Transport of glial cell acid phosphatase by endoplasmic reticulum into damaged axons.

Earlier observations indicated that cutting the photoreceptor (R) cell perikarya in the retina of the flies Musca domestica and Calliphora erythrocephala resulted in an extremely rapid degeneration of the R-cell axons. The process manifested itself within minutes and secondary lysosomes appeared early on in the degenerating axons. In this study, biochemical assays of the classical lysosomal marker enzyme acid phosphatase (AcPase) showed a rapid increase in activity upon cutting the retina, reaching a peak around 5 min, followed by a drop and a subsequent slow steady rise in activity between about 4 and 24 h after the cut. Inhibitor studies indicated that at least 2 different acid phosphatases were involved, which showed identical activity changes. EM cytochemical studies with either beta-glycerophosphate or cytidine monophosphate as substrates indicated that the degeneration-dependent AcPase activity originated exclusively in one specific glial cell type in the distal lamina, the satellite glia. These cells are contiguous with R-cell axons in the pseudocartridges, directly proximal to the basement membrane of the retina. In normal uncut flies, reaction product indicative of AcPase activity was found in satellite glial cells in both rough ER (and perinuclear cisternae) and in smooth ER, the 2 types of cisternae being clearly in continuity. The electron-dense reaction product resulting from AcPase activity often showed continuity between the smooth ER of satellite glial cells and extracellular sites between the satellite glia and R-axons. This may result from the low levels of AcPase being synthesized in rough ER, and then exported to extra-cellular sites. Within minutes of cutting the retina the freqeuncy of satellite glia smooth ER staining for AcPase increases significantly. Increases in AcPase activity were subsequently found sequentially in extracellular sites, in axons in the distal lamina, and finally in the axon terminals. The time course for these increases in AcPase activity correlated well with the time course of the fine-structural pathological changes in the axons. A significant feature of the satellite glia cells is the massive packing of unidirectional microtubules (MTs), running perpendicular to the projections of the R-axons--in the same direction as AcPase transport. The MTs terminate at the glial membrane directly adjacent to the axon. The smooth ER cisternae interdigitate among the MTs and may be structurally connected to them by thin fibrils. Thick-section cytochemistry and stereology were used to reveal the 3-dimensional extent of the AcPase-reactive smooth ER system. Evidence is presented which suggests that this system represents GERL, a specialized region of smooth ER involved in lysosome formation, that in this glial cell appears to function also to export hydrolytic enzymes.


Studies on the subcellular localization of human neutrophil alkaline phosphatase.

The intracellular localization of alkaline phosphatase has been determined in human neutrophils with analytical subcellular fractionation by density gradient centrifugation and EM cytochemistry. Centrifugation on sucrose gradients containing 1 mM DETA and 5 units/ml of heparin showed that alkaline phosphatase was associated with a membranous component distinct from plasma membrane, mitochondria, specific granules and azurophil granules. There was no resolution from the endoplasmic reticulum. Density gradient centrifugation on a sucrose-imidazole-heparin gradient showed a clear resolution of the alkaline phosphatase-containing membranes from the Golgi and endoplasmic reticulum. Density gradient centrifugation of neutrophils that had been disrupted in the presenceof 0.12 mmol/l. digitonin clearly separated alkaline phosphatase-containing membranes from the endoplasmic reticulum. Part of the gamma-glutamyl transferase has a similar localization to that of alkaline phosphatase. EM cytochemistry of neutrophils, neutrophil homogenates and of the density gradient fractions identified alkaline phosphatase-containing granules as irregular-shaped, often tubular, structures. It is suggested that alkaline phosphatase and part of the gamma-glutamyl transferase activity are localized to a unique organelle in the human neutrophil.


Quantitative immunoelectron-microscopic analyses of the distribution of cytochrome P-450 molecules on rat liver microsomes.

Specific antibodies to phenobarbital-induced cytochrome P-450 were prepared by affinity chromatography and coupled to ferritin with glutaraldehyde. The ferritin antibody conjugates with molecular ratio of approximately one were isolated by gel filtration and were used for immunochemical and immunoelectron-microscopic analyses of the distribution of cytochrome P-450 on microsomes from untreated, phenobarbital- and methylcholanthrene-treated rats. Binding assay showed that at the saturation level of the antibodies, microsomes from untreated, phenobarbital- and methylcholanthrene-treated rats bind 0.25, 0.41 and 0.14 mol of the antibody per mol of cytochrome P-450, respectively. From these data, the maximum number of the ferritin particles which can bind with microsomes was calculated. This number was in good agreement with the average number of ferritin particles bound per microsome which was determined by electron-microscopic observations of the microsomes incubated with the antibody conjugates at saturation level. Electron-micriscopic observations also indicated that smooth microsomes can bind more conjugates than rough microsomes and this finding was consistent with the biochemical data that, on the protein basis, smooth microsomes comtain more cytochrome P-450 than rough microsomes, even after correction for ribosomal proteins. The number of ferritin particles bound per smooth microsome was proportional to the diameter and non-random distribution of the ferritin particles on the microsomal vesicles, which was deduced simply by inspection in the previous paper from this laboratory, was confirmed by statistical analyses of electron micrographs of the labelled microsomes.


Studies on scale morphogenesis in the Golgi apparatus of Pyramimonas tetrarhynchus (Prasinophyceae).

Ultrastructural investigations of scale formation in the cisternae of the Golgi apparatus have been carried out on the prasinophycean flagellate Pyramimonas tetrarhynchus, whose cell surfaces are covered with 6 different scale types, 3 on the flagella and 3 on the cell body. Our results suggest that at least 4 and probably all 6 scale types can be formed together within the same cisterna and that there is some degree of intracisternal differentiation, since the formation of 2 scale types (the small underlayer scales on cell body and flagella) is restricted to the cisternal peripheries, whereas the remaining scale types are formed in the more central portions. Detailed studies of morphogenesis of the larger body scales reveal the earliest identifiable stages as 8-armed figures, with 8 thin arms in the intermediate body scales (IBS), and 4 thick and 4 thin arms in the outer body scales (OBS). From these incipients structures that bear little resemblance to the finished products, the complex, 3-dimensional mature body scales are elaborated in each of the cell's 4 distyosomes, and maintain throughout their different developmental sequences a close relationship to the inner surfaces of the cisternal membranes, as well as a particular orientation within the dictyosomes. Preliminary calculations of total numbers of scales that cover cell and flagellar surfaces are included. The small, underlayer scales, which on the flagella are shown to be arranged in 24 rows, number about 350000; larger scales of more complex construction number about 20 000.


Capping of surface immunoglobulin on 'hairy cells' is independent of energy production.

Capping, independent of metabolic energy, of surface immunoglobulin (S-Ig) on 'Hairy cells' from patients with Hairy cell leukaemia (HCL) is described. As controls leukaemic cells from a patient with a prolymphocytic leukaemia (PLL) and blood lymphocytes from healthy individuals were used. The specificity of the energy-independent capping of the HCL-cells as compared to the controls was tested by incubation of the cells at 4 degrees C in the presence of 0.1 M sodium azide with different FITC-labelled ligands. In order to find an explanation for this phenomenon, the influence of cytochalasin B, colchicine and the combination of both drugs on capping of S-Ig and concanavalin (Con-A)-receptors at 37 degrees C was investigated. Furthermore the effect of Con A on S-Ig capping and vice versa was studied. The results show that only S-Ig on HCL cells could form caps at 4 degrees C in the presence of sodium-azide. Cytochalasin B alone induced a strong inhibition of Con A capping on all 3 cell types, whereas S-Ig capping was unaffected. Colchicine alone had practically no effect. Anti-Ig inhibited subsequent patch and cap formation with Con A on both HCL cells and PLL cells, whereas Con A caps and patches were redistributed by anti-Ig on PLL cells, but not on HCL cells. Conversely, Con A could link S-Ig to other receptors, leading to inhibition of S-Ig capping at 4 degrees C on HCL cells and to co-capping of S-Ig at 37 degrees C on both cell types. In addition Con A induced redistribution of S-Ig caps. The combination of co-capping of S-Ig by Con A, followed by redistribution of the caps by FITC-anti-Ig simulated inhibition of S-Ig capping by Con A on PLL cells. The major conclusions are: in some cases inhibition of capping may actually be caused by redistribution of caps; the energy-independent capping cannot be explained by free diffusion of S-Ig in the membrane through lack of any connexion with receptor-mobility regulating systems. It is proposed that the energy requirement of capping is needed to inactivate a specific mechanism,w which restrains receptor mobility and which is non-operative in HCL cells.


Studies of membrane fusion. III. Fusion of erythrocytes with polyethylene glycol.

Freeze-fracture electron microscopy has been used to investigate the mechanism of polyethylene glycol-induced cell fusion. Interaction of cells with the high concentrations of polyethylene glycol required for cell fusion results in cell agglutination with large planar areas of very close contact between adjacent cell membranes. An aggregation of intramembrane particles into large patches at the sites of cell-cell contact accompanies cell agglutination. Fusion occurs following the removal of most of the PEG when cells only remain in close contact at small (approximately 0.1 micrometer diameter) plaques of smooth membrane resulting in cells connected by one (or more) small cytoplasmic connexions. Expansion to form spherical fused cells occurs by a process of cell swelling.


Marginal bands in camel erythrocytes.

The elliptical, anucleate erythrocytes of camels have been examined for the presence of marginal bands and their constituent microtubules. Lysis of erythrocytes under microtubule-stabilizing conditions readily revealed marginal bands in at least 3 % of the cells, as observed by phase-contrast and darkfield light microscopy. Microtubules plus a marginal band-encompassing network of material are visible in lysed cell whole mounts with transmission electron microscopy. Marginal band microtubules are also evident in electron micrographs of thin-sectioned camel erythrocytes identifiable as reticuloyctes on the basis of submaximal electron density (reduced haemoglobin iron content) and presence of polysomes. The results suggest that marginal bands may be involved in morphogenesis of camel erythrocytes but are not required for maintenance of their ellipticity after cells are fully differentiated.


Parathyroid function and vitamin D metabolism during human growth hormone replacement.

