Inhibition of peptidoglycan biosynthesis at a postcytoplasmic reaction in a stable L-phase variant of Streptococcus faecium. Cultures of a stable L-phase variant of Streptococcus faecium F24 produced and retained peptidoglycan precursors intracellularly over the entire growth cycle in a chemically defined medium. The identity of the most abundant precursor, UDP N-acetylmuramyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine (UDP-MurNAc-pentapeptide), was confirmed by demonstrating in vitro the presence of enzymes required for the cytoplasmic stage of peptidoglycan biosynthesis. The initial membrane-bound reaction in peptidoglycan biosynthesis involving phospho-MurNAc-pentapeptide translocase and undecaprenyl-phosphate membrane carrier was catalyzed by protoplast membrane preparations but not by L-phase membrane preparations. However, both protoplast and L-phase membranes incorporated radioactivity from dTDP-L-[14C]rhamnose, the presumed precursor to a non-peptidoglycan cell surface component, into high-molecular-weight material. dTDP-L-rhamnose did not accumulate in growing cultures but was synthesized from D-glucose-1-phosphate and dTTP by cell-free extracts of the streptococcus and L-phase variant. Neither rhamnose- nor muramic acid-containing compounds were detected in culture fluids. It is suggested that continued inhibition of cell wall biosynthesis in this stable L-phase variant is the result of a defect expressed at the membrane stage of peptidoglycan biosynthesis specifically involving the translocation step.


Oxygen and nitrate in utilization by Bacillus licheniformis of the arginase and arginine deiminase routes of arginine catabolism and other factors affecting their syntheses. Bacillus licheniformis has two pathways of arginine catabolism. In well-aerated cultures, the arginase route is present, and levels of catabolic ornithine carbamoyltransferase were low. An arginase pathway-deficient mutant, BL196, failed to grow on arginine as a nitrogen source under these conditions. In anaerobiosis, the wild type contained very low levels of arginase and ornithine transaminase. BL196 grew normally on glucose plus arginine in anaerobiosis and, like the wild type, had appreciable levels of catabolic transferase. Nitrate, like oxygen, repressed ornithine carbamoyltransferase and stimulated arginase synthesis. In aerobic cultures, arginase was repressed by glutamine in the presence of glucose, but not when the carbon-energy source was poor. In anaerobic cultures, ammonia repressed catabolic ornithine carbamoyltransferase, but glutamate and glutamine stimulated its synthesis. A second mutant, derived from BL196, retained the low arginase and ornithine transaminase levels of BL196 but produced high levels of deiminase pathway enzymes in the presence of oxygen.


Amine dehydrogenase of Pseudomonas putida: properties of the heme-prosthetic group. There was approximately five times more hemoprotein (amine dehydrogenase) in crude extracts obtained from Pseudomonas putida grown on benzylamine than present in extracts from succinate-grown cells. The difference (reduced minus oxidized) spectrum of the purified enzyme possessed alpha,beta, and gamma bands at 550, 523, and 416 nm, respectively. The difference spectrum of the pyridine hemochrome derivative had absorption maxima at 416, 520, and 550 nm. These results, together with the fact that the heme group was covalently bound to the enzyme, indicated that the amine dehydrogenase from P. putida was a hemoprotein which contained heme c. The heme content was calculated at 2.01 mol/mol of enzyme. The enzyme was composed of two nonidentical subunits, but heme was present solely in the heavier unit. Carbon monoxide did not inhibit enzymatic activity, nor would it combine with the reduced or oxidized form of the enzyme. Amine dehydrogenase activity was inhibited by carbonyl agents with semicarbazide and cuprizone acting noncompetitively, whereas KCN and isoniazid inhibited by competitive and uncompetitive mechanisms, respectively. Spectral observations suggested that inhibition by these reagents was not due to an interaction with the heme moiety.


A study of the effect of computer feedback on polypharmacy. Between July 1973 and February 1976, clinicians in the DMH Institutions of a midwestern state received regular, computer generated information about those of their patients who had been prescribed more than 4 psychotropic drugs during the preceding month. The effect of this feedback on prescribing habits was assessed, using information derived from monthly itemized billing record returns. The results showed that, while a highly significant reduction in polypharmacy did take place, it antedated the circulation of the specific feedback, coinciding instead with the discussions between the computer project staff and institution superintendents at the planning stage of the project.


Restless legs, anxiety and caffeinism.

Restless legs, anxiety and caffeinism. This clinical study of 62 patients with restless legs syndrome and associated anxious-depressed and other clinical states seems to indicate that caffeine is the major etiological factor in the causation of the restless legs syndrome. Anxiety, while modifying the subjective experience of the dysphoric sensation of restless legs, is not a causative factor. Caffeine is responsible for the increased nervous system arousal as well as for the direct peripheral contractile effect on the striated muscle. This arousal is often reflected psychologically in anxiety and sometimes depressive manifestations, insomnia, heightened proprioceptive awareness and physiologically in the toxic sensory experience of restless legs associated with increased neuromuscular reactivity which may include myoclonus and myokomia.


Bleuler, Schneider and schizophrenia.

Bleuler, Schneider and schizophrenia. Three important elements in Bleuler's work are described and criticized: the fundamental-accessory dichotomy, the primary-secondary dichotomy, and question of diagnosis. The major influences on Schneider's thinking are outlined and his general approach to psychopathology, criteria for the diagnosis of schizophrenia, and approach to clinical evaluation are described. The work of Mayer-Gross and Langfeldt, whose diagnostic formulations integrate the thinking of Bleuler and Schneider is briefly described. Finally, the contributions of these 4 authors are compared and contrasted, and their respective impact on the current study of schizophrenia is assessed.


The hypertensive psychiatric patient: pharmacologic problems. Psychiatric symptoms secondary to antihypertensive drugs and adverse drug interactions between antihypertensive and psychotropic drugs are described. Recommendations are made concerning the drug therapy of the hypertensive psychiatric patient.


Lithium and hypothyroidism.

Lithium and hypothyroidism. There is general agreement that hypothyroidism is a possible consequence of lithium treatment but there is little agreement as to what the incidence of lithium related hypothyroidism is, or what clinical and laboratory tests could best be used to evaluate thyroid function. This study involved a survey of 70 clinicians, a chart review of 2,590 patients and a review of the pathophysiology of lithium-induced hypothyroidism. The major finding of this investigation is that lithium related thyroid dysfunction is not a common problem. Goiter during lithium therapy is 0.3%, clinical hypothyroidism is 1-2%, and TSH is the most specific laboratory test for evaluating thyroid function.


Sex and values.

Sex and values. Concerned professionals in the United States warn that sexuality is in danger of being dehumanized by a new frankness in the mass media as well as in sex therapy. However, with sensitivity and common sense responsible physicians realize that sexuality and moral values are inextricably interwoven for self as for patients, mandating that excellence of care take this fact into careful account. Sexual ignorance is neither innocence nor bliss. Physicians of all disciplines may make significant contributions by providing understanding leadership and sane sex education to patients as well as to communities in search of information and direction.


Screening for cognitive impairment among inpatients. Screening hospital patients for cognitive impairment is often required for effective treatment planning. Awareness of cognitive deficit is particularly important in working with patients who have drinking problems because of the relationship between alcohol consumption and cognitive impairment. Trail-Making Test is examined as an economic, quick, and accurate indicator of cognitive impairment in non-neurological sample of patients in a Veterans Administration Hospital. Results show that performance discriminates between normal and deficient cognitive function as assessed by established IQ and neuropsychological tests--the Wechsler Bellevue Intelligence Scale and the Halstead Reitan Battery. Nonsignificant correlations with personality variables suggest discriminant validity for the Trail-Making Test as an indicator of cognitive impairment.


Jaundice and eosinophilia associated with amitriptyline. Eosinophilia and jaundice occured in a depressed patient treated with amitriptyline, an association which is previously unreported. These complications cleared with withdrawal of the drug. This clinical picture should be added to the known hepatic complications of amitriptyline.


Caffeine and schizophrenia.

Caffeine and schizophrenia. Two cases are described in which markedly increased consumption of caffeine led to an exacerbation of a schizophrenic process. The original description of this phenomenon and the clinical and basic science literature regarding the psychotropic effects of caffeine are reviewed. The cases are discussed in light of the clinical and research implications.


Cadmium toxicity and liver mitochondria. I. Different effects of cadmium administered in vivo to adult, young, and ethionine-fed rats. The changes in liver mitochondrial respiratory activities and cytochrome concentrations were investigated when cadmium chloride was administered orally to adult, young, and ethionine-fed rats. Following a seven-day administration of 30 ppm cadmium in drinking water, adult rats showed no change, while young rats and ethionine-fed rats exhibited a marked increase in mitochondrial respiration with concomitant decrease of respiratory control index and P/O ratio. The concentrations of cytochromes aa3, b, and c + c1 in liver mitochondria were unchanged in adult rats, but increased significantly in ethionine-fed rats. In young rats receiving cadmium the liver mitochondrial protein increased with a slight change in the cytochrome concentration in mitochondria. It was further found that in adult rats a higher concentration (300 ppm) of cadmium in drinking water was toxic to the liver mitochondrial functions. Thus, the effect of oral administration of cadmium on the liver mitochondrial function depends on the condition of the animals.


Increase in the susceptibility of hemoglobin to proteases upon treatment with p-mercuribenzoate. Native human oxyhemoglobin, which has a rigid conformation resistant to proteases such as trypsin and subtilisin, could be hydrolyzed by these proteases at pH 7.0 after treatment with p-chloromercuribenzoate. The digestion curve of hemoglobin as a function of concentration of the mercurial was essentially parallel to the titration curve of hemoglobin with the mercurial, indicating that a relationship exists between susceptibility to proteases and modification of thiol groups of the protein. On the other hand, when myoglobin was used as a substrate, the degree of proteolysis did not increase after treatment with the mercurial. Circular dichroism measurements and gel-filtration experiments showed that the observed increase in susceptibility of hemoglobin to proteases was not due to a conformational change involving unfolding of alpha-helical structure, but was due to the dissociation of the tetrameric hemoglobin molecule into dimer and monomer after treatment with the mercurial.


The terminal bases of ribonucleic acid from Caulobacter RNA phage phiCp2. The terminal bases of the viral ribonucleic acid from the Caulobacter ribonucleic acid phage phiCp2 were examined. The viral ribonucleic acid contained guanosine triphosphate (pppG) at the 5'-terminus and adenosine (AOH) at the 3'-terminus.


