Isolation and characterization of vitamin K-dependent region of bovine blood clotting factor X.

A 39-residue peptide from the tryptic digestion of bovine blood clotting factor X has been isolated by specific adsorption on barium citrate. The amino- and carboxyl-terminal sequences of the peptide were determined and compared to the vitamin K-dependent Ca2+-binding region from bovine prothrombin. The factor X peptide was found to contain gamma-carboxyglutamic acid residues, and the results of independent analysis are consistent with all 14 glutamic acid residues as gamma-carboxyglutamic acid. The similarity of the factor X peptide to the prothrombin peptide supports the hypothesis that the vitamin K-dependent blood clotting proteins are descended from a common ancestral gene.


Stochastics of cycle completions (fluxes) in biochemical kinetic diagrams.

Over a long time period, the rate constants for cycle completions (one-way fluxes) in steady-state biochemical diagrams can be expressed explicitly in terms of the elementary rate constants for transitions between states of the diagram. These cycle rate constants determine the mean one-way fluxes in the diagram and also fluctuations about the means. These properties are confirmed by Monte Carlo computer simulations on special cases. Two other topics are considered briefly: the effect of the starting state or states on the numbers of cycle completions in computer simulation runs; and the more detailed stochastic approach required if individual cycle completions are to be followed (i.e., if the "long time" restriction is removed).


Lymphocyte cytotoxicity to autologous liver cells in chronic active hepatitis.

Lymphocyte function in vitro was evaluated in patients with chronic active hepatitis and compared to normal controls. Circulating lymphocytes of patients were spontaneously cytotoxic to 51Cr-labeled human Chang liver cells and to suspensions of autologous liver cells obtained at the time of liver biopsy when tested at a lymphocyte target cell ratio of 200:1. Prednisone treatment of patients with chronic active hepatitis inhibited both spontaneous and concanavalin A-stimulated lymphocyte cytotoxicity to human Chang liver cells. Similarly, chronic prednisone administration substantially reduced lymphocyte cytotoxicity towards the patients' own liver cells in vitro, which correlated with a clinical, biochemical, and histological response to such therapy. Thus, patients with chronic hepatitis have circulating lymphocytes that are capable of causing destruction of their own liver cells in vitro. The beneficial effect of prednisone therapy in such patients may be related to this inhibition of lymphocyte cytotoxicity.


Amino-acid sequence of parvalbumin from rabbit skeletal muscle.

Determination of the complete amino-acid sequence of rabbit skeletal muscle parvalbumin is described. The sequence of 86 of the 109 total residues was determined automatically by sequenator analyses of peptides obtained after cleavage with CNBr or with trypsin. The positions of the remaining 23 residues were determined by subtractive Edman degradation of tryptic and chymotryptic peptides. The protein has an acetylated amino terminus. Comparison of the rabbit parvalbumin with those from carp, hake, and pike and with the calcium binding subunit of rabbit muscle troponin indicates that these proteins are homologous. Among the parvalbumins a high degree of identity is observed, especially of residues involved in the binding of calcium or in the formation of the hydrophobic core.


Patients with Ehlers-Danlos syndrome type IV lack type III collagen.

One of the genetically distinct collagens (type III) normally found in skin, aorta, and intestine is missing from the tissues of patients with the Ehlers-Danlos syndrome type IV. While skin fibroblasts from other individuals synthesize both types I and III collagen. Ehlers-Danlos syndrome IV cells synthesize only type I. These results suggest that the fragile skin, blood vessels, and intestines of Ehlers-Danlos syndrome IV patients result from an absence of type III collagen.


Human epidermal growth factor: isolation and chemical and biological properties.

A polypeptide hormone has been isolated from human urine, human epidermal growth factor. It was assayed by its ability to compete with 125I-labeled mouse-derived epidermal growth factor in binding to human foreskin fibroblasts. The biological effects of the human polypeptide are similar to those previously described for the mouse hormone. These include the stimulation of the growth in vitro of human foreskin fibroblasts and corneal epithelial cells in organ culture, and the in vivo induction of precocious eyelid opening in the newborn mouse. The amino acid compositions of the two polypeptides differ, although certain similarities are present. The estimated molecular weight of the human polypeptide, 5300-5500, is slightly lower than that of the mouse hormone. Both polypeptides apparently compete for the same site on the cell membrane; and antibodies to the mouse polypeptide crossreact to some extent with the human hormone.


Donnan potential of rabbit skeletal muscle myofibrils I: electrofluorochromometric detection of potential.

