Protein associations and basic protein conformation in the myelin membrane. The use of difluorodinitrobenzene as a cross-linking reagent. The near-neighbor relationships of proteins in the myelin membrane were examined using dinitrodifluorobenzene and other cross-linking reagents. When intact cat dorsal column or isolated myelin fragments were treated with cross-linking reagents, up to 20% of the myelin basic protein dimerized. The only other cross-linked product formed in the intact cat dorsal column was a heterodimer consisting of myelin basic protein and either the major or minor proteolipid protein. The remaining myelin proteins, including the major proteolipid protein, were cross-linked into very high molecular weight aggregates. In contrast, when the myelin membrane was dipersed in sodium dodecyl sulfate before the addition of cross-linking reagent, all the proteins remained essentially monomeric, with the exception of myelin basic protein which dimerized to some extent. In the absence of cross-linking reagent, it was shown by radioimmunoassay that small amounts of myelin basic protein dimer and the heterodimer were normally present in sodium dodecyl sulfate-polyacrylamide gels. We found no evidence of intramolecular cross-links between the two peptides formed by N-bromosuccinimide cleavage or between the two peptides formed by cyanogen bromide cleavage of the basic protein monomer. The regions of the myelin basic protein molecule involved in dimerization were also determined by similar cleavage of the cross-linked dimer. A rudimentary model for the structure of basic protein dimer in myelin is presented.


The nonpolar peptide segment of cytochrome b5. Binding to phospholipid vesicles and identification of the fluorescent tryptophanyl residue. The nonpolar peptide segment of cytochrome b5 consisting of the COOH-terminal 43 amino acid residues binds rapidly to dimyristyl lecithin vesicles above the transition temperature of the phospholipid. The binding is complete as indicated by density gradient centrifugation and is accompanied by approximately a 2-fold increase in the fluorescence emission of the protein, and insertion in the bilayer is apparently in an orientation indistinguishable from that of the whole cytochrome b5 molecule. Quantitative reaction of the protein with N-bromosuccinimide destroys the fluorescence of the protein with a stoichiometry which indicates that a single tryptophanyl residue is responsbile for the fluorescence. The fluorescent tryptophanyl residue is one of 2 adjacent residues, Trp-108 or Trp-109, as shown by carboxypeptidase digestion of N-bromosuccinimide-reacted nonpolar peptide.


Structural and functional properties of the membrane binding segment of cytochrome b5. Derivatives of cytochrome b5 that had been selectively shortened at the COOH-terminal, membrane binding segment of this amphipathic protein were employed to examine the minimum structural requirements for binding to phospholipid vesicles and for catalytic interactions in the stearyl-CoA desaturase system. Three derivatives shortened by 6, 18, and 27 amino acid residues were produced by controlled proteolysis with carboxypeptidases. The two largest derivatives bound to synthetic lipid vesicles and interacted with cytochrome b5. The third derivative neither bound to vesicles nor reacted with the desaturase. Whole nonpolar peptide and the nonpllar peptides of the two largest derivates contain only 29 to 34% polar residues, whereas the nonpolar peptide of the third derivative contains 44% polar residues. The secondary structure of the membrane binding segment was studied by circular dichroism of whole nonpolar peptide and the corresponding peptides of the three derivatives. The data for whole nonpolar peptide are consistent with a structure containing approximately 50% helical and 25% beta sheet structure. The CD of the nonpolar peptides of the two largest derivatives are consistent with structures containing 56% helix and 19% beta sheet structure, and 40% helix and 20% beta sheet structure. These data support a predicted model for secondary structure, proposed previously, based upon the primary structure (Fleming, P. J., Dailey, H. A., Corcoran D., and Strittmatter, P. (1978) J. Biol. Chem. 253, 5369-5372).


Mechanism of enhanced renal prostaglandin biosynthesis in ureter obstruction. Role of de novo protein synthesis. Perfusion of a rabbit kidney 72 h after ureter obstruction resulted in a progressive increase in bioassayable prostaglandin-like substances released in response to a fixed dose of bradykinin with time. Contralateral or normal kidneys showed no progressive increase with time of prostaglandin-like substances released in response to the same dose of agonist during perfusion. Actinomycin D, an inhibitor of RNA synthesis and cycholeximide, reversibly blocked the time-dependent progressive increase in renal prostaglandin-like substances released from the obstructed kidney. Acetylsalicylic acid, which covalently acetylates the cyclooxygenase, inhibited initial bradykinin-stimulated prostaglandin biosynthesis by 95% in the ureter-obstructed kidney, but within 60 to 90 min of perfusion there was progressive bioassayable prostaglandin E2 release in response to bradykinin which paralleled the non-aspirin-treated control. In the aspirin-treated contralateral (unobstructed control) and normal kidneys bradykinin-stimulated release of prostaglandin-like substances was inhibited by 85% and did not recover during the perfusion experiments consistent with the evidence that the control kidneys are not synthesizing new enzyme. These experiments suggest that the progressive enhanced prostaglandin release to fixed bradykinin doses in the ureter-obstructed kidney is dependent on de novo cyclooxygenase synthesis.


A low molecular weight DNA polymerase beta in the sea urchin Strongylocentrotus purpurantus. Partial purification, properties, and changes in development. A low molecular weight DNA polymerase which sediments at 3.3 S on sucrose gradients has been purified from total cell homogenates of rapidly dividing embryos of the sea urchin Strongylocentrotus purpuratus. In the presence of 2 mM N-ethylmaleimide, it is the major polymerase activity in whole cell homogenates when assayed with an oligo(dT)10.poly(dA)200 template; a template which it uses about 200 times more efficiently than activated DNA. The requirement for N-ethylmaleimide exists only in crude cell fractions where it acts to inhibit a template digesting nuclease activity. The polymerase is highly stable if maintained in the presence of 20% glycerol, is completely dependent on added template, and shows no end addition activity. The physical and enzymatic properties of this enzyme clearly distinguish it from the DNA polymerase previously described by Loeb (Loeb, L. A. (1969) J. Biol. Chem. 244, 1672-1681) which sediments as a high moeluclar weight (5.6 to 6.6 S) enzyme and prefers the activated DNA template. In addition, these two DNA polymerase enzymes show distinctive chromatographic properties using DEAE-cellulose and phosphocellulose columns as well as their sensitivity to N-ethylmaleimide. The properties of the low molecular weight polymerase indicate close similarity to the beta-polymerase isolated from mammalian cells. These low molecular weight enzymes are both sensitive to phosphate salt and able to utilize the artificial ribohomopolymer template oligo(dT)10.poly(rA)200. A quantitative analysis of the low molecular weight DNA polymerase during early embryonic development indicates that the activity of this enzyme increases at least 2-fold immediately following fertilization and again during early blastula stage (hatching). Such quantitative changes in a beta enzyme activity are in contrast to findings with the alpha-polymerase which remains constant during early development.


Analysis of the adult and embryonic chicken globin genes in chromosomal DNA. Globin-specific mRNA has been purified from the red blood cells of anemic adult hens and from those of 5-day and 7-day chick embryos. These RNA preparations were used to synthesize labeled cDNA for solution and filter hybridization (Southern blotting) experiments. Hybridization of cDNAs prepared with separated adult alpha- and beta-mRNAs and of rabbit globin-specific probes to restriction enzyme-digested, filter-bound chicken chromosomal DNA has shown that the adult globin genes of the chicken exist within EcoRI-cleaved chromosomal DNA fragments which are 4.3, 6.0, and 12.5 kilobase pairs (kbp) in size. These fragments contain the majority or entirety of the adult alpha D, beta, and alpha A genes, respectively. Furthermore, we present evidence that the predominant chicken embryonic globins are contained within EcoRI fragments 9.4 and 15 kbp in size. Evidence is also presented that the same globin organization exists in several different breeds of chickens and in several chicken culture cell types. Finally, it is demonstrated that the pattern of globin-specific hybridization to reticulocyte chromosomal DNA digested with several restriction enzymes is unchanged during erythropoietic development.


Hepatic malonyl-CoA levels of fed, fasted and diabetic rats as measured using a simple radioisotopic assay. A simple radioisotopic assay for malonyl-CoA is described. The method is based on the malonyl-CoA-dependent incorporation of labeled acetyl-CoA into palmitic acid catalyzed by fatty acid synthetase in the presence of NADPH. Its main advantages over the more conventional spectrophotometric procedure is that it is extremely sensitive and allows the simultaneous determination of picomole quantities of malonyl-CoA in multiple tissue extracts. It should prove particularly suitable for studies on the regulation of lipid metabolism in isolated hepatocytes where the quantity of tissue available for analysis is frequently very small. Application of the method to the measurement of malonyl-CoA in livers from fed, fasted, and diabetic rats yielded values that were consistent with the recently postulated role of malonyl-CoA in the regulation of hepatic ketone body production.


The role of malonyl-coa in the coordination of fatty acid synthesis and oxidation in isolated rat hepatocytes. Fatty acid synthesis and fatty acid oxidation were examined in rat hepatocytes under a variety of experimental conditions. In cells from fed animals, glucagon acutely switched the direction of fatty acid metabolism from synthesis to oxidation. Addition of lactate plus pyruvate had the opposite effect. The inhibitory action of glucagon on fatty acid synthesis and its stimulatory effect on fatty acid oxidation were largely, but not completely, offset by the simultaneous addition of lactate plus pyruvate. Changes in cellular citrate and malonyl-CoA levels indicated that glucagon exerted its inhibitory effect on fatty acid synthesis at two levels: (i) blockade of glycolysis; and (ii) partial inhibition of a more distal step, probably acetyl-CoA carboxylase. Under all conditions, fatty acid oxidation was related in a linear and reciprocal fashion to the rate of fatty acid synthesis and the tissue malonyl-CoA content. The latter fluctuated through a range of 1 to 6 nmol per g wet weight of cells. Since malonyl-CoA inhibits carnitine acyltransferase I of liver mitochondria with a Ki in the region of 1 to 2 micron, the present studies support the concept that this compound plays a pivotal role in the coordination of hepatic fatty acid synthesis and oxidation. The ketogenic effect of glucagon on liver appears to be manifested in large part through the ability of the hormone to reduce the tissue malonyl-CoA concentration.