Changes in calcium and phosphorus metabolism were studied in nine children with GH deficiency before and during human GH replacement therapy. Parathyroid function and serum concentrations of physiologically important vitamin D metabolites were examined to determine their relationship to changes in mineral metabolism. By comparison with pretreatment values, the GH-treated children showed significant increases in growth rate and renal tubular phosphate reabsorption and a significant decrease in urinary calcium excretion after a standardized oral load. There was no significant change in serum concentrations of parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or 24,25-dihydroxyvitamin D or in nephrogenous cAMP excretion. Although GH has been proposed as a regulator of vitamin D metabolism, the present study demonstrates that the anabolic changes in calcium and phosphorus metabolism accompanying GH therapy are not mediated via changes in parathyroid hormone or vitamin D status.


Twenty-four-hour secretory patterns of growth hormone, prolactin, and cortisol in narcolepsy.

Twenth-four-hour patterns of plasma GH, PRL, and cortisol concentrations concomitant with sleep stages were studied in four male patients with typical narcolepsy, aged 30--34 yr, and four normal subjects. All medications were withdrawn 2 weeks before the study. Blood was drawn every 20 min during a 24-h fasting period, except for the first sleep cycle of nocturnal sleep when samples were drawn at 5-min intevals. In all of the narcoleptics, a plasma GH peak associated with slow wave sleep at the nocturnal sleep onset was absent (n = 2) or markedly decreased (n = 2). The normal rise of PRL during sleep was present only in a narcoleptic, whereas a significant fall in plasma PRL concentrations occurred immediately after the sleep-onset rapid eye movement period and lasted 1--1.5 h in the remaining three patients. A sleep-onset rapid eye movement period occurred in all of the patients, and this abnormal phenomenon characteristic of narcolepsy was considered to be related to the suppression of GH release at the sleep onset and to the decrease of plasma PRL levels during the early part of sleep. In contrast, the normal circadian periodicity of cortisol secretion was evident in all of the narcoleptics.


Calcitonin secretion in primary hyperparathyroidism.

Plasma calcitonin (CT) was studied by RIA in 55 patients with surgically proven primary hyperparathyroidism. Basal hormone measurements were performed in all patients and provocative tests of CT secretion were performed in 7. Biochemical measurements were also made before and after parathyroidectomy in 34 patients. Plasma CT was significantly increased above normal in the male but not the female group of patients with primary hyperparathyroidism. A similar sex difference in plasma CT was also seen during provocative testing. In contrast to normal subjects, plasma CT was also significantly correlated to serum calcium concentration in the males but not the females. Hormone concentrations returned to normal after parathyroidectomy in the males and did not significantly change in the females. These studies demonstrate that some patients with primary hyperparathyroidism, especially males, may have an increase, perhaps compensatory, in plasma CT. As with normal females, females with primary hyperparathyroidism seem to have decreased CT reserve.


Changes in serum concentrations of 3,3',5'-triiodothyronine and 3,5,3'-triiodothyronine during prolonged moderate exercise.

The effect of moderate bicycle exercise (3.5 h) on peripheral thyroid hormone metabolism was studied under two conditions (with and without glucose infusion) in four normal males. Serum T3, rT3, total protein, plasma glucose, and FFA were determined. Exercise induced an increase in rT3 from 29 to 40 ng/dl (P less than 0.01), a decrease in T3 from 154 to 147 ng/dl (P less than 0.01), and an increase in T4 from 7.1 to 7.5 micrograms/dl (P less than 0.05). When glucose was infused during exercise, the changes in rT3 were blunted (P less than 0.01) and the changes in T3 and T4 were diminished. During exercise, rT3 correlated with FFA (r = 0.95) and plasma glucose (r = -0.87). When glucose was infused during exercise, these correlations decreased (r = 0.81 and -0.56, respectively). Since moderate, prolonged exercise induces a state of early or acute starvation it is concluded that the changes in peripheral thyroid hormone metabolism reported here are similar to those found in starvation. The temporal changes of rT3, FFA, and plasma glucose during exercise suggest a relationship between thyroid hormone metabolism and the uptake and utilization of FFA and glucose or the mixture of these body fuels.


Insulin allergy: reaginic antibodies to insulin and proinsulin.

To investigate the involvement of proinsulin (one of the contaminant proteins of therapeutic insulin) in systemic insulin allergy, we studied seven diabetic patients who presented with generalized insulin allergy. Commercial and highly purified (single component) insulins produced almost identical responses on the intradermal tests. In all cases, [125I]bovine insulin and [125I]bovine proinsulin bound to the circulating reaginic immunoglobulins. The binding of [125A]proinsulin was blocked completely by unlabeled insulin and was uneffected by bovine C-peptide, indicating a cross-reaction of proinsulin with antinsulin reaginic immunoglobulins and the absence of proinsulin-specific reaginic antibodies. These observations suggest insulin, but not proinsulin, as the mediator of the immediate insulin allergic reaction.


Gastric inhibitory polypeptide response to hyper- and hypoglycemia in insulin-dependent diabetics.

The response of gastric inhibitory polypeptide (GIP) levels to oral glucose in 11 insulin-dependent diabetics was compared to that in 8 age- and sex-matched healthy controls to determine whether they would show the pattern of GIP hypersecretion reported by other workers in maturity-onset, insulin-independent diabetes. One gram of glucose per kg bw resulted in a higher level of glycemia and a significantly diminished GIP response in diabetics when compared to controls (6,018 +/- 1,337 vs. 11,343 +/- 2,353 pg/ml.180 min min, respectively). There was virtually no beta cell response in the diabetics, as measured by changes in the levels of free insulin and connecting peptide. A significant lowering of glucagon levels occurred in the controls, while an inconsistent response was seen in the diabetics. An insulin infusion test was administered to test the hypothesis that insulin suppresses GIP secretion. Although hyperinsulinism, hypoglycemia, and suppression of endogenous insulin secretion were produced in the controls, no suppression of baseline GIP was detected. Similarly, hyperinsulinism and hypoglycemia failed to suppress baseline GIP levels in the diabetics. These results do not support a direct role for insulin in suppressing GIP in normal or diabetic subjects.


Estradiol formation from testosterone by continuously cultured human breast cancer cells.

Two human breast cancer cell lines (MCF-7 and MDA-MB-231) and one cell line derived from normal human breast (HBL-100) were examined for the presence of aromatase activity by determining the amounts of [3H]estradiol ([3H]E2) formed by cell cultures incubated with [3H]testosterone. Aromatase activity was demonstrable in both breast cancer cell lines, but estradiol synthesis was not observed in HBL-100 cultures. The [3H]E2 content of MCF-7 cultures rose as a function of incubation time and substrate concentration. Furthermore, [3H]E2 formation by this cell line was suppressed by several known inhibitors of human placental aromatase. These observations represent the first evidence that some lines of continuously cultured human breast cancer cells, like some human breast tumors, are capable of forming estrogen from an extracellular precursor steroid. Cultured breast cells may provide model systems for investigating the relative importance of intracellular estrogen formation in the regulation of human breast cancer cell growth.


Longitudinal study of plasma testosterone in male pseudohermaphrodites during early infancy.

Plasma testosterone was longitudinally studied during the first months of life in 7 XY infants with male pseudohermaphroditism. In two, the physiological postnatal rise of plasma testosterone was absent or blunted. A combined adrenal and testicular enzymatic defect was demonstrated in these two boys. In 5, a normal postnatal testosterone rise demonstrated a normal Leydig cell function. The longitudinal study of the physiologic postnatal rise of testosterone may be useful to distinguish secretory defects from responsiveness abnormalities thus improving the choice of gender in male pseudohermaphrodites.


Modified coagglutination procedure for the serological grouping of streptococci.

Cowan I staphylococci coated with antisera to streptococcal groups A, B, C, D, F, and G were used as coagglutination reagents in a modified coagglutination procedure (MCAP). Streptococcal group antigens were extracted with a Streptomyces albus-lysozyme enzyme mixture for 30 min at 55 degrees C and centrifuged, and the supernatant was tested by slide coagglutination. Positive coagglutination reactions occurred within 30 s. The cell pellets from overnight broth cultures and colonies taken directly from sheep blood agar plates were tested and compared with the results of the Lancefield capillary precipitin method. Of the 102 strains of broth-grown cells tested, 100 were grouped by the MCAP and the Lancefield capillary precipitin method. The remaining two isolates were serologically identified only by the MCAP. Of the original 102 strains, 97 were tested by MCAP after extraction of five well-isolated colonies from a sheep blood agar plate. When this latter method was used, 95.9% of the strains were correctly identified. Nonspecific reactions were observed only while testing the MCAP with the direct plate assay. These cross-reactions were remedied promptly by either absorption or dilution of the antisera involved. The MCAP was found to be a rapid and reliable technique for the serological grouping of streptococci.


Susceptibility of Staphylococcus aureus and group A, B, C, and G streptococci to free fatty acids.

The susceptibility of 242 strains of Staphylococcus aureus and 117 strains of streptococci of groups A, B, C, and G to decanoic, dodecanoic, octadeca-9,12-dienoic, and octadeca-9,12,15-trienoic acids was estimated by determination of minimal inhibitory concentrations. S. aureus strains appeared to be generally less susceptible to all four fatty acids than streptococcal strains of all groups. Dodecanoic acid was the most inhibitory fatty acid against both staphylococci and streptococci. Both saturated fatty acids used were more active than the unsaturated acids. Among the unsaturated acids, octadeca-9,12,15-trienoic acid appeared to be more inhibitory for Staphylococcus and Streptococcus strains than octadeca-9,12-dienoic acid. No differences in susceptibility to fatty acids among staphylococcal and streptococcal strains isolated from skin, throat, or other sites were found.


Laboratory evaluation of amikacin susceptibility testing by the AutoBac I system.

A total of 319 clinical isolates were compared for amikacin susceptibility by AutoBac I and Bauer-Kirby disk diffusion methods. There was an overall agreement of 98.5% between AutoBac I and Bauer-Kirby. An additional 23 strains resistant to amikacin, obtained from Bristol Laboratories, registered a 65% overall agreement. The sensitivity readings differed between the two methods for 13 organisms: 11 were minor discrepancies, intermediate by one of the two methods, and 2 were very major discrepancies, resistant by disk diffusion and susceptible by AutoBac I.