The fluorescence of the dye CC-6 [(3-hexyl-2-(3-hexyl-2-benzoxazolinylidene)-1-propenyl)-benzoxazolium iodide] has been shown to indicate Donnan potentials in rabbit skeletal muscle myofibrils. These results are in agreement with previously published work in which the potentials were measured with microelectrodes on glycerol-extraced muscle fibers. The magnitude of the Donnan potential of the myofibrils has been shown to be dependent on the state (rigor or relaxed) of the system.


Hemoglobin interaction in sickle cell fibers. I: Theoretical approaches to the molecular contacts.

Computerized molecular model building has been used to deduce the arrangement of sickle cell hemoglobin molecules (Hb-S) in the tubular fibers which form within sickling cells and in concentrated cell-free solutions of deoxygenated Hb-S. A "best" solution has been found which satisfies all of the reported properties of these fibers. In the proposed arrangement the contact between adjacent Hb-S molecules in the direction parallel to the fiber axis is primarily hydrophobic and in addition contains two salt bridges between the molecules. This contact would be disrupted with the Glu of Hb-A at the beta6 position instead of the Val of Hb-S, and it would not make a long fiber with oxygenated Hb-S. Residues in the A helix and the GH corner of the beta2 chain of one molecule are in contact with residues of the A, B, and E helices and the GH corner of the alpha1 chain of its neighbor. The intermolecular contact in the direction perpendicular to the fiber axis is mainly between the end of the E helix and the EF corner of the beta1 chain on the first molecule and the F helix and FG corner of the alpha2 chain of its neighbor. Some of the implications of these contacts are reported here, and others will be presented in subsequent papers.


Crystal structure of bovine Cu,Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands.

An electron density map at 3 angstrom resolution has been calculated for Cu2+, Zn2+ superoxide dismutase from bovine erythrocytes, and the course of the main chain has been traced. The dominant structural feature is an 8-stranded barrel of antiparallel beta-pleated sheet. There is one very short helical section and two long loops of non-repetitive structure. The Cu and Zn are bound between the loops and one side of the beta barrel and are about 6 Angstrom apart, with a common histidine ligand. The Cu has four histidine ligands in a somewhat distorted square plane, and the Zn has three histidines and an aspartate in approximately tetrahedral arrangement. The two coppers of a dimer are about 34 Angstrom apart. The two subunits have essentially the same conformation and have an extensive contact area that mainly involves hydrophobic side chain interactions. The overall folding pattern of the polypeptide chain is very similar to that of an immunoglobulin domain.


Detection and ultrastructural localization of human smooth muscle myosin-like molecules in human non-muscle cells by specific antibodies.

Spectrin, a protein complex which is peripherally attached to the cytoplasmic surface of the human erythrocyte membrane, cannot be detected (by complement fixation with anti-spectrin antibodies) in homogenates of several different human non-muscle cells studied. On the other hand, a protein antigenically identical or similar to human smooth muscle myosin was detected (by complement fixation with antibodies to uterine smooth muscle myosin) in these cells. In the case of human fibroblast line WI38, this smooth muscle myosin like component was shown (by ferritin-antibody experiments in electron microscopy) to be at least partly associated with cytoplasmic surface of the plasma membrane of the cell. It is proposed that the spectrin complex of the erythrocyte membrane and the smooth muscle myosin-like component of the fibroblast membrane play similar roles in regulating the translational mobilities of integral proteins in their respective membranes.


Synthesis of acetylcholine receptor by denervated rat diaphragm muscle.

Acetylcholine receptor was purified by affinity chromatography from denervated rat hemidiaphragms that had been incubated in organ culture for 24 hr in medium containing [35-S] methionine. Radioactive acetylcholine receptor was identified in purified preparations by zone sedimentation in a sucrose gradient, by isoelectric focusing, and by precipitation with an antiserum to the acetylcholine receptor from electric eel. When innervated and denervated hemidiaphragms were incubated with [35-S] methionine in organ culture, and the acetylcholine receptors from each were purified separately, only the preparation from denervated muscles contained radioactive receptor as determined by zone sedimentation. We conclude that newly synthesized receptor is accumulated as a result of muscle denervation.


A beta-D-galactoside binding protein from electric organ tissue of Electrophorus electricus.

Extracts of electric organ tissue of Electrophorus electricus contain a saccharide-binding protein, named electrolectin, which agglutinates trypsin-treated rabbit erythrocytes and is specifically inhibited by disaccharides containing nonreducing terminal beta-D-galactosyl residues. Electrolectin seems at least partially membrane-bound but is also found in soluble fractions of homoge-nates from which it can be purfied by affinity chromatography on cross-linked and desulfated agarose (ECD-Sepharose) as a protein of molecular weight 33,000. About 400 mg of electrolectin are present per kg of tissue. It has an affinity for lactose of 1.0 mM-1 and 5.5mM-1 as estimated, respectively, by hapten inhibition and fluorescence spectroscopy. Studies on the distribution of beta-D-galactoside-binding activity in animal tissues reveal particularly high levels in sheletal muscle tissue and in cultures of embryonic skeletal muscle and neuroblastoma cells.