Platelet factor 4. Crystallization and x-ray diffraction studies. Human platelet factor 4 was crystallized with ammonium sulfate. The crystals were orthorhombic, space group P21212, with unit cell dimensions a = 78.7 A, b = 80.6 A, and c = 54.6 A. Unit cell volume and mass of the protein (7800 daltons) indicated four or five molecules in each asymmetric unit cell.


Distribution of membrane marker enzymes in cultured arterial endothelial and smooth muscle cells. The subcellular location of oleoyl-CoA:1-acyl-sn-glycero-3-phosphocholine acyltransferase. The subcellular distribution of oleoyl-CoA:1-acyl-sn-glycero-3-phosphocholine acyltransferase (E.C.2.3.1.23) in cultured swine aorta endothelial cells and smooth muscle cells was investigated. Isolated membrane pellets were centrifuged through linear sucrose gradients, and the distributions of the activities of seven membrane-bound enzymes were measured. The distribution of acyltrasferase activity was similar to that of the endoplasmic reticulum enzymes. Gradient fractions which contained intact mitochondria had very low activities of acyltransferase. Experiments using mixed fractions and measurements made under conditions which inhibit phospholipase A2 showed that no acyltransferase activity from this location was masked by competing activities. When membranes were treated with digitonin, plasma membranes specifically increased in density, facilitating their separation from endoplasmic reticulum membranes. The plasma membranes were free of acyltransferase activity. We conclude that in cultured swine arterial smooth muscle and endothelial cells, acyltransferase is located primarily in the endoplasmic reticulum.


Isolation and characterization of GD3 ganglioside having a novel disialosyl residue from rabbit thymus. A major component of the di- and trisialoganglioside fraction of rabbit thymus was isolated. By neuraminidase treatment, methylation analysis, and CrO3 oxidation, it was identified as GD3 ganglioside with the novel disialosyl residue, NeuNGlyc(alpha, 2-8)NeuNAc(alpha, 2-3)Gal-(beta, 1-4)Glc(beta, 1-1)ceramide. Its concentration was 21.92 nmol/g of wet tissue (12.10% of the total gangliosides) and it contained 91.52% of the lipid-bound sialic acid in di- and trisialogangliosides of rabbit thymus.


Cholesterol distribution between the two halves of the lipid bilayer of human erythrocyte ghost membranes. The binding of filipin with cholesterol in sealed and unsealed ghosts prepared from human erythrocytes and in right-side-out and inside-out vesicles prepared from ghosts follows second order kinetics (first order in each reactant). The second order rate constant of interaction of filipin with cholesterol, determined by stopped flow measurements of the initial rate, is slower in sealed ghosts than in unsealed ghosts by a factor of 2.0, whereas identical rate constants were obtained with right-side-out and inside-out vesicles. These results suggest that the cholesterol accessible to rapid reaction with filipin is distributed symmetrically between the inner and outer halves of the lipid bilayer of erythrocyte ghost membranes.


Polyadenylation of RNA in a cell-free system from mouse myeloma cells. Isolated nuclei frommouse myeloma cells which were active in RNA synthesis did not synthesize detectable amounts of poly(A)-containing RNA. On addition of a soluble protein extract from crude nuclei, the highly purified nuclei synthesized significanamounts of poly(A)-containing RNA, as analyzed by chromatography on poly(U)-Sepharose. The poly(A) tract was totally synthesized de novo and was indistinguishable from poly(A) synthesized in vivo. Twenty per cent of the RNA polymerase II products were polyadenylated. More than 80% of the newly synthesized poly(A) was present on molecules at least partially transcribed in vitro. The transcription and polyadenylation reaction could be separated temporally and a portion (10%) of the polyadenylated RNA was released into the extra nuclear fraction. We conclude that this system carries out one RNA processing reaction, polyadenylation, faithfully.


Boar malpha-acrosin. Purification and characterization of the inital active enzyme resulting from the conversion of boar proacrosin to acrosin. The preparation of highly purified malpha-acrosin is described. Purification was achieved by controlled activation of partially purified proacrosin, followed by gel chromatography over Sephadex G-100 at pH 3.0. The final malpha-acrosin preparation resulted in a single protein band with a molecular weight of 49,000 as determined by sodium dodecyl sulfate-disc gel electrophoresis. Disc arginine naphthylamide hydrolyzing band with a relative migration of 0.39 malpha-acrosin catalyzed the hydrolysis of synthetic substrates containing arginine and lysine, but not phenylalanine. Although calcium ions were not required for enzymatic activity, the addition of calcium chloride stimulated the activity through an increased substrate affinity and an increased maximal velocity. Polyamines stimulated the maximal velocity of the reaction, but were without effect on the substrate affinity. malpha-Acrosin was inhibited by lima bean, ovo-mucoid, and seminal plasma proteinase inhibitors. Diisopropyl fluorophosphate and 1-chloro-3-tosylamide-7-amino-L-2-heptanone treatment resulted in an irreversible inhibition, while L-arginine, benzamidine, and p-aminobenzamidine were competitive inhibitors with respect to substrate. These properties of malpha-acrosin are very similar to those previously reported for mbeta-acrosin and suggest that the portion of the molecule lost during the conversion of malpha-acrosin to mbeta-acrosin contributes little to the topography of either the active site or regulatory sites of the enzyme.


Role of dehydrogenase competition in metabloic regulation. The case of lactate and alpha-glycerophosphate dehydrogenases. Many tissues expressing capacities for both anaerobic and aerobic glycolysis contain significant amounts of both lactate dehydrogenase and alpha-glycerophosphate dehydrogenase. Since the first serves in oxidation-reduction balance during anaerobic metabolism, while the second serves in the alpha-glycerophosphate cycle during aerobic metabolism, a provision seemed to be made (through competition for coenzyme) to encourage relatively exclusive function of either one or the other dehydrogenase. Competition for coenzyme was found to depend upon the isoenzyme form of each dehydrogenase (which determines the sensitivity of each reaction to modulators) and the concentration of two key metabolites, alpha-glycerophosphate and creatine phosphate, which differentially influence alpha-glycerophosphate dehydrogenases and lactate dehydrogenases. The sensitivities of various dehydrogenase isoenzymes to these modulators correlated well with their expected roles in the tissue of origin.


Interaction of the parathyroid and 1,25-dihydroxyvitamin D3 in the control of renal 25-hydroxyvitamin D3 metabolism. Parathyroid extract and 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3) were found to antagonize each other's action to regulate the kidney hydroxylation of 25-hydroxyvitamin D3. Parathyroid extract prompted an increase in serum 1,25-(OH)2D3 in thyroparathyroidectomized rats whereas the administration of exogenous 1,25 (OH)2D3 resulted in stimulated 24,25-dihydroxyvitamin D3 and suppressed 1,25-(OH)2D3 serum levels. The actions of parathyroid and 1,25-(OH)2D3 to modulate kidney 25-hydroxyvitamin D3 hydroxylase enzyme activities were not additive; rather, the hormone and metabolite acted to suppress each other's in vivo regulatory action. The specificity and rate of 25-hydroxyvitamin  D3 hydroxylation was determined by the interdependent modulatory actions of parathyroid extract and 1,25-(OH)2D3. Such results suggest that the kidney 25-hydroxyvitamin D3-1- and 24-hydroxylase enzyme systems are regulated in response to the relative modulatory activities of parathyroid hormone and 1,25-(OH)2D3.


Ligand responses of alpha-bungarotoxin binding sites from skeletal muscle and optic lobe of the chick. Binding properties of detergent-solubilized receptors for alpha-bungarotoxin from skeletal muscle of the 13th day chick embryo and from optic lobe of the hatching chick were compared. It was found that both types of receptor are nicotinic, although they differ in their affinities for individual ligands and in the rank order of ligands. In contrast to the muscle receptor, the neuronal receptor binds the toxin in a reversible fashion (KD = 2.1 X 10(-10) M at 23 degrees C). Small ligands inhibit brain equilibrium procedures. Toxin and ligands compete for a single type of noninteracting site, and the ratio of toxin binding sites to ligand-binding sites is unity. The inhibitory potency of ligands parallels their ability, at higher concentrations, to accelerate receptor . toxin by interaction with the same site on the receptor derived from the optic lobe.


Biphasic association of p-nitrophenyl 2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside and concanavalin A as detected by stopped flow spectroscopy. Kinetics of binding of p-nitrophenyl 2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (M2) to concanaviln A (con A) were examined. The time course of formation of a M2 . con A complex is clearly biphasic, whereas the association with con A of p-nitrophenyl 2-O-methyl-alpha-D-mannopyranoside and other monosaccharides is a monophasic process. The biphasic time course of the binding of M2 to conA is most simply explained in terms of a model wherein the disaccharide can bind to con A two different ways. In the initial rapid phase of the biphasic reaction, both complexes form in amounts determined by the relative values of the rate constants for association. In the subsequent slow phase, the complexes equilibriate according to the relative values of the initial constants for formation of each complex. The enthalpy of activation for formation of the initial complexes with M2 is about 4 kcal/mol less favorable than for monosaccharides, whereas the entropy of activations about 14 e.u. more favorable for binding of the disaccharide. These differences in the activation parameters for binding M2 and monosaccharides suggest that con A interacts simultaneously with groups on both mannopyranosyl residues.


Rates of DNA synthesis during the S-phase of HeLa cells. The rates of DNA synthesis were determined for each of two consecutive journeys through S-phase by highly synchronized HeLa cells. Cells at various times after release from the metabolic block were pulsed with [3H]thymidine. The amount of radioactivity in whole cells, purified DNA, and Okazaki fragments provided indexes of the rates of DNA synthesis. Measurements of the average DNA content per cell by the diphenylamine method and the individual DNA content per cell by DNA:propidium fluorescence provided better estimations of the actual rates of DNA synthesis, independent of thymidine metabolism. Unsynchronized cells that had been pulsed with [3H]thymidine were sorted into early, middle, and late S-phase preparations for estimations of the amount of radioactivity per cell. There were differences in the rates predicted by each of the various methods. Rates estimated by fluorescence measurements of DNA content per cell, or by diphenylamine measurements of average DNA content per cell exhibited a pattern of an initial burst, followed by a decreased rate then a final burst. Similar patterns were obtained for the amount of radioactivity in Okazaki fragments, and in early, middle, and late S-phase cells separated from a log-phase culture by electronic cell sorting. Rates estimated by measurements of the amount of radioactivity in whole cells, and the specific activity of purified DNA exhibited a different pattern of an initial slow rate, followed by a maximal rate then a slow rate.