Immunochemical study of diverse surface antigens of a Staphylococcus aureus isolate from an osteomyelitis patient and their role in in vitro phagocytosis.

The cellular antigens of a strain of Staphylococcus aureus, isolated from a bone fragment from osteomyelitis, were analyzed immunochemically and by interaction with human phagocytic cells. When this strain was allowed to interact with human polymorphonuclear cells in the presence of antiserum, the strain was shown to have specific antiphagocytic antigens. An acidic polysaccharide consisting of galactose and glucuronic acid was isolated from the cell surface of the organism, and in vitro opsonization tests indicated that this acidic antigen impeded in vitro phagocytosis by human polymorphonuclear cells. It was also observed that antibodies directed against the mucopeptide constituents of homologous and heterologous bacterial cell walls were effective in promoting the in vitro opsonization of the organism. In the presence of antimucopeptide serum and human polymorphonuclear cells, a variant strain was isolated from the wild type, and immunochemical analysis indicated that this strain consisted of galactose and immunodominant amino-galacturonic acid residues. In vitro phagocytosis studies employing this variant strain indicated that the homologous human convalescent serum contained higher levels of opsonins against the variant strain than the original isolate, the wild type. This observation is discussed.


Improved blood culture medium for radiometric detection of yeasts.

The influence of medium composition on the rate of CO2 production by yeasts in simulated blood cultures was determined in the Bactec radiometric system. A yeast nitrogen base broth containing [14C]glucose and Triton X-100 allowed the detection of positive cultures earlier than the regular Bactec blood culture media.


Isolation of Legionella pneumophila from a transtracheal aspirate.

Isolation of Legionella pneumophila from a transtracheal aspirate was achieved by using simple in vitro culture methods. Clinical microbiologists should routinely culture for this organism from appropriate body fluids obtained from normally sterile areas.


Rhizopus rhizopodiformis: emerging etiological agent of mucormycosis.

Mucormycosis is caused principally by members of the genus Rhizopus, especially R arrhizus and R. oryzae. Infection attributable to R. rhizopodiformis has rarely been documented. Of 13 cases of mucormycosis diagnosed during a 4-year period (1974 to 1978) at The Mount Sinai Hospital, 6 cases, occurring within 9 months, were caused by R. rhizopodiformis. The six isolates were identified mainly by: growth at 50 degrees C; production of short, sometimes branched, sporangiophores arising from opposite rhizoids; elongated columellae; and small spherical-to-elliptical, smooth-to-finely striated sporangiospores. The possibility that this explosive occurrence of R. rhizopodiformis at our institution was because of nosocomial acquisition was strongly supported by the recovery of this same mycotic agent from adhesive bandages used in the cardiac intensive care unit, where a patient developed subcutaneous R. rhizopodiformis infection after cardiac surgery. The invasive potential of R. rhizopodiformis was manifested by the extensive subcutaneous and systemic infections in each of the six patients, three of whom developed antibody against this mucormycotic agent.


Method for rapid separation of immunoglobulin M from immunoglobulin G antibodies by using reorienting gardients in vertical rotors.

The parameters for the use of reorienting gradients in vertical rotors for rapid separation of immunoglobulin M from immunoglobulin G on a preparative scale for the rapid diagnosis of infectious diseases are described.


Cholinergic stimulation of norepinephrine release in man. Evidence of a sympathetic postganglionic axonal lesion in diabetic adrenergic neuropathy.

Amplification of endogenous cholinergic activity-produced by the intravenous injection of edrophonium, an acetylcholinesterase inhibitor which does not enter the central nervous system, into normal subjects-resulted in significant and briefly sustained increments in the plasma concentrations of norepinephrine (153+/-15-234+/-29 pg/ml, P < 0.01) and epinephrine (16+/-3-34+/-5 pg/ml, P < 0.01) measured with a single-isotope derivative method. These increments were not attributable to reflex responses to hemodynamic changes and similar increments in plasma norepinephrine occurred in adrenalectomized (epinephrine deficient) patients. Thus, cholinergic activation results in direct stimulation of sympathetic postganglionic neurons, with augmented norepinephrine release, and of the adrenal medullae, with augmented epinephrine release, in man. Four diabetic patients with hypoadrenergic postural hypotension exhibited blunted sympathetic postganglionic neural responses, and normal adrenomedullary responses, to cholinergic stimulation (and to standing) indicative of the presence of a sympathetic postganglionic axonal lesion in diabetic adrenergic neuropathy. Nondiabetic patients with hypoadrenergic postural hypotension due to documented or probable central nervous system lesions exhibited normal responses to cholinergic stimulation produced in this fashion demonstrating the presence of intact sympathetic postganglionic neurons and adrenal medullae in these patients and providing further support for the conceptual soundness of this approach to the study of human adrenergic physiology and pathophysiology.


Paradoxical effects of clofibrate on liver and muscle metabolism in rats. Induction of myotonia and alteration of fatty acid and glucose oxidation.

Chronic clofibrate intake, on occasion, results in a muscular syndrome in man. We have investigated the effects of chronic clofibrate administration in rats on the electrical activity of a skeletal muscle (gastrocnemius), its composition, and its oxidation of palmitate and glucose. These effects have been compared with those in the liver. Clofibrate administration altered electromyographic pattern of gastrocnemius muscle (characteristic of myotonia), decreased its protein content, and impaired its oxidation of palmitate and glucose. These effects were quite different in the liver, because clofibrate intake increased the liver protein content and oxidation of palmitate without affecting the oxidation of glucose by this tissue. Whereas chronic clofibrate administration markedly increased the concentration of carnitine as well as the activity of mitochondrial carnitine palmitoyl-transferase in the liver, it decreased the activity of this enzyme in the gastrocnemius muscle without a significant effect on carnitine concentration in this tissue. Greater in vivo fatty acid oxidation by clofibratefed than by control rats was evidenced (a) by greater rate of production of (14)CO(2) in the expired air after injection of a tracer dose of [(14)C]palmitate and (b) by greater plasma and tissue concentrations of ketone bodies. We conclude that (a) paradoxical effects of clofibrate on fatty acid oxidation by the liver and skeletal muscle are related to changes in the activity of carnitine acyltransferase, (b) an increase in hepatic fatty acid oxidation may contribute to hypolipidemic effect of clofibrate, and (c) impairment of fatty acid and glucose oxidation by the muscle may be a factor in the development of muscular syndrome in patients receiving clofibrate treatment.


Tyramine kinetics and metabolism in cirrhosis.

Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injections of [3H]-tyramine (180--200 muCi 12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (alpha-phase) followed by a slower decline (beta-phase) with an average t 1/2 of 20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 microgram/min, respectively. In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent different in beta-t 1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 microgram/min) in these patients was significantly greater (P less than 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) as compared with normals. Although the tyramine clearance rates are similar in normals and cirrhotics, different mechanisms may be responsible for catabolism.


Complement lysis of human erythrocytes. Differeing susceptibility of two types of paroxysmal nocturnal hemoglobinuria cells to C5b-9.

Although enhanced sensitivity of erythrocytes to complement-mediated lysis is a hallmark of paroxysmal nocturnal hemoglobinuria (PNH), subpopulations of erythrocytes in such patients vary significantly in this respect. One PNH erythrocyte subpopulation (termed type III) comprises exquisitely sensitive cells, whereas type II PNH erythrocytes are intermediate in complement sensitivity between PNH type III and normal human erythrocytes. Differences in the action of the terminal complement components that would account for the differing lytic behavior of types II and III PNH erythrocytes have been proposed but not directly demonstrated. The present studies, making use of carefully selected cases with pure populations of type II or type III erythrocytes, confirm a prior observation that antibody-coated PNH erythrocytes of both types II and III display comparably supranormal C3 binding in whole human serum. However, when lysis was induced by the isolated C5b-9 membrane attack mechanism, bypassing the requirement for C3 binding, only type III PNH cells exhibited greater than normal lysis. This finding suggests that type III PNH erythrocytes have an additional membrane abnormality not present in type II cells. Thus, the differing lytic behavior of these two cell types in whole serum may reflect the additive effects on type III cells of both exaggerated C3 binding and enhanced sensitivity to C5b-9, whereas the more moderate lysis of type II PNH cells may be determined mainly or entirely by the earlier-acting mechanism producing augmented C3 binding. The failure of guinea pig C8 and C9, as opposed to human C8 and C9, to reveal the true lytic sensitivity of PNH-III E in our earlier study is illustrated, and its implications briefly discussed.


Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70.

We examined the sensitivity of lymphocytes from different age groups to inhibition by prostaglandin E2. Phytohemagglutinin-stimulated cultures of peripheral blood mononuclear cells from 12 healthy subjects over the age of 70 were much more sensitive to inhibition by exogenously added prostaglandin E2 than were cells from 17 young controls (ID50 congruent to 10 nM for the subjects over 70 vs. greater than 3 micronM for the young controls). The more senstivie lymphocytes from a subject over 70 were to prostaglandin E2, the lower was his or her response to phytohemagglutinin (r = 0.75, P less than 0.01). The mean responses to phytohemagglutinin of the peripheral blood mononuclear cells from the subjects over 70 were significantly depressed compared to the young controls. Addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures resulted in an increase in [3H]thymidine incorporation of 140 +/- 16% in the cells of the subjects over 70 vs. a 36 +/- 3% increase in the young controls (mean +/- SEM, P less than 0.001). The mean phytohemagglutinin response of the subjects over 70 was 40% of the control response without indomethacin. With addition of indomethacin the response of subjects over 70 rose to 72% of control. Thus, increased sinsitivity to prostaglandin E2 appears to be responsible in part for the depressed mitogen response of peripheral blood mononuclear cells from healthy subjects over 70.


Effects of carnitine in ischemic and fatty acid supplemented swine hearts.

