Purified liver microsomal NADPH-cytochrome P-450 reductase. Spectral characterization of oxidation-reduction states. NADPH-cytochrome P-450 reductase was isolated from liver microsomes of phenobarbital-induced rats. The enzyme exhibits an apparent minimal molecular weight of 76,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and contains 1 molecule each of FMN and FAD. Trypsin treatment of the reductase yields an enzyme with an apparent minimal molecular weight of 69,000 which retains the ability to reduce cytochrome c but has no activity toward cytochrome P-450. Various spectrophotometric titrations were performed to examine the electron-accepting properties of the purified NADPH-cytochrome P-450 reductase and, in particular, to determine the oxidation state of the stable semiquinone form produced by air oxidation of NADPH-reduced enzyme. Titration of the air-stable semiquinone form of the reductase with ferricyanide indicated that 1 mol/2 mol of flavin was required for complete oxidation. Furthermore, a spectrum corresponding to that of the air-stable semiquinone form was produced by the addition of approximately 0.5 mol of reductant/2 mol of flavin when the oxidized enzyme was titrate with NADPH or dithionite under anaerobic conditions. The spectral changes which accompanied the overall reduction of oxidized enzyme to the reduced form with dithionite produced four sets of isosbestic points, and the spectrophotometric titration curve consisted of four approximately equal phases. In the titration with NADPH, no significant further reduction was observed after the addition of approximately 1.5 mol/2 mol of flavin. However, the enzyme was fully reduced by NADPH when an NAPH-generating system was used to prevent the accumulation of NADP. Our results establish that the air-stable semiquinone form is a 1-electron-reduced form, rather than a half-reduced (2-electron-reduced) form as maintained by others and are in agreement with earlier studies (Iyanagi, T., Makino, N., and Mason, H.S. (1974) Biochemistry 13, 1701-1710) with the purified trypsin-solubilized reductase. Accordingly, the air-stable species represents a form of the NADPH-cytochrome P-450 reductase in which one of the two flavins exists in the semiquinone state and the other in the oxidized state.


Human cationic trypsinogen. Purification, characterization, and characteristics of autoactivation. Human pancreatic cationic trypsinogen has been purified to homogenity from an acetone powder of pancreatic tissue. After an initial ion exchange chromatography step on sulfopropyl (SP)-Sephadex at pH 2.6, cationic trypsinogen was separated from the majority of trypsin activity by passage through an affinity column of lima bean trypsin inhibitor-agarose at high ionic strength. The zymogen was then further purified by affinity chromatography on the same material at low ionic strength. Highly purified trypsinogen was resolved from containing chymotrypsinogen by ion exchange chromatography on SP-Sephadex at pH 6.0. The purified zymogen was shown to be homogeneous by polyacrylamide gel electrophoresis at pH 2.1 and at pH 4.3 as well as by discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The autoactivation of human trypsinogen was investigated at pH 5.6 and at pH 8.0. The rate of autoactivation of the human zymogen is rapid at pH 5.6 and is maximal in approximately 1 mM Ca2+. These results are in marked contrast to those previously reported for autoactivation of bovine trypsinogen, which is extremely slow at pH 5.6 and which shows a dependence on at least 50 mM Ca2+ for maximum rate of activation (MacDonald, M. R., AND Kunitz, M. (1941) J. Gen. Physiol. 25, 53-73).


Studies on nicotinic acetylcholine receptors in mammalian brain. Interaction of solubilized protein with cholinergic ligands. Binding of alpha-bungarotoxin, labeled with 125I, has been studied in detergent extracts and affinity purified acetylcholine receptor from rat cerebral cortex. Binding to detergent extracts is saturable and appears to be due to one class of binding sites present at a level of 0.27 pmol/mg of protein. The association constant is 2 X 10(7) liters mol-1 . Competition with cholinergic ligands indicates that toxin binding to both detergent solubilized and affinity purified receptor retains its nicotinic nature. Values for the ligand concentrations required to produce 50% inhibition of extent and rate of toxin binding are presented.


Induction of urea cycle enzymes of rat liver by glucagon. All five urea cycle enzymes of rat liver increased in activity 48 h after subcutaneous administration of crystalline zinc glucagon to male rats and remained elevated after 7 days of continuous glucagon infusion. The maximum ratios of enzyme activities over those of controls were 2.0 for carbamyl phosphate synthetase, 1.3 for ornithine transcarbamylase, 2.7 for argininosuccinate synthetase, 3.2 for argininosuccinase, and 2.2 for arginase. Actinomycin D or puromycin prevented these responses to glucagon. The increase in arginase activity after zinc glucagon treatment was matched by an increase in immunoprecipitable enzyme. All five enzymes were induced by physiological plasma levels of glucagon. Tube feeding of casein hydrolysate for 2 days increased all five enzyme activities 1.5- to 2.2-fold and resulted in plasma glucagon levels similar to those required for induction by exogenous glucagon. Thus, glucagon is an inducer of the entire urea cycle in rat liver and plays a role in the induction of the cycle by protein feeding.


The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. The complete amino acid sequence of human insulin-like growth factor I (IGF-I), a polypeptide isolated from serum, has been determined. IGF-I is a single chain polypeptide of 70 amino acid residues cross-linked by three disulfide bridges. The calculated molecular weight is 7649. IGF-I displays obvious homology to proinsulin: positions 1 to 29 are homologous to insulin B chain and positions 42 to 62 to insulin A chain. A shortened "connecting" peptide with 12 residues (positions 30 to 41) compared to 30 to 35 in proinsulins shows no homology to proinsulin C peptide. An octapeptide sequence at the COOH-terminal end is also a feature not found in proinsulins. The number of differences in amino acid positions between IGF-I and insulins suggests that duplication of the gene of the common ancestor of proinsulin and IGF occurred before the time of appearance of the vertebrates. Of the 19 residues known to be invariant in all insulins so far sequenced, only glutamine A5 and asparagine A21 are replaced in IGF-I by glutamic acid and alanine, respectively. The fact that all half-cystine and glycine residues and most nonpolar core residues of the insulin monomer are conserved is compatible with a three-dimensional structure of IGF-I similar to that of insulin.


Regulation of cholesterol synthesis in cultured canine intestinal mucosa. The regulation of intestinal cholesterol synthesis was studied utilizing canine ileal mucosa maintained in organ culture for 6 h. Viability was monitored by light and electron microscopy, measurement of cellular enzymes, and the ability to actively transport a glucose analogue. The activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.4.3.4), the rate-limiting enzyme of cholesterol synthesis, increased 4-fold during a 6-h culture. A parallel increase occurred in the rate of acetate incorporation into digitonin-precipitable sterols during this period. This increase could be prevented by the addition of cycloheximide to the culture. Pure cholesterol, 7-ketocholesterol, and 25-hydroxycholesterol, when present during the last 4 h of culture, also caused significant suppression of the rise in HMG-CoA reductase activity (final HMG-CoA reductase with the three sterols was 77 +/- 4%, 68 +/- 5%, and 58 +/- 3% of control postculture value). Bile salts at low, nontoxic concentrations also inhibited the increase of enzyme activity (2 mM taurocholate = 63 +/- 3% of control, 0.5 mM taurochenodeoxycholate = 76 +/- 6% of control). In contrast, dog lipoproteins separated by ultracentrifugation failed to significantly affect intestinal cholesterol synthesis in these short term organ cultures.


A novel type of covalently bound coenzyme in trimethylamine dehydrogenase. Bacterial trimethylamine dehydrogenase contains a covalently bound yellow coenzyme, the properties of which distinguish it from all known riboflavin, pyridoxine, and pteridine derivatives. A pure dodecapeptide containing the covalently linked coenzyme has been isolated from tryptic-chymotryptic digests. Treatment with aminopeptidase M converts it to a ninhydrin-positive aminoacyl coenzyme, which has also been isolated in chromatographically pure form. The coenzyme as isolated is virtually nonfluorescent but, being extremely photolabile, it is rapidly converted on illumination to products, the predominant one being highly fluorescent. Analysis for phosphate and the influence of phosphatase treatment on electrophoretic mobility show that the coenzyme is isolated as a monophosphate, while periodate titrations prove the presence of a pentityl side chain, to which the phosphate is attached. Oxidation of the aminoacyl coenzyme with performic acid, followed by acid hydrolysis, yields 2',5'-anhydroriboflavin and some free riboflavin, products also obtained on similar treatment of FMN. These observations and the very tight binding to apoflavodoxin show that the coenzyme is a flavin derivative. The absorption and NMR spectra, however, clearly set it apart from 8alpha-substituted flavins and suggest that the coenzyme is the first representative of a new class of covalently bound flavins.


A study of the corrosion of dental amalgam using the ring-disk electrode. The rotating ring-disk electrode technique has been applied to the study of anodic dissolution of dental amalgam in a simulated saline solution. The electroactive domains of the silver, tin, and mercury couples (the main constituents of the amalgam) were determined from current-potential curves obtained at a rotating gold-disk electrode in solutions containing salts of the respective metals. Subsequently, anodic currents were applied to a rotating amalgam-disk electrode and the soluble products produced were identified using a concentric gold ring electrode, i.e., using the rotating gold-ring, amalgam-disk electrode. Species generated at the amalgam disk are transferred to the gold ring by convective diffusion. Tin ions were found to be the only soluble species generated at the amalgam disk. No evidence for dissolution of other components was found. The selective dissolution of tin from the amalgam is also consistant with potential shifts observed in reptititve current-potential curves of an amalgam disk. This study provides a direct proof for the selective dissolution of tin during corrosion of dental amalgam in an in vitro environment.


Stress relaxation of dental amalgam alloys. Short-term stress relaxation of four dental amalgam alloys was studied. Test materials included two conventional lathe-cut restoratives, a spherical alloy, and a dispersed phase product. Specimens were 24-hr-old 4 X 8-mm cylinders. The specimens were compressed and held at constant strain on development of a stress (So) of 28 MN/m2. Subsequent stress relaxation (Dt) was recorded for 60 sec. Data were obtained at eight nominal temperatures between 0 and 55 degrees C. Over the experimental temperature range, fractional stress losses at 60 sec (Dt/So/60) for specimens made from lathe-cut alloys increased from 10% to 58%. The spherical material and the dispersed phase alloy showed fractional stress losses (Dt/So/60) ranging from 9% to 47% and 9% to 31%, respectively. It would appear that particle morphology and alloy composition affect stress-relaxation behavior of dental amalgam. Stress decay patterns enhance significantly the mechanical characterization of amalgam alloys.