Is there a third type of filament in striated muscles? Using glycerinated rabbit psoas myofibrils we demonstrate by electron microscopy that there is a filamentous material which remains after extraction of the fibrils with a modified Hasselbach-Schneider solution (containing 1.0 M KCl) followed by extraction with 0.6 M KI. The fibrils were visualized by conventional negative staining techniques using either 2% ammonium molybdate or 1% uranyl acetate. The appearance of the extracted fibrils together with their solubility properties strongly suggests that the extraction-resistant filamentous material is composed of connectin, an elastic protein recently characterized from muscle tissues.


Fine structure of connectin nets in cardiac myofibrils. A net-like structure extending through Z lines of myofibrils in frog cardiac muscle was clearly demonstrated under an electron microscope after the removal of myosin and actin. The diameter of the very thin filaments forming the nets was approximately 2 nm; this width was thinner than that of the actin filament. The net structure is ascribed to connectin, an elastic protein of muscle.


Prehospital burn care for emergency medical technicians. The development, objectives, content, and evaluation of a unique, 60-minute synchronized slide/tape program on prehospital burn care for Emergency Medical Technicians is described. A design for valid content-referenced formative evaluation is presented.


Conception and construction of a teaching simulator (umbilical vessel catheterization). Difficult medical procedures, such as umbilical vessel catheterization, are more easily and safely taught with a simulator than with the actual patient. The need, conception, design, and construction of such a simulator is presented in the hope that others may recognize its value and be encouraged to design their own teaching simulators for their particular needs.


'Communication in American medical centers' revisited. ... The university medical centers are the principal foci of research and education; so are they also the proper foci for medical communication. Each school complex can and will organize departments of medical communication which will bring together the many proficiencies and equipment complexes of modern communication technology. Thus, medical research, education, care, administration, and information may all be served with the speed, facility, and precision which the times demand.


Biomedical communications units and their parent organizations: a survey. A survey of the 89 biomedical communications units in U.S. institutions offering baccalaureate or higher level programs in the health sciences shows 32 units assigned to the headquarters of academic health centers, 39 assigned to constituent schools within centers, and 18 assigned to single schools not in centers. Sixty-five of the units are perceived to have a high level of importance by their parent organizations. Approximately 50% of the parent organizations authorize some physical decentralization of unit activities. Instructional development support is provided by 81% of the parent organizations, and biomedical communications units are delegated this responsibility twice as frequently as are other units within these organizations.


Magnesium but not calcium accumulation is inhibited by beta-adrenergic stimulation in S49 lymphoma cells. The uptake of 28Mg and 45Ca was measured in S49 lymphoma cells. The beta-adrenergic agonist (-)-isoproterenol markedly inhibited the rate of 28Mg accumulation but had no effect on 45Ca accumulation. The effect of (-)-isoproterenol was blocked by (-)-propranolol. In variants of the S49 cell line deficient in adenylate cyclase activity (cyc-) or in hormone receptor-adenylate cyclase coupling (unc), (-)-isoproterenol had no effect on 28Mg accumulation. The S49 lymphoma cells also possess prostaglandin E1 receptors coupled to adenylate cyclase, and, like (-)-isoproterenol, prostaglandin E1 decreased the rate of 28Mg uptake. Experiments with the mouse erythroleukemia cell line GM86 also showed a beta-adrenergic-mediated decrease in the rate of accumulation of 28Mg. Previous work has shown that Mg2+ increases the affinity of agonists for the beta-adrenergic receptor (Bird, S.J., and Maguire, M.E. (1978) J. Biol. Chem. 253, in press). In view of these effects of Mg2+, it is suggested that Mg2+, but not Ca2+, may regulate the sensitivity of S49 cell adenylate cyclase to stimulation by catecholamines.


Demonstration of a delay time during aggregation of diluted solutions of deoxyhemoglobin S and hemoglobin CHarlem in concentrated phosphate buffer. Diluted solutions (less than 100 mg/dl) of deoxygenated sickle hemoglobin (Hb S) and Hb CHarlem were found to aggregate with a clear demonstration of a delay time when dissolved in concentrated phosphate buffer. The delay time could be shortened by increasing the concentration of either hemoglobin or phosphate. Upon cooling or bubbling with carbon monoxide, the aggregates melted quickly. The logarithmic plot of reciprocal delay time versus hemoglobin or phosphate concentration shows a linear line with a slope of 2.7 for hemoglobin and 44 for phosphate. This suggests that diluted solutions of Hb S aggregate by the nucleation mechanism which is similar to that reported in the gelation of concentrated Hb S solution.


A new affinity label for guanosine nucleotide sites in proteins. A new guanosine analogue has been synthesized, 5'-p-fluorosulfonylbenzoyl guanosine, which has an electrophilic moiety capable of reacting covalently with several classes of amino acid side chains found in proteins. This compound reacts with bovine liver glutamate dehydrogenase to desensitize it irreversibly to inhibition by GTP, without affecting its intrinsic catalytic activity. The specific addition of GTP or GTP and TPNH to the reaction mixture prevents the loss of sensitivity to GTP inhibition. The corporation of approximately 1 mol of 5'-p-sulfonylbenzoyl guanosine/enzyme subunit is associated with the decreased responsiveness of the enzyme to regulation by GTP. It is proposed that 5'-p-fluorosulfonylbenzoyl guanosine may be reacting within the allosteric GTP site of glutamate dehydrogenase and that this compound may have general applicability in the affinity labeling of regulatory and catalytic sites of proteins which normally bind guanosine nucleotides.


Identification of a wheat germ ribosome dissociation factor distinct from initiation factor eIF-3. A ribosome dissociation factor(s) has been partially purified from extracts of wheat germ. This factor can be detected by its ability to prevent the reassociation of ribosomal subunits when the magnesium concentration is raised from 1 mM to 5 mN. The majority of the dissociation factor activity is found in the postribosomal supernatant of the cell and can be precipitated between 0 and 40% ammonium sulfate. Chromatography of this material on DEAE-cellulose yields a fraction which contains both the dissociation factor activity and initiation factor eLF-3. However, the majority of the dissociation factor activity can be readily separated from eIF-3 by chromatography on phosphocellulose. The dissociation factor appears to be distinct from any of the othe known wheat germ initiation factors.


Glucagon stimulation of rat hepatic phenylalanine hydroxylase through phosphorylation in vivo. Phenylalanine hydroxylase activities in extracts of livers from rats pretreated with glucagon are higher than in controls. This time-dependent activation is seen when the hydroxylase is assayed in the presence of tetrahydrobiopterin, but not in the presence of 2-amino-4-hydroxy-6,7-dimethyltetrahydropterin. A maximum 4-fold stimulation of hydroxylase activity was correlated with a conversion of the multiple forms of the enzyme to a single form. This form is characterized by an increased extent of phosphorylation compared to the unactivated enzyme. Incorporation of radioactive inorganic phosphate into phenylalanine hydroxylase following administration of glucagon was determined after specific immunoprecipitation of the enzyme from partially purified preparations. Sodium dodecyl sulfate disc gel electrophoresis showed that stimulation of enzyme activity is accompanied by incorporation of 32Pi into the protein to the extent of 0.7 mol/mol of hydroxylase subunit. These results demonstrate the phosphorylation of hepatic phenylalanine hydroxylase in vivo and strongly support the idea that the activity of this enzyme can be hormonally regulated through a phosphorylation mechanism.


Mechanism of phosphatidylinostiol stimulation of lysosomal bis (monoacylglyceryl)phosphate synthesis. A soluble enzyme preparation obtained from rat liver lysosomes catalyzed the conversion of phosphatidyl-[1',3'-14C]glyceryol to [14C]bis(monoacylglyceryl)phosphate. When this preparation was delipidated with n-butyl alcohol, very low activity was observed when incubated with phosphatidyl[1',3'-14C]glycerol alone. The activity could be restored by incubating with aqueous dispersions of lysosomal phospholipids; lysosomal neutral lipid and glycolipid fractions were inactive. When the pospholipid fraction was separated into individual classes, activity was found only in phosphatidylinositol. With a more extensively delipidated soluble enzyme preparation from lysosomes, bis-(monoacylglyceryl)P synthesis without added lipid was 0.05 nmol mg-1 h-1 versus 5.9 nmol-1 h-1 at the optimal phosphatidylinositol concentation. The mechanism of this marked stimulation of bis(monoacylglyceryl)P synthesis by phosphatidylinostiol was examined. Evidence is presented which demonstrates the incorporation of 3H-labeled fatty acids from [3H]phosphatidylinositol into bis(monoacylglyceryl)P. Phosphatidylinositol stimulates the reaction by serving as an acyl donor to phosphatidylglycerol or lysophosphatidylglycerol, the substrates for bis(monoacylglyceryl)Psynthesis.


Reconstitution of carbamylcholine-dependent sodium ion flux and desensitization of the acetylcholine receptor from Torpedo californica. Membranes rich in acetylcholine receptor were isolated from Torpedo californica by a modification of the procedure of Sobel et al. (Sobel, A., Weber, M., and Changeux, J.-P. (1977) Eur. J. Biochem. 80, 215-224). The receptor was extracted with 2% potassium cholate in the presence of 2.5% soybean phospholipids. After reconstitution by the cholate dialysis procedure, the vesicles exhibited a rapid, carbamylcholine-dependent uptake of 22Na+, which was inhibited by alpha-bungarotoxin and several other known inhibitors. At concentrations above 5 x 10(-5) M carbamylcholine, the fast phase of Na+ influx lasted less than 10 sec. At 5 x 10(-6)M, it lasted 30 sec but was only about 50% of the maximal total uptake observed at optimal agonist concentration. The phenomenon of desensitization was exhibited by the reconstituted vesicles. When 2 x 10(-4)M carbamylcholine was added, 15 sec before 22Na+, the rapid Na+ influx phase was no longer observed.


