asplanchna sieboldi. Brachionus calyciflorus contained no detectable tocopherol (vitamin E) when cultured for long periods on the yeast Rhodotorula glutinis. Using a spectrofluorometric assay and the Asplanchna body-wall-outgrowth response bioassay the limits of detection were 6.4 ng and 3.78 pg alpha-tocopherol per g dry weight Brachionus, respectively. These tocopherol-free Brachionus reproduced normally both parthenogenetically and sexually, producing active and potent males and fertilized resting eggs which developed  into viable young rotifers. The apparent lack of a tocopherol requirement for male fertility in B. calyciflorus probably also applies to Asplanchna sieboldi and A. brightwell -- rotifers whose male-producing (mictic) females are induced by dietary tocopherol and whose males therefore are never tocopherol-deficient. The adaptive significance of the tocopherol requirement for the initiation of sexual reproduction in Asplanchna sieboldi--formerly hypothesized to be the result of a tocopherol requirement for male fertility--is now thought to be related to the role of tocopherol in controlling female polymorphism in this species.


The ubiquitous occurrence of chondroitin sulfates in chick embryos. The synthesis of sulfated glycosaminoglycans has been studied in a wide variety of embryonic chick tissues. All tissues studied have the capability to manufacture, but not necessarily accumulate, the chondroitin sulfates as well as other glycosaminoglycans. The relative distribution of glycosaminoglycans differs between tissues and changes with age.