Carbon fiber-reinforced carbon as a potential implant material. A carbon fiber-reinforced carbon is being evaluated as a promising implant material. In a unidirectional composite, high strengths (1200 MN/m2 longitudinal flexural strength) and high modulus (140 GN/m2 flexural modulus) may be obtained with an interlaminar shear strength of 18 MN/m2. Alternatively, layers of fibers may be laid in two directions to give more isotopic properties. The compatibility of the material with bone has been studied by implanting specimens in holes drilled in rat femora. For a period of up to 8 weeks, a thin layer of fibrous tissue bridged the gap between bone and implant; but this tissue mineralizes and by 10 weeks, bone can be observed adjacent to the implant, giving firm fixation. Potential applications include endosseous dental implants where a greater strength in the neck than that provided by unreinforced carbon would be advantageous.


Biocompatibility testing of polymers: in vitro studies with in vivo correlation. An in vitro method has been developed for screening of candidate biomaterials in an early phase of their development. The test is based on L-929 mouse fibroblast cultures and their response to powdered polymer samples. It applies microscopic observation for the detection of morphological changes, uses dye exclusion testing for cell viability determination, and utilizes estimation of population doublings as an end point. The test is shown to be reliable and reproducible and is compared to in vivo implantation studies in rats, previously reported.


Protein sorption on polymer surfaces measured by fluorescence labels. Fluorescence labeling can be used in studying protein sorption on various surfaces with a sensitivity of about 10(-8) g/cm2, commensurate with radioactive labeling. Fluorescamine proved to be the most suitable compound for studying protein sorption on hydrophilic gels, because, unlike fluoresceine isothiocyanate and dansylchloride, free fluorochrome does not interfere with measurements. Sorption properties of labeled serum albumin were tested on poly(2-hydroxyethyl methacrylate), on the copolymer of 2-hydroxyethyl methacrylate with methyl methacrylate, and on polyethylene. Labeling does not cause aggregation of the protein, but, as expected, it shifts and somewhat broadens its electrophoretic band while at the same time slightly raising its affinity toward hydrophobic surfaces.


The biocompatibility of materials for internal fixation of fractures. Surgically produced fractures of rabbit tibiae were internally stabilized with intramedullary rods of stainless steel (316LVM), titanium (6A1,4V), polyacetal (Delrin), and polyamide (Nylon 101). Periodic radiographs were taken until sacrifice at 16 weeks after fracture. Structural properties of the tibiae were determined in torsion with the rods in situ, and then the tissue was prepared for histology or microradiography. The results demonstrated that fracture remodeling was adversely affected by the metal rods. New bone was seen to have formed over the ends of the metal rods, and cortical bone resorption was observed in the fracture region, suggestive of transfer of mechanical stress to the rods, resulting in stress shielding of the diaphysis. Negligible osseous response to the polymeric rods was observed; fracture callus remodeling was extensive. The torsional test results demonstrated that fractures with polymeric rods were significantly stronger and tougher than those with metallic rods. With the exception of titanium, the strength of healed fractures was inversely related to the elastic moduli of the implant materials.


"Floating-socket" total shoulder replacement: anatomical, biomechanical, and surgical rationale. A prosthesis based on a new concept of gleno-humeral motion has been developed and clinically tested for the past 2 years. The "floating-socket" total shoulder replacement contains a nondislocatable, dual spherical bearing system consisting of a small sphere within a larger sphere with their centers offset to provide the physiologic "floating fulcrum" for mechanically advantageous motion. This geometric configuration allows a prosthetic range of motion in excess of anatomical limits to allow soft tissue structures to limit motion rather than mechanical impingement. The device is constructed from Co--Cr--Mo alloy and RCH-1000 polyethylene such that no metal--metal contact can occur. Experimental results in a 112-lb adult male chimpanzee and six clinical cases have revealed superior fixation strength of both glenoid and humeral components, as well as functional adaptation of the prosthesis without fracture of fixturing bone or prosthetic dislocation.


Rhythmic daily shedding of outer-segment membranes by visual cells in the goldfish. Goldfish were placed on a daily light cycle of 12 h light and 12 h darkness for 18 days or longer. The visual cells and pigment epithelium of the retina were then examined by microscopy at many intervals throughout the cycle. Goldfish rods and cones follow a rhythmic pattern in eliminating packets of photosensitive membranes from their outer segments. Rods shed membranes early in the light period. The detached membranes are ingested by pigment epithelial cells or by ameboid phagocytes, which degrade them during the remainder of the light period. Cones discard membranes from the ends of their outer segments early in the dark period. During the next several hours, this debris is digested by the pigment epithelium or by ameboid phagocytes. Thus, the disposal phase of the outer-segment renewal process is similar in rods and cones, but is displaced in time by about 12 h. There is evidence that this daily rhythm of membrane disposal in rods and cones is a general property of vertebrate visual cells.


Microtubular apparates of melanophores. Three-dimensional organization. Microtubular organization in the melanophores of the angelfish, Pterophyllum scalare, has been studied by serial thin sectioning. The course of microtubules has been followed in sets of transverse serial sections taken from the centrosphere and a segment of a cell process, respectively. Microtubules arise from a prominent zone in the cell center, the central apparatus, which is composed of numerous, small, electron-dense aggregates. the number of these loosely distributed densities is highest in the center of the centrosphere, but they may also be found at its periphery. Microtubules insert into, or becomes part of, the dense material, or at least start in its vicinity. Dense aggregates may be separated from centrioles by several micrometers rather than only being closely associated with these organelles. At some distance from the organizing zone, most of the microtubules gradually assume a cortical arrangement, i.e., take a course within about 100 nm of the limiting membrane. Serial sections were used to trace all microtubules within a 6mum-long segment of a cell process. 94 percent of the microtubules observed in this segment run its entire length; it is conceivable, therefore that a considerable number of microtubules extend between the initiating site in the centrosphere and the outermost cell region. A three-dimensional model of the 6mum-long segment reveals that, despite changes in the cell process outline, microtubules maintain a strictly cortical arrangement which gives the impression of a microtubule "palisade" lining the cortex of the cell process. The features of the microtubular apparatus of angelfish melanophores are discussed in relation to factors controlling microtubule initiation and distribution.


Rapid activation of the medullary bone osteoclast cell surface by parathyroid hormone. Quantitative transmission electron microscope methods were used to determine the response of functionally inactive avian medullary bone osteoclasts to parathyroid hormone (PTH). Egg-lying Japanese quail were used during a period of the egg cycle when medullary bone was not being resorbed for egg shell calcification and when medullary bone osteoclasts were functionally inactive. Ruffled borders adjacent to bone surfaces were rarely, if ever, found on these cells. 20 min after the administration of PTH, over 70% of the osteoclast profiles had ruffled borders adjacent to bone surfaces. These ruffled borders were bounded by filamentous-rich "clear zones" and resembled ruffled borders found on functionally active cells. There was also a marked increase in plasma calcium levels after PTH administration. This study demonstrates that PTH stimulates the de novo generation of ruffled borders on osteoclasts in vivo and suggests that osteoclasts may be involved in the acute regulation of calcium metabolism by exogenous PTH.


Lectin binding to neural crest cells. Changes of the cell surface during differentiation in vitro. To examine possible changes in cell surface carbohydrates, fluorescent lectins were applied at various times during differentiation of neural crest cells in vitro. The pattern and intensity of binding of several lectins changed as the crest cells developed into melanocytes and adrenergic cells. Considerable amounts of concanavalin A (Con A) and wheat germ agglutinin (WGA) bound to all unpigmented cells throughout the culture period. Melanocytes, however, bound much less of these lectins. Soy bean agglutinin (SBA), unlike Con A and WGA, only bound later in development to unpigmented cells at about the time when catecholamines were detected histochemically. Binding of SBA could be induced in younger cultures by pretreating the cells with neuraminidase. Melanocytes, however, did not bind detectable amounts of SBA even if treated with neuraminidase. The SBA-binding sites were often concentrated on cytoplasmic extensions and on contact points between neighboring cells, even when receptor mobility was restricted by prefixation of the cells or adsorption of lectin at 0 degrees C. All three lectins bound to cell processes resembling nerve fibers in particularly high amounts.


Cell adhesion and cell surface topography in aggregates of 3T3 and SV40-virus-transformed 3T3 cells. Visualization of interior cells by scanning electron microscopy. A technique for exposing the interior of aggregates of cultured cells has been developed and is described in this report. Using this technique, we have examined for the first time, by scanning electron microscopy, cell morphology and cell contact ultrastructure in the interior of aggregates of BALB/c 3T3 and SV40-transformed 3T3 cells. The 3T3 cells make initial intercellular contact by means of microvillar processes. Over a period of 3-8 h, some of these microvillar contacts are replaced by broader projections. In contrast, the SV40-transformed cells make initial intercellular contact by means of blebs or blunt projections which are also broadened and extended over a period of 3-8 h. For both 3T3 and SV40-3T3 cells, the surfaces of the cells which form the outer layer of the aggregate resemble the surfaces of single cells fixed in suspension, regardless of how long the aggregates have been cultured. Thse cells are covered with many cellular processes and are roughly hemispherical in profile. The surfaces of the internal cells of the aggregates, however, lose many of their cellular processes, develop smooth patches, and many become irregular in shape. This smooth morphology was also observed on the interior surfaces of the peripheral cell layer. From these observations we conclude that: (a) the stabilization of adhesive contacts is a slow process which takes at least 3-8 h; (b) the outer surfaces of peripheral cells differ significantly from the surfaces of interior cells; and (c) clear differences in surface topography exist between nonmalignant 3T3 cells and their malignant SV40 transformants.