Solubilization of the O2(-)-forming activity responsible for the respiratory burst in human neutrophils. On exposure to suitable activating agents, neutrophils sharply alter their oxygen metabolism, showing large increases in oxygen uptake, O2 and H2O2 production, and glucose consumption via the hexose monophosphate shunt. These metabolic alterations, which together are designated the "respiratory burst," are due to the activation of a system which catalyzes the reaction: 2O2 + NADPH leads to 2O2(-) + NADP. This O2(-)-forming system is found in a particulate fraction isolated from neutrophils which had been activated with opsonized zymosan. When these particles were treated with detergent under suitable conditions, the O2(-)-forming activity was released in a form which passed through a membrane filter capable of retaining species of Mr greater than 3000,000. Soluble O2(-)-forming activity was obtained from normal activated neutrophils, but not from normal resting neutrophils or from activated neutrophils obtained from patients with chronic granulomatous disease, an inherited condition in which the respiratory burst is defective. O2(-)production by the soluble system required a reduced pyridine nucleotide as electron donor, and showed a quadratic dependence on the concentration of the solubilized preparation.


Cooperative functioning between antifreeze glycoproteins. Antifreeze glycoproteins from polar fish bloods are a mixture of closely related components which differ structurally by size and by the presence of proline in the smaller components. Although the smaller components containing proline exist in higher amounts than do the larger ones, their presence puzzled investigators because they had very weak antifreeze activity. A very important function for these smaller components has now been found. These smaller antifreeze glycoproteins (10 to 25 mg/ml) have now been tested as mixtures with the larger active antifreeze glycoproteins (2 to 4 mg/ml) and a very large (2- to 8-fold) potentiation of antifreeze activity has been observed. There appears to be a cooperative functioning between the larger and smaller components.


Purification and characterization of tetrahydrofolate.protein complex in bovine liver. Gel filtration of bovine liver extract on a Sephadex G-200 column resolved three macromolecular fractions with dihydropteridine reductase-dependent cytochrome c reducing activity. One of the active fractions was purified from the extract through the steps of solvent fractionation, chromatography on DEAE-Sephadex, and gel filtration. Biochemical and microbiological analyses showed that the purified complex consists of a Mr = 70,000 protein and tetrahydropteroyldiglutamate. In contrast to the extreme lability of free tetrahydropteridines the complex was quite stable against autooxidation under aerobic conditions.


Photosynthetic pigments of green sulfur bacteria. The esterifying alcohols of bacteriochlorophylls c from Chlorobium limicola. Bacteriochlorophyll c, the light-harvesting pigment from the green sulfur bacteria Chlorobium limicola, has been resolved into over a dozen chemically similar components by a new high pressure reversed-phase chromatographic procedure based on a stationary phase of polyethylene power. Detailed spectroscopic characterization of the resolved components has resulted in the identification of four different chlorins and six different esterifying alcohols. The major esterifying alcohol is trans, trans-farnesol, but smaller amounts of geranylgeraniol, tetrahydrogeranylgeraniol, phytol, cis-9-hexadecen-1-ol and 4-undecyl-2-furanmethanol are also observed. The high information content intrinsic in the compositional analyses of the complex pigment mixtures found in green sulfur bacteria appears to provide a new probe of the mechanisms of pigment biosynthesis in these organisms.


The binding of metal ions to bovine factor IX. The binding isotherms of Ca2+ and Mn2+ to bovine factor IX have been determined at pH 6.5 and pH 7.4, at 25 degrees C. At pH 7.4, at least 2 strong Ca2+ sites, with an average KDISS of 0.1 +/- 0.02 mM, are found. An additional 10 to 11 weaker Ca2+ binding sites, with an average KDISS of 1.3 +/- 0.2 mM are noted, at high levels of Ca2+. At pH 6.5, again at least 2 strong Ca2+ sites on factor IX are evident, with an average KDISS of 0.11 +/- 0.02 mM; but slightly fewer (7 to 8) weaker sites, with an average KDISS of 1.9 +/- 0.3 mM, are obtained. Qualitatively, the binding of Mn2+ to bovine factor IX appears similar to that of Ca2+. At pH 6.5, approximately 2 strong Mn2+ binding sites, with an average KDISS of 13 +/- 1.5 micrometer, and an additional 5 to 6 weak sites, with an average KDISS of 160 +/- 15 micrometer, are present. Manganese does not completely displace Ca2+; and Ca2+ does not completely displace Mn2+ from their respective binding sites. On the other hand, Tb3+ and Sm3+ readily displace Ca2+, at pH 6.5, from its sites on factor IX. The rate and extent of activation of bovine factor IX, by bovine factor XIa, is dependent on the Ca2+ concentration, up to concentrations of Ca2+ which saturate its effect on the system. Substitution of Sr2+ for Ca2+ leads to approximately 50% of the maximum rate of factor IXa formation, and final yield of factor IXa, in this activation system. Manganese does not substitute for Ca2+ in this activation, but does inhibit the stimulatory effect of Ca2+. Both Tb3+ and Sm3+ are effective inhibitors of Ca2+ in factor IX activation by factor XIa.


Demonstration of diphtheria toxin receptors on surface membranes from both toxin-sensitive and toxin-resistant species. A detailed binding study of 125I-labeled diphtheria toxin to isolated cell surface membrane-enriched fractions is reported. The study was undertaken to determine if toxin-resistant species exhibit a defet in either the binding step or the transport step of the intoxication process. Surface membrane fractions were obtained from liver and mammary glands of toxin-sensitive species, rabbit and giunea pig, and toxin-resistant species, rat mouse. All membrane fractions exhibited reversible binding of 125I-toxin which was competitively inhibited by unlabeled toxin. Toxin receptors from liver co-purified with plasma membranes and the plasma membrane marker 5'-nucleotidase. One-half saturation of all receptors occurred between 5 x 10(-8) and 1.8 x 10(-7) M. Scatchard plots were nonlinear and concave upwards. Total receptor sites ranged from 3.4 to 16 pmol/mg of membrane protein, tissue differences being more pronounced than difference between sensitive and nonsensitive species. Over 95% of the toxin specific binding was inhibited by removal of divalent cation from the medium or by the inclusion of 1 mM ATP, procedures which have been shown to protect sensitive cells from intoxication by diphtheria toxin. We conclude that the rat and mouse have surface membrane receptors for diphtheria toxin and that the toxin insensitivity of these species results from a defect in or a lack of the transport process.


Effect of diet on adenylosuccinase activity in various organs of rat and chicken. Adenylosuccinase activity of rat liver is depressed by prolonged starvation, cortisol administration, high protein diets, and alloxan diabetes. The loss of activity is not due to the accumulation of a dissociable inhibitor or loss of a cofactor. Starvation produces no loss in activity for 1 day; thereafter the activities of the liver and spleen enzyme decay with a half-life of about 0.9 day. Starvation produces no change in the activity of the kidney, brain, and skeletal muscle enzyme. Refeeding restores the activity of the liver enzyme to the fed level, with only a slight overshoot. The recovery of adenylosuccinase activity is equally rapid after refeeding a balanced diet, or corn oil, or glucose, and is not inhibited by injection of glucagon, in contrast to malic enzyme activity. Recovery is inhibited by cycloheximide, indicating the involvement of protein synthesis. Althouth adenylosuccinase is depressed in liver of starving rat it is elevated in liver of starving chicken. Starvation depresses malic enzyme activity and elevates alanine aminotransferase activity in both species. When rats are starved, the rate of de novo synthesis of adenine mononucleotide decreases in spleen and liver but not in kidney, suggesting a regulatory role for adenylosuccinase in purine biosynthesis. The low activity of adenylosuccinase in liver of severely starved rats is inconsistent with the proposal (Moss, K. M., and McGivan, J.D. (1975) Biochem. J. 150, 275-283) that the purine nucleotide cycle plays a major role in ammonia production for urea synthesis, at least under these conditions.


Properties of the factor Xa binding site on human platelets. The affinity (Ka) of human coagulation Factor Xa for thrombin-treated (to stimulate the release reaction) platelets has been determined to be 3 to 4 x 10(10) M-1 by equilibrium binding studies using 125I-labeled Xa. The binding of Factor Xa to platelets results in an increase of 300,000-fold in the apparent enzymatic activity of Xa in the conversion of prothrombin to thrombin. The activity of platelet surface Xa is approximately 15-fold greater than that observed with optimum concentrations of bovine Factor V and phospholipids in place of platelets. Ca2+ is required for the Xa-platelet interaction; the optimum concentration is 2.5 mM. Related coagulation factors, including Factor X, Factor IXa, diisopropylphosphoryl Factor Xa, and prothrombin do not complete with Factor Xa for the Xa binding sites. The rate of thrombim formation at saturating amounts of Xa is directly proportional to the number of platelets from 1 x 10(7) to 5 x 10(8) platelets/ml. Factor Xa bound to platelets is not inactivated by antithrombin III. An antibody that inhibits both human and bovine coagulation Factor V activity blocks both Xa binding to released platelets and the rapid thrombin formation associated with this binding, suggesting that Factor V from platelets is involved in the Xa-platelet interaction.


Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. The C5a molecule is one of two spasmogenic fragments (i.e. C3a and C5a) released from serum components C3 and C5 during complement activation. These fragments are called anaphylatoxins because their ability to stimulate mast cell histamine release, smooth muscle contraction, and increased vascular permeability may lead to a fatal reaction resembling anaphylactic shock in experimental animals. In addition, the C5a molecule, which is a glycoprotein, is perhaps the most potent of all humoral chemoattractants for polymorphonuclear leukocytes. Most of the structural analyses in this study were performed on the desArg 74 form of human C5a (C5adesArg). C5adesArg represents a natural form of C5a that is recovered from activated serum when no inhibitors are added to block the action of serum carboxypeptidase. The complete primary structure of the human C5a polypeptide portion is reported here. A partial characterization of intact human C5a has been previously reported (Fernandez, H. N., and Hugli, T. E. (1976) J. Immunol. 117, 1688--1694). The polypeptide portion of C5a contains 74 amino acids, accounting for a molecular weight of 8,200 while the carbohydrate portion accounts for approximately 3,000. The carbohydrate portion of C5a exists as a single complex oligosaccharide unit attached to an asparagine at position 64. An unusual feature of the C5a molecule is its large content of half-cystine, which accounts for more than 9% of its total residues. Two repeating Cys sequences occur in the linear structure and 6 of the 7 half-cystines in C5a are located at nearly identical positions to those in the human C3a molecule. In fact, sequence similarities between C3a and C5a indicate their common genetic ancestry. The role of C5a and C5adesArg as chemotactic factors prompted comparisons of their structural features with those of the chemotactically active formyl-Met peptides (Schiffman E., Corcoran, B. A., and Wahl, S. M. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 1059--1062). Removal of the COOH-terminal arginyl residue from C5a reduces chemotactic activity; therefore, the terminal portion of this molecule appears to play an active role in stimulating leukocyte migration. Hence the COOH-terminal sequence of C5a was examined for structural similarities to that of the formyl-Met peptides. Since methionine assumes a special functional importance in the formyl-Met peptides, attention is focused on the single methionyl residue in C5a. This methionyl residue, located near the COOH terminus of the molecule, may play an active role in the functional expression of C5a as a chemotactic factor. Although human and pig C3a show a close structural and functional relationship to C5a they lack the ability to excite leukotaxis, and this difference may correlate with the absence of a methionyl residue near the COOH terminus of C3a.