The mechanism of quenching of liver alcohol dehydrogenase fluorescence due to ternary complex formation. Difference fluorescence emission spectra, reciprocal Stern-Volmer plots, and variable excitation wave-lengths have been used to evaluate the selective quenching of the two tryptophan residues/subunit of liver alcohol dehydrogenase. Trp-15, at the surface of the enzyme, is quenched by KI consistent with a collisional mechanism, and has a blue-shifted excitation and red-shifted emission spectrum when compared with the spectral properties of TRP-314, which is in a hydrophobic milieu at the subunit interface of the dimeric enzyme. With excitation at 295 nm, Trp-314 is 80% quenched by formation of a ternary enzyme.NAD+.trifluoroethanol complex, and the quenching is essentially additive to that caused by KI. Alkaline pH also results in selective quenching of Trp-314. These results, and considerations of the three-dimensional structure of the enzyme, indicate that the quenching of protein fluorescence of liver alcohol dehydrogenase by either ternary complex formation or alkaline pH is due to resonance energy transfer to tyrosinate. Likely candidates as energy acceptors are the Tyr-286 residues are within transfer distance for each Trp-314 residue, as well as being at the surface of the enzyme and 30 A from the active center zinc atom. Alkaline pH directly ionizes this tyrosine residue, while ternary complex formation causes a conformational change resulting in its ionization.


Cloning of a double-stranded cDNA that codes for a portion of chicken preproalbumin. A general method for isolating a specific DNA sequence from partially purified mRNA. A scheme is presented for cloning a double-stranded cDNA molecule that codes for a portion of chicken preproalbumin. This method, which does not require pure mRNA or cDNA, has widespread applicability. Chicken preproalbumin was identified as a Mr = 72,000 polypeptide by immunoprecipitation of proteins synehesized in a wheat germ cell-free translation system from total, guanidine.HCl-extracted, rooster liver RNA. After removal of the bulk of the ribosomal RNA by poly(U)-Sephadex G-10 chromatography, albumin mRNA was enriched approximately 2-fold by centrifugation through low salt, isokinetic sucrose gradients, until it represented about 30% of the mRNA sequences present. Double-stranded cDNA prepared from this mRNA was then inserted into the Pst 1 site of the plasmid PBR322 by the "G-C tailing" technique and the recombinant DNA was used to transform Echerichia coli stran X1776. Transformants containing putative albumin DNA sequences were identified by colony hybridization with a cDNA probe that was highly enriched for albumin cDNA sequences. This probe was isolated by hybridizing the partially purified RNA preparation to its cDNA, under conditions of RNA excess, to a R0t value such that only the most abundant cDNA sequences had hybridized. Unhybridized, less abundant, sequences were destroyed by subsequent S1 nuclease digestion. The identity of clones that hybridized to this abundant class cDNA was established by DNA-mRNA hybrid-arrested cell-free translation. Hybridization of nick-translated, albumin-containing, plasmid DNA to total liver poly(A)+ RNA, that had been separated on methyl mercury agarose gels and transferred to diazobenzyloxymethyl paper, established that avian albumin mRNA has a molecular weight of 850,000. This molecular weight corresponds to approximately 2,600 nucleotides, or 600 nucleotides longer than the size required to code for the preproalbumin polypeptide.


Progression in idiopathic scoliosis: A preliminary report of a possible mechanism. Recent surveys have shown that idiopathic structural scoliosis of mild degree is generally not progressive. We will propose a mechanism which may be responsible for deterioration in the few. It has been observed that the spinal cord, although displaced towards the concavity, does not rotate in company with the vertebrae, thus exposing the emerging nerve roots to the effects of traction and possibly of entrapment. We suggest that progression occurs when the neuraxis is unable to adjust to the change in the anatomy of vertebral column. Our proposition is based upon our findings in a complete spinal column obtained from a baby with structural scoliosis. Support is provided by intercostal angiography, and by observations upon normal anatomy, the pathological anatomy of mature scoliotic spines and the anatomy of contrived scoliosis in normal spines. Although our histological and electrophysiological investigations are incomplete we can demonstrate a significant increase in degenerate cells in the dorsal root ganglia at the apex on the convex side. Lack of suitable necropsy material prevents us from confirming our observations so that our report is inevitably preliminary. We enter a plea that careful examination of the neuraxis be undertaken whenever a specimen of a scoliotic spine becomes available.


Perthes' disease of the hip in three regions of England. Throughout 1976 orthopaedic surgeons in three regions of England forwarded details of all new patients with Perthes' disease attending outpatient clinics or admitted as inpatients. The incidence in the Mersey region (11.1 per 100 000 children under fifteen years) was twice that in Wessex (5.5) with Trent having an intermediate incidence (7.6). The ratio of male to female incidence varied between the regions as did the age distribution of male cases. These findings point to the importance of environmental factors in the aetiology of the disease, and suggest the need for further epidemiological studies.


Measurement of the spinal canal by diagnostic ultrasound. A method is described of measuring the lumbar spinal canal by pulsed echo ultrasound. It is simple, safe and has a high degree of accuracy. The lumbar canal has been measured in over 800 subjects including 100 mining recruits and fifty nurses between the ages of fifteen and eighteen years. Ultrasound can demonstrate the degree and extent of bony stenosis. It may have value in preventive medicine, identifying the subject at risk.


The spinal canal in symptomatic lumbar disc lesions. The oblique sagittal diameter of the lumbar spinal canal was measured by diagnostic ultrasound in seventy-three patients with symptomatic disc lesions, and compared with measurements from 200 asymptomatic subjects. Results suggest that the available space in the spinal canal is highly significant in the symptomatology of disc lesions, and in the patient's response to treatment.


Low-friction arthroplasty after fracture-dislocations of the hip. Sixty-six patients are presented who have had a total hip replacement by the Charnley low-friction technique after injuries of the hip, the majority of which were fracture-dislocations. The clinical results of the arthroplasties in this relatively young group of patients are shown to be very good. The selection of young patients for total hip replacement arthroplasty is discussed.


Charnley low-friction arthroplasties of the hip in rheumatoid arthritis. A study of the complications and results of 378 arthroplasties. During the years 1971 to 1975, 378 Charnley low-friction arthroplasties of the hip were performed on 278 patients with rheumatoid arthritis. The average age at operation was thirty-nine years. The follow-up time ranged from one to six years (mean two and a half years). Forty per cent of patients were receiving steroids at the time of operation. The most common complications were loosening of the prosthesis (3.4%), perforation of the femoral cortex and fracture. Deep infection occurred in 0.7%, dislocation in 0.7%, and thromboembolic episodes in 1.3%. Ninety-five per cent of patients were free of pain at follow-up compared to 84% who were severely handicapped by pain before operation. In addition, the increased mobility in 98.5% of patients and their improved independence makes hip replacement a recommendable procedure in these patients.


Closed Küntscher nailing of femoral shaft fractures. A series of 100 consecutive patients. One hundred and two fractures of the femoral shaft, including eighteen pathological fractures, in 100 patients were internally fixed by closed Küntscher nailing. Sixty-eight fractures resulted from motor vehicle accidents; ten were compound. Seventy-five patients were under the age of thirty years and thirty-four had multiple injuries. Sixty-nine fractures were nailed on the day of the accident and the operative technique is described. Complications during and after operations were few. Fifty-eight patients left hospital within four weeks and 77% of those working returned to work in less than four months. There were no wound or bone infections. The results are discussed and it is concluded that, with the correct equipment and careful attention to detail, closed nailing is a straightforward procedure with few complications. Advantages include the wide range of fractures that can be nailed, the short hospitalisation, the rapid return of function to the knee, the early return to work and the absence of infection.


Ipsilateral fracture of the femur and tibia. The hospital records of 222 cases of ipsilateral fractures of the femur and tibia were reviewed, and patients were grouped according to the type of fracture and the method of treatment. Thirty-five per cent of patients required late operation for delayed union or non-union, osteomyelitis, refracture and malunion, regardless of the treatment group. A disturbing factor was the 30% incidence of osteomyelitis in patients treated by fixation of both fractures, almost three times the incidence when only one fracture was fixed. A 30% incidence of delayed union or non-union occurred in patients managed conservatively. Of sixty-three patients personally examined, the worst results found were those following conservative management of both fractures. More use of rigid external fixation and of cast bracing is recommended in the management of the fractured tibia, combined with internal fixation of the femoral fracture. Examination of the knee suggested that, with ipsilateral fractures, disruption of ligaments is a common occurrence and should always be suspected.


The use of suction drainage in the operation of meniscectomy. A prospective trial has been carried out to determine the value of suction drainage in the operation of meniscectomy. One hundred operations were analysed, in half of which drains had been used. The use of the drain could not be shown to result in any sustained advantages. The demand for analgesics after the operation was reduced but not to a statistically significant level. The size of the early effusion was significantly reduced, but this benefit was lost when the knee was mobilised. The return of power to the quadriceps and of movement to the knee were not hastened. The average volume of fluid drained was 134 millilitres and it has been shown that forty-eight hours is a suitable time for removal of the drain. The use of suction drainage is not advocated for the uncomplicated operation of meniscectomy.


The repair of cruciate ligaments with flexible carbon fibre. A longer term study of the induction of new ligaments and of the fate of the implanted carbon. Carbon fibre appears to induce the formation of tendon in both animals and humans. Experiments have been conducted in sheep in which new anterior cruciate ligaments have been induced in response to the implantation of filamentous carbon fibre. Long-term studies indicate that the carbon fibre slowly breaks up at the site of implantation and later begins to appear in the regional lymph nodes.


Chronic tenosynovitis of the posterior tibial tendon with new bone formation. Chronic non-specific tenosynovitis of the posterior tibial tendon is a well-known clinical entity, characterised by pain, swelling and tenderness behind the medial malleolus. There are no reports in the literature of any case associated with any radiological abnormality. Three such cases are discussed, each presenting with the clinical findings typical of the syndrome but with associated radiological changes. These changes may pose diagnostic problems and several primary conditions need to be excluded. Surgical decompression of the tendon may be necessary to relieve symptoms, to prevent erosion and rupture of the tendon, and to establish the diagnosis.


Peroneal spastic flat foot. Its treatment by osteotomy of the os calcis. A series of patients treated by osteotomy of the os calcis for the relief of peroneal spastic flat foot is reviewed. The late results have been evaluated, and the literature reviewed. It is suggested that this is an effective method of treatment which has advantages over tarsal fusions.