Chlamydomonas flagellar mutants lacking radial spokes and central tubules. Structure, composition, and function of specific axonemal components. The fine structure, protein composition, and roles in flagellar movement of specific axonemal components were studied in wild-type Chlamydomonas and paralyzed mutants pf-14, pf-15A, and pf-19. Electron microscope examination of the isolated axoneme of pf-14 showed that it lacks the radial spokes but is otherwise structurally normal. Comparison of isolated axonemes of wild type and pf-14 by sodium dodecyl sulfate-acrylamide gel electrophoresis indicated that the mutant is missing a protein of 118,000 mol wt; this protein is apparently a major component of the spokes. Pf-15A and pf-19 lack the central tubules and sheath; axonemes of these mutants are missing three high molecular weight proteins which are probably components of the central tubule-central sheath complex. Under conditions where wild-type axonemes reactivated, axonemes of the three mutants remained intact but did not form bends. However, mutant and wild-type axonemes underwent identical adenosine triphosphate-induced disintegration after treatment with trypsin; the dynein arms of the mutants are therefore capable of generating interdoublet shearing forces. These findings indicated that both the radial spokes and the central tubule-central sheath complex are essential for conversion of interdoublet sliding into axonemal bending. Moreover, because axonemes of pf-14 remained intact under reactivating conditions, the nexin links alone are sufficient to limit the amount of interdoublet sliding that occurs. The axial periodicities of the central sheath, dynein arms, radial spokes, and nexin links of Chlamydomonas were determined by electron microscopy using the lattice-spacing of crystalline catalase as an internal standard. Some new ultrastructural details of the components are described.


Freeze-fracture observations of the lactating rat mammary gland. Membrane events during milk fat secretion. Membrane events during milk fat secretion were analyzed by freeze-fracture of the rat mammary gland. Two modes of milk fat secretion were observed: extrusion of fat droplets surrounded by a portion of the apical plasma membrane of the alveolar epithelial cells and, less frequently, release into the alveolar lumen of fat droplets contained in intracytoplasmic vacuoles. The extrusion process consists of two asynchronous events: clearing of membrane particles (probably including integral membrane proteins) and bulging of the apical plasma membrane. Most fat droplets are extruded with a bilayer membrane envelope (milk fat globule membrane) partially devoid of particles. The segregation of membrane particles may represent the onset of a process of structural degradation of the milk fat globule membrane.


[The place of intrahepatic peripheral anastomoses in neoplastic obstruction of the upper bile duct junction. Report of 20 cases (author's transl)]. In 32 patients with carcinoma involving the bifurcation of the hepatic ducts 17 intrahepatic cholangiojejunostomies and 3 intrahepatic gastrotomies were performed. The post-operative mortality rate is high (35%), the median survival time is 9 months. These results suggest that resection should by attempted when possible or dilatation used rather than by-pass of the tumor.


[Torsion of Riedel's lobe. Two cases (author's transl)]. The authors report two cases of torsion of Riedel's lobe. The first case resembled acute cholecystitis. Resection was followed by a cure. The second case presented in the form of a complicated abdomino-pelvic tumor. Its removal did not prevent a fatal issue due to fibrinolysis probably related to advanced ischemic infarction of Riedel's lobe of the liver. It seems that these complications are exceptional.


[Surgery of obturator hernia by closure of the obturator canal with the round ligament]. Almost 2/3rds of obturator hernias occur after 70 years. Favoured by changes in pelvic and spinal position, this hernia is uncommon in women and exceptional in men. Revealed by strangulation, it is in one third to one quarter of cases, unrecognised before operation, often due to failure to recognise the cause of crural neuralgia in a patient with acute intestinal obstruction. Even when the diagnosis is made, laparotomy is the best approach. It makes intestinal resection easier, this is necessary in 50% of cases, and above all, it is easier to cure the hernia for which the authors propose the use of the round ligament folded on itself and fixed to the borders of the hernial orifice. Delay in treatment explains the high mortality in this rare hernia.


[The gastro-intestinal effects of portal hypertension. Role of highly selective vagotomy. Experimental study in the rat (author's transl)]. Portal hypertension was obtained by portal ligature in the rat by an original procedure. Hemodynamic and pathological studies were performed at the end of the 4th postoperative month. Portal hypertension causes macroscopic and histological lesions in particular in the stomach and small intestine. The lesions observed were superficial desquamation, interstitial oedema, submucosal fibrosis, ulcers, and superficial or total necrosis of the intestine. Splenic fibrosis with congestion of the medullary sinuses is usual. A collateral circulation towards the liver and caval system develops rapidly. We never observed oesophageal varices. The main cause of splanchnic modifications was vascular stasis to which should perhaps be added humoral changes. Highly selective vagotomy does not protect the splanchnic area against lesions induced by portal ligature.


[103 revascularisations of the internal carotid artery by a venous graft (author's transl)]. 103 venous shunts were performed between the common carotid and the internal carotid arteries. Apart from the usual indications analogous to those of arterial disease in other sites (aneurysms, dissecting aneurysms, trauma), insufficient blood supply to the brain justified 92 grafts out of 496 reconstructive operations carried out between 1960 to 1976: atheromatous stenosis with subjacent loop, diffuse stenosing lesions of the common carotid or rising high up on the internal carotid, acute thrombosis and reoperations are the main indications. There was only one complication of the method, a venous graft of small calibre required replacement by a dacron prosthesis.


Sensitive gas chromatographic methods for the determination of vinyl epoxide synthetase activity using trichloroethylene as a model substrate. Two specific and very sensitive methods for the determination of vinyl epoxide synthetase activity in liver microsomes are described. Trichloroethylene, which is used as a substrate, is converted into trichloroethylene oxide by a hepatic epoxide synthetase. Chloral hydrate, the final rearrangement product of trichloroethylene oxide, is determined by electron-capture gas chromatography, either after derivatization with pentafluorophenylhydrazine or after its conversion into chloroform under alkaline conditions. The kinetic parameters of the epoxidation reaction were determined on rat hepatic microsomal suspensions.


Quantitative high-performance liquid chromatography of nucleosides in biological materials. A rigorous, comprehensive, and reliable reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the analysis of ribonucleosides in urine (psi, m1A, m1I, m2G, A, m2(2)G). An initial isolation of ribonucleosides with an affinity gel containing an immobilized phenylboronic acid was used to improve selectivity and sensitivity. Response for all nucleosides was linear from 0.1 to 50 nmoles injected and good quantitation was obtained for 25 microliter or less of sample placed on the HPLC column. Excellent precision of analysis for urinary nucleosides was achieved on matrix dependent and independent samples, and the high resolution of the reversed-phase column allowed the complete separation of 9 nucleosides from other unidentified UV absorbing components at the 1-ng level. Supporting experimental data are presented on precision, recovery, chromatographic methods, minimum detection limit, retention time, relative molar response, sample clean-up, stability of nucleosides, boronate gel capacity, and application to analysis of urine from patients with leukemia and breast cancer. This method is now being used routinely for the determination of the concentration and ratios of nucleosides in urine from patients with different types of cancer and in chemotherapy response studies.


Laboratory and clinical investigation of recovery of Salmonella typhi from blood. An experimental study was undertaken of isolation of Salmonella typhi from artificially infected whole blood and blood clot prepared either with small numbers of freshly isolated strains or with the S. typhi Ty2 strain. Results showed that 8 ml of whole blood required a minimum of 50 ml of bile salt broth to dilute the bactericidal effect of the serum. However, the isolation rate for recovery in 210 cases of enteric fever was only 64% when 50 ml of medium was used, as compared to 92% recovery from blood clot from the same group incubated in streptokinase bile salt broth. This probably reflects a very low grade bacteremia in many of the patients. Further investigation showed that, ideally, between 150 and 200 ml of medium is required for satisfactory whole-blood culture. Both the experimental study of artificially infected clots and recovery rates from patients indicate that rapid clot dissolution with streptokinase is preferable to whole-blood culture; this experience has been amply confirmed by almost 5,000 cases over a 20-year period. A 15-ml volume of bile salt broth with 100 U of streptokinase is adequate for the clot from 8 ml of blood, and savings on media and incubator space have considerable cost benefits in developing countries.


Bromothymol blue broth: improved medium for detection of Ureaplasma urealyticum (T-strain mycoplasma). Bromothymol blue (B) broth for the cultivation, detection, and identification of Ureaplasma urealyticum is described. In this medium, strains Cook and 960 had shorter generation times (60 min or less) and reached higher populations (over 10(8)) than have yet been reported for this species. Furthermore, the indicator changes color before the end of logarithmic growth, and the cultures retain viability for at least 1 day thereafter, greatly simplifying the handling of the organism. When the populations in cultures of these two strains and seven new isolates were determined, growth was detected earlier and proceeded to higher final titers in B broth than in urease test color medium (U-9 broth). The inclusion of antibiotics in B broth for use in clinical laboratories (B/NL broth) made the medium selective, specific, and more sensitive for the isolation of U. urealyticum. Comparison of B/NL broth with genital mycoplasma (GM) agar and U-9 broth for the primary isolation of U. urealyticum was made with 183 urethral swabs. All 70 isolates were detected on B/NL broth, but only 66 and 63 isolates were detected on GM agar and in U-9 broth, respectively. Moreover, the cultures in B/NL broth were pure and at titers that generally showed good correlation with colony counts on GM agar.


Rapid plate agglutination procedure for serotyping Pasteurella haemolytica. A specific, rapid plate agglutination procedure for serotyping Pasteurella haemolytica was performed. The procedure did not require special antigen preparation and yielded essentially the same results as the indirect hemagglutination procedure.