Covalent interaction of L-2-amino-4-oxo-5-chloropentanoic acid with rat renal phosphate-dependent glutaminase. Evidence for a specific glutamate binding site and of subunit heterogeneity. Rat renal phosphate-dependent glutaminase is rapidly inactivated by incubating with L-2-amino-4-oxo-5-chloropentanoic scid. Concentrations of phosphate, which increase the glutaminase activity, decrease the rate of inactivation by chloroketone. In addition, inactivation is not blocked by glutamine. Instead, glutamate was shown to specifically reduce the rate of chloroketone inactivation. Upon sodium lauryl sulfate-polyacrylamide gel electrophoresis, the purified glutaminase preparation exhibits at least five protein staining bands which range in molecular weight from 57,000 to 75,000. Studies with 14C-labeled chloroketone indicate that this reagent reacts with each of these peptides. The mean stoichiometry of binding was calculated to be 1.3 mol/mol of enzyme. Therefore, these results indicate that the glutaminase may contain a specific site for binding glutamate and that the purified enzyme consists of a series of related peptides which may have resulted from partial proteolysis.


Neurofilament protein is phosphorylated in the squid giant axon. We have observed the phosphorylation of neurofilament protein from squid axoplasm. Phosphorylation is demonstrated by 32P labeling of protein during incubation of axoplasm with [gamma-32P]ATP. When the labeled proteins are separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), two bands, at 2.0 x 10(5) daltons and greater than 4 x 10(5) daltons, contain the bulk of the 32P. The 2.0 x 10(5)-dalton phosphorylated polypeptide comigrates on SDS-PAGE with one of the subunits of squid neurofilament protein. Both major phosphorylated polypeptides co-fractionate with neurofilaments in discontinuous sucrose gradient centrifugation and on gel filtration chromatography on Sepharose 4B. The protein-phosphate bond behaves like a phospho-ester, and labeled phospho-serine is identified in an acid hydrolysate of the protein. The generality of this phenomenon in various species and its possible physiological significance are discussed.


Integrated stereological and biochemical studies on hepatocytic membranes. III. Relative surface of endoplasmic reticulum membranes in microsomal fractions estimated on freeze-fracture preparations. New methods are required for identifying membranes in subcellular fractions with respect to their origin, if such preparations are to be evaluated morphometrically. One method is freeze-fracturing which reveals intramembrane particles whose size, pattern, and numerical density differ for various membrane types. The question is examined whether the differences in numerical particle density per square micrometer of membrane (alpha) can be used to differentiate membrane vesicles found in microsomal fractions from liver cells with respect to their origin in the hepatocytes. It is found that the range of alpha for the protoplasmic face (PF) of endoplasmic reticulum (ER) membrane (1,900 less than alpha less than 3,250) is intermediate between those for plasma and mitochondrial membranes. Since PF(ER) should appear in the outer leaflet of microsomal vesicles, alpha was estimated on concave profiles of freeze-fracture preparations; the numerical frequency distribution of vesicles with respect to alpha was trimodal, with a major peak around 2,900/micrometer2 and 66% of the vesicles in the range determined for PF(ER). Using a new stereological method, it was calculated that 63% of the membrane surface in these microsomal fractions was of ER origin by this criterion. On the same preparations, an attempt was made to label the ER-derived membranes cytochemically for glucose-6-phosphatase. A line intersection count revealed 62% of the membrane surface to be of ER origin on the basis of marker enzyme labeling. These findings indicate a smaller part of ER membranes in microsomal fractions than would be predicted from biochemical data (77%). The possible reasons for such discrepancies are discussed; shifts in particle densities due to the preparation procedure could lead to an underestimate by freeze-fracturing, whereas the prediction from biochemical data could be overestimates if marker enzymes were not homogeneously distributed.


Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age. Stereological analysis of hepatic fine structure in Fischer 344 male rats at 1, 6, 10, 16, 20, 25, and 30 mo of age revealed differences in the amounts and distributions of hepatocellular organelles as a function of sublobular location or animal age. Between 1 and 16 mo of age, both the centrolobular and periportal hepatocytes increased in volume by 65 and 35%, respectively. Subsequently, the cell volumes declined until the hepatocytes of 30-mo-old rats approached the size of those found in the youngest animals. Regardless of animal age, the centrolobular cells were consistently larger than the corresponding periportal hepatocytes. The cytoplasmic and ground substance compartments reflected similar changes in their volumes, although there was no significant alteration in the nuclear volume. The volumes of the mitochondrial and microbody compartments increased and decreased concomitant with the changes in average hepatocyte size. Both lobular zones in the 30-mo-old rats contained significantly smaller relative volumes of mitochondria than similar parenchyma in 16-mo-old animals. The volume density of the dense bodies (lysosomes) increased markedly in both lobular zones between 1 and 30 mo of age, confirming reports of an age-dependent increase in this organelle. The surface area of the endoplasmic reticulum in the centrolobular and periportal hepatocytes reached its maximum level in the 10-mo-old rats and subsequently declined to amounts which approximated those measured in the 1-mo-old animals. This age-related loss of intracellular membrane is attributable to a significant reduction in the surface area of the smooth-surfaced endoplasmic reticulum (SER) in animals beyond 16 mo of age. The amount of rough-surfaced endoplasmic reticulum (RER) in the periportal parenchymal cells was unaffected by aging, but the centrolobular hepatocytes of 30-mo-old animals contained 90% more RER than similar cells in the youngest rats. The centrolobular parenchyma contained more SER and the portal zones more RER throughout the age span studied. These quantitative data suggest that (a) certain hepatic fine structural parameters undergo marked changes as a function of animal age, (b) there exists a gradient in hepatocellular fine structure across the entire liver lobule, and (c) there are remarkable similarities in hepatocyte ultrastructure between very young and senescent animals, including cell size and the amount of SER.


Formation of gap junctions by treatment in vitro with potassium conductance blockers. Gap junctions were regularly seen in thin sections of canine tracheal smooth muscle incubated in vitro. Their number was increased in tissued exposed in vitro to either of two potassium conductance blockers, tetraethylammonium (TEA) and 4-aminopyridine (4-AP), and at the same time the muscles became mechanically active, with spontaneous contractions. The presence of gap junctions in this smooth muscle may provide one basis for cell-to-cell coupling, and their increase after TEA- and 4-AP-treatment could account for a decreased junctional resistance between cells, contributing to a longer space constant. However, an increase in gap junctions was not sufficient to change the behavior of trachealis smooth muscle from multiunit to single-unit type. Gap junctions in increased numbers persisted after washout of 4-AP, which caused inhibition of spontaneous contractions, and despite inhibition of the contractile effects of 4-AP by atropine. The rapid induction of gap junction formation was not dependent on de novo synthesis of protein. The fact that the number of gap junctions can be increased by chemical agents has important implications for control of their formation and provides a tool for analysis fo their role in cell-to-cell coupling.


Chemical and structural changes of neurofilaments in transected rat sciatic nerve. The sequence of changes occurring in transected rat sciatic nerve was examined by electron microscopy and by sodium dodecyl sulfate (SDS) polyacrylamide disc gel electrophoresis. Representative segments of transected nerves were processed for ultrastructural examinations between 0 and 34 days after the transection of sciatic nerves immediately below the sacro-sciatic notch. The remainder of the transected nerves and the intact portions of sciatic nerves were desheathed and immediately homogenized in 1 percent SDS containing 8 M urea and 50 mM dithioerythritol. Solubilized proteins were analyzed on 12 percent gels at pH 8.3 in a discontinuous electrophoretic system. Initial changes were limited to the axons of transected nerve fibers and were characterized by the loss of microtubules and neurofilaments and their replacement by an amorphous floccular material. These changes became widespread between 24 and 48 h after transection. The disruption of neurofilaments during this interval occurred in parallel with a selective loss of 69,000, 150,000 and 200,000 mol wt proteins from nerve homogenates, thus corroborating the view that these proteins represent component subunits of mammalian neurofilaments. Furthermore, the selective changes of neurofilament proteins in transected nerves indicate their inherent lability and suggest their susceptibility to calcium-mediated alterations. Electrophoretic profiles of nerve proteins during the 4-34-day interval after nerve transection reflected the breakdown and removal of myelin, the proliferation of Schwann cells and the deposition of endoneurial collagen. A marked increase of intermediate-sized filaments within proliferating Schwann cell processes was not accompanied by the appearance of neurofilamentlike proteins in gels of nerve homogenates.


Oxygen-sensitive stages of the cell cycle of human diploid cells. We had established that growth of human diploid WI-38 cells is reversibly inhibited by elevated partial pressures of oxygen (PO2) and we were interested in determining where in the cell cycle growth was delayed. A technique combining cytospectrophotometry and autoradiography was used to determine cell cycle parameters. Confluent cells that were subcultivated and exposed to a PO2 of 365 +/- 8 mm Hg were delayed primarily after DNA synthesis but before metaphase. At a PO2 of 590 +/- 35 mm Hg, most cells did not initiate DNA synthesis, and the few that did, failed to complete the process. When exponentially growing cells that had already begun DNA synthesis were exposed to a PO2 of 590 p 35 mm Hg, they accumulated after completing DNA synthesis but before initiating mitosis. The rate at which (3H)thymidine was incorporated into DNA was inversely correlated with oxygen tension (PO2 of 135--590 mm Hg). These results suggest that the process most sensitive to oxygen causes cells to be delayed after DNA synthesis but before metaphase. Slightly higher PO2's were needed to inhibit the initiation of DNA synthesis. Further, the rate of DNA synthesis is decreased by elevated oxygen tensions.