Extensive homology between the subunits of the phytohemagglutinin mitogenic proteins derived from Phaseolus vulgaris.

The phytohemagglutinin mitogenic proteins derived from Phaseolus vulgaris comprise a class of five glycoproteins that are isomeric tetramers composed of varying proportions of two different subunits (L and R). Within the native tetramer, the L subunit is a potent leukoagglutinin and mitogen that lacks hemagglutinating properties, whereas the R subunit is a potent hemagglutinin with little or no mitogenic activity. The subunits have been isolated in homogeneous form by isoelectric focusing in 8 M urea. Previous work has shown that they have equal molecular weights and differ in amino-acid sequence from residues 1-7, but are identical in positions 8-24 [(1973) J. Exp. Med. 138, 939-951]. We now report amino-acid composition studies which reveal striking similarities between the subunits. Both lack methionine and cysteine. The twelfth residue in each subunit is a glycosylated asparagine, with the identical  carbohydrate composition in each. The last three residues of the subunits, as determined by carboxypeptidase A digestion, are identical. Tryptic peptide mapping of the succinylated phytohemagglutinin subunits reveals a high degree of similarity. We conclude that the substantial difference in biological properties among the tetrameric phytohemagglutinin mitogens is a result of relatively restricted differences in the primary structure of their constituent subunits.


Role of epithelial architecture and intracellular metabolism in proline uptake and transtubular reclamation in PRO/re mouse kidney.

The homozygous PRO/Re mouse has less than 1 percent of the very high proline oxidase activity that characterizes normal kidney cortex. In PRO/Re mouse the endogenous proline concentration is eight times normal in plasma and four times normal in kidney cortex cell, but 50 times normal in urine. The integrity of the membrane transport systems for proline uptake at the antiluminal surface of absorbing epithelium is retained in PRO/Re kidney, as determined by the slice method. Clearance studies in vivo under steady-state conditions indicate that  the integrity of the luminal uptake system shared by glycine and proline, and serving proline absorption, is also intact. The exaggerated renal clearance of proline in PRO/Re mice (50 times normal) is explained when its raised intracellular concentration, caused by impaired proline oxidation, is considered. Backflux into urine flowing down the nephron will occur under these conditions, thus impairing net reclamation of proline in PRO/Re kidney. The findings reveal that membrane transport and intracellular metabolism of a substrate are, indeed, independent functions, but that metabolism of a substance can influence its transcellular transport.


Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro.

The differentiation in vitro of clonal pluripotent teratocarcinoma cells is reported. The first stage of this process is the formation of simple embryoid bodies which are identical to those found in animals bearing intraperitoneal teratocarcinomas. They consist of an inner core of embryonal carcinoma cells surrounded by a layer of endodermal cells which produce Reichert's membrane. The endodermal cells become apparent shortly after the embryonal carcinoma cells have formed aggregates which are loosely attached to the substratum. One clonal teratocarcinoma line was found to produce complex cystic embryoid bodies in vitro. Following formation of the endodermal cells, extensive differentiation to a wide variety of cell types occurs. There are similarities between the process of embryoid body formation and the early events of differentiation of the mouse embryo.


Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency.

The endoperoxide prostaglandin G2 (PGG2) induced platelet aggregation as well as the platelet release reaction (release of ADP and serotonin) when added to human platelet-rich plasma. Formation of a metabolite of PGG2 [8-(l-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid] and a lipoxygenase product [12L-hydroxy-5,8,10,14-eicosatetraenoic acid] accompanied the release reaction caused by aggregating agents such as collagen, ADP, epinephrine, and thrombin. Indomethacin inhibited the release reaction and PGG2 formation induced by these agents but had no effect on PGG2-induced release reaction. The aggregating effect of PGG2 was abolished by furosemide, which is a competitive inhibitor of ADP-induced primary aggregation. These data indicate that the aggregating effect of PGG2 is due to release of ADP and that PGG2 synthesis is required for induction of the release reaction by various aggregating agents. A subject with a hemostatic defect due to abnormal release mechanism [decreased aggregation with epinephrine (second wave) and collagen and normal platelet ADP] had a deficiency of the cyclo-oxygenase that catalyzes formation of PGG2. Normal aggregation and release reaction were obtained with added PGG2. Ii is concluded that the endoperoxide (PGG2) is essential in normal hemostasis because of its role in initiating the release reaction required for aggregation by collagen and the second wave of aggregation caused by, e.g., ADP.


