Non-random centromere division: a mechanism of non-disjunction causing aneuploidy?

Early centromere separation was investigated in 12 normal children, 14 patients with Down's syndrome and in 12 patients of children with autosomal trisomies. A significantly non-random centromere division of chromosomes was found in each of the cases. A higher frequency of early separated G chromosomes was observed in Down's syndrome. In 2 mothers of trisomy-18 patients, the early division of chromosomes 18, generally seen in normal individuals, could not be demonstrated. The possible assoication between altered sequence of centromere disision and non-disjunction needs further confirmation.


Factors affecting the stimulating capacity of mitogen-transformed, glutaraldehyde-treated mouse spleen cells in the mixed lymphocyte reaction.

Mouse spleen cells transformed by certain mitogens and subsequently fixed with glutaraldehyde can be utilized as stimulators in the mixed lymphocyte reaction. In addition to bacterial lipopolysaccharide which has been shown previously to be effective, we have found the other B cell mitogens, dextran sulfate and Concanavalin A-Sepharose, to be functional. The ability of the treated cells to activate allogeneic cells in MLR depends upon the concentration of glutaraldehyde and the type of tissue culture medium utilized.


Cell-mediated immunity in measles using the leucocyte migration test.

The cell-mediated immune response was investigated in 21 children with acute measles and in 8 healthy children using the intradermal Heaf and leucocyte migration tests. Tuberculin and purified protein derivative were used as antigens. Whereas all the children with measles were anergic in the in vivo test, two groups of children, i.e. 'reactors' and 'non-reactors' could be delinerated with the in vitro test. The mechanisms responsible for the anergy are discussed.


Anticomplementary properties of plasmin-treated human G immunoglobulin and its components.

Plasmin-treated human gamma-globulin, isolated plasmin residual portion (PRG), Fab and Fc fragments were tested for anticomplementary properties. The plasmin digest had very low anticomplementary activity while some of its components were anticomplementary, the latter probably due to alterations resulting from the isolation procedures employed. The highest activity was found in the isolated Fc fragment, no activity being detected in the isolated Fab fragment. Various mixtures of the isolated components were also tested, the results indicating that the increase in anticomplementary activity of the PRG and the Fc fragment was markedly lower when the Fab fragment was present.


[Dandruff (pityriasis simplex capillitii)].

In this review of new studies about dandruff, methods for clinical (subjective) evaluation and quantitative (objective) appraisal of dandruff are described. Current concepts about histopathology, cytology, biochemistry and etiopathogenesis of this common condition of the scalp are detailed.


[Gold therapy in psoriasis arthropathica].

For two patients with psoriasis arthropathica therapy with gold salts was started. In both cases a serious psoriasis pustulosa occurred after the first injection together with a leucemic reaction. The mechanism of gold side effects is discussed on the basis of the literature and these cases. The value of the therapy of the psoriatic arthropathie with gold is questioned.


[Roentgen therapy of dermatoses: indications and hazards].

Indications for radiotherapy of benign dermatoses have decreased markedly during the past decades. The remaining indications are reviewed. Side effects of ionizing radiation therapy are discussed in detail, with special emphasis on radiodermatitis and radiation cancer of the skin, mutagenic and genetic effects of x rays, and induction of carcinogenesis of interanl organs. Thyroid cancer is used as an example to discuss modern theories of radiocarcinogenesis and risk coefficients of various organ systems. Guide lines for radiotherapy of benign dermatoses are proposed.


Hearing handicap scores and categories for subjects with normal and impaired hearing sensitivity.

The hearing handicap scale, a commonly used self-assessment measure, was administered to 50 subjects with normal hearing and hearing impairment. These subjects were then divided into three groups based on pure tone test results so that the range of hearing handicap scale scores could be determined for different hearing sensitivities. Subjects in one group of 20 exhibited hearing sensitivity of 10 dB hearing threshold level or better. A second group of 10 subjects had hearing sensitivity of 11--25 dB hearing threshold level. The third group of 20 subjects had sensitivity poorer than 25 dB hearing threshold level. Percentage scores for the subjects with the most sensitive hearing clustered from 0 to 20% with a mean score of 7.8%. The intermediate group had a mean score of 25.6%. Scores for the hearing-impaired group clustered between 40 and 70% with a mean score of 54%. Score variability was about twice as great in the two groups with poorer sensitivity. It is suggested that hearing handicap performance may be classified into one of four categories, ranging from no handicap to severe handicap.


Defect in biosynthesis of the linkage unit between peptidoglycan and teichoic acid in a bacteriophage-resistant mutant of Staphylococcus aureus.

The biosynthesis of the linkage region between peptidoglycan and the ribitol teichoic acid was investigated in the bacteriophage-resistant, teichoic acid-less mutant Staphylococcus aureus 52A5 (Chatterjee et al., J. Bacteriol. 100:846--853, 1969). Membrane preparations of this strain were found to be incapable of forming the first intermediate of the biosynthetic pathway, namely, the transfer of N-acetyl-D-glucosamine (GlcNAc) from UDP-GlcNAc to the acceptor molecule, which presumbably is undecaprenol phosphate (R. Bracha and L. Glaser, Biochem. Biophys. Res. Commun. 72:1091--1098, 1976). The addition of heat-inactivated membrane preparations of S. aureus 52A2 (which normally has ribitol teichoic acid) that had been preincubated with UDP-GlcNAc to membranes of strain 52A5 enabled the synthesis of teichoic acid. These data suggest that the mutational defect in the teichoic acid-less organism is in the synthesis of the first compound of the linkage unit, and this is apparently the reason for its absence in the cell walls.


Carbodiimide-resistant mutant of Escherichia coli: suppression of resistance to dicyclohexylcarbodiimide by growth on glucose or glycerol.

We have previously reported on the isolation of a mutant strain of Escherichia coli, RF-7, that has a dicyclohexylcarbodiimide (DCCD)-resistant, membrane-associated adenosine triphosphatase (ATPase) activity (R. H. Fillingame, J. Bacteriol. 124:870--883, 1975). We report here that the DCCD resistance of the ATPase of this mutant varies significantly, depending upon the carbon source used for growth. When strain RF-7 was grown aerobically on either glycerol or glucose or anaerobically on glucose rather than on a combination of succinate, acetate, and malate, ATPase activity was more sensitive to inhibition by DCCD because the carbodiimide-reactive proteolipid reacted more readily with DCCD.


Energy transduction in Escherichia coli: new mutation affecting the Fo portion of the ATP synthetase complex.

A mutation affecting the intrinsic membrane portion (BFo) of the ATP synthetase complex is described. The phenotype is different from previously reported BFo mutants. This mutation results in the ability of membranes lacking the extrinsic membrane portion (BF1) of the ATP synthetase complex to maintain a transmembrane pH gradient. Unlike other BFo mutants, this strain, NR71, is capable of utilizing ATP hydrolysis for the formation of a transmembrane pH gradient.


Transient regulation of protein synthesis in Escherichia coli upon shift-up of growth temperature.

Synthesis of total cellular proteins of Escherichia coli was studied upon transfer of a log-phase culture from 30 (or 37) to 42 degrees C. Cells were pulse-labeled with [3H]leucine, and the labeled proteins were analyzed by gel electrophoresis in the presence of sodium dodecyl sulfate. The rates of synthesis of at least five protein chains were found to increase markedly (5- to 10-fold) within 5 min after temperature shift-up and gradually decrease to the new steady-state levels, in contrast to the majority of proteins which gradually increase to the steady-state levels (about 1.5-fold the rate at 30 degrees C). Temperature shift-down did not cause any appreciable changes in the pattern of protein synthesis as detected by the present method. Among the proteins greatly affected by the temperature shift-up were those with apparent molecular weights fo 87,000 (87K), 76K, 73K, 64K, and 61K. Two of them (64K and 61K) were found to be precipitated with specific antiserum against proteins that had previously been shown to have an adenosine triphosphatase activity. The bearings of these findings on bacterial adaptation to variation in growth temperature are discussed.


Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid.

Construction and characterization of a class of multicopy plasmid cloning vehicles containing the replication system of miniplasmid P15A are described. The constructed plasmids have cleavage sites within antibiotic resistance genes for a variety of commonly employed site-specific endonucleases, permitting convenient use of the insertional inactivation procedure for the selection of clones that contain hybrid DNA molecules. Although the constructed plasmids showed DNA sequence homology with the ColE1 plasmid within the replication region, were amplifiable by chloramphenicol or spectinomycin, required DNA polymerase I for replication, and shared other replication properties with ColE1, they were nevertheless compatible with ColE1. P15A-derived plasmids were not self-transmissible and were mobilized poorly by Hfr strains; however, mobilization was complemented by the presence of a ColE1 plasmid within the same cell.


Does cycloheximide-induced loss of phosphate uptake activity in Neurospora crassa reflect rapid turnover?

Addition of cycloheximide to Neurospora crassa germlings growing in liquid medium caused an exponential loss of phosphate uptake activity (half-life, ca. 2 h). No loss of activity resulted when germlings were resuspended, at the time of cycloheximide addition, in medium of a substantially lower phosphate concentration. It is concluded that the phosphate uptake systems are not subject to rapid turnover.


Mu-induced polarity in the unc operon of Escherichia coli.

Mutant strains of Escherichia coli were isolated in which mutator (Mu) phage was inserted into various unc genes. Partial diploid strains were prepared from each of the Mu-induced unc mutants by using F-plasmids carrying mutations in one of the known unc genes (uncA, uncB, uncC, or uncD). The partial diploid strains and the corresponding segregant strains were examined for their ability to grow on succinate. The aerobic growth yields on limiting concentrations of glucose were also determined. Magnesium-stimulated adenosine triphosphatase activities, ATP-dependent transhydrogenase activities, and Atebrin fluorescence quenching activities were determined by using membrane preparations from each strain. Genetic complementation was assessed from the results obtained, and it was concluded that the four unc genes examined are part of a single transcriptional unit and that they are transcribed in the order uncBADC.


Biochemical and genetic study of D-glucitol transport and catabolism in Bacillus subtilis.

The catabolic pathway of D-glucitol (sorbitol) in Bacillus subtilis Marburg 168M is characterized. It includes (i) a transport step catalyzed by a D-glucitol permease which is affected by the gutA mutations, (ii) an oxidation step of the intracellular D-glucitol catalyzed by a D-glucitol dehydrogenase, generating intracellular fructose, affected by gutB mutations, and (iii) phosphorylation of the intracellular fructose either at the C1 site or at the C6 site as described previously (A. Delobbe et al., Eur. J. Biochem., 66:485-491, 1976; A. Delobbe et al., EUR. J. Biochem. 51:503-510, 1975). Additional data are given concerning the phosphorylation of fructose by a fructokinase (fructose ATP 6-phosphotransferase), which is affected by the fruC mutation. The isolation of regulatory mutants affected in gutR that synthesize constitutively both the permease and the dehydrogenase indicates the existence of a D-glucitol operon in B. subtilis. Unlike the wild-type strain, these mutants are able to utilize D-xylitol as sole carbon source.