FREE FATTY ACIDS (FFA) IN EXCESS FFA: albumin molar ratios have been determined to additionally compromise mechanical performance in ischemic hearts. Carnitine, an intracellular carrier of FFA and an agent which is lost to the heart during ischemia, has been postulated to in part restore function with its replacement. To test whether its benefits are also operative in a setting of excess FFA, these studies were performed. In the main protocol, four groups of perfused swine hearts (n = 45) were compared during 50 min of control flow (179.7 ml/min) and 40 min of global ischemia (106.1 ml/min). Initial base-line serum FFA:albumin molar ratios and carnitine levels in all groups were 1.3:1 and 8.5 nmol/ml, respectively. In two of these groups FFA:albumin ratios were increased to 5.9:1 with constant infusions of Intralipid. In two alternate groups (one with and one without extra FFA supplements) dl-carnitine was supplied, sufficient to increase serum levels nearly 200-fold. Ischemia per se in 14 hearts significantly decreased several parameters of global and regional mechanical function including left ventricular (LV) and mean aortic pressures, LV isovolumetric pressure development (max dp/dt), LV epicardial motion, and LV work, together with concomitant decreases in myocardial oxygen consumption. Elevated FFA in 12 hearts rendered similarly ischemic further decreased mechanical function (LV pressure: -20.8%, P < 0.05; mean aortic pressure -26.9%, P < 0.05; LV max dp/dt: -39%, P < 0.05; regional LV shortening: -51.1%, P < 0.05; and LV work: -50.3%, P < 0.05) as compared with nonsupplemented hearts. dl-Carnitine treatments in nine hearts, not supplemented with extra FFA were without apparent effect in improving overall hemodynamic performance. However, dl-carnitine in 10 high FFA-ischemic hearts effected several improvements as compared with the untreated group: LV pressure was increased 25.6%, P < 0.025; mean aortic pressure: +43.5%, P < 0.05; LV max dp/dt: +41.5%, P < 0.05; regional LV shortening: +241.3%, P < 0.001; and LV work: +76.2%, P < 0.05 at comparable levels of myocardial oxygen consumption. In a separate protocol, the effects of stereospecificity were also studied by comparing l- with dl-carnitine in globally perfused, palmitate-supplemented hearts (five hearts in each treatment group). At similar conditions of flow and serum FFA, changes in mechanical function were comparable, except for a tendency to perform greater LV work at reduced flows in the l-carnitine-treated hearts. Thus, it was demonstrated that carnitine in ischemic hearts is capable of preserving mechanical function under conditions of excess FFA, presumably by modifying the toxic effects of FFA intermediates. The major therapeutic actions appeared to derive from the l-isomer of carnitine.


Effect of prostaglandin E2 on chloride transport across the rabbit thick ascending limb of Henle. Selective inhibitions of the medullary portion.

Prostaglandins are present in large quantities in the kidney and have been shown to directly affect transepithelial transport. The present studies were designed to examine whether prostaglandin E2 could affect chloride transport across the thick ascending limb of Henle. Isolated segments of the cortical and medullary thick ascending limb of Henle were perfused in vitro and the transepithelial voltage and net chloride flux were measured. Exposure of the medullary thick ascending limb to 2 microM prostaglandin E2 resulted in a fall in net chloride transport of 40--50% with a concomitant fall in voltage. In contrast, net chloride transport in the cortical thick ascending limb was not affected by prostaglandin E2. Under similar conditions, the medullary thick ascending limb possessed twice the capacity to transport chloride than did the cortical thick ascending limb. The results suggest that endogenous renal prostaglandins may play a modulating role in the addition of salt to the renal medullary interstitium and may, under some circumstances, by chloruretic.


Glomerular hemodynamics in rats with chronic sodium depletion. Effect of saralasin.

In chronic sodium depletion the glomerular filtration rate may be reduced, and alterations in proximal tubular function may contribute to the maintenance of antinatriuresis. Measurements were made by micropuncture technique in superficial nephrons of the Munich-Wistar rat of (a) the determinants of glomerular filtration rate, (b) peritubular capillary hydrostatic and oncotic pressure, and (c) proximal tubular fractional and absolute reabsorption in both a control group (group 1, n = 12) and a group of chronically sodium-depleted rats (group 2, n = 12). Single nephron filtration rate (sngfr) was 37.2+/-1.2 in group 1 and 31.6+/-1.0 nl/min/g kidney wt (P < 0.05) in group 2. Of the factors potentially responsible for the observed reduction in sngfr, there was no change in systemic oncotic pressure or the transglomerular hydrostatic pressure gradient. Sngfr was lower in group 2 because of both a reduced single nephron plasma flow (rpf) (128+/-6 vs. 112+/-5 nl/min per g kidney wt, P < 0.05) and additionally to a decrease in the glomerular permeability coefficient, L(p)A, from a minimum value of 0.105+/-0.012 in group 1 to 0.054+/-0.01 nl/s per g kidney wt per mm Hg (P < 0.01) after chronic sodium depletion. There was no difference in fractional proximal tubular reabsorption between group 1 and group 2. Absolute proximal reabsorption (APR) was reduced from 20.8+/-1.3 in group 1 to 16.3+/-0.9 nl/min per g kidney wt in group 2. The role of angiotensin II (AII) in maintaining glomerular and proximal tubular adaptations to chronic sodium depletion was assessed in subsets of groups 1 and 2 by the infusion of the AII antagonist Saralasin at a rate of 1 mug/kg per min. In group 1 rats, Saralasin had no effect on sngfr, rpf, or L(p)A, because animals remained at filtration pressure equilibrium. In group 2 rats, AII blockade was associated with an increase in sngfr from 31.6+/-1.0 to 37.1+/-1.7 nl/min per g kidney wt (P < 0.01). Rpf increased during Saralasin infusion solely as a result of a decrease in afferent arteriolar resistance from 21.7+/-2.3 to 15.2+/-2.3 10(9) dyn-s-cm(-5) (P < 0.01). Saralasin infusion did not affect the reduced L(p)A in group 2, as L(p)A remained 0.056+/-0.02 nl/s per g kidney wt per mm Hg and rats remained disequilibrated. In spite of the increase in sngfr in group 2, AII antagonism further decreased APR to 13.1+/-1.5 (P < 0.01). Distal delivery therefore, increased from a control value of 15.3+/-1.3 to 24.3+/-1.5 nl/min per g kidney wt (P < 0.01). In conclusion, both a decrease in L(p)A and a reduction in rpf were major factors mediating the decrease in glomerular filtration rate observed in chronic sodium depletion. Saralasin infusion revealed a significant effect of AII on rpf and afferent arteriolar resistance in chronic sodium depletion, but no effect of AII on either efferent arteriolar resistance or the decrease in L(p)A could be demonstrated. Saralasin had no effect in rats that were not chronically sodium depleted. In group 2 rats AII antagonism reduced APR even though sngfr increased, suggesting an influence of AII on proximal reabsorption. The marked changes observed during Saralasin infusion in the chronically sodium-depleted rat reveal important modifying effects of endogenously generated AII on both the glomerulus and proximal tubule.


Effects of reduced renal mass and dietary protein intake on amino acid release and glucose uptake by rat muscle in vitro.

Epitrochlearis muscles obtained from normal male Holtzman rats used as controls (C) and rats with reduced renal mass (Nx) fed isocaloric diets of varying protein content were incubated in Krebs-Ringer buffer containing 5 mM glucose for 1 or 3 h with or without insulin. Alanine (ALA) release rates from muscles of Nx rats were increased 40% above C values after 1 h of incubation regardless of protein intake. Addition of insulin decreased the ALA release from muscles of Nx rats to C values in animals fed 10 and 20% casein and chow but did not in rats fed 40% casein. After 3 h of incubation, all ALA release rates decreased by congruent with40%. The ALA release from muscles of Nx rats fed 10% casein was comparable to C values and decreased further with the addition of insulin. On the other hand, ALA release from muscles of Nx rats fed 20 and 40% casein as well as chow remained significantly elevated above C values, but responded to the addition of insulin with a reduction in release rates to C values, except from the muscles of Nx animals fed 40% casein. Tyrosine (TYR) and phenylalanine (PHE) release rates also were increased in muscles from Nx rats compared with C after 1 h of incubation. Release rates were highest in the Nx group fed 10% casein and decreased with increasing protein intake. Addition of insulin decreased the release rates of Nx rats to C values in each group. After 3 h of incubation, release rates of TYR and PHE in muscles from Nx rats remained significantly above C values for all groups, but responded to the addition of insulin with a decrease to C values. Glutamine and glutamate release were not significantly affected by reduction in renal mass.Base-line glucose uptake by all groups of muscles from Nx rats was significantly greater than corresponding C values, but maximal insulin-stimulated glucose uptake was comparable in all groups. Tissue pool sizes for glycogen, ATP, phosphocreatine, ALA, glutamate, and glutamine were unaffected by reduction in renal mass. The results indicate that Nx is associated with accelerated ALA, TYR, and PHE release from muscle. ALA release rose with increasing protein intake and decreased to values observed from C muscles after addition of insulin except in Nx animals fed 40% casein. TYR and PHE release decreased with increasing protein intake and also decreased to C values with the addition of insulin. The data also suggest that ALA release is not dependent upon glucose uptake in muscles from either C or Nx rats.


A critical assessment of the mechanism by which hyperoxia attenuates exercise-induced asthma.

Recent data demonstrate that the magnitude of the heat loss that occurs from the respiratory tract during exercise correlates with the degree of post-exertional obstruction that develops in asthmatics. Respiratory heat loss relates directly to the minute ventilation and heat capacity of the inspired gas and inversely to its water content and temperature. Because it has been shown that inhaling 100% oxygen during exercise blunts the obstructive response, we wondered if this effect could be accounted for by differing values of heat exchange with air and oxygen breathing. To examine this question, we studied 10 asthmatics by measuring multiple aspects of pulmonary mechanics before and after four bouts of exhausting leg work during which the subjects inhaled either air or oxygen conditioned to provide widely differing thermal burdens on their airways. Under all inspired gas conditions, oxygen breathing produced significantly less obstruction than air. Minute ventilation was also significantly less with oxygen as was the total heat lost. As the latter fell, so did the magnitude of the postexercise obstruction. When the differences in ventilation and respiratory heat loss between air and oxygen were eliminated by eucapnic hyperventilation, the differences in the obstructive responses also disappeared. Thus, the effects of hyperoxia on exercise-induced asthma can be accounteed for solely by alterations in heat exchange.


Effect of volume expansion on hemodynamics of the hypoperfused rat kidney.