Immunological relationship between acetylcholine receptor and thymus: a possible significance in myasthenia gravis.

A defined immunological cross-reaction was observed between acetylcholine receptor fraction from the electric eel, Electrophorus electricus, and two calf thymus fractions. The cross-reaction was demonstrated on the cellular level by means of the lymphocyte transformation technique, and on the humoral level, by means of the microcomplement fixation assay. In the human disease myasthenia gravis both acetylcholine receptor at the neuromuscular junction and the thymus are affected, probably by an autoimmune mechanism. The immunological cross-reaction between acetylcholine receptor and thymic components may explain the association between endplate and thymus disorders in myasthenia gravis.


A group of thermodynamic potentials applicable to ligand binding by a polyfunctional macromolecule.

The binding of ligands by a macromolecule can be well described by a group of potentials derivable from the energy and of which the original binding potential is one. The group is Abelian and is isomorphic with a group of symmetries. Each member corresponds to a particular set of experimental conditions--system open to some, closed to others, of the ligand-and the group as a whole is an immediate source of all possible linkage relations applicable to the macromolecule. Seen in terms of information theory it can be interpreted as a program for the response of the macromolecule to its ligands according to the conditions with which it is faced. The group provides a ready formulation of the effect of a ligand on the equilibrium constant for a reaction involving a set of macromolecules, and it leads to a clear-cut distinction between true and pseudolinkage.


The amphisbaenian ear: Blanus cinereus and Diplometopon zarudnyi.

Observations on the structure and function of the ear in amphisbaenians have been extended to two new species: to Blanus cinereus of the family Amphisbaenidae and Diplometopon zarudnyi of the family Trogonophidae. Blanus, considered one of the most primitive of this group of reptiles, shows a distinctive form of sound-receptive mechanism. The usual extracolumella is lacking, and the columella attaches to a cartilaginous plate beneath the skin posterior to the facial area. Diplometopon zarudnyi, a highly modified trogonophid, shows a columella and extracolumella of massive dimensions, with considerable calcification of the latter process. Cochlear potential measurements revealed the levels of auditory sensitivity in these species. A peculiar feature is the degree of stability of the ear's responses in the presence of large variations in body temperature.


Localized Derepression on the Human Inactive X Chromosone in Mouse-Human Cell Hybrids.

Evidence for derepression of the gene for hypoxanthine phosphoribosyltransferase (HPRT; IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) on the human inactive X chromosome was obtained in hybrids of mouse and human cells. The mouse cells lacked HPRT and were also deficient in adenine phosphoribosyltransferase (APRT; AMP: pyrophosphate phosphoribosyltransferase; EC2.4.2.7). The human female fibroblasts were HPRT-deficient as a consequence of a mutation on the active X but contained a normal HPRT gene on the inactive X. The two human X chromosomes were further distinguished by differences in morphology: the inactive X was morphologically normal while the active X included most of the long arm of autosome no. 1 translocated to the distal end of the X long arm. Forty-one hybrid clones were first isolated by selection for the presence of APRT; when these clones were selected for HPRT, six of them yielded derivatives having human HPRT with incidences of about 1 in 10-6 APRT-selected hybrid cells. The HPRT-positive derivatives contained a normal-appearing X chromosome indistinguishable from the inactive X of the parental human fibroblasts. The active X with the translocation was not found in any of the HPRT-positive hybrid cells. Human phosphoglycerokinase (ATP:3-phospho-D-glycerate 1-phosphotransferase. EC 2.7.2.3) and glucose-6-phosphate dehydrogenase (D-glucose 6-phosphate: NADP 1-oxidoreductase, EC 1.1.1.49), which are specified by X-chromosomal loci, were not detected in the hybrids expressing HPRT even though they contained an apparently intact X chromosome. The observations are most simply explained by the infrequent, stable derepression of inactive X chromosome segments  that include the HPRT locus but not the phosphoglycerokinase and glucose-6-phosphate dehydrogenase loci.


Trisomy of chromosome 15 in spontaneous leukemia of AKR mice.

Karyotypes of spontaneous thymomas of AKR mice were determined by trypsin-Giemsa banding methods. Trisomy of chromosome 15 occurred in 10 of 11 leukemic mice. Seven of the thymomas were predominantly trisomic for chromosome 15, one was trisomic for chromosome 12, and one exhibited multiple trisomies of chromosomes 3, 12, 15, and 17. Trisomy was not found in the norm-l AKR tissues examined.


Two classes of translational control RNA: their role in the regulation of  protein synthesis.