Electron transport phosphorylation coupled to fumarate reduction by H2- and Mg2+-dependent adenosine triphosphatase activity in extracts of the rumen anaerobe Vibrio succinogenes.

Vibrio succinogenes, an anaerobic bacterium, obtains its energy for growth from H2 or formate oxidation coupled to the reduction of fumarate to succinate. Membrane preparations have been obtained from this organism that catalyze the synthesis of ATP during H2 oxidation coupled to fumarate reduction. Esterification of orthophosphate is dependent on electron transfer, as evidenced by the requirement for both H2 and fumarate. Phosphorylation is also dependent on ADP and is destroyed by boiling the membrane preparations. H2 utilized for fumarate reduction and succinate formed are stoichiometric. The phosphorylation is markedly uncoupled by pentachlorophenol and gramicidin, but to a lesser extent by dinitrophenol and methyl viologen. 2-n-Heptyl-4-hydroxyquinoline-N-oxide causes severe inhibition of H2 oxidation as well as phosphorylation, but oligomycin or antimycin A has no demonstrable effect. Among several electron acceptors tested, significant phosphorylation is observed only with fumarate. A Mg2+-dependent adenosine triphosphatase activity is present in both the membrane and soluble protein fractions. Highest activity is obtained with ATP as the substrate, and considerably less activity is obtained with other nucleoside triphosphates. The possibility that phosphorylation during "fumarate respiration" may play an important physiological role in the growth of many anaerobic and facultatively anaerobic bacteria is discussed.


Calcium sensitivity of mantle muscle of squid.

Ca2+-sensitivity of squid muscle proteins was studied by competition tests between squid actin and carp myosin on squid myosin B and by cross combination tests between squid myosin and actin and between carp myosin and squid thin filament fraction. The results suggest that the regulatory system of the squid mantle muscle is actin-linked as in skeletal muscle rather than myosin-linked. This view is supported by the presence of troponin-like components on SDS-disc electrophoresis of squid thin filament fraction.


Observation of steady streamings in a solution of Mg-ATP and acto-heavy meromyosin from rabbit skeletal muscle.

Steady streaming of the solution was observed for more than one and a half hours in a circular slit between two concentric cylinders where rabbit skeletal F-actin was fixed on to the wall of the slit and heavy meromyosin was in the Mg-ATP solution in the slit. The streaming only appeared when the actomyosin-ATPase activity was present in the system.


Preparative study on the isolation of single sarcomeres from rabbit skeletal muscle.

Single sarcomeres were prepared from fresh rabbit myofibrils by digestion with a calcium-activated factor (CAF). The rabbit single sarcomere has functional properties quite similar to those of single sarcomeres obtained from chicken muscle by a usual method. Thus it was found that the single sarcomeres obtained by CAF digestion were useful as a muscle model, though they were not completely intact.


Properties of membrane adenosine triphosphatase of the obligately anaerobic bacterium Veillonella alcalescens.

Some properties of membrane ATPase activity in Veillonella alcalescens were examined. Mg2+ is required for the activity of the enzyme, and Ca2+ also activates the enzyme to some degree. Of the nucleotide triphosphates, GTP and ITP were hydrolyzed to a lesser extent than ATP. The apparent Km for ATP hydrolysis was 0.25 to 0.63 mM. ADP inhibited the enzyme and the kinetic data of its inhibition showed that the presence of ADP resulted in positive cooperativity. The enzyme activity was strongly inhibited by DCCD, azide, fusidic acid and the antibody to purified soluble ATPase from the thermophilic bacterium PS3. Oligomycin, dinitrophenol, and ouabain showed no significant effect.


Preparation of a myosin-extracted "ghost" myofibril Sephadex conjugate column and its application to the separation of myosin subfragment-1 giving and not giving the initial burst of phosphate.

A "ghost" myofibril (myosin-extracted myofibril) Sephadex conjugate which specifically binds myosin, HMM and S-1 in the absence of Mg-ATP or Mg-PP can be prepared in a few days by conjugating "ghost" myofibrils to Sephadex beads. Binding ability is retained for over a month. It is used, therefore, for actin-affinity chromatography of myosin and its active fragments. It is under debate whether the two heads of the myosin molecule are functionally identical. Recently several reports have indicated that S-1 could be separated into two kinds of S-1, one giving the initial burst of phosphate and the other not, by assuming a difference in the affinity of the two kinds of S-1 to F-actin. Attempts are reported here to obtain these two components of S-1 separately by using the "ghost" myofibril Sephadex conjugate column. The method of S-1 separation reported by Shibata-Sekiya and Tonomura ((1976) J. Biochem, 80, 1371-1380), which used S-1 treated with CMB, was applied to the "ghost" myofibril Sephadex conjugate column. This resulted in the successful separation of S-1 modified with CMB giving no initial burst of phosphate and unmodified S-1 giving the initial burst of phosphate. A separation method based essentially on the principle employed by Taniguichi and Tawada ((1976) J. Biochem. 80, 853-860) gave an unsuccessful result.


Effects of tryptic digestion on the enzymatic activites of chicken gizzard myosin.

Tryptic digestion of gizzard myosin resulted in the degradation of the 20K light chain (G1) to its 17K fragment, which could not be phosphorylated. The rapid loss of Ca2+-dependent activation of actomyosin ATPase activity accompanied the degradation of G1. Increase in the Ca2+-ATPase activity and decrease in the EDTA-ATPase activity of myosin accompanied the degradation of myosin heavy chain, but not the cleavage of G1.


Myosin-like protein and actin-like protein from Escherichia coli K12 C600.

Myosin-like protein was obtained from E. coli by extraction with a sucrose solution and by precipitation with rabbit skeletal actin. The preparation of E. coli myosin-like protein looked very similar, in the sodium dodecyl sulfate-gel electrophoretic pattern, to that of rabbit skeletal myosin. The myosin-like protein was able to reversibly bind to rabbit actin. It had the activities of EDTA-, Ca-, and Mg-ATPases. The product in the EDTA-ATPase reaction catalyzed by the myosin-like protein was identified as ADP by ion exchange chromatography. The Mg-ATPase activity of E. coli myosin-like protein was activated by either rabbit actin or E. coli actin-like protein though the activation was much stronger by the latter. However, the myosin-like protein did not exhibit superprecipitation either with rabbit actin or with E. coli actin-like protein. Actin-like protein was also obtained from E. coli by essentially the same procedures as those described for preparation of rabbit skeletal actin. E. coli actin-like protein was capable of activating Mg-ATPase of rabbit myosin, and also of superprecipitation with rabbit myosin. Extraction from both the whole cells and the membrane fraction of E. coli strongly suggested that the myosin-like protein and the actin-like protein are both localized in the membrane fraction rather than in the cytoplasmic fraction.


Nuclear mutations conferring oligomycin resistance in Neurospora crassa.

Mutants of Neurospora crassa have been isolated that are highly resistant to inhibition by oligomycin, an inhibitor of mitochondrial ATPase activity. Dixon plots (Dixon, M., and Webb, E.C. (1964) Enzymes, 2nd Ed, pp. 328-330, Academic Press, New York) of oligomycin inhibition curves of the parent strain and the resistant mutants are linear, indicating that oligomycin interacts at a single site within the ATPase complex. The Ki values obtained from the mutants vary from 150 to 900 times greater than the Ki obtained for the parent strain. The parent strain and the oligomycin-resistant mutants are also inhibited by bathophenanthroline, a lipophilic chelating agent that inhibits F1 ATPase activity. Dixon plots of bathophenanthroline inhibition curves are also linear and Ki values obtained are all approximately equal. Crosses of the oligomycin-resistant mutants to the oligomycin-sensitive parent strain show a mendelian segregation of the resistance characteristic. These data show that mutations leading to oligomycin resistance in Neurospora are due to alterations in nuclear genes.


Kinetic studies on bacterial plasma membrane ATPase (F1). Nucleotide-induced long term inactivation of ATP hydrolyzing activity is linked to the formation of multiple "tight" enzyme nucleotide complexes.

ADP and the ATP analogs Nb-S6ITP (6-[(3-carboxy-4-nitrophenyl)thio]-9-beta-D-ribofuranosylpurine 5'-triphosphate) and AMP-P(NH)P (adenyl-5'-yl imidodiphosphate) interact with soluble plasma membrane ATPase (F1) from Micrococcus species in two ways: (i) at short incubation times, these inhibitors exhibit the kinetics of competitive inhibition, (ii) at long incubation times, these inhibitors induce an inactivation of the ATPase which can be reversed only in the case of AMP-P(NH)P. Kinetic treatment of the long term inactivation by ADP or Nb-S6ITP reveals a pseudo-first order process via the formation of an enzyme-inhibitor complex for which a Km analogous constant is obtained that is identical with the corresponding Ki value of the competitive inhibition. The long term inactivation by ADP and Nb-S6ITP involves the successive "tight" binding of 6 +/- 1 nucleotides/F1 molecule. One additional ADP molecule/F1 complex which is also "tightly" bound has no effect on the ATPase activity. The long term inactivation by ADP and Nb-S6ITP is inhibited at higher inhibitor concentrations according to a kinetics analogous to a substrate excess inhibition. Evidence is presented indicating that the mechanism of ATP hydrolysis by F1 and the long term inactivation by ADP or Nb-S6ITP are related processes. The mechanism of long term inactivation by AMP-P(NH)P appears to be different from that of ADP or Nb-S6ITP.


Phosphofructokinases from Escherichia coli. Purification and characterization of the nonallosteric isozyme.

The main phosphofructokinase of Escherichia coli (PFK I) is an extensively studied allosteric enzyme specified by the pfkA gene. A nonallosteric phosphofructokinase was reported (Fraenkel, D.G., Kotlarz, D., and Bluc, H. (1973) J. Biol. Chem. 248, 4865-4866) in strains carrying the pfkB1 mutation, a suppressor of pfkA mutants, and very low levels of this enzyme have also been detected in strains not carrying the suppressor (i.e. pfkB+). The nonallosteric protein has now been prepared pure from three strains, one carrying pfkB1 and pfkA+, one carrying pfkB1 and completely deleted for pfkA, and one carrying pfkB+ and also deleted for pfkA. It is apparently the same enzyme (PFK II) in all three strains, which shows that pfkB1 is a mutation affecting the amount of a normally minor isozyme. PFK II is a tetramer of slightly larger subunit molecular weight than PFK I (36,000 and 34,000, respectively). No immunological cross-reactivity was detected between PFK II and PFK I. Unlike PFK I, PFK II does not show cooperative interactions with fructose-6-P, inhibition by P-enolpyruvate, or activation by ADP. Also unlike PFK I, PFK II is somewhat sensitive to inhibition by fructose-1,6-P2 and can use tagatose-6-P as substrate. Both enzymes can perform the reverse reaction, fructose-6-P + ATP from fructose-1,6-P2 + ADP in vitro, but not in vivo. The normal function of PFK II is not known.