Clinical and immunological study of percutaneous revaccination in children who originally received smallpox vaccine subcutaneously. In a large multicenter smallpox vaccination study carried out from 1970 to 1973, it was found that 39% of children who were initially immunized by the subcutaneous route and then challenged percutaneously with a standard vaccination did not have measurable neutralizing antibody upon follow-up. Because of this finding, a percutaneous revaccination study was conducted at the St. Louis study center in 1975 and 1976. There were four study groups, which were composed on the basis of route of primary immunization (subcutaneous or percutaneous) and whether neutralizing antibody was detectable following the original percutaneous challenge immunization. Of 52 children revaccinated, all but four had accelerated reactions. There was no difference in size of lesions or day of maximum erythema among the four study groups. Only 66% of children originally vaccinated subcutaneously who did not have postchallenge neutralizing antibody had measurable neutralizing antibody following revaccination. Transformation studies with vaccinia viral antigen before and after revaccination were performed on lymphocytes from 50 children. There was no appreciable differences in responses either before or after revaccination when the four groups were compared. However, the mean stimulation ratio for the total group increased from 2.4 before revaccination to 4.6 3 weeks later. In primary subcutaneous vaccine recipients without pre-revaccination neutralizing antibody, lymphocyte transformation correlated directly with the neutralizing antibody response.


In vitro stimulation of bovine peripheral blood lymphocytes: comparison of round- and flat-bottom microtiter plates for detection of tuberculin hypersensitivity. Lymphocytes from Mycobacterium bovis-sensitized and normal cattle were cultured in round- and/or flat-bottom microtiter plates and stimulated with M. bovis purified protein derivative (PPD) tuberculin. Blastogenic responses of lymphocytes from M. bovis-sensitized cattle to PPD cultured in round-bottom plates were significantly greater than those of lymphocytes cultured in flat-bottom microtiter plates. Normal lymphocytes of nonsensitized cattle were not stimulated by PPD in either round- or flat-bottom microtiter plates. Kinetics of lymphocyte responses in round-bottom plates are presented.


Highly sensitive solid-phase radioimmunoassay suitable for determination of low amounts of cholera toxin and cholera toxin antibodies. A direct solid-phase radioimmunoassay procedure was developed for the determination of cholera toxin and cholera toxin antibody. The reported method employed anti-choleragenoid antibody attached to polystyrene tubes as a solidified binder for cholera toxin. The binding of radioidinated cholera toxin on its solidified antibody was inhibitable by unlabeled cholera toxin and cholera toxin antibody. With the help of this method, the heat stability of cholera toxin was also studied. Radioiodinated cholera toxin was shown to be labeled in both of its subunits. The stability of the iodinated cholera toxin at the reported specific radioactivity is remarkable. It was found that the labeled cholera toxin can be used in the solid-phase radioimmunoassay even 4 months after iodination.


Aerobic bacterial flora of oral and nasal fluids of canines with reference to bacteria associated with bites. Oral and nasal fluids of 50 dogs were examined to determine the prevalence of aerobic bacteria frequently associated with animal bite wounds. The most frequently isolated microorganisms included: IIj, EF-4, Pasteurella multocida, Staphylococcus aureus, Staphylococcus epidermidis, group D streptococci, Corynebacterium sp., Enterobacteria, Neisseria sp., Moraxella sp., and Bacillus sp. Other species and genera were infrequently recovered and may represent transient flora. The high incidence of IIj, EF-4, P. multocida, and S. aureus, all known human pathogens, suggests that they should be considered as probably contaminants in bite wounds.


Rose Bengal plate agglutination and counterimmunoelectrophoresis tests on spinal fluid in the diagnosis of Brucella meningitis. Rose Bengal and counterimmunoelectrophoresis, two tests that detect antibodies against different structural antigens, when carried out on spinal fluid permitted rapid diagnosis of human Brucella meningitis. The Rose Bengal test was positive in five out of five patients studied, and counterimmunoelectrophoresis was positive in all but one. The Brucella meningitis was characterized by an increase of immunoglobulin G in the cerebrospinal fluid.


Achromobacter xylosoxidans isolates in Hawaii. Clinical and bacteriological features of nine cases in which Achromobacter xylosoxidans were isolated in Hawaii are described. Five cases were ear infections mixed with other gram-negative bacteria. Colonial morphology, xylose oxidation, peritrichous flagella staining, and antibiotic susceptibility pattern assisted in separating this bacterium from other nonfermentative, oxidase-positive, gram-negative rods.


Spectrum of renal tubular damage in renal failure secondary to cirrhosis and fulminant hepatic failure. Measurements of urinary lysozyme were used to evaluate renal tubular integrity in 34 patients with cirrhosis or fulminant hepatic failure who had developed renal impairment. In 18 of the patients the lysozyme values were normal but in the remaining 16 were increased, supporting previous concepts that renal failure complicating hepatocellular disease may occur both without and with tubular necrosis. The lysozyme values were inversely related to the creatinine clearance, suggesting that the development of tubular necrosis may be determined by the level of renal perfusion. The validity of simpler laboratory tests often used to assess renal tubular integrity--namely, the urine sodium concentration, the urine:plasma osmolality ratio, and casts in the urine sediment--was evaluated by comparison with the lysozyme measurements. The urine sodium concentration was of most value and the findings in the sediment were of no value at all.


Benign oesophageal papillomatosis. A case report with a review of the literature. An 18-year-old boy presented with a four-year history of dysphagia which had been treated repeatedly by endoscopic removal of papillomata of the oesophagus. Eventually, due to increasing dysphagia and repeated recurrences of the papillomata, resection of the affected lower third of the oesophagus was deemed necessary. The resected segment of the oesophagus was carpeted with numerous benign squamous papillomata. The clinical features, radiographic appearances, and pathology of this extremely rare tumour are presented. Only two acceptable cases of oesophageal papillomata can be found in the literature, making this the third case, and apparently the only one with multiple lesions.


Squamous carcinoma of the breast.

Squamous carcinoma of the breast. Two cases of primary squamous carcinoma of the breast are described. One of the tumours appeared to have an origin in an epidermoid cyst and had a pseudosarcomatous stroma. The other tumour arose from metaplastic ductal epithelium. A review of the literature is given.


Lymphocyte transformation in cancer patients: variation in results according to technique. Lymphocyte transformation to phytohaemagglutinin (PHA) was measured simultaneously by two methods (heparin and methyl cellulose) in 16 patients with non-lymphoid cancer and 21 normal subjects. Twelve cancer patients showed transformation levels below the normal heparin range, but only two patients showed levels below the normal methyl cellulose range. These findings suggest that in interpreting lymphocyte transformation studies close attention should be given to the methods employed.


Crossreaction of antilymphocyte globulin with human granulocyte colony-forming cells. Clinical preparations of horse antilymphocyteglobulin (ALG) were found to inhibit human bone marrow granulocyte colony growth. This effect was enhanced by complement and was dose dependent, being almost complete at ALG concentrations of 100 microgram/ml. Inhibition was a property of ALG but not of normal horse globulin. However, short incubation of ALG with bone marrow cells occasionally stimulated colony growth and normal horse globulin regularly stimulated it. Three hours' incubation of bone marrow cells with ALG was needed to produce consistent colony inhibition, which was measurable as a reduction in the expected number of colonies and as a fall in the colony: cluster ratio of surviving cell aggregates. Absorption of ALG on acute myeloid leukaemia blast cells removed the inhibiting property of the ALG while preserving its lymphocytotoxic action. Serum from two patients receiving ALG treatment inhibited colony growth for up to 48 hours after ALG administration. The results suggest the presence in ALG of antibodies specifically cytotoxic to myeloid stem cells which may relate to its myleosuppressive properties in vivo, and also indicate that it should be possible to remove antimyeloid antibodies from ALG by absorption. The use of such purified ALG would have advantages in clinical bone marrow transplantation.


The case for laboratory aides in district clinical chemistry departments. A case of need is made out for the general introduction into district clinical chemistry departments of the existing experimental grade of laboratory aide or assistant. Subject to direct supervision by qualified personnel the aide has a useful role to fulfil. Important advantages to staff and patients accrue from the employment of this semiskilled laboratory worker.


Effect of bacterial flora on staphylococcal colonisation of the newborn. The umbilical and nasopharyngeal flora of newborn infants was examined on days 3, 14, and 42 of life. An analysis of the bacteriological findings suggests that colonisation by either Staphylococcus aureus or Staph. epidermidis prevents colonisation by the other staphylococcus. Similarly, colonisation by Gram-negative  bacteria prevents colonisation by staphylococci. Further, this bacterial interference lasts for as long as 42 days, which suggests the possibility of artificially colonising newborns with nonpathogens to prevent subsequent colonisation and disease by virulent microorganisms.


Cerebral ventriculitis associated with Achromobacter xylosoxidans. Six patients in the neurosurgical ward of Fukushima Medical College Hospital suffering from ventriculitis due to Achromobacter xylosoxidans infection had undergone craniotomy or cranial trepanation before the infection. The strains of A. xylosoxidans isolated from the patients were resistant to streptomycin, ampicillin, cephaloridine, gentamicin, and colistin. They were also resistant to chlorhexidine digluconate (Hibitane) in a concentration of 2%. When a study of the chlorhexidine used in the hospital was carried out four strains of A. xylosoxidans were isolated from 20 containers of chlorhexidine solution in the surgical ward but not from those in the operating theatre.


A comparison of four potential agents for reducing necrosis after prolonged coronary occlusion. In anesthetized closed-chest dogs, four vasodilators were compared after prolonged coronary occlusion induced by catheter wedging in a coronary branch. With treatment given between 1 hour and 2 hours of occlusion, five groups were studied: no treatment, isosorbide dinitrate, nitroprusside, dipyridamole, and methylprednisolone. Measured were heart rate, cardiac pressures and blood flow (with 85Kr); and cardiac index, left ventricular ejection fraction with vascular resistance, left ventricular minute work index, and an oxygen consumption index were calculated. At sacrifice, ischemic inner/outer wall isotope distribution and myocardial K+, Na+, and H2O were determined. With no treatment, left ventricular end-diastolic pressure and vascular resistances rose while cardiac index, ejection fraction, minute work index, and index of myocardial oxygen consumption fell, with no further change between 1 and 2 hours. Vasodilators did not affect coronary hemodynamics or isotope distribution. Hemodynamic effects of isosorbide dinitrate and nitroprusside differed qualitatively from dipyridamole and methylprednisolone. The latter drugs caused increases in ejection fraction, and dipyridamole also significantly increased cardiac index and minute work index. Only nitroprusside decreased minute work index and O2 consumption index. Only nitroprusside and dipyridamole, despite differing hemodynamics, tended to reduce K+ loss and Na+ and H2O gain in ischemic tissue. Further extended studies with these agents are warranted.