Two classes of translation control RNA (tcRNA) have been isolated from embryonic chick muscle. One of these classes, the tcRNA isolated from messenger ribonucleoprotein particles (mRNP-tcRNA), is effective in inhibiting the translation of mRNP-mRNA while having little if any effect on polysomal mRNA. The other class, polysome-tcRNA, has no effect on mRNP-mRNA while it stimulates the translation of polysomal mRNA. The mRNP tcRNA contains approximately 50 percent uridylate residues and forms small but stable hybrids with poly (A), while polysome-tcRNA contains fewer uridylate residues and is much less effective in forming a hybrid with poly (A). A proposed model concerning the role of these two classes of tcRNA in the regulation of protein synthesis is presented.


Isorhodopsin II: artificial photosensitive pigment formed from 9,13-dicis retinal.

We have found that in addition to the 11-cis and 9-cis isomers of retinal which are known to couple with the visual pigment apoprotein opsin to form pigments, a third isomer 9,13-dicis retinal also will form a pigment. That this isomer is indeed bound to opsin has been shown unequivocally by removing the chromophore without isomerization and subsequent identification by high-speed liquid chromatography. Using similar techniques, we have shown that the product of bleaching by light of all three pigments in Trition X-100 is the all-trans isomer. This specificity in the product of bleaching, as with many other properties of visual pigments, is not shared by the free chromophore. Of particular interest is that when 9,13-dicis retinal is combined with opsin to form a pigment,  a single photon can isomerize it about two double bonds, to the all-trans isomer.


Development of receptive fields in rabbit visual cortex: changes in time course due to delayed eye-opening.

Rabbit pups had one eye sutured closed before the time at which the eyes normally open. At 20-27 days of age, single-unit recordings were made both from the striate cortex contralateral to the sutured eye (deprived cortex) and from that contralateral to the eye which had opened normally (control cortex). The percentages of units encountered which fell into various receptive  field categories differed on the two sides. The deprived cortices had a lower percentage of visually responsive cells, a higher percentage of indefinite cells, and totally lacked cells sensitive to orientation of a stimulus bar. In these respects they closely resembled previous observations on rabbit pups just before normal eye-opening. By contrast, the control cortices of the same animals were comparable to normally reared rabbits of the same age. We conclude, therefore, that developmental events which normally follow eye-opening can be affected in their time course by delaying eye-opening.


Relative numbers of human globin genes assayed with purified alpha and beta complementary human DNA.

Purified alpha and beta globin complementary DNAs (cDNAs) have been separated from total radioactively labeled human globin cDNA using mRNA purified from liver of a hydrops fetalis (alpha thalassemia). The beta cDNA hybridizes to the hydrops fetalis mRNA while the alpha cDNA remains single-stranded. the purified alpha and beta cDNAs were assayed for their purity by their hybridization to mRNA prepared from reticulocytes of nonthalassemia, alpha thalassemia, and beta thalassemia subjects. The results indicate that the separated cDNAs are selective in hybridization to alpha or beta globin mRNAs, respectively. The previously reported deficiency of globin mRNA in thalassemia cells has been confirmed with these purified cDNAs. The purified alpha and beta cDNAs were hybridized to cellular DNA to non-thalassemia, beta+ thalassemia, and hydrops fetalis (alpha thalassemia) DNA. The alpha cDNA hybridized to hydrops fetalis liver DNA to a much lower extent that beta cDNA, confirming the previously reported deletion of alpha globin genes in hydrops fetalis. By contrast, both the alpha and beta DNA probes hybridized to the same extent to spleen DNA from non-thalassemia and from beta+ thalassemia patients. Between two and five globin genes in non-thalassemia and beta+ thalassemia DNA hybridize to beta cDNA and one to five to alpha cDNA. These studies indicate that in beta+ thalassemia, there is no detectable deletion in beta globin genes. The genetic defect in beta+ thalassemia appears to be due to either repression of transcription of beta globin genes or abnormal processing of beta globin mRNA.


Identification of cardiac beta-adrenergic receptors by (minus) [3H]alprenolol binding.