The natural history of hooked forefoot.

The natural history of hooked forefoot. This paper reports on a prospective study undertaken to determine the natural history of untreated idiopathic hooked forefoot. The progress of 130 affected feet in eighty-three children was followed for an average of seven years. At review 86% of the feet were normal or only mildly deformed and all were fully mobile; 10% were still moderately deformed but were asymptomatic; 4% remained deformed and stiff. It was not possible to detect these resistant cases before the age of three years, but the low failure rate would seem to justify a policy of expectant treatment.


The surgical treatment of equinovarus deformity in adults with spasticity. Adults with deformities of the lower limb due to spasticity may be considerably improved by operation, but thorough pre-operative assessment as an inpatient is essential in order to pinpoint the disability. The commonest deformity is equinovarus which often responds to simple operative procedures. The results of seventy-seven operative procedures in fifty patients are recorded. Correction once achieved is stable and the deformity does not recur.


An analysis of residual deformity in club feet submitted to early operation. The contributions made by metatarsus primus varus, medial subluxation of the navicular, and angulation of the neck of the talus to the residual deformity in treated club feet were assessed from radiographs. Their relation to the appearance of the feet, to the age of the patient, to the results of operations, and to the age at the time of the first operation were investigated. Lateral rotation of the ankle and flattening of the talus were also studied. Medial subluxation of the navicular was found to be the most important factor influencing both the appearance of the feet and the lateral rotation of the ankle. Relocation of the talonavicular joint correlated with the success of operative treatment; and the timing of the primary operation determined the degree of relocation which could be achieved. Metatarsus primus varus and angulation of the talus were of little importance. Increased emphasis is given to the need for early relocation of the talonavicular joint.


The refractory painful arc syndrome.

The refractory painful arc syndrome. Twenty-three patients with a severe refractory painful arc syndrome have been treated by excision of the outer end of the clavicle and division of the coracoacromial ligament through a deltoid-splitting approach. After a follow-up of more than six months all patients have been relieved of night pain. Six still have slight pain on movement, but the rest are symptom-free.


Thoracoscapular fusion for facioscapulohumeral dystrophy. Eleven thoracoscapular fusion operations have been done on six patients. The indication is symptomatic winging of the scapula caused by thoracoscapular muscle paresis with intact function in the deltoid. This situation almost exclusively occurs in facioscapulohumeral dystrophy. The operation is successful in achieving stability of the scapula and in greatly improving function and cosmesis. Although the course of this type of muscular dystrophy is variable, the benefits of operation have not deteriorated with progression of the disease over a maximum follow-up period of twenty-three years.


Clinical application study of multifunctional prosthetic hands. A control system for a multifunctional hand prosthesis, which requires a minimum of training for the amputee, has been developed. The great advantage of the pattern recognition technique in making it possible to control as many as six prosthetic movements has prompted this study. The development of a complete miniaturised system has allowed a clinical trial on four patients. Two different tests have been employed to evaluate this system: an objective computer test and a test representing activities of daily living (ADL test). The computer test shows that a high rate of correct recognition is obtained immediately after the prosthesis is applied to the amputee. The ADL test shows that forearm rotation, and flexion and extension of the wrist are used in most activities, indicating that few compensatory movements are performed. It is suggested that this control system is feasible and that long periods of training are unnecessary.


Adjuvant chemotherapy in the treatment of clinically localised Ewing's sarcoma. The results are presented of thirty-seven patients with Ewing's sarcoma; ten were treated by a combination of operation, radiotherapy and cyclic chemotherapy, the remainder by radiotherapy and chemotherapy but without operation. The drugs, vincristine, cyclophosphamide and adriamycin were used in combination and were continued for two years. The follow-up ranged from twelve to sixty-two months. The mortality rate and the incidence of metastases were both markedly lower than in a comparable previous series treated by radiotherapy alone, or by operation plus radiotherapy, but all without chemotherapy. The percentage of local recurrences and of metastases was much higher in the twenty-seven patients who had radiotherapy and adjuvant chemotherapy, than in the ten in whom operation was also performed. It is suggested that on the basis of these results (and on theoretical grounds) treatment should consist of radiotherapy combined with chemotherapy plus, whenever feasible, operative excision of the primary tumour.


The effects of varying oxygen tensions upon bone resorption in vitro. Calvaria from six-day-old infant mice were grown on a grid culture in a chemically defined medium under varying oxygen tensions. Quantitative isotope studies demonstrated a linear association between bone resorption and oxygen tension in the physiological range. This result was supported by histological, histochemical and vital staining experiments. The clinical finding of osteoporosis in areas of hyperaemia could therefore be attributed to a rise in oxygen tension causing increased bone resorption.


The uptake by the canine tibia of the bone-scanning agent 99mTc-MDP before and after an osteotomy. The residue and extraction of technetium-labelled methylene diphosphonate (99mTc-MDP), a substance used in bone scanning, was examined in the canine tibia and found to be low. Examination of washout curves suggested that there were four compartments in cortical bone, a vascular, a perivascular, a bone fluid and a bone compartment. After an osteotomy in the canine tibia the residue of 99mTc-MDP increased. This was believed to be due to an increase in the blood supply to the bone and to an associated increase in new bone available for exchange. Bone scanning in a fracture is therefore a reflection of the vascular status of the bone being examined and of the uptake by bone. This is dependent on there being an adequate blood supply to the bone and an increased number of mineral-binding sites.


Enlargement of the right ventricle using a viable atrial pedicle graft. A viable muscle pedicle of right atrial wall was used to enlarge the right ventricle in 5 dogs. The procedure consistently resulted in an increase in right ventricular circumference of approximately 20%. Although ventricular function was adequate to permit survival, cardiac index did not increase appropriately to an elevation in preload. Morphologic studies demonstrated later scarring and thickening of the muscle pedicle suggesting the graft had not maintained its contractile nature.


Hypernatraemic dehydration following tricuspid valve replacement. The development of abnormally high plasma sodium and plasma osmolality levels is described in 5 patients following open-heart surgery involving prosthetic replacement of the tricuspid valve. These biochemical abnormalities developed in the early post-operative period and were associated with an excessive diuresis during the first 3 to 4 days after operation. Biochemical correction required a prolonged, high volume intravenous water load, and was paralleled by progressive clinical improvement, notably in peripheral circulation, tissue turgor and cerebral function. Plasma sodium and osmolality levels and observed fluid balance in 20 patients undergoing similar surgical procedures for tricuspid valve lesions fail to show this hypernatraemic, hyperosmolar state, and indicate that the majority of such patients have a markedly positive observed fluid balance in the early post-operative period. These differences are statistically highly  significant (p less than 0.001). Consideration of urine/plasma osmolality levels reveals a transient but highly significant impairment of renal concentration in the hypernatraemic patients (p less than 0.001).


Estimation of adequate subendocardial blood flow by online computation of systolic pressure time index and diastolic pressure time index after cardiopulmonary bypass. Subendocardial perfusion was monitored in 48 patients subjected to valve replacement by calculation of diastolic pressure time index (DPTI), systolic pressure time index (TTI) and DPTI/TTI. An on-line computer which derives these values from the systemic pressure and wave-form was applied. For myocardial protection general body hypothermia (esophageal temperature 25 degrees C) and hypothermic injection cardioplegia were employed. No low cardiac output state occurred and no inotropic drugs were required. In all patients DPTI/TTI rose above 1 within 60 minutes from termination of cardiopulmonary bypass so that the necessity to intraaortic balloon counterpulsation could be denied in all cases. We believe that the calculation of DPTI/TTI after extracorporeal circulation is a useful modality to predict the adequacy of subendocardial perfusion and monitor myocardial performance.


The effect of furosemide on renal function in open heart surgery. The effect of furosemide on renal function in patients undergoing open heart surgery was investigated, using creatinine clearance, urine flow, sodium and potassium excretion as the parameters. The effect of furosemide (2 mg/kg i.v.) on blood flow in arteria renalis and the tissue oxygen tension of the renal cortex and medulla were also investigated experimentally in six dogs. The flow was measured with an electromagnetic flowmeter and the tissue oxygen tension with IBC tissue oxygen electrodes. Prolongation of the perfusion time to more than 60 minutes resulted in a decline of creatinine clearance to appr. 50% of the initial level. Prophylactic furosemide given prior to the perfusion brought down the creatinine clearance to 64% of the initial level. Furosemide, administered either prophylactically just before the cardiopulmonary bypass or after urine flow had declined below 0.5 ml/kg/h, had no effect on the potassium balance in the long perfusion group (over 60 minutes), though it clearly increased the negative potassium balance in the short perfusion group (below 60 minutes). In an experimental work on dogs, furosemide was found to elevate the tissue oxygen tension in the renal cortex and and medulla, and slightly to increase the blood flow in arteria renalis.


Morphological and biochemical correlates of skeletal muscle contractility in the cat. I. Histochemical and electron microscopic studies. Three cat hind limb muscles have been examined, histochemically and ultrastructurally, in a multiparameter correlative study of structure and function in skeletal muscle contractility. The soleus, a histochemically pure, slow-twitch muscle possesses ultrastructural features which are, in many cases, significantly different from those of almost pure fast twitch caudofemoralis muscle. Although stereological analysis of fiber types indicates a correlation between speed of relaxation and volume of sarcoplasmic reticulum, morphological features such as fenestrated collars and triad morphology are identical in all fiber types. The fast twitch-oxidative-glycolytic fiber possesses features common to both slow twitch fibers (high mitochondrial content) as well as fast twitch fibers (high sarcoplasmic reticulum content) in addition to Z band width which falls in between these two fiber types. Sarcoplasmic microtubules have been described in all three fiber types in all muscles examined. They occur in predictable orientation and their possible function(s) is described.


Intraoperative blood measurements following revascularization of the lower extremities with chronic arterial occlusive disease. We have measured blood flows in 155 limbs with chronic arterial occlusive disease after revascularization procedures. Blood flows were recorded during standard electromagnetic flowmeter techniques. Base line flows after maximal vasodilatation with papaverine were recorded. The most important measurement to determine immediate results was the percentage increase of the basal flow after intraarterial injection of 30 mg papaverine. In aorto-iliac revascularization we found a significant difference according to the outflow tract, whether the superficial femoral was patent or occluded. Grafts in which proximal anastomosis were at the aorta on the axillary artery yielded better flows than those from the opposite femoral artery. A vein graft of inadequate caliber may determine a pressure gradient higher than 10 mm. Hg. In these circumstances the the blood flow is lower. Blood flow measurements may aid in the selection of the adequate surgical procedure in cases of arterial lesions of doubtful significance.