Purification and characterization of 3-dehydroshikimate dehydratase, an enzyme in the inducible quinic acid catabolic pathway of Neurospora crassa.

3-Dehydroshikimate dehydratase catalyzes the third reaction in the inducible quinic acid catabolic pathway of Neurospora crassa and is encoded in the qa-4 gene of the qa gene cluster. As part of continuing genetic and biochemical studies concerning the organization and regulation of this gene cluster, 3-dehydroshikimate dehydratase has been purified and characterized biochemically. The enzyme was purified 1650-fold using the following techniques: 1) (NH4)2SO4 fractionation; 2) ion exchange chromatography on DEAE-cellulose; 3) gel filtration on Sephadex G-100; 4) ion exchange chromatography on Cellex QAE (quaternary aminoethyl); and 5) hydroxylapatite chromatography. 3-Dehydroshikimate dehydratase is a monomer with a molecular weight of about 37,000 and a sedimentation coefficient of 3.27 S. It has a Km value of 5.9 X 10(-4) and an average isoelectric point of 4.92. The purified enzyme is extremely sensitive to thermal denaturation but can be significantly stabilized by Mg2+ ions. The purified enzyme also exhibits maximal catalytic activity only when assayed in the presence of certain divalent cations, e.g. magnesium. The NH2-terminal residue of 3-dehydroshikimate dehydratase is proline, and its alpha-amino group is unblocked.


Purification of the Ca2+-stimulated ATPase activator from human erythrocytes. Its membership in the class of Ca2+-binding modulator proteins.

The activator of the Ca2+-stimulated ATPase of erythrocyte membranes was purified 13,000-fold to homogeneity from human erythrocytes. The protein gave a single band upon electrophoresis both with and without detergent, and upon isoelectric focusing. This protein was compared with Ca2+-binding modulator proteins from bovine brain and rat testis. All three proteins were homogeneous and co-migrated on electrophoresis both in the presence of detergent and without detergent at pH values on both sides of the isoelectric point of the protein. The amino acid compositions of the three proteins were nearly indistinguishable, and all three proteins contained 1 residue of the unusual amino acid, trimethyllysine. All three were also indistinguishable as measured by their ability to further stimulate the Ca2+-stimulated ATPase of human erythrocyte membranes. Thus, we conclude that they represent functionally the same protein. Upon storage of all three proteins, a second band was detectable by detergent gel electrophoresis; the biochemical activity and the behavior on nondetergent gels were not changed. The presence of this second band is probably responsible for previous reports of differences between the rat testis and bovine brain modulator protein. The possibility is discussed that this protein is a general intracellular Ca2+ receptor, which mediates the activities of Ca2+ as an intracellular messenger.


Characterization of a second myosin from Acanthamoeba castellanii.

We purified a 400,000 molecular weight myosin, myosin-II, from Acanthamoeba castellanii. The sequence of ion exchange chromatography, actomyosin precipitation, actin extraction, and gel permeation chromatography yields per 100 g of cells about 11 mg of myosin-II which is 90 to 96% pure. ATPase activity is highest in the presence of Ca2+, but the enzyme is also active in EDTA provided high concentrations of K+ are present. The molecule consists of two 175,000 molecular weight heavy chains, one or two 17,500 molecular weight light chains, and two 16,500 molecular weight light chains. Myosin-II is rich in acidic residues and contains about 32 residues of cysteine/mol. The sedimentation coefficient is 5.9 S. Intrinsic viscosity is 126 cc/g. By equilibrium ultracentrifugation, the molecular weight averages depended upon the initial loading concentration in a way that suggested a 400,000 molecular weight species is in equilibrium with a 200,000 molecular weight species. By electron microscopy the molecule was seen to have two globular heads at one end of a tail 90 nm long. In KCl solutions of less than 0.25 M, the myosin-II tails self-associate to form the backbone of very small (6.6 x 205 nm) bipolar filaments with central bare zones 97 nm long. Myosin-II binds to actin filaments, forming periodic arrowhead-shaped complexes, but its Mg2+ ATPase activity is activated only 50% or less by actin. When radioactive myosin-II is incubated up to 90 min in unlabeled Acanthamoeba homogenates, it is not degraded into smaller fragments, such as the 190,000 molecular weight myosin-I. Our observations and the detailed enzymatic data presented by Maruta and Korn ((1977) J. Biol. Chem. 252, 6501-6509) argue that the smaller Acanthamoeba myosin-I (Pollard, T. D., and Korn, E. D. (1973) J. Biol. Chem, 248, 4682-2690) does not arise by fragmentation of myosin-II in the homogenate or extract.


Effect of phosphate esters, nucleotides and nucleosides on 5'-nucleotidase of cultured mouse macrophages.

Mouse peritoneal macrophages elicited by intraperitoneal injection of sodium caseinate exhibit low levels of ecto-5'-nucleotidase (E. C. 3.1.3.5) activity in contrast to macrophages obtained by peritoneal lavage. When elicited cells were cultured under standard conditions in the presence of serum, a 2.5-fold increase in 5'-nucleotidase activity was observed over a period of 48 hours. Addition of adenosine monophosphate to the culture medium led to an augmented (5-fold) increase in the specific activity (per unit cell protein) as well as an absolute increase (per culture plate) of 5'-nucleotidase. Other adenosine-containing compounds also had stimulatory effects. The levels of this enzyme thus appear to be regulated by the extracellular levels of adenosine nucleotides. The product of the enzymatic reaction--adenosine--when added to the medium exhibited a toxic effect on these cells--as did adenosine monophosphate. However, the former substance did not augment the increase in enzyme activity during culture. The toxic effect could be suppressed when the cells were cultured in the presence of uridine 5'-monophosphate. The latter substance also depressed the stimulation of enzyme activity due to AMP.


[Urine steroid profiles of hirsute women (author's transl)].

Steroid profiles of women suffering from idiopathic hirsutism show in more than 50% of the cases of 10--100 fold increase in the excretion of dehydroepiandrosterone (DHEA) compared with normal values. The excretion of DHEA was reduced much more than that of other 17-ketosteroids if the adrenals (NNR) were suppressed by dexamethasone (DXM). Within one week they reached values at the compound noise level of the gas chromatograms. If the ovaries were stimulated with human chorionic gonadotropin during continued suppression of the NNR with DXM no increase of DHEA could be detected.


Separation of androsterone from epiandrosterone, and dehydroepiandrosterone from its 3-hydroxy epimer by thin-layer chromatography.

The application of thin-layer chromatography to the separation of 13 steroids, including androstanes, 4-androstenes and 5-androstenes, using silica gel and 1,2-propanediol-impregnated cellulose is described. After group-wise separation of various C19 steroids on silica gel, the 3-hydroxy epimers of 5alpha-androstanes and 5-androstenes can be separated by thin-layer chromatography on impregnated cellulose plates. The chromatographic procedure is rapid and makes the prior formation of steroid derivatives unnecessary.


Impaired cell-mediated immunity in Hodgkin's disease mediated by suppressor lymphocytes and monocytes.

In Hodgkin's disease a possible mechanism for impaired cellular immunity is cell-mediated suppression, defined as the inhibitory interaction between suppressor cells and effector lymphocytes. To test for the presence of suppressor cells in peripheral blood, we have modified the standard, one-way mixed lymphocyte culture by adding mitomycin C-treated mononuclear cells from the responder. Suppression, expressed as a percent of the base-line mixed lymphocyte culture in which these extra cells are not present, results in a reduction of thymidine incorporated in the modified culture (i.e., 100% suppression = no net thymidine incorporation; 0% suppression = identical thymidine incorporation in both the modified and baseline culture). Suppression was found to be significantly increased in patients with both active Hodgkin's disease (78+/-4.6%) and remission Hodgkin's disease (58+/-9.3%) compared to normal individuals (21+/-6.9%) (mean+/-SE). The degree and frequency of suppression were not influenced by disease stage or prior therapy. Cell purification techniques revealed (in 10 patients studied) the suppressor cell to be a monocyte in 6, and a thymus-derived lymphocyte in 4. Possible genetic restriction of the suppressor cell interaction was indicated by a failure of suppressor cells to alter the response of lymphocytes from unrelated individuals, but suppression was obtained with lymphocytes from a histocompatible sibling. Although mononuclear cells from normal individuals suppress less frequently than cells from patients with Hodgkin's disease, normals may demonstrate suppression comparable to that observed in Hodgkin's patients. This finding suggests that suppression is a normal immunoregulatory mechanism which is altered in Hodgkin's disease.


Effect of aminoglutethimide on blood pressure and steroid secretion in patients with low renin essential hypertension.

An inhibitor of adrenal steroid biosynthesis, aminoglutethimide, was administered to seven patients with low renin essential hypertension, and the antihypertensive action of the drug was compared with its effects on adrenal steroid production. In all patients aldosterone concentrations in plasma and urine were within normal limits before the study. Mean arterial pressure was reduced from a pretreatment value of 117+/-2 (mean+/-SE) mm Hg to 108+/-3 mm Hg after 4 days of aminoglutethimide therapy and further to 99+/-3 mm Hg when drug administration was stopped (usually 21 days). Body weight was also reduced from 81.6+/-7.2 kg in the control period to 80.6+/-7.0 kg after 4 days of drug treatment and to 80.1+/-6.7 kg at the termination of therapy. Plasma renin activity was not significantly increased after 4 days of treatment but had risen to the normal range by the termination of aminoglutethimide therapy. Mean plasma concentrations of deoxycorticosterone and cortisol were unchanged during aminoglutethimide treatment whereas those of 18-hydroxydeoxycorticosterone, progesterone, 17alpha-hydroxyprogesterone, and 11-deoxycortisol were increased as compared to pretreatment values. In contrast, aminoglutethimide treatment reduced mean plasma aldosterone concentrations to about 30% of control values. Excretion rates of 16beta-hydroxydehydroepiandrosterone, 16-oxo-androstenediol, 17-hydroxycorticosteroids and 17-ketosteroids, and the secretion rate of 16beta-hydroxydehydroepiandrosterone were not significantly altered by aminoglutethimide treatment whereas the excretion rate of aldosterone was reduced from 3.62+/-0.5 (mean+/-SE) in the control period to 0.9+/-0.2 mug/24 h after 4 days and to 1.1+/-0.3 mug/24 h at the termination of aminoglutethimide treatment. The gradual lowering of blood pressure and body weight during aminoglutethimide therapy is consistent with the view that the antihypertensive effect of the drug is mediated through a reduction in the patients' extracellular fluid volume, probably secondary to the persistent decrease in aldosterone production. The observation that chronic administration of aminoglutethimide lowered blood pressure in these patients and elevated their plasma renin activity to the normal range without decreasing production of the adrenal steroids, deoxycorticosterone, 18-hydroxydeoxycorticosterone, and 16beta-hydroxydehydroepiandrosterone, makes it unlikely that these steroids are responsible either for the decreased renin or the elevated blood pressure in patients with low renin essential hypertension.