Pharmacologic studies with cefaclor, a new oral cephalosporin. Cefaclor, a new oral cephalosporin, was administered to 18 normal human volunteers in either single or multiple doses of 250 and 500 mg. Mean serum concentrations of 6.09 and 12.8 microgram/ml were achieved 1 hour after single oral doses of 250 and 500 mg, respectively. The serum concentrations declined rapidly and no drug was detected at 4 hours. Very high concentrations of cefaclor were found in urine during the first 8 hours after ingestion of the drug. Forty-three per cent of the total dose was excreted in urine during the first 8 hours. There was no accumulation of drug in serum during the multiple-dose studies.


Clinical effects of meperidine in hospitalized medical patients. Of 26,294 hospitalized medical patients monitored in a drug surveillance program, 366 (1.4%) received meperidine orally and 3268 (12.4%) received meperidine parenterally during one or more admissions. Neoplastic disease was the most common category of primary diagnosis (43%) among oral recipients; among parenteral recipients cardiovascular and neoplastic diseases (23% each) were most common. Oral meperidine was prescribed almost exclusively (93%) for pain relief, whereas the parenteral drug also had substantial use (41%) as a diagnostic and preoperative adjunct. Oral meperidine was judged by attending physicians to have provided unsatisfactory pain relief in 22% of recipients, while parenteral meperidine was rated unsatisfactory in 11%. The drug was less effective in patients with a primary diagnosis of neoplastic disease than in patients with other primary diagnoses. Minor gastrointestinal disturbances were the most commonly reported adverse reactions among oral meperidine recipients (2.7%); among parenteral recipients central nervous system effects were most common (1.2%). Seven recipients had life-threatening adverse reactions. However, only two of these were judged definitely related to meperidine, and in both instances other drugs were also definitely implicated. Adverse reactions were dose related.


Absorption kinetics of hydroflumethiazide. The pharmacokinetics of hydroflumethiazide after oral administration of a 100-mg dose to 12 volunteers were evaluated to determine whether absorption of the drug is best described by zero-order or first-order absorption. Comparison of the two absorption models was based on three criteria: (1) correlation coefficients; (2) standard deviations of the parameter estimates; and (3) visual fits. Evaluation of the individual results in light of each criterion showed that the zero-order absorption model is the more appropriate one for describing the hydroflumethiazide data.


Bioavailability of erythromycin ethylsuccinate in pediatric patients. A parallel treatment group bioavailability study was undertaken in children 6 to 65 months of age, comparing fasting and nonfasting erythromycin serum levels after a single oral dose of erythromycin ethylsuccinate granules. Results demonstrated significantly higher levels in the nonfasting than in the fasting state, while fasting state levels were comparable to those found in studies of adult subjects receiving recommended doses of the same compound.


Evaluation of intravenous clonidine in hypertensive emergencies. Nineteen patients with severe essential hypertension or hypertension due to renal parenchymal disease were treated with intravenous clonidine. In 14 patients the elevated blood pressure was complicated by one or more crises: left ventricular failure in seven patients, encephalopathy in six, and subarachnoid hemorrhage, cerebral hemorrhage, dissecting aortic aneurysm, acute renal failure, and severe epistaxis, one episode each. Clonidine 0.15 or 0.30 mg, was given intravenously every 40 minutes until the diastolic blood pressure was decreased to 120 mm Hg or below. Blood pressure was taken every 10 minutes. Both systolic and diastolic blood pressure were reduced significantly after intravenous clonidine, the former by 96 mm Hg (P less than 0.001), the latter by 52 mm Hg (P less than 0.001) within a period of 40 minutes to 2 1/2 hours. The clonidine dose varied from 0.15 to 0.90 mg, mean 0.52 mg. Heart rate was decreased significantly by 20 beats/minute (P less than 0.001) by the drug. Serious side effects were not observed except for an episode of transient sinoatrial block. Renal function was not affected. Patients who were on chronic diuretic therapy prior to treatment with intravenous clonidine showed a significantly greater decrease in both systolic (P less than 0.01) and diastolic (P less than 0.001) blood pressure after the first clonidine dose. In one patient intravenous clonidine was not effective (i.e., blood pressure remained 200/150 mm Hg) in spite of a total clonidine dose of 0.9 mg. Two patients died, one from severe cerebral hemorrhage, the other from an extensive dissecting aortic aneurysm, but the fatal outcome was not related to clonidine.


Afferent projections to the rat locus coeruleus as determined by a retrograde tracing technique. Afferent connections to the rat locus coeruleus (LC), which contains exclusively noradrenergic neurons, have been traced using the technique of retrograde transport of horseradish peroxidase (HRP). In order to ensure accurate placement of adequate amounts of HRP in the LC, a microiontophoretic delivery technique coupled with single cell recording was employed. The use of electro physiological "landmarks" as aids in placing the injections is described. Following HRP injections into the LC, forebrain structures containing labelled neurons included the insular cortex, the central nucleus of the amygdala, the medial, lateral and magnocellular preoptic areas, the bed nucleus of the stria terminalis, and the dorsomedial, paraventricular and lateral hypothalamic areas. In the brainstem reactive neurons were observed in the central grey substance, the reticular formation, the raphe, vestibular, solitary tract and lateral reticular nuclei. In particular, the areas of catecholamine cell groups A1, A2 and A5 appeared to contain many reactive cells. Labelled neurons were also observed in the fastigial nuclei and in the marginal zones of the dorsal horns of the spinal cord. This pattern of afferent innervation supports suggestions for a role for the LC in behavioral arousal mechanisms and autonomic regulation.


The effects of denervation and stimulation upon synaptic ultrastructure. Quantitative studies of synaptic ultrastructure were made in the upper layers of cat cerebral cortex. Tissues were from intact cortex and from long-term (chronic) undercut cortex with or without electrical stimulation. The synaptic effects of chronic electrical stimulation of denervated cortex are most readily understood as growth and remodeling of synaptic elements. Associated with chronic stimulation were increases in: symmetric membrane contacts; areas of round and flat vesicle containing terminals; dendritic shaft contacts; and synaptic contact lengths. Even without stimulation there were indications of synaptic plasticity in denervated cortex; compared with intact cortex, synapses having symmetric membrane contacts showed an increase in bouton area and an increase in synaptic contacts on dendritic shafts. These data are consistent with the observations of others in which axonal terminal growth occurred after differentation. But it appears that chronic electrical stimulation in the adult nervous system promotes significantly more plasticity than occurs without stimulation. In a functional sense stimulation in the present experiments produced effective inhibition which did not occur with denervation alone. Thus the plasticity observed with stimulation had both structural and functional components.


Projections of the superior cerebellar peduncle in rats and the development of new connections in response to neonatal hemicerebellectomy. The normal distribution pattern of cerebellar efferents was determined using the Fink-Heimer technique in adult rats that sustained stereotaxic transection of the superior cerebellar peduncle. This pattern was found to be essentially similar to earlier studies and corroborated more recent reports of projections to the pontine gray and inferior olivary nuclei. Comparisons were made to a second group of animals that underwent neonatal hemicerebellectomy in addition to adult transection of the contralateral superior cerebellar peduncle. Abnormal projections to the ipsilateral red nucleus and ventral thalamus were observed in addition to evidence suggestive of axonal sprouting within the oculomotor complex. These animals also demonstrated an absence of cells in the pontine gray and inferior olive on the side contralateral to the hemicerebellectomy and in the lateral reticular and lateral cuneate nuclei on the ipsilateral side.


Acute whisker removal reduces neuronal activity in barrels of mouse SmL cortex. The autoradiographic 2-deoxy-D glucose (2-DG) method has been used to map relative changes in metabolic activity in the CNS during various functional states (Plum et al., '76). Here we describe the application of the 2-DG method to assay regional activity in the posteromedial barrel subfield (PMBSF) region of the mouse SmI cortex after acute removal of mystacial vibrissae. One day prior to isotope injection, various combinations of vibrissae (e.g., all vibrissae, row-C only, rows-B and -D only) were plucked from adult male Swiss Webster mice under anesthetic. The next day, 5 muCi of 14C-2-DG were injected into a tail vein, and the mice were allowed to actively explore an empty cage for 45 minutes. The animals were then sacrificed, the brains quickly removed, frozen, and sectioned either parallel or perpendicular to the pia at 80 mum in a cryostat. The sections were mounted, dried on coverslips, and were used to expose X-ray film, after which the sections were stained with thionin and the X-ray film developed. The tissue sections and matching autoradiograms were compared directly from photomicrographs of each. The autoradiograms showed areas of higher activity in barrels for which corresponding vibrissae were present and lower activity in barrels for which appropriate vibrissae were missing. In tangential sections from animals with all vibrissae intact, the PMBSF was uniformly and consistently higher in activity than in cases with all vibrissae missing. The removal of row-C or rows-B and -D resulted in strips of decreased activity in the corresponding PMBSF rows. The same patterns of increased or decreased activity were also seen in sections normal to the pia, but the changes in activity, while greatest in layer IV, extended through all layers of the cortex. Finally, in a number of the autoradiograms, density patterns could be recognized which later were shown to relate directly to sides of individual barrels. The results indicate: (1) Acute removal of the peripheral vibrissal hairs is sufficient to deprive the related contralateral cortical barrel neurons of normal activity. Thus in the mouse somatosensory system it may be possible to determine the relative importance of sensory deprivation and neonatal peripheral lesions in normal cortical development. (2) The barrels are part of a functional cortical columnar organization similar to that in other sensory systems. And, (3) the 14C-2-DG-X-ray technique is sufficiently sensitive to reveal parts of individual barrels in autoradiograms and thus, with some modification, may be suitable for the study of small populations of neurons.