Experimental remarks on leg ischemia following popliteal artery injuries. Popliteal artery injuries are followed, in many cases, by amputation of the leg. Results after re-construction depend on the time of ischemia. In this experimental work 12 dogs with injury of the popliteal artery had a direct end to end anastomosis or an anastomosis using saphenous vein graft. Blood flow was checked by an electromagnetic flowmeter or ultrasounds, blood samples for Hb, oxyhaemoglobin saturation, Hct and ph were taken before and after operation. Changes in these values depend on the time elapsing between injury and re-establishment of circulation. Operative angiography was done in all dogs. Except in two dogs, no early or late thrombosis occurred. Three dogs required amputation. The outcome of the operation is related to the time elapsing between injury and restoration of circulation.


The effects of electrical field stimulation and tetrodotoxin on ion transport by the isolated rabbit ileum. To determine whether intramural nerves affect intestinal ion transport, we studied the effect of electrical field stimulation (EFS) on the movement of ions across isolated rabbit ileum. EFS increased the transmural electrical potential difference and the short circuit current (Isc), caused C1 secretion, and reduced conductance, but did not alter fluxes of Na or the residual current (JRnet). The neurotoxin, tetrodotoxin, prevented all the changes caused by EFS but did not prevent the increase in Isc caused by theophylline (5 mM), carbachol (10 micrometer), or glucose (10 mM), or the reduction in Isc caused by norepinephrine (10 micrometer), implying that tetrodotoxin prevented responses to EFS by affecting electrically excitable cells rather than epithelial cells. Tetrodotoxin also enhanced the mucosa to serosa fluxes of Na and C1, reduced the potential difference and Isc, and increased conductance. The site of tetrodotoxin action is uncertain because it may affect the release of at least four neuro-transmitters and the release of peptides from endoctine cells. The Isc response to EFS was not affected by atropine (10 micrometer), physostigmine (10 micrometer), or by hemicholinium (1 micrometer). The mechanism by which EFS causes C1 secretion remains to be determined.


Human skin aryl hydrocarbon hydroxylase. Induction by coal tar. Coal tar products, which are widely used in treating dermatologic disease, contain numerous polycyclic aromatic hydrocarbons, including 3,4-benzo[a]pyrene (BP). BP is among the most potent environmental chemical carcinogens and is known to evoke tumors in the skin of experimental animals and perhaps also of man. In this study the effect of cutaneous application of coal tar solution (U. S. Pharmacopeia) on aryl hydrocarbon hydroxylase (AHH) activity in the skin of patients usually treated with this drug was investigated. AHH, a cytochrome P-450 dependent carcinogen-metabolizing enzyme appears to play an important role in the activation of polycyclic hydrocarbons into reactive moieties that can bind to DNA and that may directly induce cancer. Application of coal tar solution to human skin caused a two to five-fold induction of cutaneous AHH in nine subjects. In further studies, the incubation of human skin with coal tar solution in vitro also caused variable induction of cutaneous AHH. Maximum responses in both systems occurred after 24 h and enzyme activity in vitro was time- and tissue- and substrate-concentration dependent. Studies in experimental animals showed that topical application of coal tar solution caused induction of AHH in skin and, after percutaneous absorption, in liver as well. Assay of several defined constituents of coal tar for AHH induction showed that BP was the most potent inducer of AHH tested. These studies indicate that topical application of coal tar solution in doses ordinarily used in treating dermatologic disease causes induction of AHH in human skin and suggest that such induced enzymatic activity could relate to carcinogenic responses to this agent in skin or, after percutaneous absorption, in other tissues as well.


Receptor specific clearance by the reticuloendothelial system in chronic liver diseases. Demonstration of defective C3b-specific clearance in primary biliary cirrhosis. An approach to the assessment of reticuloendothelial function that quantitates clearance specifically mediated by membrane receptors for C3b and immunoglobulin (Ig)G has been applied in man. Clearance of isologous erythrocytes coated with IgM or C3b or coated with IgG were examined in patients with primary biliary cirrhosis (PBC), chronic hepatitis, or alcoholic cirrhosis and normal control subjects and compared with the clearance of aggregated human serum albumin. Clearance of these three types of particles varied independently. None of the patients studied had a defect in the clearance of aggregated albumin. No patient with PBC (0:6) had delayed clearance of IgG-coated erythrocytes; one of six patients with chronic hepatitis had delayed clearance of these cells. Indeed, four of six with PBC had increased rates of IgG-mediated clearance. In contrast, six out of six patients with PBC had an unequivocal defect in clearance mediated by C3b receptors. The patients with PBC varied widely in terms of duration of symptoms, degree of cholestasis, and histologic stage of disease. No defect of C3b-mediated erythrocyte clearance was found in the patients with chronic hepatitis or alcoholic cirrhosis. Furthermore, a patient with severe cholestasis secondary to large duct biliary obstruction exhibited normal C3b-mediated clearance. The defect in C3b-mediated clearance in PBC did not correlate with serum levels of individual complement components or inhibitors or with the presence of circulating immune complexes as measured by the Clq precipitation assay. Thus, measurements of receptor specific clearance, but not clearance of aggregated proteins, have revealed a highly specific defect in reticuloendothelial function in PBC.


Purification and characterization of an abnormal factor IX (Christmas factor) molecule. Factor IX Chapel Hill. Human Factor IX (Christmas factor) was isolated from the plasma of a patient with mild hemophilia B. The patient's plasma contained 5% Factor IX clotting activity but 100% Factor IX antigenic activity as determined by immunological assays, which included inhibitor neutralization and a radioimmunoassay for Factor IX. This abnormal Factor IX is called Factor IX Chapel Hill (Factor IXCH). Both normal Factor IX and Factor IXCH have tyrosine as the NH2-terminal amino acid. The two proteins have a similar molecular weight, a similar amino acid analysis, the same number of gamma-carboxyglutamic acid residues (10 gamma-carboxyglutamic acid residues), and a similar carbohydrate content. Both exist as a single-chain glycoprotein in plasma. The major difference between normal Factor IX and Factor IXCH is that the latter exhibits delayed activation to Factor IXa in the presence of Factor XIa and Ca2+. Thus, Factor IXCH differs from other previously described abnormal Factor IX molecules.


Surface markers of complement receptor lymphocytes. Normal blood lymphocytes bearing complement receptors (CRL) were divided into two populations, one expressing both CR1 (C4b-C3b receptor) and CR2 (C3d receptor) and a second expressing only CR1. Nearly all of the population that expressed both CR1 and CR2 also bore membrane surface immunoglobulins (Ig) and Ia antigens. The majority of cells that had only CR1 lacked detectable surface Ig. These Ig- CR1+ CR2- cells could be distinguished from the majority of monocytes and immature granulocytes, in that the latter ingested latex particles and expressed CR2 as well as CR1. The Ig- CR1+ cells were further subdivided into an Ia-bearing subpopulation and another that lacked Ia. Among the Ig- Ia- CR1+ cells, one third formed spontaneous rosettes with sheep erythrocytes while all of the remaining CRL were erythrocyte-rosette negative. Essentially all CRL in normal blood had IgG Fc receptors, but a qualitative heterogeneity in the Fc receptors of Ia+ CRL vs. Ia- CRL was observed in their binding of different immune complex systems.


Effect of chronic potassium loading on potassium secretion by the pars recta or descending limb of the juxtamedullary nephron in the rat. Recently we demonstrated potassium secretion by the pars recta or by the descending limb of the juxtamedullary nephron. The purpose of this present investigation is to study the effect of a chronic high-potassium intake on this phenomenon. Fractional reabsorption of water and sodium by the juxtamedullary proximal nephron was decreased when compared to that in normal hydropenic rats. There was a striking increase in the fraction of filtered potassium at the end of the juxtamedullary descending limb from 94+/11% to 180+/18%, which was principally a result of enhanced potassium secretion. When the concentration of potassium in the collecting tubule fluid of potassium-loaded rats was reduced after the administration of amiloride, a sharp fall was observed in the amount of potassium which reached the end of the descending limb (64+/8%). A direct correlation was observed between the fraction of filtered potassium at the descending limb and the potassium concentration in the final urine (P less than 0.001). The findings suggest that potassium, like urea, normally undergoes medullary recycling, which is enhanced by chronic potassium loading.


Low serum dopamine beta-hydroxylase activity. A marker of congestive heart failure. To gain information about the nature of disturbances in sympathetic nervous system control in congestive heart failure, serum dopamine beta-hydroxylase (DBH) activity was measured in 30 patients with heart failure of diverse etiologies and 29 healthy normotensive controls. The heart failure patients had been symptomatic for at least 6 wk and had elevated filling pressures, low cardiac indices, low ejection fractions, and wide arteriovenous oxygen differences. DBH activity was 47.1+/-4.7 (mean+/-SE) for the controls and 14.4+/-2.7 IU for the heart failure patients (P < 0.001). Sera from some patients with heart failure had potent inhibitory effects on DBH activity of normal sera. The inhibitor was heat stable and dialyzable and could be demonstrated despite presence of N-ethylmaleimide or Cu(++) in the reaction mixture. However, some inhibitory activity was also present in sera of normal patients; this inhibitory property was not demonstrable in unheated normal serum, but was unmasked when DBH was heat inactivated. It is proposed that although the inhibitor may have been a factor in low serum DBH activity in some patients with heart failure, the major cause of the low activity in the heart failure group was a reduced rate of synthesis or release of the enzyme by sympathetic nerves. This may reflect a dissociation between rates of neural release of norepinephrine and release of DBH in chronic, severe heart failure. The observation of low serum DBH levels in patients with heart failure suggests that measurement of DBH levels may serve as a useful indicator of cardiac dysfunction.