Systolic anterior motion of the tricuspid valve in idiopathic hypertrophic subaortic stenosis.

A 37 year man with combined subpulmonic and subaortic idiopathic hypertrophic stenosis proved by cardiac catheterization had typical echocardiographic findings of idiopathic hypertropic subaortic stenosis (IHSS) and systolic anterior motion of the anterior leaflet of the tricuspid valve. This motion of the tricuspid valve may relate to the subpulmonic infundibular gradient in the same way that the systolic anterior motion of the anterior mitral leaflet relates to the subaortic left ventricular gradient in patients with IHSS.


Echocardiographic and clinical correlations in systemic hyper-tension.

Echocardiographic measurements in 47 asymptomatic hypertensive patients were correlated with duration and severity of blood pressure elevation and with optic fundoscopic findings. These observations were also compared with electrocardiographic and chest roentgenographic measurements. Echo left ventricular wall thickness (LVWT) correlated best with duration of known hypertension. For 22 recent hypertensive patients the LVWT mean was .9 +/- .3 cm whereas mean LVWT for 25 patients hypertensive for five or more years was 1.3 +/- .2, (p less than or equal to .01). More severe initial diastolic pressure and the presence of hypertensive fundi also correlated with increased wall thickness. Increased left atrial diameter (greater than or equal to 2 cm m2) was observed primarily in the presence of longstanding disease. ECG and cardiothoracic ratio by xray did not correlate highly with the echo abnormalities. These observations suggest that echocardiography may be a sensitive and early means of recognizing cardiac changes in hypertensive patients.


[Enzymatic ocular hypertension: a statistical study (author's transl)].

The authors have carried out a statistical study on two large groups of patients operated on for cataract and in whom the enzyme alph-chymotrypsin has been used, and the occurrence of ocular hypertension has been examined. One group, which contained 1,003 operations most of which were under the microscope using a firm closure technique, was compared with another group of 324 cases operated under the same conditions but without using the enzyme. In all cases the intraocular pressure was measured 24-48 hours after the operation. The rise in pressure, the rapidity of its development were studied together with its duration and the concentration of the enzyme. In addition these findings were compared with another group of 2,334 eyes operated on several years previously with standard techniques using a less hermetic wound suture, without a microscope, with alpha-chymotrypsin, but whose tensions were controlled from the third week. The results show conclusively that there is a greater frequency of the occurrence of raised intra-ocular pressure when the enzyme is used (40,3%) than when it is not used (25,3%). This ocular hypertension persists in all cases to the end of three weeks. The time of the appearance of the hypertension, the numbers affected and the duration of the intraocular pressure were not significantly meaningful in the statistical analysis.


[The frequency of alterations of the lipid and hydrocarbon levels in retinal detachment].

The biological lipid levels and hyperglycaemia measured in patients of varying ages with retinal detachment have shown that:--in 59.7% there is a hyperlipaemia or hyperlipoproteinaemia. This is more usually a hyperpre-beta-lipoproteinaemia (37.1%);--in 32% a disturbance of lipid metabolism was associated with a disturbance of glucose metabolism: diabetes or a pre-diabetic state;--49% of patients affected with hyperlipidaemia present with a clinical vascular condition;--42% of all the patients present with a clinical vascular condition. The numbers are considerable and they show the frequency of atherogenic factors in retinal detachment.


Teaching self-hypnosis to patients with chronic pain.

For the past twenty years hypnotherapy and self-hypnosis have been utilized as valid tools for the successful management of severe protracted pain. Control often has been achieved in cases where other modalities of pain management had been inadequate. Hypnosis properly applied can bring some degree of improvement to 90 percent of patients. More remarkable degree of pain relief is achievable in the 25 percent of patients who have high hypnotic "talent," and with very limited expenditure of time and effort. The author discusses basic theories of pain, pain-control pain-control and hypnosis, and he clarifies the effects of physiological, biochemical, and psychological variables which can affect the procedures and the results. Presentation of a clinical case with quoted excerpts of verbalization serves to illustrate the most important points.


Progressive changes in cytotoxic potential during mixed lymphocyte culture.

In a previous study it was shown that at least one round of DNA synthesis is required for initial expression of cytotoxic function in mouse lymphocytes responding to alloantigen in vitro. In the experiments reported here we ask whether subsequent rounds of cell division are required simply for clonal expansion of this initial level of cytotoxic function within the population, or whether the amount of cytotoxicity per cytotoxic cell is altered during subsequent rounds of cell division. The amount of cytotoxicity per unit number of cells at various stages of culture was compared with the frequency of cytotoxic cells as estimated principally by effector-target cell conjugates. Our results strongly suggest that the amount of cytotoxicity per cell (cytotoxic potential) is not a static property of cytotoxic cells, but can be modulated up or down during the course of a reaction.


Activation of human B lymphocytes. IX. Modulation of antibody production by products of activated macrophages.

Human monocytes, after in vitro activation by mixed lymphocyte culture (MLC) supernatants produce a monokine (MK) that enhances the plaque-forming cell (PFC) response of pokeweed mitogen (PWM)-stimulated human B lymphocytes. Technical conditions and kinetics of MK production were established. Irradiation of monocytes (5000 rads) does not abolish MK production but heat-killed cells are unable to release the factor. Highly T cell-depleted monocyte populations still produced the PFC-enhancing factor. The same MK has an inconsistent enhancing effect on the PFC responses of lipopolysaccharide (LPS) and nocardia water-soluble mitogen (NWSM)-stimulated B cells. Other macrophage activators such as LPS, phytohemagglutinin (PHA), and latex particles failed to induce consistently the liberation of the PFC-enhancing MK. The target cell for the MK activity on PWM-stimulated B cells appears to be the B lymphocyte itself. These studies demonstrate that soluble monocyte products can have substantial modulatory effects on human B cell function.


Effects of costimulator on immune responses in vitro.

We recently described a factor, costimulator, that is required for the concanavalin A-induced proliferation of CBA mouse thymocytes in vitro (see Reference 1). Using the costimulator dependence of mouse thymocytes as an assay, we have now determined that spleen cells from congenitally athymic (nude) BALB/c mice do not produce costimulator in response to Con A,  and spleen cells depleted of Thy 1-positive cells do not respond to it in the presence of Con A. Thus, costimulator both requires thymus-derived (Thy 1+ lymphocytes for its production and has an effect on this type of cell. (However, the costimulator-producing and responsive cells may be different.) Purified costimulator preparations are a source of the required second component for the stimulation of adult, CBA/J thymic lymphocytes by PHA, normally a poor mitogen for these cells. They also enhance the level of DNA synthesis in a mixed leukocyte reaction, and the specific generation of cytotoxic lymphocytes to allogeneic tumor cells in vitro. Costimulator is not H-2 restricted in its effects, and it is produced in mixed leukocyte reactions. Finally, it has been possible to grow normal, primary thymic lymphocytes in culture for about 20 days by adding partially purified costimulator to the cultures.


Renal handling of lysozyme in experimental Fanconi syndrome.

The relationship between lysozyme and sodium reabsorption by the kidney tubule was studied in the experimental Fanconi syndrome. Female, anesthetized Sprague-Dawley rats were injected intravenously with maleic acid (an inhibitor of sodium transport) neutralized with sodium hydroxide in doses of either 2 or 8 mmol/kg. Clearance studies were performed immediately afterward, and plasma and urine were analyzed for inulin, pH, sodium, glucose, and lysozyme. Two hours after the maleic acid injection, renal cortical tissue was removed and homogenized. Specific activity of Na-K-ATPase was assayed in the light microsomal fraction. The results showed that both concentrations of maleic acid caused significant increases in urinary volume, glucose excretion, and pH. There were significantly correlated decreases in TNafract and TLyfract. The slope of the regression line (TLyfract = 1.03 TNafract - 5.82; r = 0.92) approximated unity. Renal cortical Na-K-ATPase activity was significantly decreased by 25% in the animals receiving 2 mmol maleic acid and 43% in the animals receiving 8 mmol. The evidence suggests that lysozyme reabsorption in the proximal tubule might be mediated directly or indirectly by active tubular transport of sodium, a process that is related to the Na-K-ATPase transport system.


Hypertrophy or dilatation? A vectorial analysis of echocardiographically determined left ventricular enlargement.

Echocardiograms (ECHO) and Frank vectorcardiograms (VCGs) were obtained in three groups of patients: Group I (n = 16), concentric left ventricular hypertrophy (LVH) with increased interventricular septal (IVS) and left ventricular posterior wall (LVPW) thickness in the presence of a normal left ventricular internal dimension (LVID); Group II (n = 17), left ventricular dilatation (LVD) with an enlarged LVID, normal IVS and LVPW thickness, and Group III (n = 22), no catheterization evidence of heart disease with normal IVS, LVPW and LVID. VCGs were analyzed with respect to magnitude of the QRS maximal deflection vector (MDV) and +/- 10 msec QRS vectors, horizontal plane (HP) maximal posterior force, time of HP MDV inscription, distal and proximal HP loop areas and HP loop configuration utlizing criteria of Varriale et al. The results indicate that: 1) HP QRS vector magnitude cannot reliably differentiate concentric LVH from isolated LVD and 2) proximal-distal loop area relationships and pattern of the HP QRS loop, when reviewed together, are superior to other criteria for distinguishing whether ECHO determined LVH or LVD is the primary correlate of an enlarged left ventricle.


Anterior QRS loop in hypertrophic cardiomyopathy.