The hemodynamics of the rat kidney were studied during reduction of renal arterial pressure to 35-40 mm Hg (H), and after volume expansion at that pressure with 0.9% NaCl (IS), 1.7% NaCl (HS), 5% mannitol in 0.9% NaCl (MS), 5% mannitol in water (MW), or 50 mM mannitol + 125 mM NaCl. During H, left renal blood flow (RBF) was 0.8+/-0.1 ml/min. Expansion with IS did not alter RBF, but expansion with HS, MS, MW, and 50 + 125 mM NaCl elevated RBF to 200-250% of hypoperfusion values. Glomerular capillary pressure rose significantly from 15.7+/-0.7 mm Hg during H to 22.3+/-1.1, 24.4+/-0.7, and 26.6+/-0.7 mm Hg following expansion with HS, MS, or MW, respectively. Efferent arteriolar pressure also rose significantly to 6.9+/-0.5, 9.7+/-0.8, and 9.5+/-0.9 mm Hg, respectively. Preglomerular resistance fell to 18-24% of H values, and postglomerular resistance fell to 58-74% of H values after expansion with HS, MS, or MW. Glomerular filtration (GFR) could not be detected during H or after IS expansion. HS and mannitol-containing solutions restored GFR to 0.10+/-0.02-0.15+/-0.02 ml/min, and single nephron glomerular filtration to 6-12 nl/min. Papaverine, acetylcholine, and kinins had no effect on RBF or GFR at a perfusion pressure of 35-40 mm Hg. We conclude that mannitol and HS have the capacity to augment RBF during hypoperfusion by reducing arteriolar resistance. The mechanism of the rise in RBF is uncertain; it may be due to changes in effective osmolality of the extracellular fluid or to a direct action of mannitol on vascular smooth muscle. Other potent vasodilators were ineffective during hypoperfusion. Restoration of GFR occurs as a result of the combined effects of augmented RBF and elevated net filtration pressure.


Effects of anion-transport inhibitors on NaCl reabsorption in the rat superficial proximal convoluted tubule.

The effects of anion-transport inhibitors on volume reabsorption, and total CO(2) concentrations were examined by in vivo microperfusion of superficial proximal convoluted tubules of rats. The luminal perfusion solution was a high-chloride, low-bicarbonate solution like that in the in vivo late proximal tubule. The anion-transport inhibitors were only added to the luminal perfusion solutions. In tubules perfused with the control high-chloride solution, the rate of volume reabsorption (J(v)) was 2.3+/-0.2 nl/mm.min (n = 18), and the collected total CO(2) concentration was 4.0+/-0.3 mM. Furosemide (3 mM) caused a marked reduction in volume reabsorption to 0.8+/-0.3 nl/mm.min (n = 20) and only a slight increase in the total CO(2) concentration of collected samples of perfusate (7.8+/-0.5 mM). 0.8 mM acetazolamide caused a more pronounced rise in the collected total CO(2) concentrations to 10.7+/-0.5 mM but only a slight fall in J(v) to 1.7+/-0.3 nl/mm.min (n = 19). Hence, we inferred that inhibition of carbonic anhydrase only partially accounted for the inhibition of J(v) by furosemide. 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid (0.1 mM), a well-characterized inhibitor of erythrocyte anion exchange mechanisms, also reduced J(v) to 1.6+/-0.3 nl/mm.min (n = 15) without changing the total CO(2) concentrations of the collected perfusates (3.6+/-0.4 mM). The effect of 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid on volume reabsorption could not be explained by carbonic anhydrase inhibition because there was no increase in the total CO(2) concentration of the collected fluids. Furosemide did not significantly inhibit the rate of tracer glucose efflux out of the tubules, which suggests that the effect of furosemide on volume reabsorption was not a result of some nonspecific depression of active sodium transport. These results are discussed with respect to the possible effects of anion-transport inhibitors on the paracellular shunt pathway, active sodium reabsorption, and neutral sodium chloride transport.


Neutropenia, inflammation, and the kinetics of transfused neutrophils in rabbits.

A rabbit model was used to study the effects of neutropenia and inflammation on the intravascular distribution, survival, and tissue accumulation of transfused neutrophils. Donor blood labeled with [(3)H]thymidine was infused into normal or neutropenic (vinblastine treated) animals. Inflammation was created by subcutaneous implantation of polyvinyl sponges, some with added endotoxin. Initial circulating neutrophil pool recovery, survival, and inflammatory site accumulation of labeled neutrophils were measured. Neutropenia was associated with a relative increase in the marginal pool size, manifested by a diminished initial circulating pool (CNP) recovery of transfused cells. The CNP recovery was directly proportional to recipient neutrophil count. Neutropenia had no effect on the intravascular survival of transfused cells and was accompanied by only a modest decrease in the inflammatory site recovery of the transfused neutrophils (10.4+/-5.4 vs. 14.4+/-4.0% in normals). Inflammation in the form of subcutaneous polyvinyl sponges was accompanied by an increase in margination with initial CNP recoveries of 24.3+/-4.7 and 27.6+/-8.8% at zero and 4 h after implantation respectively (normal, 38.2+/-9.9%). Transit through the CNP was hastened by inflammation with a t((1/2)) of 2.02+/-0.72 h (normal, 3.2+/-1.0 h). Addition of endotoxin to the sponges further perturbed cell kinetics. CNP recoveries were considerably lower and half-lifes were initially shorter and subsequently uninterpretable in studies done after endotoxin sponge insertion. Inflammatory site accumulation was markedly diminished to 7.4+/-1.9% of injected neutrophil label in the endotoxin sponge animals, suggesting that many of the transfused cells were functionally unavailable rather than marginated. These studies demonstrate that neutropenia and inflammation with or without endotoxin markedly alter the kinetics of transfused neutrophils and that CNP recovery of transfused cells is not necessarily predictive of their inflammatory site accumulation.


Biphasic effects of prostaglandin E2 on the human fat cell adenylate cyclase.

Adenylate cyclase of human fat cell ghosts shows a biphasic response towards prostaglandin E2 with inhibition occurring at nanomolar concentrations of the hormone and stimulation at concentrations beyond 10(-6) mol/liter. The expression of the inhibitory effect is critically dependent on GTP. Under the conditions employed (1 mmol/liter ATP, 5 mmol/liter Mg2+, 30 degrees C) the inhibitory component of prostaglandin E2 became apparent at GTP concentrations exceeding 10(-6) mol/liter. The prostaglandin E2-induced inhibition displayed characteristic features of prostaglandin action in intact fat cells with respect to the effective concentrations and degree of inhibition. It is concluded that prostaglandin E2 is capable of inducing antagonistic effects upon lipolysis via interaction with the membrane-bound adenylate cyclase.


Conditioning effects of chronic infusions of dobutamine. Comparison with exercise training.

We studied the conditioning effects of chronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 mug/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 10 degrees incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning. To assess ventricular function, we intravenously infused methoxamine both before and after conditioning. The slope of the line that related systolic aortic blood pressure and mean left atrial pressure increased in the animals conditioned with either dobutamine or exercise, indicating enhanced myocardial contractility. Left ventricular blood flow was lower in these two groups of animals than it was in the normal saline group. Left ventricular weight did not differ among the three groups. Our results show that chronic infusion of dobutamine produced cardiovascular and metabolic conditioning effects like those produced by exercise training, and further suggest that sympathetic stimulation during exercise plays a role in physical conditioning.


Reflex cardiovascular depression during unilateral lung hyperinflation in the dog.

We have examined whether lung hyperinflation in the anesthetized dog reflexly depresses cardiac output, stroke volume, heart rate, and blood pressure and whether these changes persist for more than a minute. To eliminate any mechanical restriction to venous return and pulmonary blood flow during lung hyperinflation, a model was developed in which all pulmonary artery blood flow and all ventilation were directed to the right lung in dogs with widely open chest and the left lung was hyperinflated before and after left cervical vagotomy. Heart rate, stroke volume, and blood pressure decreased by 24, 20, and 27%, respectively, within 15 s of left lung inflation to 30 cm H(2)O. Heart rate increased to preinflation levels by 1 min, but stroke volume and blood pressure remained depressed during lung hyperinflation for at least 15 min. Upon deflation, stroke volume and blood pressure returned to control levels within 1 min. Division of the left vagosympathetic trunk at the neck interrupted all autonomic afferent and efferent nerves of the left lung, but left intact the right vagal sympathetic and parasympathetic afferent and efferent nerves of the heart. After left cervical vagotomy the transient fall in heart rate, stroke volume, and blood pressure during left lung hyperinflation was greatly reduced or eliminated. These results suggest that unilateral lung hyperinflation reflexly depresses heart rate and blood pressure, which are partially compensated with time, and reflexly depresses stroke volume, which persists uncompensated until the lung is deflated. These findings may explain the depressed cardiovascular function observed during regional lung overdistention especially when it occurs during positive pressure ventilation.


Aortic input impedance during nitroprusside infusion. A reconsideration of afterload reduction and beneficial action.

Beneficial effects of nitroprusside infusion in heart failure are purportedly a result of decreased afterload through "impedance" reduction. To study the effect of nitroprusside on vascular factors that determine the total load opposing left ventricular ejection, the total aortic input impedance spectrum was examined in 12 patients with heart failure (cardiac index <2.0 liters/min per m(2) and left ventricular end diastolic pressure >20 mm Hg). This input impedance spectrum expresses both mean flow (resistance) and pulsatile flow (compliance and wave reflections) components of vascular load. Aortic root blood flow velocity and pressure were recorded continuously with a catheter-tip electromagnetic velocity probe in addition to left ventricular pressure. Small doses of nitroprusside (9-19 mug/min) altered the total aortic input impedance spectrum as significant (P < 0.05) reductions in both mean and pulsatile components were observed within 60-90 s. With these acute changes in vascular load, left ventricular end diastolic pressure declined (44%) and stroke volume increased (20%, both P < 0.05). Larger nitroprusside doses (20-38 mug/min) caused additional alteration in the aortic input impedance spectrum with further reduction in left ventricular end diastolic pressure and increase in stroke volume but no additional changes in the impedance spectrum or stroke volume occurred with 39-77 mug/min. Improved ventricular function persisted when aortic pressure was restored to control values with simultaneous phenylephrine infusion in three patients. These data indicate that nitroprusside acutely alters both the mean and pulsatile components of vascular load to effect improvement in ventricular function in patients with heart failure. The evidence presented suggests that it may be possible to reduce vascular load and improve ventricular function independent of aortic pressure reduction.