Binding of chemotactic collagen-derived peptides to fibroblasts. The relationship to fibroblast chemotaxis. We previously showed that collagen, alpha-chains, and collagen-derived peptide fragments induce chemotactic migration of human fibroblasts in vitro. We now describe biochemical and immunological evidence showing there are binding sites for collagen peptides on fibroblast membranes.By the use of (14)C-labeled alpha1(I) chain, binding to intact fibroblasts was demonstrated. The process was reversible, and time- and fibroblast concentration-dependent. Scatchard plot analyses of the data obtained for the binding of alpha1(I) suggested that there are congruent with 16 x 10(6) binding sites per fibroblast with an association constant of 1.1 x 10(7)/M for alpha1(I). Dissociation of the bound radioactivity and subsequent chromatographic analysis on agarose A-1.5 m revealed that the alpha1 was unaltered. The binding of (14)C-labeled alpha1 was inhibited by each of the CNBr peptides derived from alpha1 chain of chick skin collagen and CNBr peptide mixtures of various genetic types of collagen chains. Immunofluorescence studies with anti-alpha1 antibody showed that alpha1-treated fibroblasts exhibited strong immunofluorescence. The intensity of fluorescence was markedly diminished by prior absorption of the antibody with alpha1. The alpha1-treated cells stained with preimmune sera did not show significant fluorescence.Dose-response curves of fibroblast chemotaxis induced by alpha1 and the binding of alpha1 by fibroblasts correlate closely. Furthermore, the potency of alpha1-CNBr peptides as chemotactic agents correlates with their ability to inhibit the binding of labeled alpha1(I). These data suggest the hypothesis that collagenderived peptides cause fibroblast chemotactic migration by acting on fibroblast membranes.


Heterozygote expression in propionyl coenzyme A carboxylase deficiency. Differences between major complementation groups. We measured propionyl coenzyme A carboxylase (PCC) activity in extracts of skin fibroblasts and peripheral blood leukocytes from controls and obligate heterozygotes for PCC deficiency. 6 heterozygotes were from the pcc A complementation group; 12 were from the other major complementation group, designated pcc C. Mean PCC activity in fibroblast extracts from pcc A heterozygotes was 52% of that in controls, whereas mean PCC activity in pcc C heterozygotes was indistinguishable from that of controls. Similar results were obtained with extracts of peripheral blood leukocytes. In none of eight families (three pcc A and five pcc C) in which PCC activity was studied in both parents of an affected child were significant intrafamilial differences observed. The activities of two other mitochondrial enzymes (beta-methyl-crotonyl CoA carboxylase and glutamate dehydrogenase) were comparable in controls and both groups of heterozygotes. Whereas the data from pcc A heterozygotes are consistent with expected gene dosage effects, those from pcc C heterozygotes are not. Inasmuch as mammalian PCC is a large molecular weight tetramer, each protomer of which is probably composed of two nonidentical subunits, the latter results are most consistent with unbalanced rates of synthesis and(or) degradation of the two subunits in normal cells with compensatory balancing in pcc C heterozygotes.


Iron uptake from rat plasma transferrin by rat reticulocytes. Fast and slow rat transferrins were isolated by isoelectric focusing and prepared in their di- and monoferric forms. A comparison of the rates of iron release between fast and slow monoferric transferrins when incubated with reticulocytes or injected in vivo showed no significant difference in the behavior of the two isotransferrin species. Reticulocyte uptake of diferric transferrin resulted in the removal of both iron atoms from the transferrin molecule. A twofold greater iron uptake was observed from diferric as compared with monoferric iron, provided reticulocyte receptors were saturated. It is concluded that the two species of transferrin and their individual sites function similarly in their release of iron to tissue receptors.


Renin-angiotensin system inhibition in conscious dogs during acute hypoxemia. Effects on systemic hemodynamics, regional blood flows, and tissue metabolism. The role of the renin-angiotensin system in mediating the circulatory and metabolic responses to hypoxia was studied in three groups of conscious dogs that were infused continuously with normal saline, teprotide (10 mug/kg per min), and saralasin (1 mug/kg per min), respectively. Hypoxia was produced by switching from breathing room air to 5 or 8% oxygen-nitrogen mixture. Plasma renin activity increased from 2.3+/-0.4 to 4.9+/-0.8 ng/ml per h during 8% oxygen breathing, and from 2.8+/-0.4 to 8.4+/-1.8 ng/ml per h during 5% oxygen breathing. As expected, cardiac output, heart rate, mean aortic blood pressure, and left ventricular dP/dt and dP/dt/P increased during both 5 and 8% oxygen breathing in the saline-treated dogs; greater increases occurred during the more severe hypoxia. Teprotide and saralasin infusion diminished the hemodynamic responses to 5% oxygen breathing, but did not affect the responses to 8% oxygen breathing significantly. In addition, the increased blood flows to the myocardium, kidneys, adrenals, brain, intercostal muscle, and diaphragm that usually occur during 5% oxygen breathing were reduced by both agents. These agents also reduced the increases in plasma norepinephrine concentration during 5% oxygen breathing, but had no effects on tissue aerobic or anaerobic metabolism. In dogs pretreated with propranolol and phentolamine, administration of teprotide (0.5 mg/kg) during 5% oxygen breathing reduced mean aortic blood pressure and total peripheral vascular resistance, and increased cardiac output and heart rate, but did not affect left ventricular dP/dt, dP/dt/P, and end-diastolic pressure. Simultaneously, renal and myocardial blood flows increased and myocardial oxygen extraction decreased, while myocardial oxygen consumption did not change significantly. These results suggest that the renin-angiotensin system plays an important role in the hemodynamic responses to severe hypoxia. It appears that angiotensin not only exerts a direct vasoconstrictor action, especially upon the coronary and renal circulations, but also potentiates the cardiovascular effects of sympathetic stimulation that occur during severe hypoxia.


Human antihapten antibodies in trimellitic anhydride inhalation reactions. Immunoglobulin classes of anti-trimellitic anhydride antibodies and hapten inhibition studies. Inhalational exposure to trimellitic anhydride (TMA) produces an immediate-type asthmatic or a late respiratory systemic syndrome in certain workers after a latent period of work exposure. TMA has been found to react with proteins to produce a hapten-protein complex (trimellitate [TM] protein) or become hydrolyzed in aqueous, alkaline solutions to produce a salt, NaTM. Using a solid-phase radioimmunoassay technique, antibodies of different Ig classes were detected against TM-protein conjugates. IgE antibody was detected in three of five workers with asthma. IgG and IgA antibodies were detected in most exposed workers but higher levels of antibody were found in symptomatic workers even after long periods without direct TMA exposure. IgM antibody activity against TM-human serum albumin (TM-HSA) was detected but did not differentiate symptomatic from asymptomatic workers. NaTM served as a hapten for study because it does not react with proteins to form a hapten-protein complex as TMA does. The NaTM only partially inhibited IgG antibody activity against TM-HSA and much smaller amounts of TM-HSA than of NaTM were required to neutralize IgG antibody. A similar result was found with TM-ovalbumin. The latter results suggest that some IgG antibody is directed against a TM-protein moiety, probably a TM-amino acid determinant. In contrast to IgG, marked inhibition by NaTM of IgA and IgM antibody against TM-HSA was found in the sera studied.


Cell-cell interaction in erythropoiesis. Role of human monocytes. Erythroid burst forming units (BFU-E) are proliferative cells present in peripheral blood and bone marrow which may be precursors of the erythroid colony forming cell found in the bone marrow. To examine the possible role of monocyte-macrophages in the modulation of erythropoiesis, the effect of monocytes on peripheral blood BFU-E proliferation in response to erythropoietin was investigated in the plasma clot culture system. Peripheral blood mononuclear cells from normal human donors were separated into four fractions. Fraction-I cells were obtained from the interface of Ficoll-Hypaque gradients (20-30% monocytes; 60-80% lymphocytes); fraction-II cells were fraction-I cells that were nonadherent to plastic (2-10% monocytes; 90-98% lymphocytes); fraction-III cells were obtained by incubation of fraction-II cells with carbonyl iron followed by Ficoll-Hypaque centrifugation (>99% lymphocytes); and fraction-IV cells represented the adherent population of fraction-II cells released from the plastic by lidocaine (>95% monocytes). When cells from these fractions were cultured in the presence of erythropoietin, the number of BFU-E-derived colonies was inversely proportional to the number of monocytes present (r = -0.96, P < 0.001). The suppressive effect of monocytes on BFU-E proliferation was confirmed by admixing autologous purified monocytes (fraction-IV cells) with fraction-III cells. Monocyte concentrations of >/=20% completely suppressed BFU-E activity. Reduction in the number of plated BFU-E by monocyte dilution could not account for these findings: a 15% reduction in the number of fraction-III cells plated resulted in only a 15% reduction in colony formation. These results indicate that monocyte-macrophages may play a significant role in the regulation of erythropoiesis and be involved in the pathogenesis of the hypoproliferative anemias associated with infection and certain neoplasia in which increased monocyte activity and monopoiesis also occur.


Studies on the tubulo-glomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide. The specific mechanism whereby superficial nephron glomerular filtration rate (sngfr) is reduced after the administration of benzolamide, a carbonic anhydrase inhibitor with a primary inhibitory effect in the proximal tubule, have been examined by measuring pertinent pressures, flows, and glomerular permeabilities in the hydropenic Munich-Wistar rat, a strain with surface glomeruli. Because benzolamide decreases absolute proximal reabsorptive rate, the rate of delivery of tubular fluid to the distal nephron should be at least transiently increased and may reduce sngfr by activating the tubulo-glomerular feedback system. Sngfr fell from 29.2+/2.0 to 2.1+/3.1 nl/min (P less than 0.01) after benzolamide (group 1), a percentage reduction equal to kidney glomerular filtration rate and similar to sngfr obtained in collections from distal tubules. Separate studies (group 2) revealed that if transient increases in distal nephron delivery were prevented by insertion of a long oil block in proximal tubules before control, the decrease in sngfr was prevented (30.3+/1.0 vs. 30.3+/1.8 nl/min, P greater than 0.9). In paired "unblocked" nephrons in the same rats, sngfr fell in group 2 (33.0+/1.0 vs. 25.2+/2.3 nl/min, P less than 0.01). In "blocked" nephrons in which sngfr reduction was prevented, the rate of fluid leaving the proximal tubule increased from 16.9+/ to 23.1+/1.0 nl/min (P less than 0.01). In group 1 studies in which sngfr fell and transient increases in flow out of the last segment of the proximal tubule (distal delivery) (approximately equal to 8 nl/min) were not prevented, steady-state distal delivery was unchanged by benzolamide (13.9+/1.1 vs. 14.2+/2.2 nl/min). Also, sngfr returned toward control, pre-benzolamide values, when a proximal oil block was placed for 15 min and the rate of distal delivery reduced after benzolamide administration, which suggests that this activation was reversible. These data suggest that activation of tubulo-glomerular feedback by transient increases in distal delivery was responsible for decreases in sngfr. Analysis of all determinants of glomerular ultra-filtration revealed that the efferent mechanism leading to reduced sngfr after benzolamide was decreased nephron plasma flow (101+/13 vs. 66+/13 nl/min, P less than 0.01). Hydrostatic pressure and the glomerular permeability coefficient did not contribute to reductions in sngfr with benzolamide. Because the rate of distal delivery remained constant in spite of large changes in both sngfr and absolute proximal reabsorptive rate, it is suggested that the rate of distal delivery may be the physiologic entity that is regulated by the tubulo-glomerular feedback system via alterations in sngfr.