Frank vectorcardiograms (VCGs) were reviewed in 45 patients with hypertrophic cardiomyopathy (HCM), 26 with obstruction and 19 without obstruction. Twelve of the 19 patients without obstruction and five of the 26 patients with obstruction were found to have predominantly anterior QRS loops. Fourteen patients had a large left anterior QRS loop with increased anterior and leftward force; the posterior and terminal rightward force were within the normal range, and the T loops were displaced posteriorly and to the right opposite to the QRS loop. Asymmetric septal and apical hypertrophy were noted echocardiographically and/or angiographically. Increased electrical force from the asymmetric hypertrophy of the septal and apical area is proposed to explain this large left anterior loop. Three patients had a QRS loop located anteriorly and to the right with electrocardiograms (ECGs) resembling those of posterolateral myocardial infarction or right ventricular hypertrophy. These finding suggest that (1) hypertrophic cardiomyopathy may be another cause of an anterior QRS loop; (2) the recognition of the large left anterior loop in the VCG in patients with a left ventricular hypertrophy pattern in the ECG is helpful in the diagnosis of HCM, especially the nonobstructive form; and (3) hypertrophic cardiomyopathy should be considered in the differential diagnosis of myocardial infarction or right ventricular hypertrophy.


Vectorcardiographic criteria of high posterior infarction: differentiation from normal subjects, right ventricular hypertrophy and primary myocardial disease.

In order to differentiate the vectorcardiogram (VCG) in high posterior infarction (HPI) from VCGs of normal subjects, right ventricular hypertrophy (RVH) and primary myocardial disease (PMD), the following criteria were presented; cases satisfying the criteria could be diagnosed as high posterior infarction. In cases with posterior component/anterior component (P/L) less than 1.0 (Group A); (1)--45 degrees vector/ab less than or equal to 0.25, (2) the maximal T vector in the horizontal plane greater than or equal to + 20 degrees, (3) I (inferior component)/L (left component) less than 1.0 and (4) no anterior convexity of the afferent limb of the left sagittal QRS loop. In cases with P/A greater than or equal to 1.0 (Group B);--45 degrees vector/ab less than or equal to 0.2, (2) the maximal T vector in the horizontal plane greater than or equal to + 20 degrees, (3) I/L less than 1.0 and (4) no anterior convexity of the affernt limb of the left sagittal QRS loop. Only one false negative case in HPI was found and only seven false positive cases in normal subjects, RVH and PMD. A correct diagnosis can be made with 97.4% accuracy. These criteria for differentiation were tested by reexamining the cases with selective coronary arteriography. Five cases satisfied the criteria of this method. Complete obstruction of the circumflex coronary artery was found in four of these cases, and severe stenosis (greater than or equal to 90%) in one case. Akinesis or hypokinesis of the posterobasal segment in the left ventricle was also observed in all five cases.


Isometric force development, isotonic shortening, and elasticity measurements from Ca2+-activated ventricular muscle of the guinea pig.

Isometric tension and isotonic shortening were measured at constant levels of calcium activation of varying magnitude in mechanically disrupted EGTA-treated ventricular bundles from guinea pigs. The results were as follows: (a) The effect of creatine phosphate (CP) on peak tension and rate of shortening saturated at a CP concentration more than 10 mM; below that level tension was increased and shortening velocity decreased. We interpreted this to mean that CP above 10 mM was sufficient to buffer MgATP(2-) intracellularly. (b) The activated bundles exhibited an exponential stress-strain relationship and the series elastic properties did not vary appreciably with degree of activation or creatine phosphate level. (c) At a muscle length 20 percent beyond just taut, peak tension increased with Ca(2+) concentration over the range slightly below 10(-6) to slightly above 10(-4)M. (d) By releasing the muscle length-active tension curves were constructed. Force declined to 20 percent peak tension with a decrease in muscle length (after the recoil) of only 11 percent at 10(-4)M Ca(2+) and 6 percent at 4x10(-6)M Ca(2+). (e) The rate of shortening after a release was greater at lower loads. At identical loads (relative to maximum force at a given Ca(2+) level), velocity at a given time after the release was less at lower Ca(2+) concentrations; at 10 M(-5), velocity was 72 percent of that at 10(-4)M, and at 4x10(-6)M, active shortening was usually delayed and was 40 percent of the velocity at 10(-4) M. Thus, under the conditions of these experiments, both velocity and peak tension depend on the level of Ca(2+) activation over a similar range of Ca(2+) concentration.


Exteroceptive vibration-induced finger flexion reflex in man.

A tonic finger flexion reflex, induced by mechanical vibration (100 Hz) of the fingers, was studied in 20 healthy subjects. The outcome of nerve blocking experiments indicated that the reflex is mainly exteroceptive, distinct from the tonic vibration reflex of muscle spindle origin. Mechanoreceptors with fast conducting nerve fibres in the distal phalanx seem to constitute the major afferent source. We suggest that afferent signals from such receptors by a feedback mechanism can influence the motor performance of the exploring fingers.


Histochemical changes in fast and slow muscles of nutritionally dystrophic rabbits.

Rabbits were rendered dystrophic by feeding them a diet deficient in vitamin E and their fast-twitch EDL and slow-twitch SOL muscles were examined histochemically. The soleus muscle of control rabbits consisted largely of type I fibres with occasional areas of scattered type II fibres. In the nutritionally dystrophic rabbits type II fibres were consistently found homogeneously distributed throughout the entire muscle and in increased proportion. A very similar pattern was observed in the solei of rabbits following sciatic nerve section. The normal EDL contained three fibre types (I, IIoxidative and IIglycolytic). Vitamin E deficiency appeared to be associated with a shift towards an increase in the proportion of IIglycolytic fibres at the expense of IIoxidative. In denervation as well as vitamin E deficiency the type I fibres of the EDL appeared to be spared. A small number of the E-deficient rabbits exhibited degenerative changes in their sciatic and sural nerves. When animals were both denervated and E-deprived the resulting muscle changes were very much more severe than in the case of either challenge in isolation. We suggest that although some of the signs of vitamin E deficiency resemble those of a neural defect there is, in addition, a direct myopathic effect.


Localization of fibrinolytic activity and inhibition of plasmin in the spinal cord of rat, guinea pig, and rabbit.

Fibrinolytic activity (caused by a plasminogen activator) in the spinal cord was highest in the rat, lowest in the rabbit, and intermediate in the guinea pig; In all species the activity was highest in relation to the pia mater. The central spinal canal was active in the rat and the rabbit, but mostly inactive in the guinea pig. Foci of activity were more numerous in the gray matter than in the white matter corresponding to the greater vascularity of the former. In all species ability to inhibit plasmin was related mainly to the gray matter, with an additional area related to the dura mater. The high fibrinolytic activity of the spinal leptomeninges may play a role in the pathogenesis of hemorrhagic processes related to the spinal cord.


Observations on the infectivity of parasitic third-stage larvae of Uncinaria lucasi Stiles 1901 (Nematoda: Ancylostomatidae) of Northern fur seals, Callorhinus ursinus Linn., on St. Paul Island, Alaska.

Twelve fur seal pups, which had not nursed their mothers, were used in an infectivity experiment. Pups were exposed to parasitic 3rd-stage larvae of Uncinaria lucasi from belly tissues of fur seal bulls, bachelors, and pregnant cows, to determine maturation capability of the larvae. Hookworms were not recovered from the intestines of 3 pups receiving larvae from belly blubber of bulls, 6 pups receiving larvae from belly blubber of bachelors, and 1 nonexposed pup. Maturation of hookworms did occur in 2 pups exposed to larvae from a mixture of belly blubber, mammary tissue, and milk of pregnant cows. Parasitic 3rd-stage hookworm larvae from belly tissues of pregnant and "non-pregnant" fur seal cows averaged 938.1 and 802.1 micron long, and 34.1 and 31.5 micron wide, respectively; however, larvae from belly tissues of a fur seal bull, bachelors, 2-year-old males, male and female yearlings and pups, and Steller Sea Lion subadults averaged 640.5-732.0 micron long and 20.9-24.9 micron wide.


Pediatric residents and young handicapped children: curriculum evaluation.

The systematic evaluation of a curriculum designed to improve the knowledge, skills, attitudes, and clinical judgment of pediatric residents with regard to young handicapped children and their families is described. Residents were assigned to experimental and control groups, and changes were analyzed across several dimensions. The results revealed a number of significant changes due to the implementation of the curriculum. In particular, knowledge of various aspects of handicapping conditions increased as did the tendency to characterize the behavior of handicapped children in a positive manner. In addition, an experimental design is presented that is uniquely compatible with scheduling factors during residency training.


Karyological and electron-microscopic studies in myocardial cells of primates after experimentally induced cardiac hypertrophy.

Precocious polyploidization in hypertrophic hearts of infants with congenital malformation can be reproduced banding the ascending aorta of young rhesus monkeys. Electron micrographs show hypoxic changes, signs of DNA, RNA, and protein synthesis as well as degenerative changes comparable to human hearts. Enforced polyploidization of cor pulmonale is found in rhesus exposed to coal quartz dust for 48 months. The pig heart, containing disturbed mitoses, serves as a model for incomplete mitoses. During evolution they became the rule for the myocardial cells of primates.


An epidemiology of physical conditions of destitutes (beggars) in Lagos.

This paper attempts to classify the destitutes (beggars) in Lagos by their physical handicaps (deformities) in order to provide necessary baseline data in planning for their effective rehabilitation. The study was carried out on 183 destitutes in Gbagada camp in Lagos. 121 (66.1%) destitutes had physical handicaps. The limbs were the most frequently affected parts (55.1%) followed by eyes (45.4%). About a third of those disabled had congenital deformities which were not treated in any hospital and another third acquired their disability through illness (e.g. common preventable communicable diseases). 105 (86.8%) of the disabled could benefit from training for vocational employment. The need for a free medical sevice and rehabilitation of the disabled destitutes in Lagos is highlighted.


The influence of etiology on the surgical management and prognosis of the massively dilated ureter in children.

The massively dilated ureter is a major therapeutic challenge that faces the pediatric urologist. In those instances when more conservative measures, such as control of infection or correction of the primary pathology, have failed or are likely to fail surgical treatment must be directed to the massively dilated ureter itself. The goals of reconstructive procedures are the elimination of residual urine, effective ureteral peristalsis, and efficient and/or urgent urinary drainage. We encountered these clinical settings in 244 children with 366 massively dilated ureters from 1965 through 1974. The underlying pathologic processes included primary megaureter, refluxing megaureter, posterior urethral valves, ureteral duplication with upper role ectopic ureterocele or lower pole refluxing megaureter, simple ureterocele, ureterovesical junction obstruction, neurogenic vesical dysfunction, prune belly syndrome and acquired (iatrogenic) megaureter. The results of several reconstructive techniques are reviewed according to the excretory urogram, cystogram, renal function studies and the presence or absence of urinary infection. Analysis of the results with respect to the underlying pathologic entity responsible for the massively dilated ureter indicates that the etiology is a crucial factor in determining whether surgical treatment should be recommended and the type of surgical treatment that will most likely be successful.


Curves of the achondroplastic spine: a new hypothesis.