(Minus) [3-H] alprenolol, a potent beta-adrenergic antagonist, was used to identify binding sites in a fraction of canine cyocardium. Beta adrenergic agonists and antagonists compete for these binding sites in a manner which directly parallels their known affinity for the cardiac beta-adrenergic receptor. Thus, binding was highly stereo-specific, with the (minus) isomers of beta-adrenergic agonists or antagonists being at least two orders of magnitude more potent than were the (plus) isomers in competing for these sites. The order of potency for inhibition of binding by beta-adrenergic agonists was (minus) isoproterenol greater than (minus) epinephrine greater than (minus) norepinephrine. The dissociation constant (KD) of (minus) alprenolol for the beta-adrenergic receptors was 7-11 nM as determined independently by direct binding studies or by inhibition of isoproterenol-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. The beta-adrenergic antagonist (minus) propranolol also had high affinity for the binding sites (KD equals 12 nM). The physiologically inactive catechol-containing compounds pyrocatechol and (plus or minus) dihydroxymandelic acid, as well as the metabolite (plus or minus) normetanephrine, and the alpha-adrenergic antagonist phentolamine did not compete for the binding sites at a concentration of 160 muM. Binding was rapid (t1/2 less than 30 sec) and was rapidly reversible (t1/2 less than 15 sec). The binding sites were saturable and bound 0.35 pmol of (minus) [3-H] alprenolol per mg of membrane protein. These characteristics suggest that these binding sites represent the cardiac beta-adrenergic receptors.


Induction of maturation (meiosis) in Xenopus laevis oocytes by three organomercurials.

Three organomercurials, p-hydroxymercuribenzoate, p-hydroxymercuriphenylsulfonate, and mersalyl, induce maturation (meiosis) in a large percentage (20-100 percent) of Xenopus laevis oocytes. Maturation takes place even when the follicle cells which surround the oocytes have been withdrawn. Organomercurial- and progesterone-induced maturations have many features in common: they do not occur when the inducer is injected into the oocytes, they require the presence of Ca++ in the medium, they are inhibited by cycloheximide but not by actinomycin D. In both cases, the maturation producing factor and the pseudomaturation inducing factor are produced. Organomercurial-treated oocytes react normally to activating stimuli; their protein synthesis increases, but uptake of amino acids is strongly inhibited. Progesterone and p-hydroxymercuriphenyl-sulfonate act synergically in inducing maturation. The main difference between the two agents is that p-hydroxymercuriphenylsulfonate must act for several hours, whereas, short contact with progesterone is sufficient to induce maturation.


Modulation of lymphocyte receptor mobility by locally bound concanavalin A.

Binding of concanavalin A (con A) to the lymphocyte surface at room temperature leads to restriction of the mobility of a variety of cell surface receptors including those from immunoglobulin (Ig), O, H-2, beta2-microglobulin, Fc receptors results in "co-capping" of Ig, H-2, theta, Fc receptors, as well as receptors for other lectins. Addition of colchicine to the cell suspensions reverses this effect and allows Con A receptors as well as other receptors to form patches and caps. Capping of Con A receptors, and beta2-microglobulin in the absence of ligands specific for these receptors. Receptors binding Limulus hemagglutinin and wax bean agglutinin, as well as those interacting with carbohydrate-specific antibodies, were partially co-capped with Con A but receptors for wheat germ agglutinin were not co-capped, excluding the possibility that restriction of receptor mobility by Con A resulted simply from cross-linkage of mobile receptors to immobilized glycoproteins (Con A receptors). Latex beads and platelets coupled to Con A were bound to lymphocytes under the same conditions as free Con A. Binding of these particles to local regions of the cell surface resulted in restriction of the mobility of those receptors that could be co-capped with free Con A. In contrast to the findings with free Con A, however, addition of colchicine resulted in capping of the bound particles but did not cause co-capping of either the unbound Con A receptors or other receptors. These findings support the hypothesis that modulation occurs via a submembranous assembly containing microtubules, and they further suggest that the transitions of this assembly induced locally by Con A may be propagated via cooperative processes.


Immunological and chemical purity of papain-solubilized HL-A antigens.

Three preparations of purified papain-solublized HL-A antigens have been radiolabeled by reductive methylation using formaldehyde and potassium boro[3H]hydride, and their reaction with specific HL-A antisera has been investigated. Greater than 99 percent of the radioactivity in the [3H]HL-A2 preparation could be complexed with several HL-A2 antisera, but not with specificity controls. The other two preparations, which contained mixtures of HL-A antigenic specificities (HL-A7,12 an HL-A3,W25;12,27), showed 63 per cent and 70 per cent complex formation with mixtures of the appropriate HL-A antisera. The N-terminal amino acid of both subunits has been determined for the three HL-A antigen preparations. In all cases the only detectable N-terminal amino acids were isoleucine for the small subunits, beta-2-microblogulin, and glycine for the larger subunit.


Moments for sum of an arbitrary function of gene frequency along a stochastic path of gene frequency change.

A diffusion model is developed to compute any moment of the sum of an arbitrary function of the gene frequency along sample paths between any two specified frequencies. This is used to calculate the mean age of a mutant of frequency chi, including or excluding the possibility of its having been at value chi equals 1 during the process, and the total frequency of heterozygotes involving an allele since its origin.


Evolutionary relationship between immunoglobulins and transplantation antigens.