Henmon-Nelson IQ scores as predictors of WAIS full scale IQ in alcoholics. Used the Henmon-Nelson Test of Mental Abilities to predict WAIS Full Scale IQ Scores with a group (N = 41) of hospitalized alcoholics. The results suggest a moderately high correlation (r = .807), which corresponds with reports of these studies of Watson and Klett for a group of hospitalized psychiatric patients. A linear regression was calculated and a and b weights generated.


Personality characteristic of the female alcoholic. Utilized the Personal Reaction Inventory (PRI-100) on a sample of 47 hospitalized female alcoholics and a control group of 47 individually matched nonalcoholic Ss. A measure of drinking behavior was established by the Volume Variability Index (V/V) administered to each S immediately prior to the administration of the PRI-100. A test-retest experimental design over a 2-week period yielded an average reliability coefficient of .88 for the PRI-100. The findings show that the personality characteristics associated with Assertive Antisocial Behavior, one of the factors of the PRI-100, are valuable predictors of drinking behavior. The two other personality factors of the PRI-100, Lack of Order and Lively Social Presence, were found to be unrelated to drinking behavior and therefore inadequate predictors.


A multimodal treatment approach for incarcerated alcoholics. A multimodal milieu treatment approach for alcoholism was assessed in a prison setting by use of the MMPI. The participants had a mean age of 41, four prior incarcerations, and documented difficulty with alcohol abuse prior to their incarceration. Analysis of an A-B treatment design showed significant changes on the F, PT, ES (p less than .05), L, K, D, SI, and A (p less than .01) scales of the MMPI after 6 months of program participation. With the exception of the PD scale, all changes were seen as positive. It should be noted that the PD scale may not be the most appropriate indicator of positive behavioral changes in a prison setting.


The sex role identity of male drug abusers. Administered a revised version of the Bem Sex-Role Inventory (BSRI) to clients at a drug-addict rehabilitation agency in New York City (N = 203). Three samples of undergraduates were the comparison groups. In addition, information that related to demographic and family characteristics, attitudes toward parents and opposite sex, and MMPI scores were collected on the clients. Results indicate the revised BSRI has high internal consistency reliability for the addict sample. There is a modest correlation between sex-role identity score and reported reasons for drug use, as well as for the MF and SI scales on the MMPI. There were no significant correlations with demographic, family, attitude toward parents or opposite sex variables. The hypothesized difference in sex-role identity between drug-addicts and other males was confirmed for one comparative sample, but not for the two other samples.


EMG biofeedback applicability for differing personality types. Divided thirty-two male alcoholics into two groups on the basis of their MMPI profile. Group 1 consisted of Ss determined to be tense and anxious, while Group 2 included a more heterogeneous sample of personality types. Eight Ss from each group received 14 days of progressive relaxation training and EMG biofeedback; the remainder received control sessions of taped music and EMG monitoring. Group 1 experimental S achieved greater levels of relaxation than either their matched controls or Group 2 Ss. POMS scores revealed a significant difference over time for all Ss in the direction of improved mood states. No significant between-groups difference was found. Generally, these results suggest the following: (1) patients may be selected credibly for relaxation-biofeedback treatment by use of the MMPI; (2) patients who exhibit significant anxiety and tension may achieve lower levels of tension during training than patients with lower levels of pretreatment anxiety.


Demographic and clinical characteristics as predictors of readmission: a one-year follow-up. Follows up an earlier investigation in which demographic and clinical characteristics of psychiatric patients were used to predict readmission within 3 months of discharge. In the initial study, stepwise multiple regression analysis identified six variables as the optimal set of predictors for readmission within 3 months of discharge: type of discharge, number of prior psychiatric hospitalizations, race, suicide attempt within 1 month of admission, subjective report of depression upon admission, and occupational level (R = .452). In the present study the same sample was followed up at 1 year after discharge, and demographic and clinical variables were used to predict readmission within 1 year of discharge. Stepwise multiple regression analysis identified three variables as the optimal set of predictors for readmission within 1 year of discharge: past history of suicidal behavior, subjective report of depression upon admission, and number of prior psychiatric hospitalizations. Changes in predictors as a function of length of follow-up period are considered, and implications of the findings for identifying high-risk readmission candidates are discussed.


Effects of ambiguous and unambiguous stimulus word differences on popular responses of schizophrenics. Tested that aspect of response interference theory that predicts that schizophrenics give fewer dominant and more competing responses for ambiguous, but not unambiguous, conditions. It was hypothesized that schizophrenics would evidence in a word association task greater gains, after treatment, in response popularity for ambiguous, but not for unambiguous, stimulus words. The prediction was assessed by administering a specially-constructed wordlist balanced for idiodynamic semantic sets (Moran, 1966). Results, from a pre- and posttest control group design, met predictions for 24 matched pairs of schizophrenics and neurotics: after 5 weeks of treatment, schizophrenics gained significantly in popular responses for ambiguous but not for unambiguous stimulus words, whereas neurotics did not gain significantly for either condition. Positive correlation for schizophrenics between ambiguous word response popularity gains in home and community adjustment as rated by a significant other coincided with expectations from response interference theory (Broen, 1968).


Differentiating schizophrenics through parental conflict. Compared 154 parents of Schizophrenic Maladjusted, and Community young people (S, M, C) through the Conflict in Marriage Scale (CIMS), an agree-disagree card sort. Both men and women could be differentiated accurately according to the diagnostic group of their offspring (discriminant function analysis). On CIMS items that showed at least a 20% difference between any two diagnostic groups in proportion of affirmative response, S fathers were intermediate between M and C fathers significantly more often than in a high or low (extreme) position.


Suicidal, aggressive, and normal children's perception of personal and impersonal death. Tested the assumption that young children's suicidal behavior is connected to their concept of death. An additional objective was to explore whether distortions in the concept of death stem from limitations in cognitive functioning or from a defensive process. The sample consisted of 21 Ss in three equal groups of suicidal, aggressive, and normal children, ages 10-12. The variables of socioeconomic status, cultural background, and intelligence were controlled. The children were asked to respond to questions about impersonal death (the death of others) and personal death (one's own death). The results indicated that the three groups differed mainly in regard to the personal death concept. Suicidal children attributed the cause of death to suicide and referred to life after death and to resurrection more often than the other groups. Both normal and aggressive children emphasized the finality and irreversibility of death. However, normal children attributed the cause of death to natural processes, while aggressive children referred to brutality as a main cause of death. It is concluded that the suicidal children's view of death could facilitate suicidal behavior and that it should be a subject for concern in the treatment of such children.


Insomnia: anxiety, sleep-incompatible behaviors and depression. Evaluated the relevance of the physiological-arousal model, the stimulus-control paradigm, and depression to insomnia both as a unitary construct and to its components. The Manifest Anxiety Scale, the Sleep Behavior Self Rating Scale and the Zung Depression Scale were administered to 81 clinical Ss. Three separate discriminant function analyses were performed with self-reported "sleeping difficulty," "latency of falling asleep," and "total hours of sleep" as criterion variables. The above three scales and the following four sleep patterns were used as indices: number of nocturnal wakings, latency to fall asleep once awake, number of early wakings, and frequency of feelings of fatigue upon wakings. The findings indicated that the physiological-arousal model was relevant both to insomnia overall and to its component of sleep-onset insomnia. The stimulus-control paradigm was found to be relevant only to sleep-onset insomnia. Depression was not a sensitive discriminator, possibly due to the heterogeneity of the patient population studied. It is emphasized that different mechanisms might be operating with the heterogeneous symptom "insomnia," and the replication of findings with criteria that include significant others and electroencephalographic measures is suggested.


Essential hypertension and self-disclosure. A matched sample of 16 hypertensive and 16 non-hypertensive Air Force male Ss were administered the Journal Self-Disclosure questionnaire and participated in an interview that discussed high and low intimate topics. Questionnaire data, content analysis scores of interview topics, and situational stress measures supported the hypothesis that hypertensives conceal their personal thoughts and feelings from others and deny the emotion-arousing stimuli of a self-disclosure situation. Investigation of the underlying psychodynamics of hypertension in a self-disclosing situation as a potentially fruitful line of research was discussed.


Verbal reinforcement combinations in schizophrenics. Investigated the effects of verbal reinforcement paradigms on hospitalized schizophrenics and staff. Positive reinforcement that involved good was found to be relatively ineffective for all groups; furthermore, associating good with the termination of a white noise did not increase its effectiveness for schizophrenics. Verbal punishment was more effective than verbal positive reinforcement for staff, but for schizophrenics only when explicit problem-solving instructions were given. The results suggest that the reduction of deficit is not more likely via verbal punishment; if anything, deficit is increased because of increased staff performance under verbal punishment.


Personality correlates of the sex role types. Tested three hypotheses with regard to the differences among four sex-role types. Ss were 423 girls and 225 boys in five private high schools in grades 9 to 12. Each volunteer S completed the Berm Sex Role Inventory, the Interpersonal Style Inventory, and Loevinger's Sentence Completion Test. Ss were categorized or typed as Masculine, Feminine, Androgynous and Undifferentiated on the basis of their masculine and feminine BSRI scores. A discriminant function was applied to compare the groups with respect to the ISI scores. The first dimension of difference for both sexes was defined by the Masculine typed group and the second dimension by the Feminine typed group. The Androgynous typed group scored high on both axes, while the Undifferentiated scored low on both axes. The Masculine typed group was most directive, achieving, and independent. The Feminine group was highest on nurturance, tolerance and sensitivity. The Androgynous members were balanced with respect to the above characteristics. Comparison of the groups, separated by sex, as to ego development score, indicated that the male undifferentiated were significantly lower.