The profile of the achondroplastic dwarf reflects abnormalities in the shape of the spine, particularly in the lumbosacral area. We hypothesize that these abnormalities and the resultant symptoms are secondary and avoidable rather than heritable and inevitable. Because the heads of achondroplastic children are enlarged (n = 50), loading of the vertical spine is increased. Unusually lax ligaments and misshapen vertebrae predispose the spine to yielding under vertical stress. Children and adults uniformly have hip flexion contractures (n 105); these are hypothesized to be the result of uncorrected lumbosacral lordosis. The volume of the spinal canal, reduced by the spinal stenosis of achondroplasia, is decreased additionally by lordosis; some neurologic deficits of achondroplasia are caused by this abnormal curvature. This hypothesis bears practically on treating this common form of dwarfism.


Response to experimental coarctation of the aorta and pulmonic stenosis in the fetal lamb.

The following conditions were surgically created in fetal lambs at the gestational ages of 80 to 90 days: (1) preductal coarctation, (2) postductal coarctation, (3) pulmonic stenosis, and (4) constriction of the ductus arteriosus. Studies performed at the time of delivery showed the following: Preductal coarctation and postductal coarctation often are associated with a dilated ductus arteriosus that remains patent. Pulmonic stenosis often results in prestenotic and poststenotic dilatation that may include the ductus arteriosus. The fetal ventricles become hypertrophied in response to the increased pressure work imposed by the distal stenoses.


Recovery from myocardial failure after aortic valve replacement.

Left ventricular hypertrophy and function were studied in 27 consecutive patients with chronic aortic valve disease before and 6.4 +/- 2.2 (S.D.) months after aortic valve replacement with Björk-Shiley prostheses. Four patients were excluded because of postoperative paravalvular regurgitation. Five patients had aortic stenosis (AS), seven patients AS plus insufficiency (AS-AI), and 11 patients aortic insufficiency (AI). Left ventricular muscle mass (LVMI), ejection fraction (EF), mean circumferential fiber shortening rate (VCF), mean normalized systolic ejection rate (MNSER), and peak systolic wall stress (PSWS) were determined angiographically. LVMI fell significantly after corrective surgery, whereas EF, VCF, and MNSER increased. PSWS decreased after the operation. Comparison of stress ventriculograms before and after surgery in six patients with predominant AS (isoproterenol infusion, 0.3 microgram per kilogram of body weight per minute) showed an increase of EF, VCF, and MNSER and a decrease of PSWS. We conclude that hypertrophy in chronic aortic valve disease regresses after aortic valve replacement, and thereby depressed cardiac function and reserve recover.


Anomalous left coronary arter from pulmonary trunk. Long-term follow-up after ligation.

Long-term follow-up (10 to 13 years) of four patients with anomalous left coronary artery who underwent ligation of the anomalous left coronary artery is presented. Two were operated upon in infancy and the other two at 6 and 7 years of age, respectively. Postoperatively, each is asymptomatic and doing well clinically. The cardiac size on roentgenogram of the chest returned toward normal in each. Abnormalities persist on the electrocardiogram. On treadmill exercise, the electrocardiogram of the two operated upon in infancy showed an abnormal result, whereas the two patients operated upon later in childhood had no electrocardiographic abnormalities.


Evaluation of a mental health educational project in Burma.

In attempting to evaluate a brief course on care of the mentally ill given to health personnel in Burma, experience suggested: (a) that post-course questionnaires asking participants to rate usefulness of the educational experience are useless in evaluation; (b) Assessments of clinical knowledge before and after the course were useful in guiding the teachers and assessing improvement in knowledge; (c) Data on treatment prescriptions given to patients by health personnel before and after the course might be a simple and inexpensive way of assessing impact on health care. Direct measurement of changes in attitudes and improvement of skills in health personnel and of the clinical outcome of patients they treat cannot be done economically and efficiently.


Energy coupling in liver mitochondria from dystrophic mice: differential sensitivity of oxidative phosphorylation and Ca2+ uptake to K+.

Studies were carried out to examine oxidative phosphorylation, cation uptake, and electrokinetic properties of liver mitochondria from genetically dystrophic mice in comparison with those from livers of littermate controls. While no differences were seen with respect to the rates of substrate oxidation, ADP/oxygen ratio, and RCl and cytochrome content, the mitochondria from the dystropic group were characterized by an elevated basal ATPase activity in the presence of NaCl. Additionally, these mitochondria were highly sensitive to high concentrations of exogenously added K+ that, besides stimulating state 4 respiration, caused uncoupling in the mitochondria. These mitochondria accumulated Ca2+ at a higher rate, and unlike the controls, Ca2+ uptake was not sensitive to exogenously added K+. It was also observed that the net negative charge on mitochondria decreased significantly in the dystrophic state. It is thus apparent that muscular dystrophy manifests itself also in terms of alteration in the membrane properties of liver mitochondria.


[Manganese concentration by microorganisms inhabiting the soils of a manganese biogeochemical province in Georgia].

The concentrating of manganese by microorganisms was studied with bacteria, actinomycetes and fungi inhabiting soils of the manganese biogeochemical province of the Georgian Republic with different content of this element (from 1045 to 296 000 mg/kg of dry weight). The amount (from 4.0 X 10(-3) to 10 per cent per dry substance) and character of manganese accumulation by microorganisms were found to depend on the content of this element in the growth medium, the taxonomic position of microorganisms, and their adaptation to geochemical conditions.


The role of trauma in disc protrusion.

An analysis of the carefully taken histories of 68 patients whose disc lesion was verified at operation showed that 72% of them gave a history of trauma at the onset of backache. The forces involved varied from very great to minimal and 28% had no history of trauma at all. Therefore it is concluded that trauma may be a precipitating but not a primary factor. It is suggested that the primary factor is a painless nuclear herniation into the inner layers of the annulus, which are painless because they have no innervation. Trauma causes the nucleus to rupture into or through the outer five or so innervated layers, precipitating pain and symptoms.


Growth of children with Down's syndrome: birth to age 3 years.

A sample of 90 children with Down's syndrome were measured for recumbent length and weight from birth to age 36 months at the Children's Hospital Medical Center in Boston. At birth, means for both length and weight were reduced by about 0.5 SDs from the control group means. By 36 months, mean recumbent length was greater than 2 SDs below that for the control group, while the mean for weight was reduced by about 1.5 SDs from the control group mean. Growth velocity for both length and weight was most deficient within the first two years of life. About 30% of the sample demonstrated excess weight for length relations by 36 months. Children with moderate or severe heart disease were significantly smaller than those without or with mild cardiac problems at all times after birth. Measurements of a subsample of children at 4, 5, and 6 years of age suggested that growth velocity after 3 years of age may be within the range of normal. Assessment of growth of the child with Down's syndrome may be carried out with reference to charts plotting tenth to 90th percentiles based on these data.


Acute pericarditis associated with hepatitis B infection.

Patients infected with hepatitis B have demonstrated a wide spectrum of clinical manifestations other than hepatitis. Immune complex formation has been proposed as a possible mechanism for such varied disease presentations. The present report describes a case in which acute pericarditis is associated with hepatitis B surface antigen-positive disease. Speculations are made relating the pericardial changes to the formation of immune complexes following hepatitis B virus infection.


The effect of graded immersion on heart volume, central venous pressure, pulmonary blood distribution, and heart rate in man.

The present experiments have been conducted to study the immediate effects of graded immersion on the central circulation. When taking heart volume as an indicator, it was found that immersion to the diaphragm of a standing subject produces the same changes as assumption of the supine posture. Heart volume increases by approximately 130 ml. When the water level is raised to the neck, an extra pressure corresponding to a water column extending from the diaphragm to the surface of the water of approximately 25 cm H2O forces blood into the thorax. The heart becomes distended by an additional 120 ml. Correspondingly the central venous pressure at the height of the right atrium increases from 2.5 to 12.8 mm HG when the water level rises from the diaphragm to the neck. The greater filling of the pulmonary circulation is accompanied by a decrease in vital capacity and visualized by scintigrams. The preferential increase in blood volume of the apical regions is striking. When raising the water level from the symphysis to the xiphoid heart rate falls by about 15%.


Time course of cardiac distension with rapid immersion in a thermo-neutral bath.

13 subjects standing in a narrow upright tank were exposed to rapid water immersion up to the neck. The tank was filled from an elevated reservoir in less than 4 s. In 8 subjects heart size was measured by Roentgen-cinematography combined with video tape recording. Planimetry of the diastolic postero-anterior area of the heart showed an average increase in heart size of 30% within 6 s. In 5 subjects central venous pressure and the height of hydrostatic pressure in the tank were recorded. The two pressures rose and fell simultaneously without delay when the hydrostatic pressure exceeded the level of the diaphragm. Rapid immersion caused a fall in heart rate of approximately 20%. The findings speak in favor of the concept that the right heart does not constitute a resistance and that the pulmonary circulation and the systemic capacitance vessels form a functional unit.


[Sézary's syndrome (author's transl)].

The syndrome described in 1938 by Sézary and Bouvrain is characterized by a possibly hyperpigmented erythroderma with oedema and infiltration of the skin, palmo-plantar keratoderma, diffuse alopecia and large lymphadenopathies. The cutaneous histopathology frequently shows a dermal mononuclear infiltrate with, sometimes, epidermal microabcesses. But none of these signs is actually specific for the Sézary syndrom, the only criteria of which is the presence of circulating Sézary cells with their folded, cerebriform nucleus demonstrated by electron microscopy. The Sezary cell is to date clearly identified as a T lymphocyte but membrane markers and Tcell fonction studies could elicite abnormal and poor reactive T cell. In order to assert the Sézary Syndrome it is stated by the authors that the erythroderma must be associated with more than 10% of Sézary cells in peripheral blood. This feature is needed to differentiate the Sézary syndrome from the erythrodermic form of mycosis fondoïdes in which the abnormal T cell proliferation is mainly located in the skin. The relationship with the T cell chronic lymphatic leukemia and the main treatments of the Sezary syndrome are discussed.


Liver cell-mediated mutagenesis of mammalian cells by liver carcinogens.

A cell-mediated mutagenesis assay using primary cultures of rat liver cells and V79 Chinese hamster cells has been developed. Liver carcinogens and their structural analogues were studied. Mutations in the V79 cells were characterized by resistance to ouabain. Cocultivation of the liver cells and V79 cells in the presence of the carcinogens N-nitrosodimethylamine, N-nitrosodiethylamine, and aflatoxin B1 caused the induction of ouabain-resistant mutants of V79 cells. In the absence of liver cells, the carcinogens did not induce ouabain resistance. The analogues N-nitrosomethyl-tert-butylamine and aflatoxin G2 were not mutagenic. The carcinogens exhibited a dose-dependent enhancement of mutation frequency. The mutation frequency also increased with increasing numbers of liver cells seeded. It is suggested that such an experimental system may be useful for screening for chemical carcinogens.