Altered mineral metabolism in glucocorticoid-induced osteopenia. Effect of 25-hydroxyvitamin D administration.

Parameters of mineral and bone metabolism were studied in 17 patients treated chronically with supraphysiologic doses of glucocorticoids. When compared to 15 matched normal subjects, the patient group exhibited similar serum 25-hydroxyvitamin D (25-OHD) levels, decreased intestinal 47Ca absorption, increased serum immunoreactive parathyroid hormone, and decreased forearm bone mass. Iliac crest bone biopsies revealed a decreased bone formation rate and increased osteoclast number. Treatment with 25-OHD (mean dose 4.03 micrograms/d) and calcium (500 mg/d) in nine patients produced a 46% increase in 47Ca absorption (P less than 0.001) and a 54% decrease in serum immunoreactive parathyroid hormone (P less than 0.001) by 3 mo. In addition, by 12 mo the treatment group exhibited (a) a 13.2 +/- 5.1% increase in metaphyseal (P less than 0.001) and a 2.1 +/- 0.4% increase in diaphyseal (P less than 0.05) forearm bone mass, and (b) significant decreases in cortical and endosteal osteoclast number. Biochemical and bone mass changes persisted through 18 mo. No significant changes in any parameter occurred in eight control patients administered calcium 100 mg/d. It is concluded that treatment with 25-OHD and calcium can significantly improve parameters of mineral and bone metabolism in patients with glucocorticoid-induced osteopenia.


Role of cytochrome P-450 in alveolar hypoxic pulmonary vasoconstriction in dogs.

Alveolar hypoxia induces pulmonary vasoconstriction by an unknown mechanism. Cytochrome P-450 (C-P450) is found in the lung and may modify pulmonary vascular tone via its sensitivity to changes in oxygen tension or by affecting metabolism of a chemical mediator. Metyrapone and carbon monoxide are both inhibitors of C-P450. We tested alveolar hypoxic pulmonary vasoconstriction (AHPV) in 20 dogs before, during, and after separate administration of each inhibitor. Anesthetized dogs were ventilated through a double lumen endotracheal tube allowing ventilation of one lung with N(2) or CO as a hypoxic challenge and ventilation of the other lung with O(2) to maintain adequate systemic oxygenation. Distribution of lung perfusion was determined with intravenous (133)Xenon and external chest detectors. Before infusion of metyrapone, mean perfusion to the test lung decreased 30% with alveolar hypoxic challenge, but decreased only 10% during metyrapone infusion and returned to a base-line mean decrease of 31% after completion of metyrapone infusion. Prostaglandin F(2) alpha and angiotensin II infusions produced equivalent increases in pulmonary vascular resistance before and during metyrapone infusion. Before CO, mean test lung perfusion decreased 31% with alveolar hypoxia but was reduced only 10% from control when unilateral end-tidal CO% was >75%. Washout of alveolar CO with unilateral N(2) ventilation restored AHPV, with perfusion decreasing 29% from control. Thus, both metyrapone and carbon monoxide can reversibly inhibit AHPV. C-P450 may, therefore, be involved in the transduction process of the vasoconstrictor response to alveolar hypoxia.


Osmotic blood-brain barrier disruption. Computerized tomographic monitoring of chemotherapeutic agent delivery.

The present study describes a canine model of transient reversible blood-brain barrier disruption with hyperosmolar mannitol infusion into the internal carotid artery. Studies in this model show that osmotic blood-brain barrier disruption before intracarotid infusion of methotrexate results in markedly elevated (therapeutic) levels of drug in the ipsilateral cerebral hemisphere. Levels in the cerebrospinal fluid correlate poorly and inconsistently with brain levels. Computerized tomograms in this canine model provide a noninvasive monitor of the degree, time-course, and localization of osmotic blood-brain barrier disruption.


Sex differences on the Halstead-Reitan Neuropsychological Battery and on other neuropsychological measures.

Evaluated differences in performance between adult males and females with respect to Halstead's Neuropsychological Battery, additional tests employed by Reitan (Trail Making Test, Aphasia Screening Test, Perceptual Examination, dynamometer), and other neuropsychological measures (Seashore Tonal Memory Test, Logical Memory and Visual Reproduction portions of the Wechsler Memory Scale). In evaluating differences, 47 matched pairs of non-neurologic males and females were employed, as well as 47 pairs of neurologic patients. A small number of statistically significant differences were found, all of which favored males. Some of these differences occurred with respect to tasks that have very strong motor components, and these differences were shown to be related to hand size. Others pertained to tasks that have strong visual-spatial components. In general, the differences were less prominent with the neurologic than the non-neurologic samples. The question was raised as to possible over-representation of male-superior components in these tests.


Comparison of neuropsychological data in the diagnosis of brain impairment with computerized tomography and other neurological procedures.

Discussed the problem of criterion validation of neuropsychological tests. Computerized tomography (CT) is suggested as an approach in providing a criterion of focal structural lesions for evaluating predictability of neuropsychological tests. Neuropsychological tests on 62 patients were compared with CT scans, electroencephalographic results, and routine neurological examination. Results of the neuropsychology evaluation produced overall better agreement with CT scan results than did the other procedures. Diagnostic limitations of CT scanning and the unique diagnostic contribution of neuropsychological test results are discussed.


The relationship of personality style to abstract thinking deficits in schizophrenia.

Hypothesized that the correlation between Inability to Abstract and Autism measures of schizophrenics would be larger after the effects of relevant personality variables were partialed out than before. The multiple correlations of these deficit measures with 15 of the Sixteen Personality Factor scales and a measure of verbosity were determined in a sample of 100 schizophrenics. The correlations between Inability to Abstract and Autism before and after those scales that contributed significantly to the Rs had been partialed out also were calculated. Neither was significant. The results offer no support for the view that observed differences between schizophrenic subgroups in inability to abstract and autism reflect variations in personality style rather than cognitive factors.


The effects of LSD-25 and dextroamphetamine on the use of defensive language.

Verified that psychotomimetics attenuate verbal defense mechanisms. This was accomplished by reanalyzing the 5-minute monologues of 7 neurotic depressives who participated in a project (Mechaneck, Feldstein, Dahlberg, & Jaffe, 1968) that examined the effects of LSD and dextroamphetamine on timing aspects of speech. Dosages were subhallucinatory: 15-25 mg dextroamphetamine, 50-100 mg LSD, and a matching placebo. Volunteers received each drug (double-blind) seven or eight times on a random schedule over a 1 1/2-year period; there was a 3-week intertrial interval. The patient provided 5-minute monologues both before and after drug effects. The monologues were transcribed and scored for formal measures of defensive language. Results indicated that LSD caused individuals to make more personal statements and to use explanation and evaluations less often. Dextroamphetamine was found to decrease the use of nonpersonal references.


The semantic perception of life, death and suicide.

Gathered semantic distance scores between pairs of concepts (life and death, life and suicide, and death and suicide) from suicidal, psychosomatic, and hospitalized patients (N = 45). It was hypothesized that suicidal individuals would show greater semantic identity between these concepts than would the other patients. It was thought that such semantic identity on the part of the other patients. It was thought that such semantic identity on the part of the suicidal individuals would reflect their inability to discriminate between these concepts. However, it was found that the suicidal individuals differentiated between life and death to a significantly greater degree than did the comparison groups. It may be that suicidal decisions are based more on being confronted by definite clear alternative states of existence than by confusion between them.


Disability payments for psychiatric patients: is patient assessment affected?

Collected data for 348 veterans who had been patients at a psychiatric hospital: MMPI results, number of days of hospitalization already past when the MMPI was taken, length of the entire hospitalization during which the MMPI was taken are amount of disability payment at the time of the MMPI, and number of hospitalizations to date. The amount of disability payments was correlated significantly with the MMPI scales associated with psychosis. Veterans who were not receiving disability payments but who later obtained payments appeared more severely psychiatric on the MMPI than others without payments, but were less willing to report their strengths. Those who received only small payments failed to report improvement in the early part of hospitalization and were hospitalized disproportionately to their symptoms, unlike those with maximum payments or rejected claims for payments. It is concluded that patients eligible for larges payments may alter their self reports, but that disability payments nonetheless are awarded only in proportion to actual impairment.


Imagery in the associative learning of schizophrenics.

The present experiment is similar to Bower's (1970) study on imagery as a relational organizer in paired-associate (PA) learning with normals. Three groups of 20 schizophrenic patients learned three different lists of 30 word-word paired-associates, which used either interactive imagery, separation imagery, or rote repetition encoding. Ss were tested on stimulus recognition and paired-associate recall, given recognition. Differences in stimulus recognition and paired-associate recall were not significant across the three encoding methods. Results suggest that schizophrenics are unable to benefit from imaginal cues to facilitate learning in a manner similar to normals. These results are interpreted as providing additional support for the notion that the schizophrenics' cognitive deficit is associated with the relational organizing process of learning.


Comparison of process-reactive measures in schizophrenia.

Studied 12 measures of process-reactive schizophrenia to determine their relative effectiveness in predicting outcome defined as symptomatic improvement. Each patient (N = 144) was rated on the process-reactive measures and at 3- and 6-month intervals on the Present State Examination to evaluate symptom change. Major findings were that the Ego-Strength, Stage of Illness, Kanto, Langfeldt, paranoid and chronicity criteria failed to predict outcome successfully. The first four criteria do not appear to be suitable process-reactive measures when the distinction is based on symptom change. However, paranoid-nonparanoid and chronic-acute criteria merit further investigation. The Ullmann-Giovannoni, Social Competence, Phillips scales, and marital status predicted outcome accurately at both 3- and 6-month evaluations. The Philips scale was the single best predictor of outcome at 3 months, while marital status was the best at 6 months. Overall, the Phillips scale was the most powerful and useful predictor of outcome.


The effects of ego-involvement and task difficulty on actual and perceived performance of depressed college students.