Immunocytochemical localization of a large intrinsic membrane protein to the incisures and margins of frog rod outer segment disks. Immunocytochemical techniques have localized a large protein which is an intrinsic membrane component of isolated frog rod outer segments (ROS). This large protein whose apparent mol wt is 290,000 daltons comprises about 1--3% of the ROS membrane mass. Its molar ratio to opsin is between 1:300 and 1:900. Adequate immune responses were obtained with less than 30 microgram (100 pmol) of antigen per rabbit. Antibodies to the large protein were used for its localization on thin sections of frog retina embedded in glutaraldehyde cross-linked bovine serum albumin (BSA). Specifically bound antibodies were detected by an indirect sequence with ferritin-conjugated antibodies. This technique detected the protein which is represented by 1,000--3,000 molecules per disk. This indicates that the procedure is sufficiently sensitive for analysis of membrane components in low molar proportions. The large protein was specifically localized to the incisures of ROS disks which divide the disks into lobes and to the disk margin. Thus, opsin is mobile within the membrane of the disk while the large protein is apparently constrained to the disk edges. This finding raises the possibility that special functions are also localized ot his unusual region of high curvature, and that collisions of bleached opsin with these edges are physiologically important in couter segment function.


Isolation and characterization of glial filaments from human brain. Intermediate (8--9 nm) filaments of human central nervous system astrocytes were isolated from the gliosed white matter of cases of adrenoleukodystrophy (ALD). This hereditary lipidosis is characterized pathologically by demyelination, loss of axons, and replacement of the white matter of the caudal cerebrum by a glial scar. Glial filaments were composed largely of a single protein component with a mol wt of about 49,000 daltons. Smaller components (44,000--39,000 daltons) were detected in some samples, and appear to represent degradation products of the filament protein. Human neurofilaments were isolated from the normal frontal white matter of ALD cases by the standard myelin-free axon technique. Isolated glial and neurofilament proteins comigrated during acrylamide gel electrophoresis in SDS. Polypeptides resulting from cyanogen bromide cleavage of the two filament proteins were the same. Both proteins reacted with rabbit antisera raised against isolated bovine neurofilament protein and human glial fibrillary acidic protein.


Ultrastructure of the proximal region of somatic cilia in Paramecium tetraurelia. The morphology of the transition zone between the terminal plate of the basal body and the 9 + 2 region of the somatic (non-oral) cilium has been examined in Paramecium tetraurelia. Freeze-fracture and thin-section techniques disclosed both membrane specializations and various internal structural linkages. Freeze-fracture material revealed sets of particles interrupting the unit membrane. The more distal of these form plaquelike arrays while the proximal set of particles forms the ciliary "necklace." The plaque regions correspond to anionic sites on the outer membrane surface as revealed by binding of polycationic ferritin. Both the plaque particles and the necklace particles appear to be in contact with outer doublet microtubules via a complex of connecting structures. In the interior of the transition zone an axosomal plate supports an axosome surrounded by a ring of lightly packed material. Only one of the two central tubules of the axoneme reaches and penetrates the axosome. Below the axosomal plate four rings, each approx. 20 nm wide, connect adjacent outer doublets. An intermediate plate lies proximal to these rings, and a terminal plate marks the proximal boundary of this zone. Nine transitional fibers extend from the region of the terminal plate to the plasmalemma. The observations described above have been used to construct a three-dimensional model of the transition region of "wild-type" Paramecium somatic cilia. It is anticipated that this model will be useful in future studies concerning possible function of transition-zone specializations, since Paramecium may be examined in both normal and reversed ciliary beating modes, and since mutants incapable of reverse beating are available.


Intracellular transport of proteins in active and resting secretory cells of the venom gland of Vipera palaestinae. The intracellular transport of venom proteins has been studied in active and resting venom glands of the snake Vipera palaestinae by electron microscope radioautography after an intra-arterial injection of [3H]leucine. In the active gland, most of the label is initially (10 min) found over the RER. By 30 min, the relative grain density of the Golgi complex reaches its maximum, with concomitant increase in the labeling of the condensing vacuoles. Later on, a steep increase in radioactivity of the secretory granules is observed. At 3 h, these granules, which comprise about 2% of the cell volume, contain 22% of the total grains. At the following hour, their labeling declines and at the same time the radioactivity of the secreted venom is increased. It is concluded that, in the active cell, venom proteins are transported via the Golgi apparatus into membrane-bounded granules which are the immediate source of the secreted venom. An alternative pathway, which involves the RER cisternae as a storage compartment, seems unlikely, since incorporated label does not accumulate in this compartment after prolonged postpulse intervals. The route of intracellular transport of proteins in the resting glands is similar to that of the active ones, but the rate of synthesis and transport is much slower. The present results and earlier data, thus, show that the increase in the rate of secretion after initiation of a new venom regeneration cycle is the result of accelerated rates of both synthesis and transport.


Immunoelectron microscope localization of cytochrome P-450 on microsomes and other membrane structures of rat hepatocytes. Localization of cytochrome P-450 on various membrane fractions of rat liver cells was studied by direct immunoelectron microscopy using ferritin-conjugated antibody to the cytochrome. The outer surfaces of almost all the microsomal vesicles were labeled with ferritin particles. The distribution of the particles on each microsomal vesicle was usually heterogeneous, indicating clustering of the cytochrome, and phenobarbital treatment markedly increased the labeled regions of the microsomal membranes. The outer nuclear envelopes were also labeled with ferritin particles, while on the surface of other membrane structures such as Golgi complexes, outer mitochondrial membranes and plasma membranes the labeling was scanty and at the control level. The present observation indicates that cytochrome P-450 molecules are localized exclusively on endoplasmic reticulum membranes and outer nuclear envelopes where they are probably distributed not uniformly but heterogeneously, forming clusters or patches. The physiological significance of such microheterogeneity in the distribution of the cytochrome on endoplasmic reticulum membranes is discussed.


A freeze-fracture study of membrane events during neurohypophysial secretion. Freeze-fracture was used to study the membrane events taking place during neurosecretory granule discharge (exocytosis) and subsequent membrane internalization (endocytosis) in axons of neurohypophyses from control and water-deprived rats. En face views of the cytoplasmic leaflet (P face) of the split axolemma reveal circular depressions that represent the secretory granule membranes fused with the plasma membrane during exocytosis. These depressions often contain granule core material in the process of extrusion into the extracellular space. The membrane surrounding some of the exocytotic openings shows a decreased number of intramembrane particles (mean diameter, 8 nm) which are elsewhere more numerous and evenly distrubuted on the fracture face. Endocytotic sites appear as smaller plasma membrane invaginations, with associated intramembrane particles. Moreover, such invaginations often contain large particles (mean diameter, 12 nm) that appear as clusters on en face views of the membrane leaflet. Quantitative analysis indicates that the number of exocytotic images increases significantly in glands from water-deprived rats. Concomitantly, the number of endocytotic figures per unit area of membrane is raised as is the number of clusters of large particles. The observations demonstrate that, in the neurohypophysis, it is possible to distinguish exocytosis morphologically from endocytosis and that the two events can be assessed quantitatively.


Loss and reappearance of gap junctions in regenerating liver. Changes in intercellular junctional morphology associated with rat liver regeneration were examined in a freeze-fracture study. After a two-thirds partial hepatectomy, both gap junctions and zonulae occludentes were drastically altered. Between 0 and 20 h after partial hepatectomy, the junctions appeared virtually unchanged. 28 h after partial hepatectomy, however, the large gap junctions usually located close to the bile canaliculi and the small gap junctions enmeshed within the strands of the zonulae occudentes completely disappeared. Although the zonulae occludentes bordering the bile canaliculi apparently remained intact, numerous strands could now be found oriented perpendicular to the canaliculi. In some instances, the membrane outside the canaliculi was extensively filled with isolated junctional strands, often forming very complex configurations. About 40 h after partial hepatectomy, very many small gap junctions reappeared in close association with the zonulae occludentes. Subsequently, gap junctions increased in size and decreased in number until about 48 h after partial hepatectomy when gap junctions were indistinguishable in size and number from those of control animals. The zonulae occludentes were again predominantly located around the canalicular margins. These studies provide further evidence for the growth of gap junctions by the accretion of particles and of small gap junctions to form large maculae.


Freeze-fracture identification of sterol-digitonin complexes in cell and liposome membranes. To advance our understanding of the organization of cholesterol within cell membranes, we used digitonin in freeze-fracture investigations of model lipid vesicles and tissues. Cholesterol suspensions or multilamellar liposomes composed of phosphatidylcholine with and without cholesterol were exposed to digitonin. Freeze-fracture replicas of those multilamellar liposomes containing cholesterol displayed either 50--60-nm wide intramembrane corrugations or extramembrane tubular complexes. Comparable intramembrane hemitubular scallops and extra-cellular free tubular complexes were observed in thin sections. Exposure of sperm, erythrocytes (whole and ghosts), and intact tissues (skin, liver, adrenal gland, epididymis) to digitonin produced the same types of intra- and extramembrane complexes or furrows as were formed in liposomes. The plasma membrane of guinea pig serum tail had two unfurrowed regions: the annulus and the zipper. Incubating erythrocyte membranes with digitonin resulted in rapid displacement of cholesterol, accompanied by intramembrane particle clustering and membrane faceting, a feature which we did not see in the intact epithelia studied. In freeze-fractured epithelia, we found that plasma membranes, lysosomes, and some vesicular organelles commonly furrowed, but that mitochondrial membranes and nuclear envelopes were generally spared, correlating well with their known cholesterol content. Finally, plasma membrane corrugations approached but did not impinge on either gap or tight junctions, or on coated vesicles. We conclude that freeze-fracture of membranes exposed to digitonin: (a) reveals distinctive cholesterol-digitonin structural complexes; (b) distinguishes cholesterol-rich and -poor organelle membranes; and (c) demonstrates membrane domains rich or poor in cholesterol.