Autoradiographic evidence for pathways from the medial preoptic area to the midbrain involved in the drinking response to angiotensin II. The 3H-amino acid autoradiographic method was used to localize intracerebral sites from which angiotensin II (AII) elicits drinking and to identify their efferent neural pathways. Small injections (0.02-0.1 mul) of AII and 3H-amino acid mixtures were injected together or separately into widespread regions of the forebrain of adult rats in normal food and water balance. From an analysis of 39 positive and negative injection sites it was concluded that the caudal half of the medial preoptic area and the adjacent rostral part of the anterior hypothalamic area are sensitive to AII. Two anatomically defined pathways arising from neurons within this region were identified. One descends through the medial forebrain bundle and appears to terminate in the lateral hypothalamic area, the ventromedial nucleus, the mammillary body, and the ventral tegmental area. The other descends through the periventricular region and posterior hypothalamic area to end in the midbrain central gray. Additional widespread connections with the amygdala, septum, habenula, and pons appear to arise in the lateral preoptic area (Swanson, '76). Combined AII-3H-amino acid injections centered in the subfornical organ only elicited drinking in those cases in which injected label diffuse through the third ventricle to the medial preoptic area. No efferent pathways were identified in experiments in which a small injection (0.02 mul) heavily labeled cells strictly confined to the subfornical organ and there was no ventricular spread of label.


The cochlear nerve in the cat: topography, cochleotopy, and fiber spectrum. The topographical and cytological features of the cochlear nerve in normal adult cats were studied by microdissection, light microscopy, transmission and scanning electron microscopy. The 2-mm long cochlear nerve trunk is situated within the internal acoustic meatus. The nerve is wrapped like a roll with the more basal fibers situated peripheral to the more apical ones. The fibers are fasciculated according to their target in the cochlea and follow a helical course with the sharpest spiralling in the distal portion of the fiber. Apical and basal coil fibers are of approximately the same length measured from the spiral lamina to the rostral border of the anteroventral cochlear nucleus. The nerve contains about 90% thick, myelinated fibers, about 10% unmyelinated axons, and a few thin, but heavily myelinated axons. The first group shows a unimodal distribution of axonal diameters, with a gradual increase in average diameter from basal to apical coil fibers. The number of axonal microtubules and neurofilaments have a high linear correlation to axonal circumference without principal cochleotopic differences. The myelin sheaths are thicker and the internodal segments shorter than expected from similarly sized peripheral fibers in rodents. The possible nature and origin of the three fiber categories are discussed.


Temporal and spatial sequence of anterograde degeneration in the cochlear nerve fibers of the cat. A light microscopic study. This study deals with anterograde degeneration in the cochlear nerve fibers following cochlear lesions. The observations are based on 2-mum thick sections of material embedded in resin according to procedures used in electron microscopy and stained with toluidine blue. Among the various operative approaches used in this study, sparing of the modiolus afforded the least local reaction and furnished the material best suited for anterograde degneration studies in this nerve only 2 mm long. The anterograde degeneration of the cochlear nerve is characterized by segmental swelling of myelinated nerve fibers followed by shrinkage of the axoplasm and collapse of the distended myelin sheaths. The swelling, which begins at the nodal-paranodal region of the axon, is preceded by accumulation in the cytoplasm of granular organelles, presumably mitochondria and lysosomes. The portions of the cochlear fibers situated in the nerve root, i.e., within the cochlear nuclei and including the axon terminals, follow essentially the same pattern of degeneration as those in the peripheral portion of the nerve. Both peripherally and centrally degenerative changes occur first in the basal, high frequency fibers and centrally degenerative changes occur first in the basal, high frequency fibers and progress to the apical, low frequency fibers. The difference between the two extremes in the onset of degeneration is, approximately, 24 hours. Once initiated, however, the pace of degeneration is the same along the whole fiber spectrum.


Histochemical evidence for a post-lesion reorganization of cholinergic afferents in the hippocampal formation of the mature cat. We have utilized acetylcholinesterase (AChE) histochemistry to analyze possible post-lesion changes in the distribution of AChE containing afferents to the hippocampal formation of the cat following unilateral destruction of the entorhinal cortex. In the cat, the entorhinal area gives rise to a massive projection to the ipsilateral fascia dentata, and to regio inferior and regio superior of the hippocampus proper. Sixty days following unilateral entorhinal lesions, histochemical preparations for AChE indicate a dramatic increase in the density of the reaction product in the zones normally occupied by entorhinal afferents in the fascia dentata and regio inferior of the hippocampus proper, whereas little if any increase in the density of the reaction product was observed in the entorhinal terminal zone in regio superior. In addition to these increases in the density of the AChE reaction product, there was also evidence for a widening of an AChE free zone in the inner stratum moleculare of the fascia dentata denervated by the lesion. The time course of these changes in the pattern of AChE staining was analyzed by sacrificing animals 7, 10, 13, 14, 16, 17,, 19, and 20 days following entorhinal cortical lesions. The increase in the density of the AChE reaction product in the denervated zones was not apparent at seven days post-lesion, while at ten days post-lesion, a slight increase in the density of the AChE reaction product could be observed. By 13 days post-lesion, the differences between the denervated and normally innervated (contralateral) hippocampal formation were prominent, and by 16 days post-lesion, the pattern of staining appeared comparable to that which was observed at longer post-lesion intervals. The present experiments indicate that following entorhinal cortical lesions in mature cats the final post-lesion pattern of altered AChE staining is quite comparable to that which is observed following similar lesions in rats. In the rat, such changes in AChE staining have been interpreted as a reflection of a proliferation of cholinergic septal afferents within the denervated zones. If this interpretation is correct, the present results suggest a similar proliferation of cholinergic afferents following entorhinal lesions in cats. The time course of this apparent proliferation is considerably slower in the cat then in the rat, however, since the earliest changes are observed at approximately five days post-lesion in the rat, and ten days post-lesion in the cat.


Association and commissural fiber systems of the olfactory cortex of the rat. The association and commissural fiber systems arising in the olfactory cortical areas caudal to the olfactory peduncle (the piriform cortex, nucleus of the lateral olfactory tract, anterior cortical nucleus of the amygdala, periamygdaloid cortex and entorhinal cortex) have been studied utilizing horseradish peroxidase as both an anterograde and a retrograde axonal tracer. In the piriform cortex two sublaminae within layer II (IIa and IIb) layer III have been found to give rise to distinctly different projections. Retrograde cell labeling experiments indicate that the association fiber projection from layer IIb is predominatnly caudally directed, while the projection from layer III is predominantly rostrally directed. Cells in layer IIa project heavily to areas both caudal and rostral to the piriform cortex. The commissural fibers from the piriform cortex are largely restricted in their origin to layer IIb of the anterior part of the piriform cortex and in their termination on the contralteral side to the posterior part of the piriform cortex and adjacent olfactory cortical areas. A projection to the olfactory bulb has also been found to arise from cells in layers IIb and III of the ipsilateral piriform cortex, but not in layer IIa. In addition to those from the piriform cortex, association projections have also been found from other olfactory cortical areas. The nucleus of the lateral olfactory tract has a heavy bilateral projection to the medial part of the anterior piriform cortex and the lateral part of the olfactory tubercle (as well as a lighter projection  to the olfactory bulb); both the anterior cortical nucleus of the amygdala and the periamygdaloid cortex project ipsilaterally to several olfactory cortical areas. The entorhinal cortex has been found to project to the medial parts of the olfactory tubercle and the olfactory peduncle. The olfactory tubercle is the only olfactory cortical area from which no association fiber systems (instrinsic or extrinsic) have been found to originate. A broad topographic organization exists in the distribution of the fibers from several of the olfactory areas. This is most obvious in the anterior part of the olfactory cortex, in which fibers from the more rostral areas (the anterior olfactory nucleus and the anterior piriform cortex) terminate in regions near the lateral olfactory tract, while those from more caudal areas (the posterior piriform cortex and the entorhinal cortex) terminate in areas further removed, both laterally and medially, from the tract. Projection to olfactory areas from the hypothalamus, thalamus, diagonal band, and biogenic amine cell groups have been briefly described.


Comparison of Mauthner cell size in teleosts. The Mauthner cells (M-cells) are a pair of neurons found in the medulla oblongata of most fish and amphibians. This neuron is not the same size in all teleosts. Based on the hypothesis that differences in M-cell size might be related to fish family and possibly fish habitat, M-cell and nuclear size were compared between fish families. In order to minimize effects of fish length on cell or nuclear size, statistical treatment of the data was made for four separate length classes. The results indicate at least three groupings by cell or nuclear size. The cell is large in fish from the Salmonidae, Catostomidae and Cyprinidae, small in the Stichaeidae, Cottidae and Pleuronectidae and absent in Batrachoididae, Lophiidae, Ogcocephalidae and Cylopteridae. In general a correlation exists between fish that lack or have small M-cells and a demersal habitat. Since these fish may rely on camouflage for protection against predation, the M-cells may have altered excitability or function as compared to more active fish in which the M-cell is known to function in initiating the startle response (larval zebrafish and goldfish). Differences in input to M-cells of different sizes in conjunction with known electrophysiological properties of the goldfish M-cell are discussed in relation to the function of this neuron.


The effect of refeeding after neonatal starvation on Purkinje cell dendritic growth in the rat. Male rats, undernourished from birth until 30 days by restricting access to the lactating dam, were given ad libitum food supplies unitl 80 days. Body weight, whole brain weight and cerebellar remained significantly lower in these animals than in normally fed controls. Significant deficits in the area of the molecular and granular layers persisted at 80 days, although there was some recovery during the refeeding period. At the same time granule and Purkinje cell density declined, suggesting that the areal recovery was due to the expansion of the interneuronal matrix. Granule cell numbers remained unchanged between 30 and 80 days. Network analysis of Golgi-Cox preparations indicated a 28% decrease in overall size of the Purkinje cell dendritic networks, due primarily to a deficit in segment frequency which remained unchanged throughout the rehabilitation period. Segment length did, however, show some recovery; distal segments from 80-day experimental networks were significantly longer than those of 30-day undernourished animals. The results of the topological analysis suggested that dendritic remodelling had taken place during the rehabilitation period. The failure to observe a complete recovery in the size and morphology of the dendritic  network may be explained in terms of recent suggestions that dendritic development is influenced both by the metabolism of the neurons themselves, and by the number and density of adjacent afferent axons. It is suggested that refeeding from 30 days leads to the recovery of Purkinje cell metabolism, but is unable to restore the parallel fiber deficit.