Determined whether situational manipulations of personal investment/threat influence the actual and perceived performance of depressed college students on a problem-solving task. Ss were 48 undergraduate students selected on the basis of scores on the MMPI D-scale. Ss within each level of depression were assigned randomly to either ego-involvement or task-involvement conditions. Involvement was manipulated through (a) instructions given to Ss; (b) method of data identification used; and (c) E interaction with a confederate who posed as a S. Within each condition of involvement, Ss were assigned randomly to unscramble either four- or six-letter anagrams. Results showed that in the difficult task-ego-involvement condition, the high depressed Ss made significantly more negative subjective appraisals of their performance than did the low depressed. These groups did not differ from each other under other conditions. It was concluded that depressives are most likely to evaluate negatively their performance in situations that present a challenge and/or threat to them and in which they may have some personal investment.


Randomness and the "streaking" phenomenon: attentional anomalies in performance on the Whitaker Index of Schizophrenic Thinking (WIST).

Examined in detail the performance of 36 hospitalized male schizophrenics on the Whitaker Index of Schizophrenic Thinking (WIST). Results indicated two interesting phenomena. First, the performance of patients with the highest level of cognitive deficit approached a random level of responding with respect to both the type of error made and the propensity to improve after an error. Second, a subgroup of these highly impaired Ss, identified as "streakers," displayed periods of virtually error-free responding, interspersed with periods of extremely impaired performance. The streaking phenomenon, as well as the tendency toward randomness, was discussed in terms of attentional anomalies.


Aspects of personality associated with irregular sleep habits in young adults.

Studied psychological correlates of irregularity in chronic sleep routines. The California Psychological Inventory (CPI) and Cornell Medical Index (CMI) were administered to two groups of 18 male university students who were categorized as either irregular sleepers or control Ss. The control group was composed of persons who habitually slept from 12-8:00 A.M. Irregular sleepers were defined as those whose retiring and awakening times continuously varied by about 2 to 4 hours. Control Ss scored significantly higher than the irregular group on the CPI scales of Do (dominance), Sy (sociability), Sa (self-acceptance), Sc (self-control), Ac (achievement via conformance), and Ie (intellectual efficiency), but lower on the Fx (flexibility) scale. There were no significant differences between the groups in scores on the CMI or average sleep length recorded over 2 weeks. The present findings indicate that in young adults, personality functioning is related more closely to the regularity of nocturnal sleep routines than to differences in chronic sleep duration. It is postulated that stable or irregular sleeping patterns are largely dependent factors not only of the psychological characteristics that distinguished the groups, but as yet unspecified constitutional and sociocultural antecedents of the human sleep response.


Locus of control and trust in parents: a preliminary study.

Compared 50 undergraduates (7 males, 43 females) as the upper and lower third Internal and External locus of control groups, based on I-E scores, with respect to scores on separate subscales of trust in father (FT), mother (MT), and both parents (PT). While the results confirmed previous findings that internality was related positively to trust in others, the present study found significantly greater trust in father than in mother. These differential findings were interpreted as having relevance to studies of behavioral referents of locus of control as well as implications for parent-child antecedent relationships.


Factor M as a correlate of physical fitness: imagination or just more energy.

Determined whether 16PF scale scores could contribute significantly to the prediction of a measure of fitness. Sixty-three firemen from a large metropolitan area in the Southeast were Ss. Factor M contributed significantly to the prediction of one measure of fitness (i.e., treadmill time). The assumption cited in the literature that Factor M reflects "imagination" in individuals who score high on fitness measures was questioned. The article concluded that Cattell's earlier work relating high Factor M to high energy and endurance suggests a more logical interpretation of Factor M vis à vis measures of fitness.


Psychologic characteristics of patients with female urethral syndrome.

Numerous investigations have been conducted in an effort to determine the cause of the female urethral syndrome. Bacterial and anatomic causes rarely have been identified. Using the MMPI, we evaluated 56 women with thus syndrome and compared them with control patients of similar ages. Statistically significant increases in the F, hysteria, hypochondriasis, and schizophrenia scales were found in the patients with the female urethral syndrome. These scores suggest the presence of a psychophysiologic process in these patients.


Effects of structural integration on state-trait anxiety.

Studied the effects of the intervention technique of Structural Integration on state-trait anxiety. Matched pairs of Ss were assigned randomly to either the experimental (received rolfing) or control group (N = 48). State anxiety questionnaires were administered beofre rolfing and then again in 5 weeks after rolfing. Results indicated that rolfing caused a decrease in state anxiety when compared to the control group. Results were discussed in terms of the release of emotional tension stored up in the muscles due to Structural Integration.


A factor analysis of the Beck Depression Inventory in a mildly depressed population.

Investigated a factor analysis of the responses of mildly depressed college students to the items of the Beck Depression Inventory (N = 446). A varimax rotation of a principal-axis factor analysis yielded only one well-defined factor, "Hopelessness," which was characterized by sadness, pessimism, dissatisfaction and suicidal thoughts. The depression syndrome for this mildly depressed group was unlike syndromes previously reported for a psychiatric population.


A neuropsychological Key approach to diagnosis and remediation of learning disabilities.

Described a new approach in reaching clinical decisions with regard to learning disabled children. The method emphasizes a systematic deductive procedure and is presented in the form of a Key. The rationale for the diagnostic and remedial decisions reached at every node of the Key is explained and is supported by data derived from clinical and experimental studies in psychology and neurology.


The relationship between intelligence and verbal and spatial memory.

Administered the Logical Memory Test (LM) and the Rey-Osterreith Test (RO), which have been assumed to pertain to verbal and spatial cognitive functioning, to 150 Ss referred for neuropsychological screening. Ss also were administered the short version of the WAIS, plus Digit Span. It was found that LM did relate more to verbal IQ than to spatial IQ and vice-versa for RO. It was not clear exactly what aspect of cognitive functioning Digit Span was tapping. The clinical implications of the study are that LM scores must be viewed in the light of verbal IQ level, and RO scores interpreted in relation to both spatial IQ and age. Data are presented that can be used for the statistical interpretation of an individual case test scores.


Factor analysis of breadth and depth dimensions on Wechsler's Similarities and Vocabulary Subscales.

Previous research (Bailey, Lazar, & Edinger, 1977) has indicated the presence of Breadth and Depth factors on the Similarities subscale of the WAIS. The present study (N = 102) analyzed these two factors further, by using measures of Breadth and Depth on both the Similarities and Vocabulary subscales. Several other measures also were studied, including a Comprehension index, SAT scores, and GPA. Results of a factor analysis with oblique rotation revealed distinct Breadth and Depth factors, which strongly supported the theoretical rationale of the study. The Breadth factor seems to reflect broad-range skills of the type required on conventional IQ tests, while the Depth factor is less theoretically clear. It is suggested that Depth involves an effort component as well as ability because the S is required to provide more than a single correct answer for a given item.


An investigative study of the Bender-Gestalt: clinical validation of its use with a reading disabled population.

Investigated usefulness of the Bender-Gestalt in differentiating between primary and secondary reading disability. Research with 50 reading disabled Ss was carried out. The Ss were classified as having a primary or secondary reading disability according to selected criteria; then their Bender protocols were scored. It was hypothesized that developmental scores would differentiate the two diagnostic groups. A second hypothesis was that specific signs would differentiate between primary and secondary reading disabled children. The results supported the latter hypothesis, but not the former. Results also showed that those in the primary group were more reading retarded than secondary reading disability Ss and that Bender-Gestalt scores are not significantly related to reading level in such a group of reading disabled children.


Test-retest gains in WAIS scores after four retest intervals.

Administered the WAIS to 76 male college students on two occasions with a retest interval of either 1 week, 1 month, 2 months, or 4 months. Essentially all Verbal, Performance, and Full Scale IQs increased significantly on the retest. Increases in Verbal IQ for the four time intervals were 4.7, 1.8, 2.3, and .8 IQ points, respectively; the latter was the only nonsignificant gain found. The Performance IQ increased by 11.4, 9.8, 8.7, and 8.0 points for each subsequent time period, and the Full Scale IQ increased by 8.0, 5.7, 5.4, and 4.2 points for each respective time period. Test-retest correlations for the four intervals ranged from .91 to .72 for the Verbal IQ, .87 to .79 for the Performance IQ, and .94 to .74 for the Full Scale IQ. The results were pitted against similar test-retest studies, and clinical and research implications were discussed.


Level and variability of performance on neuropsychological tests.

Compared non-specific variability across subtests and overall level of performance on the Wechsler Adult Intelligence Scale (WAIS) and the Halstead-Reitan Battery (HRB) for normal, schizophrenic, acute and chronic brain-damaged Ss. Both variability and level of performance measures for each of the two test batteries significantly distinguished normal from abnormal Ss, but the HRB measures were more sensitive. Intra-S variability across subtests had a significant negative correlation with level of performance on the HRB, but not on the WAIS. This correlation could not be accounted for fully by a ceiling effect and was thought to represent in part a characteristic feature of ts performance on the HRB. While WAIS variability appeared to be independent of level of performance, it was not much help in differentiating between the four S groups. It was concluded that non-specific variability across subtests is not a helpful independent measure of neuropsychological function on the two batteries studied.


Correlates of alpha, beta and theta wave production.

Studied the correlations of alpha, beta and theta time densities with psychological and psychophysiological variables in a psychiatric population (N = 76). The correlations of the EEG variables with measures of adjustment were small and barely exceeded chance expectations. Alpha and beta were correlated positively with pain threshold, while beta was related inversely to blood pressure. Theta was correlated positively with blood pressure and negatively with pulse rate. The implications of these findings for EEG biofeedback treatment were discussed.


The effectiveness of the psychodramatic double method, the reflection method, and lecturing in the training of empathy.

Studied the effectiveness of the psychodramatic Double method, the Reflection method, and the Lecture method in improving empathic ability. Sixty-four high school sophomores were assigned randomly to four groups of 16 Ss, 8 males and 8 females, each. Three groups received one of the three training methods and the fourth served as no-training control. The Ss' level of empathy, before and after the training, was measured by a modified version of the Accurate Empathic Scale. The results showed that all three training methods produced significant improvements compared with the control group. The effect of the Double method was significantly greater than that of the other two methods. The Reflection method ranked second, yet was not significantly better than the Lecture method. Females scored higher than males both before and after the training, but there was no significant sex and training method interaction effect.


Measurement of assertive behavior: construct and predictive validity of self-report, role-playing, and in-vivo measures.