Subaxolemmal filamentous network in the giant nerve fiber of the squid (Loligo pealei L.) and its possible role in excitability. A new technique utilizing the squid giant nerve fiber has been developed which permits direct examination of the inner face of the axolemma by scanning electron microscopy. The axoplasm was removed sequentially in a 15-mm long segment of the fiber by intracellular perfusion with a solution of KF, KCl, Ca++-containing seawater, or with pronase. The action potential of the fibers was monitored during these treatments. After brief prefixation in 1% paraformaldehyde and 1% glutaraldehyde, the perfused segment was opened by a lne could be related to information on the detailed morphology of the cytoplasmic face of the axolemma and the ectoplasm. The results obtained by scanning electron microscopy were further substantiated by transmission electron microscopy of thin sections. In addition, living axons were studied with polarized light during axoplasm removal, and the identification of actin by heavy meromyosin labeling and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis was accomplished. These observations demonstrate that a three-dimensional network of interwoven filaments, consisting partly of an actinlike protein, is firmly attached to the axolemma. The axoplasmic face of fibers in which the filaments have been removed partially after perfusion with pronase displays smooth membranous blebs and large profiles which sppose the axolemma. In fibers where the excitability has been suppressed by pronase perfusion, approximately one-third of the inner face of the axolemma in the perfusion zone is free of filaments. It is hypothesized that the attachment of axoplasm filaments to the axolemma may have a role in the maintenance of the normal morphology of the axolemma, and, thus, in some aspect of excitability.


Promotion of human adipocyte precursor replication by 17beta-estradiol in culture. The influence of 17beta-estradiol and 17alpha-estradiol on adult human omental adipocyte precursors grown in a propagating culture system was studied. Cells were grown in subculture in the presence or absence of hormone. 17beta-estradiol resulted in significant promotion of adipocyte precursor replication, as determined by cell counting and incorporation of radioactive thymidine into DNA. The hormone stimulated cell multiplication in the concentration range 0.5--500 ng/ml growth medium. The highest level tested was 500 ng/ml. The maximal effects were obtained at 50 ng/ml (P less than 0.001 by paired t test, 48 h after hormone addition). All 10 cell strains (five were derived from men and five from women) that were tested responded similarly to the hormone. 17beta-estradiol did not affect cell size. 17alpha-estradiol did not promote the replication of adipocyte precursors, nor did it influence cell size. Thus, 17beta-estradiol, which is the active isomer in known target tissues, stimulates the multiplication of human adipocyte precursors in culture.


Pancreatic and gastric somatostatin release in response to intragastric and intraduodenal nutrients and HCl in the dog. The effects of the instillation of glucose, fat, casein hydrolysate, and HCl into the gastrointestinal tract upon plasma levels of somatostatin-like immunoreactivity (SLI) in the venous effluent of the pancreas, fundus and antrum of the stomach, and in the inferior vena cava (IVC) were determined in normal laparotomized dogs. Fasting SLI levels in the effluent plasma from these sites were significantly greater than IVC levels. The intragastric administration of glucose elicited a prompt and significant rise in SLI levels in pancreatic, fundic and antral venous plasma, and in IVC plasma; intraduodenal glucose elicited smaller increments. After intragastric fat, a smaller, more gradual increase in the pancreatic and fundic effluents was observed, whereas the rise in antral SLI was minute, and IVC SLI did not rise significantly. Intraduodenal fat elicited a prompt increase in the pancreatic and antral vein SLI levels, and a small but significant increase in fundic and IVC plasma which suggests faster release of enteric factors that influence SLI secretion in the pancreas and antrum. Intragastric casein hydrolysate elicited a prompt increase in SLI in both the pancreatic and fundic veins, the latter being marked, but the antral SLI response was small; IVC SLI rose significantly within 15 min. Intragastric HCl provoked a prompt and marked rise in pancreaticoduodenal and antral vein SLI but no increase in fundic vein SLI; IVC SLI levels rose significantly within 20 min. Intraduodenal HCl elicited an even more prompt and marked pancreatic SLI response, and SLI rose significantly in both the fundic and antral venous effluents; IVC SLI also rose more promptly. In dogs with a gastric fistula that prevented intraduodenal entry of HCl, intragastric HCl elicited only a very small and transient rise in pancreaticoduodenal vein SLI, markedly stimulated the antral SLI response, but completely suppressed fundic venous SLI levels. The results indicate that all three nutrients stimulate SLI release from the pancreas and stomach. The greater SLI response to intragastric, as opposed to intraduodenal, glucose suggests that unidentified local factors are of importance. The responses to the intraduodenal instillation of HCl and fat suggest a role of enteric hormones in the release of SLI from the pancreas and fundus and antrum of the stomach. Additionally, there is evidence of direct effects of HCl upon gastric SLI release.


Biosynthesis of chenodeoxycholic acid in man: stereospecific side-chain hydroxylations of 5beta-cholestane-3alpha,7alpha-diol. Stereospecific side-chain hydroxylations of 5beta-cholestane-3alpha, 7alpha-diol were studied in mitochondrial and microsomal fractions of human liver. Incubation of 5beta-cholestane-3alpha, 7alpha-diol resulted in hydroxylations at C-12, C-24, C-25, and C-26. Hydroxylations at C-24 and C-26 were accompanied by the introduction of additional asymmetric carbon atoms at C-24 and C-25 respectively, that led to the formation of two distinct pairs of diastereoisomers, namely 5beta-cholestane-3alpha, 7alpha,24-triols (24R and 24S) and 5beta-cholestane-3alpha, 7alpha,26-triols (25R and 25S). A sensitive and reproducible radioactive assay to measure the formation of the different biosynthetic 5beta-cholestanetriols was developed. Optimal assay conditions for human mitochondrial and microsomal systems were tentatively established.The mitochondrial fraction was found to predominantly catalyze the 26-hydroxylation of 5beta-cholestane-3alpha, 7alpha-diol with the formation of the 25R-diastereoisomer of 5beta-cholestane-3alpha, 7alpha,26-triol as the major product. In the microsomal fraction, on the other hand, 25-hydroxylation was more efficient than 26-hydroxylation and accounted for 6.4% of the total hydroxylations. The microsomes catalyzed the formation of both diastereoisomers of 5beta-cholestane-3alpha, 7alpha,26-triol (25R and 25S, 4.2 and 1.6% respectively). These experiments suggest that the initial step in the degradation of the steroid side chain during the biosynthesis of chenodeoxycholic acid in man is mediated by the mitochondria, and involves the formation of the 25R-diastereoisomer of 5beta-cholestane-3alpha, 7alpha,26-triol. The role of the microsomal 25- and 26-hydroxylated intermediates requires further exploration.


Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium. Lysophosphoglycerides, products of membrane phospholipid catabolism known to influence membrane function in several systems, appeared in the effluents of anoxic isolated rabbit hearts perfused at low flow and accumulated in perfused hearts and myocardium rendered ischemic in situ. Comparable concentrations of lysophosphoglycerides bound to albumin markedly and reversibly altered action potentials of isolated canine Purkinje fibers in vitro. Changes induced included diminution of the maximum diastolic potential, peak dV/dt of phase zero, amplitude, and action potential duration--alterations resembling those seen in ischemic myocardium in vivo. These electrophysiological alterations are compatible with changes implicated in predisposing to dysrhythmia dependent on reentry, a phenomenon potentiated by the presence of zones of decreased conduction. Thus, accumulation of lysophosphoglycerides induced by ischemia may contribute to the genesis of malignant dysrhythmia early after its onset.


L-triiodothyronine and L-reverse-triiodothyronine generation in the human polymorphonuclear leukocyte. Extrathyroidal monodeiodination of l-thyroxine (T(4)) is the principal source of l-triiodothyronine (T(3)) and l-reverse-triiodothyronine (rT(3)) production. To define some of the cellular factors involved, we examined T(3) and rT(3) generation from added nonradioactive T(4) in human polymorphonuclear leukocytes, using radioimmunoassays to quantify the T(3) and rT(3) generated. Under optimum incubation conditions which included a pH of 6.5 in sucrose-acetate buffer, the presence of dithiothreitol as a sulfhydryl-group protector, and incubation in an hypoxic atmosphere, significant net generation of T(3) and rT(3) was observed. Of the several subcellular fractions studied, the particulate fraction obtained by centrifugation at 27,000 g was found to possess the highest T(3)- and rT(3)-generating activities per unit quantity of protein. With respect to T(3) generation from substrate T(4), the K(m) was 5 muM and the V(max) was 7.2 pmol/min per mg protein. Propylthiouracil, methimazole, and prior induction of phagocytosis inhibited both T(3) and rT(3) generation, but T(3) generation was inhibited to a greater extent. rT(3), in a concentration equimolar to that of substrate T(4), did not alter T(3) generation, but inhibited T(3) generation when the molar ratio of rT(3) to T(4) approached 10:1. Under the incubation conditions employed, particulate fractions of leukocytes obtained from five cord blood samples displayed an essentially normal relationship between T(3)- and rT(3)-generating activities, despite the distinctly divergent serum T(3) and rT(3) concentrations in these samples. From our findings, we draw the following conclusions: (a) the human polymorphonuclear leukocyte possesses the ability to generate T(3) and rT(3) from substrate T(4); (b) the T(3)- and rT(3)-generating activities are associated principally with the 27,000 g particulate fraction and display enzymic characteristics with a sulfhydryl-group requirement; (c) T(3)-generating activity appears to be more susceptible to inhibitory influences than rT(3)-generating activity; and (d) in cord blood leukocytes, the putative enzymes catalyzing T(3) and rT(3) generation appear to be functionally intact under the experimental conditions employed.


Decreased pulmonary transvascular fluid filtration in awake newborn lambs after intravenous furosemide. We studied the effect of furosemide on pulmonary transvascular filtration of fluid and microvascular permeability to plasma proteins by measuring steady-state lung lymph flow and protein flow, pulmonary arterial and left atrial pressures in nine 1-wk-old unanesthetized lambs before and after rapid intravenous infusion of furosemide, 1 mg/kg in 10 experiments and 8 mg/kg in 5 experiments. With rapid diuresis induced by furosemide (an eightfold increase in urine flow), lung vascular pressures decreased, protein concentrations of lymph and plasma increased, and there was a consistent decrease in lymph flow and lymph protein flow, more pronounced after the larger dose. Five additional lambs received 8 mg/kg of furosemide intravenously in the presence of saline-induced pulmonary edema; in these experiments, the decrease in vascular pressures, increase in transvascular protein gradient, and decrease in lymph flow were greater than in lambs without pulmonary edema. These findings suggest that furosemide decreases transvascular filtration of fluid in the lung by diminishing the transvascular hydraulic pressure gradient and increasing the transvascular gradient for protein osmotic pressure. In five acute experiments on anesthetized lambs with kidneys removed, 8 mg/kg of intravenous furosemide decreased lymph flow one-half as much as it did in the presence of kidneys, with no change in lung vascular pressures or protein concentrations. The results of experiments in lambs without kidneys are consistent with a reduction in the vascular surface area for exchange of fluid and protein in the lung.