Quantitative analysis of the opossum's optic nerve: an electron microscope study. An electron microscope examination of the optic nerve of the opossum, Didelphis marsupialis aurita, indicates a total count of 74,7000 fibers of which approximately 20% are unmyelinated. The diameters of myelinated fibers ranged from 0.5-7 mum (mode at 1.25 mum) and those of the unmyelinated fibers ranged from 0.25-2.25 mum (mode at 0.75 mum). Myelinated and unmyelinated fibers are uniformly distributed throughout the nerve. Myelin sheath structure is similar to that described in other species and are formed by 2 to 17 myelin rings (mode at 6). There is a good correlation (r = 0.92) between axon and myelin areas. The relation between myelin thickness and axons diameter shows a wide distribution with a peak at 0.77.


The organization of central auditory pathways in a reptile, Iguana iguana. The present experiments were designed to trace the central auditory pathways in an extant reptile, the New Worlkd lizard--Iguana iguana, utilizing anterograde axonal degeneration stained by the Fink-Heimer ('67) method and the retrograde axonal transport of horseradish peroxidase (LaVail and LaVail, '74). Beginning with the projections of the auditory portion of the VIIIth nerve, the ascending pathways were traced through successive relay nuclei to the telencephalon. The auditory portion of the VIIIth nerve projects to two nuclei in the dorsomedial medulla-nucleus angularis and nucleus magnocellularis medialis. These two nuclei together with a third cll group, nucleus magnocellularis lateralis (intercalated between nucleus angularis and nucleus magnocellularis medialis), have been referred to as the auditory tubercle in previous studies (cf. Miller, '75). The axonal degeneration following large lesions of the auditory tubercle and small lesions of nucleus angularis demonstrated the second order auditory pathways. Fibers leave nucleus angularis ventrally and travel to the ventral surface of the medulla where they cross the midline and ascend to the midbrain in pathways resembling the trapezoid body and the lateral lemniscus of mammals. Along these pathways, terminal arborizations of some fibers were seen in three lower brainstem nuclei while other fibers ascent to the midbrain and terminate in the central nucleus of the torus semicircularis. Experiments in which horseradish peroxidase injections were made in the torus semicircularis demonstrated that nucleus angularis is a primary source of second order auditory fibers to the midbrain and, in addition, that two of the lower brainstem targets of the auditory tubercle project to the torus semicircularis. These lower brainstem pathways were shown to be associated with the auditory system by electrophysiologically recording sound-evoked responses from clusters of cells in the torus semicircularis. Ascending fibers arising from the central nucleus of the torus semicircularis were followed rostrally where they entered the dorsal thalamus and terminated throughout nucleus medialis. Finally, a thalamotelencephalic auditory pathway was traced from nucleus medialis into the lateral forebrain bundle. Terminations of this pathway from nucleus medialis were seen in the medial dorsal ventricular ridge and in the striatum. It was concluded that the ascending auditory pathways of the iguana bear a remarkable resemblance to both the mammalian and avian auditory pathways from the level of the first order neurons in the VIIIth nerve to the level of the telencephalon. At the same time, there are important specializations of the auditory system in birds and mammals such as the development of particular lower brainstem nuclei. Nevertheless, a basic plan for the organization of the auditory system in terrestrial vertebrates can be recognized which invites comparisons with the vertebrate classes that remained in aquatic habitats...


So-called cellulite: an invented disease. The anatomic basis of so-called cellulite, the hormonal basis for the clinical condition, the prevalence of it, the essential normality and inevitability of it in women, the supervention of it in hormonally feminized men, and the near futility of treating the non-disease are explored in this paper.


Electrosurgery by bipolar modalities.

Electrosurgery by bipolar modalities. Bipolar electrosurgery is efficient for destruction or gross removal of many benign and malignant lesions. Its technique is simple and practicable in a dermatologic office. It requires local anesthesia generally, but is nearly bloodless. Instrumentation and fine points of use are described. Contraindication of use on patients bearing cardiac pacemakers is stressed.


Pigmentations of the nails (chromonychia). Nails, particularly fingernails, may show signs that are important not only for detection of diseases of the nails themselves, but of diseases of other organs or the system as a whole. Changes of color in nail plates or nail beds sometimes seem to suggest the parts are windows to what is happening in the body. Above all, changes of color in nails that compel investigation for malignant melanoma, the most dread of diseases, are most important.


Lower limb to limb flaps for repair of traumatic ulcers. Techniques of advancing flaps to cover traumatic ulcers on legs are described briefly and illustrated in detail. In particular, the advantages of the direct, uncrossed variety are explained and shown.


Basal-cell carcinomas in the center of the face: special diagnostic, prognostic, and therapeutic considerations. In a review of 848 successive cases of basal-cell carcinomas treated during 1976 in the Chemosurgery Unit of the New York University Medical Center by far most were found on the face and scalp (751/848 = 88.6%), and those in the triangle of the face formed by lines drawn from the outer canthi to the philtrum of the upper lip that includes the nose and its alae accounted for more than one-third of the entire number (316/848 = 37.2%) or two-fifths (316/764 = 41.4%) of those on the head and neck. Further analysis of our data showed the basal-cell carcinomas in the center of the face tended to be more invasive, more destructive, more recurrent, and more difficult to treat than were those in other sites. The reasons for seriousness and difficulty in management of basal-cell carcinomas and special diagnostic, prognostic, and therapeutic considerations pertaining to them are illustrated by representative case reports.


Treatment of extensive avulsions of skin and subcutaneous tissues. This article deals with the treatment of extensive avulsion injuries. Five out of twenty-eight cases of extensive avulsion injuries are presented and illustrated. All of these injuries were caused by machinery or automobile accidents and were encountered in the three-year period from 1972 to 1975. Etiology, pathology, and treatment with mechanical and chemical debridement, porcine skin grafts, fasciotomy, delayed primary closure, stamp or mesh skin grafts, and skin flaps are detailed and discussed.


The causes and prevention of poor cosmetic results from injection of fluid silicone. A 15-year experience with fluid silicone in augmentation of facial tissue while proving that highly desirable cosmetic improvement may be had, has also produced information relative to the cause and prevention of adverse results. The principles of correct technique and the causes of poor cosmetic results are presented. Appropriate graphic illustrations are presented.


The suppurative keloid.

The suppurative keloid. There is a type of keloid that tends to suppuration. The causes and mechanisms, symptomatology, and management of suppurative keloids are discussed briefly.


Coding of information in single auditory-nerve fibers of the goldfish. Patterns of activity in single fibers of the saccular branch of the auditory nerve of goldfish were analyzed in response to acoustic stimulation. Neurons were categorized on the basis of differences in spontaneous activity patterns, rates of adaptation, and frequency response areas. The sensitivity and responsiveness of neurons are presented both in terms of impulse rate and synchronization (phase locking). Nonspontaneous neurons fall into two clear frequency response area categories based upon impulse rate criteria. Spontaneously active neurons have continuously distributed frequency response characteristics based upon synchronization criteria. Functions relating impulse rate responsiveness to frequency indicate that frequency is coded only crudely as an across-fiber pattern of impulse rates. Synchronization responsiveness functions show that frequency is coded temporally with the same precision in the goldfish auditory nerve that it is in mammals, at 1000 Hz and below.


Threshold and growth of the acoustic reflex. Measurements of the threshold and growth function of the acoustic reflex in man were made utilizing a signal-averaging technique. Pure tones (250, 500, 1000, 2000, and 4000 Hz) and broadband noise served as the contralateral stimuli delivered at intensity levels from the reflex threshold to 116 dB SPL. The acoustic conductance and susceptance components of admittance, at 220 and 660 Hz, were used to measure the reflex activity. The results are reported as changes in conductance, susceptance, and admittance in cgs mmho. The acoustic reflex thresholds were similar to those reported in other studies, with the 220-Hz probe yielding thresholds that averaged 3.5 dB higher than those obtained with the 660-Hz probe. Broadband noise and 1000-Hz stimuli produced the largest reflex magnitudes, while the smallest were observed with 250- and 4000-Hz signals. The dynamic ranges of the restricted growth functions were frequency dependent for pure tones and ranged from greater than 16 dB with 250 Hz to greater than 28 dB with 1000 Hz, while that for noise was greater than 50 dB. The first derivative of the best-fit third-degree polynomial was used to describe the slope characteristics of the growth functions, in which frequency and intensity effects were found. Relationships between the acoustic reflex and tympanometry were observed and are also discussed.


Lateralization by frequency for repeating sequences of dichotic 400- and 800-Hz tones. Subjects made lateralization judgments involving dichotic sequences of 250-ms tones, which alternated in frequency between 400 and 800 Hz, such that when one ear received 400 Hz the other ear received 800 Hz, and vice versa. With sequences consisting of 20 dichotic tone pairs there was a strong tendency to lateralize each fused tonal percept toward the ear receiving the 800-Hz signal. In certain subjects the effect also occurred even when the 800-Hz tone was substantially lower in amplitude than the 400-Hz tone, and when it was clearly lesser in loudness. However, with sequences consisting of only two dichotic tone pairs, this lateralization-by-frequency effect was substantially weaker.


Influence of the precedence effect on word identification by normally hearing and hearing-impaired subjects. The influence of the precedence effect on word identification was investigated binaurally and monaurally with normally hearing and hearing-impaired subjects. The Modified Rhyme Test was processed through a PDP-12 computer to produce delay times of 0, 5, 10, 20, 40, 80, or 160 ms. The sounds were reproduced in a room by two loudspeakers positioned at +/-30 degrees azimuths in front of a subject at 50 dB SPL for normals and at the most comfortable level for impaireds. A babble of eight voices was added to reduce scores about 15% from the best values measured in quiet. Binaural and monaural word identification remained constant over a range of delays from 0 to 20 ms and declined for longer delays for both groups of subjects. The shapes of the word-identification curves were explained by self-masking (an overlap of consonants with their own repetitions) and masking (an overlap of consonants with preceding vowels or preceding and following words in sentence). Binaural responses for ten selected initial and final consonants showed various patterns of perception with delay. Some hearing impaireds showed more deterioration in word identification than others which might indicate that they experience more perceptual difficulties than normal listeners in places with reverberation or sound amplification.