Development of spontaneous motility in chick embryos. The spinal and supraspinal component of the inhibitory effect of glycine and GABA.

Development of the effect of glycine and gamma-aminobutyric acid [GABA] on spontaneous motility was studied in 11- to 19-day-old chick embryos under normal conditions and after acute and chronic decapitation. Chronic decapitation was performed on the 2nd day of incubation. Glycine (100 mg/kg egg weight) and GABA (103 mg/kg egg weight) (applied onto the shell membrane) demonstrably inhibited spontaneous motility only from the 15th day of incubation, the inhibitory effect increasing with the embryo's age. When administered together in half doses, glycine and GABA completely inhibited spontaneous motility for the first time in 19-day-old embryos. Neither amino acid influenced depression of motility immediately after decapitation, but 24 and 48 hours after, in 17- and 19-day-old embryos, they had a paradoxical effect, i.e. they transiently activated motor activity and even caused motor paroxysms. After chronic decapitation, both glycine and GABA again had a mild, protracted inhibitory effect. A comparison of spontaneous motility in normal and chronically decapitated embryos showed that the role of supraspinal factors in spinal motor output increases significantly with development of the chick embryo from the 15th day of incubation and that inhibition of these supraspinal factors plays the decisive role in the effect of glycine and GABA.


On the mechanism of the inhibitory effect of potasium ions on amino acid incorporation into rat cerebral cortex proteins in vivo.

Earlier results on potassium ion inhibition of amino acid incorporation into the brain proteins in vivo (spreading cortical depression) led to the hypothesis that inhibition of protein synthesis is based on ATP deficiency. In the present study we tested various aspects of the aminocylation of tRNA, an ATP-dependent process, during spreading cortical depression produced by the topical application of 25% KCl. On using a 7-min interval between the subcutaneous injection of L-[U-14C] leucine and killing the rat, incorporation into the tRNA fraction was found to be reduced by 25%. Total amino acid radioactivity in the soluble fraction was unaltered. The acceptor capacity of tRNA, measured in vitro, and the proportion of non-acylated tRNA in vivo were likewise unchanged.


Effect of oxygen tension on norepinephrine-induced respiration in brown adipose tissue.

In brown adipose tissue fragments from 10-day-old rats or adult hamsters and in cells isolated from 10-day-old rats, norepinephrine (NE) activated oxygen consumption by 300-400%. NE-induced respiration was stable for 60-120 min and was inhibited by reduction of the oxygen concentration in the medium much more than respiration induced by the addition of respiratory substrates.


Changes in the potassium ion concentration in the extracellular space of rat cerebral cortex during the arousal reaction.

The integrative activity of K+ ions in the CNS was studied in urethane-anaesthetized rats. Changes in the potassium ion concentration in the extracellular space ([K+]e) of the cerebral cortex were studied by means of ion-selective K+ microelectrodes introduced into the brain with an implanted micro-drive allowing measurement in the immobilized animal. EEG desynchronizations evoked by various arousal stimuli or of spontaneous origin were accompanied by a small, but definitely measurable and reliably reproducible [K+]e increment. In arousal reactions evoked by nociceptive stimuli and ammonia fumes, [K+]e rose from a resting value of 3 mM by a mean 0.31 +/- 0.04 mM and 0.61 +/- 0.15 mM respectively. The mean duration of the increase was 37 and 305 sec and the mean duration of corresponding EEG desynchronization 47 and 48 sec; the amplitude of the [K+]e change lagged 15 and 39 sec behind maximum EEG desynchronization. Periodic spontaneous desynchronizations lasting 123 sec, which were evidently associated with the sleep cycle and were accompanied by a [K+]e increment of 0.4 +/- 0.04 mM, occurred in two rats. Repeated nociceptive stimuli led to the elaboration of a conditioned arousal reaction manifested in a [K+]e increment prior to their application. [K+]e changes in arousal reactions were found to be a more sensitive index of the general activity of the neuronal population than DC potential changes.


Circulating endothelial cells as a sign of vessel wall lesions.

A new method of endothelaemia estimation was used to investigate the production of vessel wall lesions by various drugs in rats. Increased endothelaemia was observed after endotoxin, activation of the blood contract system, hyaluronidase, streptokinase, anoxia and vasoactive drugs.


Effect of infrequent feeding and increased physical activity on cholesterol kinetics in the rat.

The authors studied the effect of chronic physical exercise (running in a rotating drum at 850 m/hour, 5 times a week for 16 weeks) on the size of the cholesterol body pools and on cholesterol kinetics in adult male Wistar rats fed on a standard diet either ad libitum or 2 hours daily [33 weeks]. These data were obtained by mathematical analysis of the curve expressing the correlation of specific plasma cholesterol activity to time after a single dose of cholesterol-4-14C. Chronic physical stress and infrequent feeding, as separate experimental stimuli, both caused cholesterol to shift from the blood plasma at a higher rate and reduced the size of one or both cholesterol body pools (with quick or slow turnover, pools A and B). Physical exercise also reduced fractional cholesterol turnover in pool A. When the two stimuli were combined, i.e. in infrequently fed and chronically stressed rats, the rate of the cholesterol shift from the blood plasma slowed down, the total and irreversible shift of cholesterol from pool A diminished and the production rate in this pool also fell.


Site on inhibition of the spino-bulbo-spinal reflex on stimulation of the anterior lobe of the cerebellum.

The effect of stimulation of the anterior lobe (AL) of the cerebellum on spinobulbo-spinal (SBS) reflex activity evoked by somatic and splanchnic afferentation was studied in chloralose-anaesthetized cats. Unit activity synchronous with the SBS component of the efferent discharge was observed at the level of motoneurons, descending axons of the dorsolateral and ventral funiculi and neurones of the reticular formation (RF). Conditioning stimulation of the AL inhibited this unit activity. Reticular formation units influenced from the AL had direct contact with segmental structures; these results showed that disappearance of the SBS reflex during AL conditioning is associated with the depressant effect of the cerebellar cortex on the reticular formation.


Insulin tolerance in rats.

Insulin tolerance was studied in young (8- to 10-week-old) Wistar rats: a) after the administration of mounting doses of long-acting insulin (10, 40, 160 and 320 units/kg bw.) to animals fed ad libitum on two different diets); b) after the administration of long-acting insulin (1 and 5 units/kg b.w.) to animals which had fasted for different lengths of time. In rats fed ad libitum on the two diets, graded doses of insulin induced (except for the smallest dose) hypoglycaemia of roughly the same intensity, but varying in duration in correlation to the dose. The administration of insulin to fasting rats showed differences in insulin tolerance which were correlated to the duration of the fast. A significant decrease in insulin tolerance was already found after 6 hours. During the given testing period (72 hours), the lowest insulin tolerance was found after a 12 hours' fast and the highest after 48 hours. Insulin tolerance after 24 and 72 hours' fasting was approximately the same; it was higher than after 12 hours, but lower than after 48 hours. The initial blood sugar level (before administering insulin) was not in any way correlated to insulin tolerance determined at various intervals during fasting.


Effect of glucocorticoids and stress on 14C-thymidine incorporation into DNA and on mitosis in regenerating rat liver.

Hydrocortisone sodium succinate (65 mg/kg body weight), Zn-ACTH (40 U/kg) and the intraperitoneal injection of Celite (200 mg/kg) decrease the incorporation of 14C-thymidine into the DNA of regenerating rat liver by about 60%. This decrease is not followed by a corresponding inhibition of cell division. The agents applied at the end of G1 phase or in the S phase of the cell cycle probably change thymidine metabolism and the observed decrease of thymidine incorporation does not represent true inhibition of DNA synthesis. The experiment with regenerating liver slices has shown that this disproportion is partly caused by decreased 14C-thymidine transport into the cells.


Na-G-penicillin penetration into rat cerebral cortex and formation of an epileptic focus.

Fluorescein isothiocyanate-labelled Na-G-penicillin was applied to the intact dura of 11 rats and the cortical layers were determined to which this epileptogenic substance must penetrate for electrophysiologically demonstrable focal activity to be induced. In 10 animals labelled penicillin was demonstrated in cortical layers I--III and in one animal in layers I and II. This concurs with the results obtained in 12 other animals in which activity was recorded from three depths of the cerebral cortex with semimicroelectrodes.


Operational amplifier with adjustable frequency response.

The authors describe an operational amplifier with an adjustable frequency response and its use in membrane physiology, using the voltage clamp and current clamp method. The amplifier eliminates feedback poles causing oscillation. It consists of a follower with a high input resistance in the form of a tube and of an actual amplifier with an adjustable frequency response allowing the abolition of clicks by one pole and of oscillation by two poles in the 500 Hz divided by infinity range. Further properties of the amplifier: a long-term voltage drift of 1 mv, a temperature voltage drift of 0.5 mv/degrees K, input resistance greater than 1 GOhm, amplification greater than 80 dB, output +/- 12 v, 25 ma, noise, measured from the width of the oscilloscope track in the presence of a ray of normal brightness, not exceeding 50 muv in the 0-250 kHz band, f1 = 1 MHz. A short report on the amplifier was published a few years ago (Gulísek and Hencek 1973).


Development of spontaneous motility in chick embryos. The spinal and supraspinal component of strychnine and picrotoxin activation.

Activation of spontaneous motility produced by the systemic administration of strychnine (1 mg/kg egg weight) and picrotoxin (1 mg/kg egg weight) was studied in 13- and 17-day-old chick embryos. In both cases the effect was studied in normal embryos, in embryos decapitated 1, 24 and 48 hours previously and in embryos decapitated on the 2nd day of incubation at stage 11-13 according to Hamburger and Hamilton (1951). At 13 days, both substances had the same short-term activating effect on the controls and all the decapitated embryos. This result is evaluated as further evidence of non-participation of the supraspinal component in the spontaneous motility of chick embryos before the 15th day of incubation. In 17-day-old decapitated embryos, strychnine and picrotoxin activation of spontaneous motility was significantly smaller than in the controls. From a comparison of activation by strychnine and picrotoxin in normal and chronically decapitated embryos it was deduced that a spinal and a supraspinal component participated in their effect. The activating effect of strychnine and picrotoxin in 17-day-old embryos was found to be mediated largely by supraspinal factors.


A new chin implant for microgenia.

We describe our experiences with a new silicone bag-gel chin implant, developed in two phases over a 4-year period. Fifty patients received the Phase I implant, and such complications as internal and external soft tissue erosion, indentation, slippage, asymmetry, infection, andd late bone resorption (two cases) were seen. Subsequently 28 patients received the Phase II implant, and have been followed up to one year. So far, the only complication has been asymmetry in one case.