Examined the predictive validity and construct equivalence of the three major procedures used to measure assertive behavior: Self-report, behavioral role-playing, and in-vivo assessment. Seventy-five Ss, who spanned the range of assertiveness, completed two self-report measures of assertiveness, the Rathus Assertiveness Scale (RAS) and the College Self-Expression Scale (CSES); two scales from the Endler S-R Inventory of General Trait Anxiousness, the interpersonal and general anxiety scales; eight role-playing situations that involved the expression of positive and negative assertiveness; and a telephone in-vivo task. In general, the study revealed the following: (1) assertiveness measures are task-dependent in that there was more overlap within task than between tasks; (2) there is a moderate degree of correspondence between self-report and role-playing measures, although this was true only for negative assertion; (3) positive and negative assertion do not appear to have the same topography of responding; and (4) there appears to be no consistent relationship between the in-vivo measure and any other type of assertiveness measure.


Verbal-nonverbal congruence in normal and delinquent families.

Assessed affect expression for both normal and delinquent families (N = 5 families) in three communication channels (verbal, tonal and facial); group differences in channel inconsistency were determined. Interactions that involved mother-father, mother-son, and father-son were assessed independently. Analysis of variance procedures yielded a number of group differences in total affect expression and verbal-nonverbal inconsistency. When co-variance procedures controlled for demographic differences, however, reliable differences between normal and delinquent families no longer obtained. Findings are discussed in terms of results from previous encoding studies and the relationships among affect expression, diagnostic status, and demographic variations.


Learned helplessness and depression among Israeli women.

Depressed and nondepressed Ss were exposed to either inescapable noise or no noise conditions in an attempt to replicate a typical learned helplessness study (Miller & Seligman, 1975) with Israeli student nurses. The inescapable noise was presented either as a personally important task or as an unimportant task. When later tested on a series of 20 patterned anagrams, no performance differences were found between depressed and nondepressed Ss as was found in previous studies, nor did the importance manipulation affect performance. Within the depressed group only, it was found that the more the Ss believed they had control over the noise, the better was their performance in the anagrams. Similarly, only among the depressed was the rated aversiveness of the noise positively related to anagram performance. Depressed were only able to assess accurately the number of failures on the anagrams, while nondepressed did equally well in assessing both positive and negative aspects of their performance. The results are discussed in terms of Seligman's learned helplessness model of depression and Beck's cognitive model of depression.


Conjugate lateral eye movements of "repressors" and "sensitizers" under threat and non-threat conditions.

Investigated the relationship between repression-sensitization and conjugate lateral eye movement (CLEM) tendencies under ego-threat and control conditions. Fifty-one right-handed college males were separated into repressors, sensitizers, or a middle group and were interviewed under a condition intended to produce ego-threat or a neutral condition. Bland and mildly intimate questions were asked of all Ss. Contrary to expectation, repression-sensitization and threat condition were unrelated to eye movement direction. A significant increase in left eye movement was found in response to mildly intimate questions, compared to neutral questions. Results are discussed with reference to earlier research on CLEM and to the cerebral hemispheric dominance theory of the effect.


Incentive effects of choosing a therapist.

Investigated the effects of offering clients (N = 55) a choice of therapeutic style on show rate and reactions to the initial interview. Individuals who called for an appointment were assigned randomly to Choice and Attention-Control conditions. Choice Ss were informed that they would be assigned to a therapist who identified with one of two descriptions of therapy styles from which they could choose. Based on this choice, these persons were scheduled with the next therapist in line who had identified him/herself with the selected style. Attention-Control clients were informed about the range of services available at the clinic and paired with a therapist regardless of style on the usual rotating basis. A significantly higher proportion of Choice than Attention-Control Ss kept their schedules appointments. However, no significant differences were found on client and therapist evaluations of the initial interview.


Factors that influence nurses' attitudes toward psychiatric patients.

Investigated attitudes of nursing staff to their patients and their treatment, using the Ellsworth Attitude Scale and three opinion statements derived from a preliminary attitude survey. Those who were most pessimistic about the extent to which patients were able to participate in treatment tended to be of lower rank and training and also scored high on the attitude of Restrictive Control and low on that of Accountability. Those who were pessimistic about the therapeutic efficacy of the hospital tended to be younger and scored higher on Protective Benevolence and lower on Accountability attitudes. Those who scored high on Authoritarianism were of significantly lower rank and training, and the opposite obtained for those who scored high on Accountability. It is suggested that the attitude of Protective Benevolence is closer to Restrictive Control than to Accountability and that this attitude should not be considered a move toward enlightened thinking; furthermore, that the prevalence of custodial and pessimistic views among the lower ranking and younger nursing staff may be due to lack of opportunity for and support in taking therapeutic responsibility.


Staff conceptions of patients' attitudes toward mental disorder and hospitalization as compared to patients' and staff's actual attitudes.

Compared ward personnel's (N = 25) conceptions of their patients' attitudes toward mental disorder and hospital atmosphere to the patients' (N = 50) and the personnel's actual attitudes by use of the CPH Factor Scale. Personnel completed the scale as (1) they themselves viewed the hospital; and (2) as they thought their patients viewed it. Patients' views also were obtained. Personnel viewed the hospital in "positive mental health" terms and considered the patients to be significantly less so. In actually, patients were less positive than personnel, but significantly less extreme than they were considered to be by the personnel. This approach suggests a means to provide an index discrepancy in attitude between patient and personnel. Identifying these descrepancies can allow for correction and improved understanding empathy, and patient care.


The performance of neurologically impaired and normal Ss on four screening techniques.

Administered four screening instruments--Peabody Picture Vocabulary Test-Form A (PPVT-A), Riley Preschool Developmental Screening Inventory-Designs (RPDD), Riley Make-A-Boy (RMB) and the McCarthy Scales of Children's Ability Designs (MSCD)--to 23 normal children with no evidence of neurological impairment and 23 neurologically impaired children under 6 years of age. The children were matched for age and sex and were from a day-care program for working parents and a therapeutic preschool program, respectively. Significant differences were found between the two groups on all instruments. The highest positive correlation for the impaired group was between the PPVT-A and the RPDD, while for the control group the highest positive correlation was between the RPDD and MSCD.


The A-B variable and preferred inpatient treatment environment.

Examined the possibility that college students' status on Whitehorn and Betz' (1954) A-B dimension would be related to their descriptions of the ideal psychiatric inpatient treatment setting. Sixty-one Ss completed the A-B scale, as well as Moos' (1974) Ward Atmosphere Scale-Ideal Form. Analysis demonstrated a statistically significant relationship between A-B status and 5 of the 10 WAS subscales. A and B Ss both differed significantly from a middle group of Ss, but did not differ from one another, in their ward ratings on these subscales. Factor analysis of the Ideal Form ratings replicated Alden's (1977) finding from analysis of Standard Form responses of a high degree of communality between 8 of the 10 WAS subscales.


Concurrent validity of the Missouri Children's Picture Series.

Administered the Missouri Children's Picture Series, a nonverbal objective test of personality to a group of normal (N = 119) children and a group of institutionalized (N = 77) aggressive children. Several of the test scales differed significantly between the two groups. The test scales of Aggression and Maturity showed the most consistent and largest differences; the institutionalized children scored, as a group, higher on Aggression and lower on Maturity Level. IQ was found to be unrelated to test scores among the normal children, but was related significantly to personality test scores among the institutionalized children.


Rorschach hostility content and its relation to anxiety, neuroticism and P-E-N measures.

Assessed the relationships between Rorschach hostility scores and anxiety, neuroticism, overt/covert hostility, intelligence, and Eysenck's Personality Questionnaire. The sample consisted of 200 (100 male, 100 female) Indian undergraduates aged 15 to 20 years. There were some indications that high hostility scores on the Rorschach tended to be worldly wise, covertly hostile, independent, stubborn, and poor fakers. A factor analysis of the intercorrelations showed six interpretable factors: Anxiety, Neuroticism, Body measures. Hostility, Psychoticism and Tender-minded, respectively. Further, it was concluded that Eysenck's Psychoticism is factorially a complex measure and that projective and direct verbal measures of hostility seem to be measuring dissimilar constructs. A few hypotheses for independent verification were proposed.


The personality of alcoholic middle-class women: a comparative study with the MMPI.

Alcoholic personality patterns have been derived largely from studies of institutionalized lower-class males. To determine whether similar patterns prevail among other alcoholic populations, 30 middle-class, white, married women who were undergoing treatment for alcoholism in a private clinic were compared with 30 nonalcoholic women of similar background, referred for various personality problems. Mean MMPI scores of both groups fell between 40 and 60, and the profiles showed an overall similarity. Alcoholism women scored significantly higher on F, PD and SC, but not on D. Both groups scored lowest on MF. The results show that data derived from institutionalized alcoholics of lower socioeconomic background have only limited applicability to this group.


Formative program evaluation and milieu therapy with alcohol abusers.

Evaluated presumably therapeutic components within a therapeutic community in terms of perceived helpfulness by patients and staff of an alcohol treatment unit. Eighteen male patients and 18 staff members participated. A nonparametric statistic was used as an index of treatment philosophy articulation or degree of value-sharing. A core of activities valued congruently by patients and staff was identified.


Fear-induced attitude change as a function of conformity and drinking pattern in alcoholics.

Investigated the effectiveness of fear arousal for inducing attitude change toward drinking in alcoholics (N = 38). Fear arousal, whereby aversive consequences are associated with some undesirable target behavior, has proved popular and sometimes effective in persuasive attempts designed to induce attitude change. A communication that linked brain damage with excessive drinking was successful in arousing fear in alcoholics and resulted in a more negative attitude toward their own drinking, but did not affect their attitude toward drinking by others. Attitude change was more pronounced in alcoholics who previously had scored high on a conformity task, but was not related to pattern of drinking. Fear arousal may have a place in alcoholism treatment, although attitude change is not necessarily accompanied by changes in behavior.


Differentiating methadone outpatients from psychiatric outpatients and normals with the Mini-Mult.

Investigated whether the Mini-Mult could differentiate outpatient heroin addicts from outpatient psychiatric and normal populations. A multiple discriminant analysis was done with 30 Ss that compared the three groups across the 11 Mini-Mult scales. Significant results were obtained at the .05 level for the following scales: L, F, 1, 2, 3, 4.