The major human and murine histocompatibility antigens are tetrameric molecules with an apparent molecular weight of about 130,000. They are composed of two types of polypeptide chains. The two light chains, previously identified as beta2-microglobulins, are bound to the two heavy, alloantigenic HL-A or H-2 polypeptide chains by noncovalent interactions only. The heavy chains are held together by disulfide bridge(s) located in the part of the molecule that is attached to the cell membrane. By limited proteolysis of the histocompatibility antigens evidence was obtained suggesting that the heavy chain may consist of three compact domains connected by more extended stretches of polypeptide chain. Each domain appeared to contain a single disulfide bride encompassing about 60 to 70 amino-acid residues. Staphylococcus aureus protein A is known to bind exclusively to the Fe region of immunoglobulin G. It was, however, observed that protein  A interacts in a similar way with the H-2 antigen heavy chain. This observation, together  withthe homology of the primary structure of beta2-microglobulin to immunoglobulin G, the tetrameric structure of the alloantigens, the ogranizations of the heavy polypeptide chain into compact domains, and the presence of a single, immunoglobulin-like disulfide loop in each domain, establishes a close similarity in structure between histocompatibility antigens and immunoglobulins. The similarity in structural features suggests a  common evolutionary origin of the two types of molecules.


Beta-cyanoalanine synthase: purification and characterization.

Beta-cyano-L-alanine synthase [L-cysteine hydrogen-sulfide-lyase (adding HCN), EC 4.4.1.9] was purified about 4000-fold from blue lupine seedlings. The enzyme was homoegeneous on gel electrophoresis and free of contamination by other pyridoxal-P-dependent lyases. The enzyme has a molecular weight of 52,000 and contains 1 mole of pyridoxal-P per mole of protein; its isoelectric point is situated at pH 4.7. Its absorption spectrum has two maxima, at 280 and 410 nm. L-Cysteine is the natural primary (amino acid) substrate; beta-chloro- and beta-thiocyano can serve (with considerably lower affinity) instead of cyanide as cosubstrates for cyanoalanine synthase. The synthase is refractory to DL-cycloserine and D-penicillamine, potent inhibitors of many pyridoxal-P-dependent enzymes. Cyanoalanine synthase catalyzes slow isotopic alpha-H exchange in cysteine and in end-product amino acids; the rates of alpha-H exchange in nonreacted (excess) cysteine are markedly increased in the presence of an adequate cosubstrate; no exchange is observed of H atoms in beta-position.


Purine metabolism in murine virus-induced erythroleukemic cells during differentiation in vitro.

Purine metabolism was studied in murine virus-induced erythroleukemia cells stimulated to differentiate in vitro in the presence of dimethylsulfoxide. The activities of the enzymes that catalyze the synthesis of the first intermediate of the de novo purine pathway, phosphoribosyl-1-amine, were decreased while the enzymes that catalyze the conversion of purine bases to purine ribonucleotides remained unchanged at the time the cells acquired the specialized function of hemoglobin synthesis. In addition, cytidine deaminase (cytidine aminohydrolase, EC 3.5.4.5) activity increased with erythropoietic maturation, as it does during murine erythropoiesis in vivo. Stimulation of cellular proliferation of stationary erythroleukemic cells resulted in a marked increase in the activities of purine biosynthetic enzymes. These data provide a convincing example of repression and derepression of the PRA synthesizing enzymes in mammalian cells in vitro, and further evidence that the regulatory mechanisms operative in the normal development of erythrocytes can be activated by exposure of erythroleukemic cells to dimethylsulfoxide.


Abnormal radionuclide deposition patterns adjacent to focal skeletal lesions.

A scintigraphic pattern is described for bone scans with 99m-Tc-polyphosphate and 99m-Tc-diphosphonate in which abnormal tracer accumulation extends beyond the known limits of certain skeletal lesions. The associated pathologic entities include benign and malignant tumors, infection, and trauma. The pathogenesis of "extended patterns" has not been proved but probably relates to regional hyperemia induced by associated lesions. Increased blood flow results in more tracer delivery to otherwise normal bone in the "watershed" areas of hyperemia, producing these patterns.


[The centric relation. I. Contribution to the study of the reliability of 3 materials for interocclusal registration].

Three materials commonly used for interocclusal registrations are tested under habitual conditions. The wax-type samples are softened in hot water to the optimal temperature, and then cooled off for hardening either in ice water, or room temperature water, or at room temperature air. These materials are stored for one month. Measurements are taken: - prior to any treatment - after hardening - after storage. The results are statistically analyzed. The least distorsion of material is obtained with the softer wax and vice versa. The room temperature air cooling has given best results. Time does not seem to modify measurements made on heat treated materials which may be accurately stored at room temperature.