Decoupling of auditory pitch and stimulus frequency: the Shepard demonstration revisited. With ten successive octave tones, Shepard demonstrated that upward shifts in frequency might be heard as downward shifts in pitch. This decoupling of auditory pitch and frequency has important consequences for any representational theory of pitch. Experiments are reported that attempt to identify the crucial features of Shepard's demonstration.


The typical noise: first step in the development of a short procedure for estimating performance of hearing protectors. An exact measurement of the effectiveness of a hearing protector requires the determination of how well it works in the specific noise in which it is to be worn. As a practical matter, though, people do not generally remain in a single noise spectrum throughout a working career or even throughout a working day, so it does not matter so much that most measurers are not likely to be equipped to perform spectrum analyses. Other techniques for judging earplugs and earmuffs are obviously necessary. Previous research has tried to find the average attenuation given by a particular device in several (or many) noises, or it has tried to deal with the attenuation given in noises given with particular C-minus-A values. In this paper, a procedure is developed for compressing these multiple-spectra calculations into a single-spectrum computation that proves to be at least as accurate as the more complex methods.


Correlation analysis of the physiological factors controlling fundamental voice frequency. A technique has been developed to obtain a quantitative measure of correlation between electromyographic (EMG) activity of various laryngeal muscles, subglottal air pressure, and the fundamental frequency of vibration of the vocal folds (Fo). Data were collected and analyzed on one subject, a native speaker of American English. The results show that an analysis of this type can provide a useful measure of correlation between the physiological and acoustical events in speech and, furthermore, can yield detailed insights into the organization and nature of the speech production process. In particular, based on these results, a model is suggested of Fo control involving laryngeal state functions that seems to agree with present knowledge of laryngeal control and experimental evidence.


Effect of speaking rate on vowel formant movements. The purpose of this experiment was to study the effects of changes in speaking rate on both the attainment of acoustic vowel targets and the relative time and speed of movements toward these presumed targets. Four speakers produced a number of different CVC and CVCVC utterances at slow and fast speaking rates. Spectrographic measurements showed that the midpoint format frequencies of the different vowels did not vary as a function of rate. However, for fast speech the onset frequencies of second formant transitions were closer to their target frequencies while CV transition rates remained essentially unchanged, indicating that movement toward the vowel simply began earlier for fast speech. Changes in both speaking rate and lexical stress had different effects. For stressed vowels, an increase in speaking rate was accompanied primarily by a decrease in duration. However, destressed vowels, even if they were of the same duration as quickly produced stressed vowels, were reduced in overall amplitude, fundamental frequency, and to some extent, vowel color. These results suggest that speaking rate and lexical stress are controlled by two different mechanisms.


Investigating the MESA (multipoint electrotactile speech aid): the transmission of segmental features of speech. Four normal-hearing young adults have been extensively trained in the use of a tactile speech-transmission system. Subjects were tested in the recognition of various phonetic elements including vowels, and stop, nasal, and fricative consonants under three receiving conditions; visual reception alone (lipreading), tactile reception alone, and tactile plus visual reception. Subjects were artificially deafened using earplugs and white noise and all speech tokens were presented live voice. Analysis of the data demonstrates that the tactile transform enables receivers to achieve excellent recognition of vowels in CVC context and the consonantal features of voicing and nasality. This, in combination with high recognition of vowels and the consonantal feature place of articulation through visual receptors, leads to recognition performance in the combined condition (visual plus tactual) which far exceeds either reception condition in isolation.


Mathematical predictions of electroacoustic frequency response of in situ hearing aids. The amplitude spectrum of an acoustic signal presented to the microphone of a hearing aid is altered drastically before it finally reaches the user's eardrum. A major part of this alteration is due to the interaction of various mechanical and acoustic resonances which are characteristic of the hearing-aid receiver and the sound transmission system linking the receiver with the eardrum. Because of the complexity of this phenomenon, there is yet no means for predicting, a priori, the true shape of the sound spectrum that will occur at the user's eardrum. This paper reports on the development and testing of just such a scheme. The accuracy of this scheme--a computer-aided mathematical technique--is measured in the laboratory on real and artificial ears. The results of those measurements show good agreement between experimental and computer-generated data below 5000 Hz.


Noncombination of pitch and loudness in multidimensional scaling. Carvellas and Schneider [J. Acoust. Soc. Am 51, 1839--1848 (1972)], using magnitude estimates of the dissimilarity of sinusoidal tones in a multidimensional scaling program, found that their data fit a city-block and a Euclidean metric equally well, but other research has indicated that subjects do not combine dimensions of sinusoidal tones to arrive at an overall estimate of stimulus similarity. Yet multidimensional scaling seems to require subjects to combine dimensions of similarity. In this leter a model is put forward to demonstrate that subjects need not combine dimensions directly in order to generate dissimilarity judgments that are very close to either the city-block or Euclidean metrics. Thus it is possible that while subjects do not combine the dimensions perceptually they can adopt a cognitive strategy that leads one to believe they do.


Frequency discrimination for pulsed versus modulated tones. Estimates of frequency discrimination for pulsed modulated tones were obtained by 11 observers at 350, 500, 1000, 4000, and 8000 Hz. At low frequencies, frequency DL's are larger for modulated than for pulsed tones; at 8000 Hz the contrary was found. Frequency DL's (difference limens) determined by different methods and procedures differed by a factor up to four; extreme individual frequency DL's, however, by a factor up to 27.


An application of a multitrait-multimethod test to validity data of a social learning treatment for aggressive children. Campbell and Fiske's (1959) multitrait-multimethod matrix was applied to data from two independent social learning measures designed to evaluate procedures used to aid aggressive children. Six parallel or like-named variables--noncomplying, crying, whining, negativism, destructiveness, and yelling--from both a home observation assessment system and a parent telephone data system were used. The data from 47 cases indicated that the categories of whining, crying, and destructiveness demonstrated significant convergent validity, but only whining demonstrated discriminant validity. The situation-specific versus cross-situational consistency aspects of the behaviors studied, and the implications for future research, were discussed.


CPQ validity: the relationship between children's personality questionnaire scores and teacher ratings. Scores on the Children's Personality Questionnaire (CPQ) were correlated with scores from rating scale items selected by a panel of raters measuring the same behavior as a CPQ scale. Data were obtained on a normal sample of school children in grades three to six and on two referred groups, underachievers and children with behavior or social problems. The teachers of the children were asked to complete two rating scales on each child. Correlations between rating scale scores and CPQ scores suggest that, in general, the CPQ does not measure the traits it purports to measure.


School adjustment of children with observable disabilities. This study investigated school behavior and achievement of children with mild degrees of observable physical disability. Children from two different disability types (cleft palate and cerebral palsy) were compared with each other and to a control group in order to determine potential similarities across disability types. Children (N = 78) from each of the two disability groups were individually matched to each other and to a normal control group (N = 39) by sex, IQ, socioeconomic status, age, and grade. They were compared on the basis of teachers' behavioral ratings and achievement test scores. All children attended regular public school classrooms. The two disability groups displayed significantly greater inhibition of impulse and lower educational achievement than did the controls. The implication of similar school adjustment across mild but observable subtypes is discussed.


Psychometric characteristics and norms for disadvantaged third and fourth grade children on the state-trait anxiety inventory for children. The STAIC was administered to 1,522 third and fourth grade Black disadvantaged children from a large metropolitan school district. Although A-State scores were equivalent to the original normative sample. A-Trait levels for boys and girls were found to be higher. Similar alpha coefficients were observed for the A-State scale; the A-Trait scale yielded slightly lower alpha coefficients than the original sample. Norms for the STAIC scales were extended to the third grade level. The small differences between the present study and the original normative study were attributed to differences in population. The STAIC provides a valid and reliable means to measure trait and state anxiety in children of elementary school age.


Neuropsychological significance of variations in patterns of academic performance: verbal and visual-spatial abilities. Forty-five 9- to 14-year-old children with learning disabilties whose WISC Full Scale IQs fell within the range of 86-114 were divided into three groups on the basis of their patterns of reading, spelling, and arithmetic achievement. Group 1 was composed of children who were uniformly deficient in reading, spelling, and arithmetic; children in Group 2 were relatively adept at arithmetic as compared to their performance in reading and spelling; Group 3 was composed of children whose reading and spelling performances were average or above, but whose arithmetic performance was relatively deficient. The performances of these children on 16 dependent measures were compared. The performances of Groups 1 and 2 were superior to that of Group 3 on measures of visual-perceptual and visual-spatial abilities; Group 3 performed at a superior level to that of Groups 1 and 2 on measures of verbal and auditory-perceptual abilities. The results are discussed in terms of the relationships between varying patterns of academic abilities and patterns of brain-related behaviors, and the nature of the neuropsychological abilities that may limit performance on arithmetic calculation tasks.


Pupillary and heart rate reactivity in children with minimal brain dysfunction. This study attempted to replicate and extend previous findings on autonomic arousal and responsivity in children with diagnoses of minimal brain dysfunction (MBD). Pupil size, heart rate, skin conductance, and skin temperature were recorded from 32 MBD and 45 control children during a session that included presentation of visual stimuli, simple reaction time (RT), a cold pressor procedure, and rest periods. The MBD children were tested both off and on clinical dosages of stimulant drugs in a crossover design. Evidence of higher than normal arousal levels in the unmedicated MBD Ss was obtained from resting skin conductance and, more tenuously, from pupil size. Lower phasic responsivity in the MBD children was evidenced by slower RT, less cardiac deceleration to both light and RT stimuli, and smaller pupil dilation to the RT stimuli. Spontaneous pupillary constrictions during "rest" periods, presumably indicating drowsiness, were observed about equally in MBD and control children. Stimulant drugs raised arousal levels but did not reverse the responsivity deficits. The lower phasic reactivity in the MBD group and the effects of stimulant drugs on arousal indices confirm earlier reports. The finding of higher arousal in drug-free MBD children is incompatible with the low arousal hypothesis of MBD but is consistent with a previous report of the effects of a stimulating environment on these children.