Soft tissue xeroradiography.

Xeroradiography of soft tissue lesions, both malignant and benign, has been performed on 121 patients, 79 of whom having also undergone conventional film radiography. In 72 cases (59%), the diagnosis was proved by surgery and histological examination. Xeroradiography was found to be more effective in representing soft tissues than film radiography in 63 cases (80%) and equally effective in 16 cases (20%). Film radiography has never given a better representation of soft structures. The main xeroradiographic aspects of soft tissue lesions are reviewed. A diagnosis of the nature of the lesions on the basis of the extraosseous xeroradiographic picture is deemed possible only for lipomas. In the remaining cases, xeroradiography may offer useful information as regards size, shape and anatomic relationships of lesions but does not allow univocal diagnosis of their nature. Advantages and drawbacks of this technique are discussed, with emphasis on radiation dosage. It is assumed that xeroradiography may prove to be a helpful second-line examination in patients with soft tissue masses or swelling. It may also offer a simple method for follow-up in tumors of soft tissues having undergone conservative treatment.


A new device to support handicapped patients during venography or myelography.

The authors describe a seating device which holds the patient in position when the x-ray table is tilted and permits non-weight-bearing venograms to be obtained in handicapped as well as normal patients. Simultaneous bilateral venography reduces the study time considerably. The device is also helpful in lumbar myelography in paraplegics.


Use of an alternating pressure pad to reduce patient back pain during neuroangiography.

The authors describe a method of reducing patient back pain during neuroangiography. An alternating pressure pad cushions the body with constantly moving air.


[Reflex factors that modify the effect of p-chlorophenylalanine on ovulation and reproduction in rats (author's transl)].

The appearance of reflex ovulation in rats under the influence of the copulation, has been studied. Evaluation of insemination, fecundation, number of embryos, ovarian cycle and ovulation in several groups of rats treated with doses of p-CPA (300 mg/Kg, i.p.), have been made. The application of p-CPA 48 hours before the estrus phase, inhibits the ovulation. This increases significantly through copulation. Reproduction is totally inhibited by p-CPA in animals under copulation conditions during 24 hours of the estrus phase. The inhibition is desappears if placed under copulation conditions during a full cycle. Inseminated rats had a 33% decrease in number of embryos with respect to the control group. The application op-CPA 24 hours before the estrus phase does not produce any inhibition effect. The decrease observed in the number of embryos is non-significant. When p-CPA is applied, instead, 48 hours before the estrus phase, there is total inhibition of the reproductive conduct.


[Myoclonic type of Huntington's chorea (author's transl)].

The authors report the case of an 8 year-old boy who, when he was 2 1/2 years old, suffered from spasmodic mouth twitches. At the age of four, various other symptoms appeared: psychomotor backwardness, frequent fails and a photomyoclonic response on electroencephalogram. At the age of 5 1/2, noticeable difficulties appeared in walking with a broad-based gait, hypotonia, and intentional trembling associated with hypokinesia and dysarthria. When he was six, the first convulsive seizure appeared, then myoclonies which became continuous. The child gradually became bedridden. The family history tends to show these disorders can be linked with a Huntington chorea affecting six generations. This case is very similar to that previously described by the authors, in an 8 year-old girl where an anatomic examination revealed the existence of lesions characteristic of Huntington's disease associated with lesions of the cerebellum. The authors, on the basis of the data provided by the literature, discuss the myoclonic and cerebellous aspect of this infantile form. Lacking anatomic evidence, they stress the interest of the biochemical disturbances affecting the cerebral monoamines noted in this observation.


Effect of in vivo exposure to allogeneic cells upon subsequent in vitro T cell responses and upon allograft rejection.

The effect of intravenous injection of 10(6) BALB/c spleen cells into C57B1/6J recipients was assayed by both mixed lymphocyte culture (MLC) of recipient lymphocytes, and by grafting donor (BALB/c) thyroids into recipient mice. It was observed that a single intravenous injection produced depression of proliferative and cytotoxic T cell responses in MLC of spleen, lymph node and peripheral blood lymphocytes of the recipients. This effect was specific for the sensitizing genotype (MLC of recipient and third-party CBA/H lymphocytes was unaffected), and persisted for several days after sensitization. The pattern of this diminished response suggested that the effect was due to a combination of recruitment of reactive lymphocytes from peripheral lymphoid populations, and the generation of alloantigen (H-2?)-specific suppressor T cells in the spleen. In contrast to these findings in vitro, a similar sensitization led only to accelerated rejection of thyroid allografts in vivo.


Stimulating capacity of human lymphoid cell subpopulations in mixed lymphocyte cultures.

The content and yield or B cells, T cells and monocytes were investigated in cell fractions separated from human peripheral blood by various techniques. These cell fractions, which were highly enriched for either B cells, T cells or monocytes, were tested for their capacity to stimulate allogenic peripheral blood mononuclear cells in mixed lymphocyte cultures (MLC). B cells were found to be strongly stimulatory. Monocytes stimulated strongly at low stimulator/responder cell ratios, while less stimulation was observed using larger amounts of cells. T cells were demonstrated to stimulate weakly, if at all.


Rhinophyma and angiosarcoma of the nose. A case report.

A case is presented in which angiosarcoma of the nose was found in a patient with rhinophyma. To the best of our knowledge, this constellation has not previously been reported.


Histochemical study of the process of intimal histolysis.

Intimal histolysis begins, histochemically, with the removal of sulfate esters of acid mucopolysaccharides and of sialic acid of glycoproteins. The disappearance of the steric hindrance exerted by these acid groups if followed by the degradation of the ground substance and fibres. Certain particular aspects of this degradation are presented.


Symptoms and signs of degenerative back disease in concrete reinforcement workers.

Concrete reinforcement work causes great static loads on the back from the prolonged adoption of bent-double work postures during the tying of steel rods and from substantial dynamic loads during the lifting and pulling of rods from the stack. Subjective manifestations and objective signs of "degenerative back disease" are common in active reinforcement workers. An age- and sex-adjusted comparison of the findings was, however, possible only with one other occupational group, computer technicians, who also often work in awkward positions. A history of sciatica and pain during forward bending in a clinical examination were significantly more common in reinforcement workers than in computer technicians. This finding suggests an effect of reinforcement work on the back, but definite conclusions require further study.


Is pump stimulation associated with positive inotropy of the heart?

A purified sodium and potassium dependent adenosinetriphosphatase isolated from cat heart was not stimulated by any concentration of ouabain that produced positive inotropy of cat papilliary muscle. Only inhibition of enzyme activity was observed. Concentrations of ouabain used ranged from 3.3 x 10(-10) molar to 5 x 10(-7) molar and produced an increased force of contraction without any evidence of toxicity. The results are inconsistent with a concept that stimulation of sodium pump activity is associated with positive inotropy.


Compensation for work-related injuries and rehabilitation of patients with chronic pain.

A group of 61 patients with problems of chronic pain were managed though a rehabilitation program based on the principles of operant conditioning. Of these patients, 35 were receiving compensation for work-related accidents, and 26 were receiving no financial compensation for their chronic pain. Of the patients not receiving compensation, 69% (18) made significant increases in their functional performances, while only 43% (15) of the compensation group made similar increases.


Electrocardiographic changes in scrub typhus patients.

Ninety-eight cases of scrub typhus were examined electrocardiographically. Various findings beyond the normal range were as follows: In the febrile stage, sinus arrhythmia with some beats below 60 per minute, flat or low T waves in the left precordial leads, sinus tachycardia, ST segment elevation of 4-l mm in V2, prominent u waves measuring 1 mm or more in amplitude, tall and peaked T waves in V2-4, incomplete right bundle branch block, T wave inversion in V3-4, first degree A-V block, Q-Tc interval prolongation, notched T waves in V3, AV junctional escapes, prominent Ta waves or depression of PR segments in V2, and right axis deviation; in the convalescent stage, sinus arrhythmia with some beats below 60 per minute, prominent u waves measuring 1 mm or more in amplitude, tall and peaked T waves in V2-4, flat or low T waves in the left precordial leads, incomplete right bundle branch block, sinus tachycardia, first degree A-V block, Q-Tc interval prolongation, T wave inversion in V3-4, ST segment elevation of 4 mm in amplitude in V2, ventricular premature contractions, atrial premature contractions, and right axis deviation. In comparison with the electrocardiographic findings in 101 asymptomatic normal subjects, flat T waves in the precordial leads, tall and peaked T waves in V2-4 in both acute and convalescent stages, and sinus arrhythmia with some beats  below 60 per minute in the convalescent stage were more frequent in cases. Electrocardiographic abnormalities were present most commonly in the acute illness, and our findings support the impression that, with few exceptions, prompt treatment of scrub typhus with antibiotics prevents the serious cardiac complications seen prior to the antibiotic era.


Treatment of hepatic metastases with a combination of hepatic artery infusion chemotherapy and external radiotherapy.

Systemic chemotherapy has given good results when compared with that of patients who received no chemotherapy. When resection was performed, the results are slightly better. The group of patients who underwent combined therapy, using infusion chemotherapy, radiation and systemic chemotherapy, had the best results. It appears that infusion chemotherapy and radiotherapy can improve the palliation available for patients with metastases in the liver from carcinoma of the colon and rectum and warrants further investigation.


Tissue culture preservation and intramuscular transplantation of pancreatic islets.

Pancreatic tissue from neonatal rats was cultured for 6 days and then transplanted into isologous animals made diabetic with streptozotocin. The cultured pancreatic tissue was implanted either into the peritoneal cavity or into muscle pockets and showed survival by functional and morphological studies for longer than 40 weeks. Pancreatic tissue from a patient subjected to subtotal pancreatectomy for chronic pancreatitis was maintained in culture for 7 days, with evidence for insulin release into medium, sterility, and histological viability of islets. Autotransplantation of this tissue into muscle pockets of the forearm was tolerated well. Glucose tolerance improved following transplantation, but evidence for function of the graft (insulin, C-peptide) remains inconclusive, 4 months after transplantation.


Anomalous origin of the right pulmonary artery from the ascending aorta associated with aortopulmonary window.

A rare case of anomalous origin of the right pulmonary artery from the ascending aorta associated with an aortopulmonary window and severe pulmonary hypertension in a 13-year-old girl is reported. The window was closed using a Dacron patch and the continuity between the anomalous vessel and the main pulmonary artery was restored with a tubular Dacron graft. After operation the pulmonary pressure dropped to about one-half of the systemic pressure, and equal perfusion and ventilation of both lungs was demonstrated. Although early recognition and surgical treatment of this condition are mandatory to prevent the onset of irreversible pulmonary vascular disease, the presence of severe pulmonary hypertension did not contraindicate surgical correction in our patient.