Skeletal muscle protein and amino acid metabolism in experimental chronic uremia in the rat: accelerated alanine and glutamine formation and release. The kinetics and factors regulating alanine and glutamine formation and release were investigated in skeletal muscle preparations from control and experimentally uremic rats. These preparations maintained phosphocreatine and ATP levels in vitro which closely approximated levels found in vivo. Alanine and glutamine release from uremic muscle were increased 45.8 and 36.0%, respectively, but tissue levels were unaltered. The increased release of alanine by uremic muscle was not accounted for by decreased rates of medium alanine reutilization via oxidation to CO(2) or incorporation into muscle protein. The maximal capacity of added amino acids such as aspartate, cysteine, leucine, and valine to stimulate net alanine and glutamine formation was the same in uremic and control muscle. Epitrochlearis preparations were partially labeled in vivo with [guanido-(14)C]-arginine. On incubation, preparations from uremic animals showed a 54.6% increase in the rate of loss of (14)C-label in acid precipitable protein. Correspondingly, these same uremic preparations showed a 62.7% increase in (14)C-label appearance in the acid-soluble fraction of muscle and in the incubation media. Insulin decreased alanine and glutamine release to an extent threefold greater in uremic than in control preparations, and increased muscle glucose uptake approximately threefold in all preparations. Although basal rates of [4,5-(3)H]leucine incorporation into protein were decreased 25% in uremic muscles as compared with control muscles, insulin stimulated [(3)H]leucine incorporation nearly equally in both preparations. These data demonstrate increased alanine and glutamine production and release from skeletal muscle of chronically uremic rats. This increase appears to derive in part from an enhancement of net protein degradation which could be caused by an acceleration in the breakdown of one or more groups of muscle proteins, or by an inhibition of protein synthesis, or by both processes. The increased alanine and glutamine formation and release in uremia appears not to result from an insensitivity to insulin action. The implications of these findings for an understanding of the abnormal carbohydrate metabolism of uremia are discussed.


Sympathetic hyperactivity during hypothalamic stimulation in spontaneously hypertensive rats. To determine whether sympathetic hyperactivity of hypothalamic origin contributes to keep blood pressures high in spontaneous hypertension, aortic pressures and sympathetic nerve spike potentials were recorded during electrical stimulation of the posterior hypothalamus in urethane-anesthetized normotensive or hypertensive rats. Basal sympathetic nerve activity was higher in spontaneously hypertensive rats than in either normotensive or deoxycorticosterone acetate-salt hypertensive ones even before stimulation began. Blood pressure elevations produced by hypothalamic stimulation were always preceded by substantial increases in amplitude and rate of neural firing. Changes in amplitude could not be quantified, but rates of neural firing accelerated much more in spontaneous hypertensives than in normotensives during stimulation with 50- and 100-muA currents. Similar differences between deoxycorticosterone acetate-salt hypertensives and either normotensives or spontaneous hypertensives were not statistically significant. Nerve activity invariably became quiescent immediately after hypothalamic stimulation was discontinued, and recovery from this poststimulatory inhibition was faster in spontaneously hypertensive than in normotensive rats. Although spontaneous hypertensives generally also had stronger pressor responses to various sympathomimetic stimuli, responses to hypothalamic stimulation were enhanced to a greater extent than those to either norepinephrine or sympathetic nerve stimulation. Because this selectivity indicates participation of mechanisms other than augmented cardiovascular reactivity, further enhancement of responsiveness to hypothalamic stimuli was attributed to the associated increase in sympathetic nerve firing. These results are in accord with the hypothesis that the blood pressure elevation in rats with established spontaneous hypertension is a result, at least in part, of sympathetic hyperactivity emanating from the posterior hypothalamus.


Effect of glucagon on glucose production during insulin deficiency in the dog. The aim of the present experiments was to determine the effects of basal glucagon on glucose production after induction of prolonged insulin lack in normal conscious dogs fasted overnight. A selective deficiency of insulin or a combined deficiency of both pancreatic hormones was created by infusing somatostatin alone or in combination with an intraportal replacement infusion of glucagon. Glucose production (GP) was measured by a primed constant infusion of [3H-3]glucose, and gluconeogenesis (GNG) was assessed by determining the conversion rate of circulating [14C]alanine and [14C]lactate into [14C]glucose. When insulin deficiency was induced in the presence of basal glucagon the latter hormone caused GP to double and then to decline so that after 4 h it had returned to the conrol rate. The conversion of alanine and lactate into glucose, on the other hand, increased throughout the period of insulin lack. Withdrawal of glucagon after GP had normalized resulted in a 40% fall in GP, a 37% decrease in GNG, and a marked decrease in the plasma glucose concentration. Induction of insulin deficiency in the absence of basal glucagon resulted in an initial (30%) drop in GP followed by a restoration of normal GP after 2--3 h and moderately enhanced glucose formation from alanine and lactate. It can be concluded that (a) the effect of relative hyperglucagonemia on GP is short-lived; (b) the waning of the effect of glucagon is attributable solely to a diminution of glycogenolysis because GNG remains stimulated; (c) basal glucagon markedly enhances the GNG stimulation apparent after induction of insulin deficiency; and (d) basal glucagon worsens the hyperglycemia pursuant on the induction of insulin deficiency both by triggering an initial overproduction of glucose and by maintaining the basal production rate thereafter.


Absence of the platelet receptor for drug-dependent antibodies in the Bernard-Soulier syndrome. The platelet membrane receptor for quinidine- and quinine-dependent antibodies was studied in three patients with the Bernard-Soulier syndrome (BSS) and in normal subjects with immunologic techniques based on the release of 51Cr from labeled platelets. The receptor could not be detected on BSS platelets but was present on platelets from each of 180 normal subjects. BSS platelets reacted normally with other allo- and autoantibodies. In confirmation of previous reports, BSS platelets were found to be deficient in glycoproteins Ib and Is. However, after apparently total cleavage of these proteins from the membrane of normal platelets by controlled hydrolysis with trypsin or chymotrypsin, 80% of the drug-dependent antibody receptor activity was retained. These observations suggest the existence of an additional, hitherto unrecognized membrane defect in Bernard-Soulier platelets.


Validity and usefulness in four WIST studies recently reported in the journal. Four articles that reported studies that used the Whitaker Index of Schizophrenic Thinking (WIST) were published in the Journal of Clinical Psychology in early 1977. These articles are reviewed by the WIST's author in terms of necessary conditions for valid and useful studies of schizophrenic thinking. Two of the studies reported used the MMPI Sc Scale: one of them failed to note its limitations and used the WIST incorrectly; the other resulted in some useful data. The other two articles report ground-breaking investigations of schizophrenic thinking as conceptual rule-learning inability. They are viewed as providing a valuable new orientation in the study of schizophrenic thinking because they investigate the phenomena first-hand instead of relying simply on ordinary psychiatric diagnosis for a criterion. Some previously unpublished data on the WIST and intelligence relevant to all four studies are reported.


Binocular locus of prior time information effect in schizophrenia. Schizophrenics and alcoholic controls estimated the duration of a single dark dot, which followed an auditory warning signal of variable duration that functioned as foreperiod duration. The effect of foreperiod duration on time estimation was an increasing one for both schizophrenics and alcoholics alike. Elimination of such foreperiod effect by prior time information in terms of correlation between pitch of the warning signal and foreperiod duration, was shown to be unique to schizophrenics. However, this prior time information effect was demonstrated only when the dot was viewed binocularly, not when viewed monocularly. This binocular locus of time expectancy in schizophrenia reflects the tendency toward spatialization of prior time information.


The relative accuracy of U.S. British, and Mexican raters in judging the emotional displays of schizophrenic and normal U.S. women. Asked U.S., British, and Mexican male students of college age to discriminate among three affective displays presented by 10 schizophrenic and 10 normal U.S. women. Significant main effects for diagnostic category, nationality of judge and for the interaction of nationality and diagnostic category were obtained. Furthermore, U.S. judges did significantly better in judging normals as compared to schizophrenics, British judges tended in the same direction, and Mexican judges did not. Co-nationality and national similarity confer an advantage in judging normals as compared to schizophrenics. The data have relevance for questions about the effects of sending and receiving nonverbal emotional messages on communications or miscommunications between doctor and patient, doctors from different cultures and people including conference negotiators, from different national backgrounds.


Reductions in experienced control and depression in psychiatric inpatients: a test of the learned helplessness model. Used a measure of reduction in experienced control to investigate two aspects of the learned helplessness model of depression. Consistent with this model, psychiatric inpatients who reported reduced control over life events prior to hospitalization were significantly more depressed than individuals who reported no such reductions. Locus of control (IE) was not related to depression scores, and it was suggested, in light of previous research, that future research on the antecedents of depression employ more specific measures of control rather than measures of generalized expectancies. Additionally, depressive as a diagnostic group reported greated reduced control than chronic schizophrenics, paranoid schizophrenics, and patients with personality disorder diagnoses. These results were interpreted as supporting the specificity of learned helplessness to depression. It was suggested that research on learned helplessness and depression, which has relied on college student analogues, can be complemented profitably by studies of reduced experience control within clinical populations.


A critique of the clinical-personological approach to idiographic personality study. Idiographic research occupies an accepted position in personological study and clinical psychology. This review critically examines one such method of investigation, the clinical-personological approach, which relies on inductive inference and attempts to provide description at the level of the "whole person." The data base is essentially clinical, psychosocial and psychometric, and information integration is achieved through "convergent validation." The approach was criticized on three grounds: (a) level of description is only at a single level, ie., the general; (b) the data base is limited to grosser system attributes and is typically of low reliability and validity; and (c) inductive inference formulation is unduly susceptible to influence by chance factors, and attempts to validate the hypothesis are rare. Of the alternative approaches, Personal Construct Theory appears a promising avenue, but is also open to criticism.


Primary affective disorder: anxiety in unipolar and bipolar depressed groups. A group of 50 patients (29 bipolar and 21 unipolar) hospitalized for depression were compared on the IPAT Anxiety Scale. The bipolar depressed group reported significantly less anxiety than the unipolar  group. This finding supports the results of other studies that reported relatively less psychopathology in bipolar groups during the acute depressive state. It is suggested that test-taking defensiveness, especially denial, might account for relatively lower anxiety and MMPI scores in bipolar groups.