The prediction of outcome from anhedonia and process-reactive scales. Earlier researchers have suggested that the ability of process-reactive measures to predict future adjustment may result from their relationships to the anhedonia dimension. In the present study the abilities of process-reactive and anhedonia measures, independent of one another, to predict rehospitalization data were compared. After anhedonia scores had been partialed out, schizophrenics' process-reactive scores were correlated modestly with length of the patients' next hospitalization and reclassification as nonschizophrenic. No such significant correlations appeared between anhedonia and adjustment measures after process-reactive scores had been partialed out. Among nonschizophrenics, a sizeable correlation between anhedonia and the probability of later diagnosis of schizophrenia appeared, which suggests that anhedonia may be a useful prodromal marker for schizophrenia.


Utilization of the Goldberg MMPI profile classification rules for the assessment of psychopathology in different clinical populations. MMPI profiles of 545 psychiatric inpatients and 560 incarcerated offenders were separated sequentially into normal, sociopathic, neurotic and psychotic groups by means of Goldberg's profile classification rules. Patient-prisoner differences in both rates of classification and profile patterns of groups within diagnostic categories were assessed quantitatively, and profiles were interpreted by use of standard MMPI codebooks. For the hospitalized Ss comparisons also were made between clinical diagnoses and Goldberg-MMPI classifications. The resulting differences in classification rates, similarities of profiles within diagnostic categories, correspondence between obtained and codebook-expected profiles, and agreement between clinical and Goldberg-MMPI classifications were not such that this approach could be used with confidence as a basis for establishing diagnostic group membership. Although Goldberg's system appears to represent certain improvements over previous criterion-related methods of profile classification, it was concluded that its value nonetheless is limited by the assumption of an invariant relationship between test patterns and nontest variables.


Performance satisfaction of depressives under high and low success conditions. Evaluated two competing predictions about the effects of high and low success experiences on depressives' satisfaction with performance. No support was found for the prediction derived from Beck's cognitive theory, which posits distorted, negative cognitions about the self as the central dynamic of depression. However, results did tend to support the learned helplessness model's contention that depression is characterized by the perception that reinforcements occur independent of the individual's responses.


Correcting for cultural factors in evaluating intellectual deficit on the WAIS. Obtained estimates of the effects of ethnic group, sex, education, and clinical diagnosis on WAIS IQ scores of 776 psychiatric patients by least squares regression methods. Estimates of expected IQ for various demographically defined segments of the general population were obtained by setting the expected IQ for white high school graduates at 101 and then adding or subtracting the specific effects associated with different ethnic group, sex, and education. A formula for norming WAIS Full Scale IQ scores to X = 100 and SD = 15 within various demographically defined segments of the population is proposed.


The Trail Making Test and Bender Background Interference Procedure as screening devices. The Trail Making Test and Bender Background Interference Procedure were evaluated with 598 Ss against both external neurologic criteria and against psychological opinion derived from a more complete evaluation. For Trails, highly significant differences in mean scores were seen when preselected neurologic patients and patients without neurologic stigmata were compared. Similarly, the distribution of classification of these patients by Bender is significantly different from chance. Application of these measures in a screening paradigm, however, yielded large numbers of false negatives against both neurological and psychological criteria. It was not possible to establish an optimal cutting score to justify application of these measures as screening devices, either alone or in concert.


Abbreviating the Halstead-Reitan neuropsychological test battery. Describes a brief and relatively data-rich abbreviated form of the Reitan. By employing the Trail Making Test, the Aphasia Screening Test, and Block Design and Digit Symbol from the WAIS, one can predict the presence and severity of organic impairment and comment on lateralization and localization. Findings are cross-validated.


Bender-Gestalt reproduction times for retarded adults. Examined the length of time required by retarded adults to complete the Bender-Gestalt test with a sample of 241 test administrations. In order to provide for normative comparisons among retarded adults, descriptive data are presented on the Bender reproduction times of adults  in three AAMD ranges of retardation based on WAIS IQs and two ranges based on Stanford-Binet IQs. Negative correlations were found between the length of Bender times and the degree of retardation. The duration of Bender times was correlated positively with the number of errors in reproduction as measured by the Koppitz developmental scoring system.


A further analysis of the Block Rotation Test. While Satz's Block Rotation Test has shown promise in its ability to detect brain dysfunction, its factorial and psychometric properties have not been investigated extensively. This study investigated the factor structure of the test across two different S groups. In addition, internal reliability and discrimination between patient groups with and without neurological impairment was assessed. Only one factor, which dealt with Time Errors and Age of the patient, was replicated across two separate factor analyses that used different patient populations. Analyses of internal consistency, using a number of different breakdowns, yielded corrected Spearman-Brown coefficients that ranged from .77 to .94. A fourth analysis showed that a simple summation of errors on the two parts of the test could discriminate reliably between different diagnostic patient groups.


The development of a WAIS short form for clinical populations. Assessed the validity of a brief form of the WAIS in the evaluation of several clinical populations. The short form was composed of three subtests: Similarities, Picture Arrangement, and Block Design. The sample consisted of 27 schizophrenics, paranoid type; 30 schizophrenics, schizoid-affective type, 29 schizophrenics, chronic undifferentiated type; and 28 organics (brain syndrome patients). Correlations were computed between the weighted IQ scores of each population and the Full Scale IQ. Correlations of .94 for chronic undifferentiated schizophrenics and .81 for organics were particularly noteworthy. Moreover, this triad of subtests underestimated the IQ score for organics by 7.11 points, which suggests that the constant used with this population should be corrected appropriately.


A comparison of the WISC and WISC-R on black child psychiatric outpatients. Administered the WISC and WISC-R in a counterbalanced design to 20 black child psychiatric outpatients. The resulting test scores revealed the two to be essentially different with lower Verbal, Performance and Full Scale IQs Subtests WISC-R scores were also lower than those on the WISC. Significant practice effects occurred when the WISC was preceded by the WISC-R, but not when the order of test presentation was reversed. The boys' combined WISC and WISC-R scores were higher than the girls' on the Information, Arithmetic, Similarities, Vocabulary, Picture Completion, Block Design, Object Assembly, and Coding Subtests and Verbal and Full Scale IQs. The girls scored higher on Coding. The tests were found to be highly correlated. The major implication is that greater numbers of black children may be given developmental disability labels.


A comparison of an ITPA estimated psycholinguistic quotient and WISC-R IQS for developmentally disabled children. Compared an estimated Psycholinguistic Quotient, based on Cronkhite and Penner's (1975) revised scoring procedure for the ITPA Psycholinguistic Age, to the WISC-R Verbal, Performance, and Full Scale IQs of developmentally disabled children. The Quotient entered into strong relationships with the WISC-R Verbal and Full Scale IQs. The diagnostic significance of these correlations was discussed. The data indicated that the estimated Psycholinguistic Quotient was a valid measure for screening intellectual status in this population.


MMPL-differences between fee-paying and non-fee-paying psychotherapy clients. Compared the MMPI profiles of 23 randomly selected fee-paying clients (FP group) of an out-patient psychiatry clinic to those of 23 clients who left unpaid bills (NFP group). All Ss had been terminated at least 2 months. No differences between groups were found on age, education, income, fee level, number of therapy sessions, sex, or marital status. The NFP group scored significantly higher on the F, Paranoia, and Schizophrenia scales. Additionally, the NFP group endorsed significantly more critical items and generated a greater number of mean scale scores over 70. These results suggest a relationship between degree of psychopathology and non-fee-payment.


Anxiety and actualization: further research. In a recent article, Wilkins, Hjelle, and Thompson (1977) argued that unlike the Dabrowski-deGrace hypothesis, self-actualized Ss should have lower levels of manifest anxiety than low self-actualized Ss. Wilkins et al. demonstrated that this was indeed a preferable hypothesis. The present experiment concerns the relationship of actualization to state and trait anxiety. Ss were administered the Personal Orientation Inventory, the Taylor Manifest Anxiety Scale, and Catteil's measure of state-trait anxiety. The results support the Wilkins et al. reformulation by demonstrating that: (1) high self-actualized Ss had lower trait anxiety scores; and (2) high self-actualized Ss were susceptible to state anxiety within the limits established by their trait anxiety level.


Sex-role stereotyping in mental health standards in Israel. Investigated sex-role stereotyping in mental health standards in Israel in a sample of 60 nonclients, 60 clients and 60 psychotherapists. Recent studies of sex-role stereotypes in America have shown that males still maintain traditional stereotypes and perceive the healthy adult female as more stereotypically feminine than either the healthy male or adult. Women, however, have changed their traditional perceptions toward female mental health and now rate the healthy adult female as similar to the healthy adult male and the healthy adult. In contrast to the recent American findings, female therapists in the Israeli study viewed the healthy female as significantly more stereotypically feminine than the healthy male. Male therapists were more equalitarian in their ratings and surprisingly rated the healthy male as significantly more feminine than did female therapists. These findings are discussed in terms of cross-cultural differences. Congruency of client-therapist sex-linked mental health standards also are examined and the implications for the therapeutic process discussed.


Analyzing affective responses to past events: women's reactions to a childbearing year. Applied content analysis scales on the work of Gottschalk and Gleser (1969) to 200 women's recollections of four stages of a recently completed child-bearing year. On 11 of 13 affective indices, significant differences were found. Pregnancy was characterized by diffuse and cognitive anxiety and hostility directed inward, and labor by mutilation anxiety. During both pregnancy and labor, general anxiety, death anxiety, ambivalent hostility, and affective costs were comparatively high. Mothers revealed least affective arousal during hospitalization. Considerable guilt and shame anxiety were experienced in the months after the birth.


A multidimensional scaling analysis of empathy. Randomly arranged 10 high stimuli into 45 pairs, and a group of psychologists made judgments as to the similarity of the pairs in terms of Truax and Carkhuff's (1967) definition of empathy along a 7-point scale. A similar procedure was followed for the 10 stimuli in the "low" group and the results analyzed by multidimensional scaling. Three similar dimensions accounted for a majority of the variance in Ss judgments in both groups. Dimension One was interpreted in terms of the appropriateness vs. inappropriateness of the therapist's voice tone and comments. Dimension Two reflected high vs. low emotional intensity. Dimension Three was interpreted as patient vs. therapist dominance. An attempt was made to relate these dimensions to those proposed by Truax and Carkhuff (1967) to be involved in the empathetic process.