The effect of motivation on loose thinking in schizophrenics as measured by the Bannister-Fransella Grid Test. Administered the Bannister-Fransella Grid Test of Schizophrenic Thought Disorder to 40 male schizophrenics. Half of them received a monetary reward for their performance, and half did not. The efficacy of this motivation-enhancing manipulation was verified by the fact that the group that was working for the money completed a card sorting task significantly faster than the group that received no compensation. However, the former group also exhibited more thought disorder on the grid test. The results were interpreted in terms of drive theory. It was argued that the rewarded group was more motivated and therefore more highly aroused and that this high arousal level disrupted performance on the more complex task. The findings do not support the hypothesis that lack of motivation contributes to schizophrenic cognitive deficit.


Sensory perception and motoric reactivity in schizophrenic patients. Explored the effect of non-signal and signal stimuli conditions upon skin conductance (SC) and finger pulse amplitude (FPA) of 8 schizophrenic patients and 6 normal controls. Both groups were assessed on a reaction time (RT) task that consisted of visual, auditory and tactile stimuli. Schizophrenics were significantly slower in the perception and reaction to visual, auditory and tactile stimuli than the normal volunteers. The autonomic reactivity of schizophrenics and normals was nonsignificant during the relaxation and non-signal stimuli conditions. However, when schizophrenics were asked to respond to signal stimuli or when an interfering stimulus was introduced, an autonomic imbalance was observed. The concept of directional fractionation provides the theoretical framework for the discussion of the autonomic results.


Sex differences in birth patterns of schizophrenics. Birth patterns of non-aboriginal, first admission, Western Australian psychiatric patients born between 1920 and 1950 were compared statistically with those of the general population. Three I. C. D. categories were examined: schizophrenia, anxiety neurosis, and depressive neurosis. For both categories of neurosis no deviations from normal birth patterns were observed. For males, marked excesses in schizophrenic births were observed in June, and for females a similar excess occurred in September. Possible explanations for this sex difference are examined.


Further evidence that M-F is bipolar and multidimensional. Conducted a study to identify a set of cognitive skills tests on which there are significant sex differences. The main study determined the comparability of several bipolar M-F scales and the relations between the full range of scores on each of those bipolar M-F scales and self-rated sexual orientation;  110 females and 113 males completed six cognitive tests, the Bem Sex Role Inventory (BSRI), the Minnesota Multiphasic Personality Inventory (MMPI) and the Kinsey Sexual Orientation scale (KSO). Correlations in the combined-sex group were substantially higher than in either of the single-sex groups. Each of the several M-F measures was related significantly to sexual orientation in the combined-sex group, and the combination of the MMPI Mf scale and the Bem Androgyny Score accounted for a small but significantly greater portion of the variance in self-rated sexual orientation than did the MMPI Mf scale alone. The data support the view that M-F may be considered to be a bipolar and probably multidimensional variable.


Correlates of depressive mood among normals. In order to determine the correlates of depressive mood, members of a women's volunteer organization were surveyed by a mailed questionnaire that included the Depression Adjective Check List (DACL) Form E and 14 depression-related measures. Correlations are presented and discussed. Highest correlations are with measures whose relationship to depressive mood are most clear.


The relationship between depression and self-concept discrepancy among different generations of Japanese-American women. Investigated the relationship between real-ideal self-concept discrepancy and depression among different generations and age groups of Japanese-American women in Hawaii. In contrast to the numerous results with Caucasian Ss, the present findings revealed that self-concept discrepancy and depression are related positively for certain generations (i.e., Nisel, young Sansei), but not others (i.e., old Sansei, Yonsei). It was speculated that the differences were due to acculturative and historical experiences that mediated personality pattern development. The findings also point out the ethnocentricity of one of the most supported notions in Western psychology (i.e., the relationship between self-concept discrepancy and maladjustment).


Machiavellianism and clinical depression in a geriatric sample. Administered a test of Machiavellianism to 20 clinically depressed psychogeriatric and 20 non-depressed psychogeriatric patients. Non-depressed males were significantly more Machiavellian than were non-depressed females. Depression in males, then, may be of a more self-aggressive, self-destructive nature, whereas depression in females may be expressed in more emotionally detached attitudes and manipulative behaviors.


Personality correlates of attitude toward death. Examined the interrelationships of two scales of attitudes toward death with four measures of personality: the Manifest Anxiety Scale, the Novelty Experiencing Scale, the Marlow-Crowne Social Desirability Scale, and the Internal-External Orientation Scale. Ss were 142 volunteer males enrolled in introductory psychology courses. A correlation of .72 was found between the Death Concern Scale and the Death Anxiety Scale. In addition, both scales showed the same pattern of correlations with the four personality measures. The highest correlations were found between death attitude and the manifest anxiety scores and the external-internal orientation scores. The importance of including these factors when one is interpreting death attitude scores was stressed, as well as the need for research to establish that these scales measures an anxiety or concern above and beyond general anxiety.


Use of the Leiter International Performance Scale with adult aphasics. Considered whether the Leiter International Performances Scales (LIPS), a general intelligence test used successfully with Ss age 2-18, can be adapted for use with aphasic adults. Six aphasic adults and 6 matched controls were given the Reitan Indians Screening Test of Aphasia and the LIPS. Results showed that the aphasic sample had total test scores comparable with the control group; however, the aphasic group required approximately 66% more time than the controls to complete the test. It was concluded that further work is merited based on the following results: (1) the test provided a sufficient range of difficulty so that each S errored on  at least one-fourth of the test items; (2) the test could be given to the adult aphasics within a feasible time frame; (3) the aphasic adults were able to work with the test materials despite visual defects and hemiparesis of the dominant side; (4) feasible modifications can be made in the test.


Personaltiy correlates of the joy of life. Hypothesized that greater diversity of joy and more intense levels of joy would be associated with low hopelessness, high sensation seeking the perception of the world as just, and high sensitization as compared with high repression. It also was predicted that female Ss would score higher in sources of joy and in intensity as compared to males. One hundred and thirty-four college students were administered the Joy of Life Scale, Hopelessness Scale, Sensation Seeking Scale, Just World Scale, and Revised Repression-Sensitization Scale. The hypothesis was supported for sensation seeking in that High Sensation Seekers assigned significantly (p less than .05) higher mean intensity ratings to experiences that produced joy of life, than did Low Sensation Seekers. Contrary to expectation, there was a nonsignificant trend for sensitizers, when compared with repressors, to select fewer joy-related experiences and to evaluate these experiences as less joyful. The experiences that most often led to high levels of joy were those referrable to positive emotional events.


The measurement of psychological states by use of factors derived from a combination of items from mood and symptom checklists. The similarities in structure and usage of two widely used adjective checklists, the Profile of Mood States (POMS) and Symptom Checklist (SCL), suggested the feasibility of pooling the items from the two scales into a single factor analysis. This procedure was clinically appealing, statistically sound, and provided an efficient method to reduce and refine assessments of psychopathology. Data from 413 Miami Symptomatic Volunteers were used in this factor analysis. Nine factor dimensions were found to meet the dual criteria of statistical salience and clinical meaningfulness. The results demonstrated the factorial stability of the SCL and the POMS and identified the dimensions of psychopathology in which items from the two scales tended to complement each other in factor structure. Some factors were found to be unique to each scale. In addition, it was found that pooling the items from both scales yielded two new factor dimensions that were not previously available from either of the individual scales.


Personality measurement in parents of retarded and emotionally disturbed children: a replication. Replicated Erickson's (1968, 1969) studies that compared MMPI profiles of parents of emotionally and behaviorally disturbed (ED), mentally retarded (MR), and non-clinic (N) children. In general, Erickson's findings that the MR and ED parents did not differ, but that both showed elevated profiles relative to N, were confirmed. The results were interpreted to provide partial supporter for Erickson's "stress reaction hypothesis," whereby the well-known clinic parent MMPI elevations presumably reflect the parents' stress as a result of having a disturbed or handicapped child.


Trait and state anxiety in Israeli student athletes. Examined trait anxiety in three groups of Israeli physical education students (N=251): competitors in individual sports, in team sports, and noncompetitors. The measure was the Spielberger, Gorsuch, and Lushene Trait Anxiety Scale (1970). Both groups of competitive athletes were lower in trait anxiety than noncompetitors. In addition, the two groups of competitive athletes were compared on State Anxiety as measured by the Spielberger scale and a physiological measure of heart rate. There were no differences in state anxiety among competitive athletes. Women competitive athletes were higher in trait, but not in state, anxiety. A high correlation was found between the psychometric and physiological measures of state anxiety.


Common factors in two methods for assessing psychiatric inpatients. Repeated measures were collected on 99 patients by use of two assessment instruments, the Brief Psychiatric Rating Scale, based on an interview, and the Psychotic Inpatient Profile, based on observations of ward behavior. For each S, scores from the two instruments were matched for day of rating and intercorrelated. Factor analysis revealed two factors, each with substantial contributions from both rating instruments. The first factor, interpreted as measuring thought disorder, accounted for 19% of the total varlance. The second factor, termed mood disorder, accounted for 12% of the variance. A third factor accounted for an additional 9% of variance, but had high loadings only on scales of the BPRS.


Behavioral correlates for within-normal-limit MMPI profiles with and without elevated K in students at a university  mental health center. Young adults who were attending a college student mental health center and who obtained MMPI profiles with clinical scales within normal limits with and without elevated K were compared to all other patients at the center on 175 descriptors obtained from intake interviews. Those items that discriminated (x2, p less than .05) students who obtained these profile types from others are reported as tentative MMPI interpretive correlates for patients in similar settings. Correlates ranged from those indicative of situational difficulties to serious psychopathology, and clear sex differences were present. It is concluded that within-normal-limit profiles do not indicate psychological normality when they occur in such a setting and that useful interpretive information can be identified for these, as well as clinically elevated profile types.


Application of the Process Scoring System to waking, dream and therapy reports. Extended the Process Scoring System, originally developed for measuring dream dynamics and content, to waking and therapy experiences and applied it in a study of 5 new and 5 experienced Ss in an intensive outpatient psychotherapy. Two areas were examined: First, differences on process and content variables related to length of time in therapy and, second, the parallel relationship in these variables between waking, dream, and therapy experiences. The Process Scoring System proved useful in measuring these variables in all three types of experiences. The results indicated significant differences between the new and experienced patients and measurable interaction between the waking, dream, and therapy areas.