[Caries-free dentitions in pre-school children and elementary school pupils in Basle during the study year of 1974].

Already in the last two years, the increasing percentage of caries-free elementary schoolchildren of Basel could be observed compared to the years before water fluoridation began. This increase could be confirmed this year, from examinations of over 95% of the children born 1964 to 1967, and of over 70% of the two kindergarten-years 1968 and 1969.


[Indications and contraindications for removable and fixed orthodontic appliances].

The treatment of the changing dentition by self-regulating measures and with removable appliances is confronted with the multiband technique. Advantages and disadvantages are described. If one considers the factors of risk and the relationship between work volume and effect, removable appliances deserve preference. However, there is still a limited range of indication for the fixed appliances.


[Orthodontic therapy using removable and fixed appliances--a statement of position].

Even in the planning process of orthodontic therapy the primary question should not be directed to the type of appliance to be used. An outline of basic considerations is presented, the evaluation of which leads in a logical way to the choice of appliance and the appropriate procedure. No controversy can evolve between "removable" and "fixed" provided the orthodontist is capable in both sectors. In regard to fixed appliance, it can be stated that the technical limitations of the edgewise mechanism--designed by Angle almost 50 years ago, in the meantime modified and again supplemented by a variety of extraoral force systems--still exceed by far the biologically imposed limitations. The technical versatility of this mechanism could fulfill until now almost all of the changing demands of orthodontic therapy which derived from the continuously enlarging spectrum of knowledge.


[Dentofacial orthopedics, fixed and removable. Current trends].

The author explains his orthodontic philosphy. He emphasizes the importance of the differential diagnosis for the choice of the appliances. He illustrates his therapeutic conception by means of four schematic cephalometric tracings. Both, the removable and the fixed appliances can very well be present in the therapeutic arsenal of the same orthodontist, provided that each one be used only on the basis of an exact indication. Three tables try to classify the cases which can be handled by removable only, fixed only or both kinds of appliances. Finally, photographs of a case treated with a mixed method are shown.


[Threedimensional cephalometric contribution to the study of mandibulo-facial dysplasias].

The cephalometric particulars of the dysplastic syndrome of the first visceral segment, the dysostosis mandibulofacialis Franceschetti-Zwahlen were investigated. Ten patients were found with the identical symptom of a typical, uni- or bilateral microtia of the external ear. The cephalometric characteristics of the syndrome may be summarized as follows: - retroposition of the middle face - retroposition of maxilla and mandible - retrorotation of the mandible - reduction of vertical and lateral dimension of the face - reduction of transverse diameter of both dental arches - shortened mandibular base - both halves of the face are affected, but more so the half with microtia - the chin is deflected toward the affected side. Most of these symptoms must be attributed to disturbed organogenesis. With the rest of them, functional adaptation cannot be exluded.


Structural-functional relationships in platelets in acute leukemia and related disorders.

Platelet ultrastructure and adenine nucleotide metabolism were studied in acute leukemia in order to elucidate mechanisms for the functional defects of platelets in this clinical setting. A number of structural defects were observed: (1) giant platelets, (2) marked variability in the number and size of cytoplasmic granules, (3) dilatation of the open channel system, (4) cytoplasmic vacuolization, and (5) poorly delineated microtubular system. Metabolic defects included reduced cellular concentrations of ATP and ADP and selective reduction of the storage pool (non-metabolic) nucleotides. Stimulation of platelets was associated with delayed and incomplete granule migration, reduced degranulation, subnormal release of ATP and ADP, and poor platelet aggregate formation. The structural and metabolic defects observed indicate abnormalities exist in the contractile mechanism and the release reaction of platelets in acute leukemia which partly explain the functional defects reported previously. Platelets from patients with pre-leukemic states share some of the structural and metabolic defects seen in acute leukemia. The defects are less uniform consistent with a lesser degree of functional impairment than seen in acute leukemia. Studies of megakaryocytic ultrastructure suggest that the structural defects seen in acute leukemia and pre-leukemia may arise in the late stages of megakaryocyte maturation.


Manifest intestinal involvement during bone-marrow remission in a case of acute lymphoblastic leukaemia.

Massive leukaemic involvement of the intestine appeared in a 9-year-old girl with acute lymphoblastic leukaemia. The unusual feature in this case was that the gut involvement occurred during complete haematological remission. Surgical and subsequent radiological treatment completely eradicated the engagement and at autopsy 9 months later there were no signs of the intestinal involvement.


School phobia in children with malignant neoplasms.

With the advent of improved therapy, many of the childhood malignant diseases have become chronic. This group of patients and their families demonstrate many problems usually not associated with the primary disease, but which can become incapacitating. School phobia was selected as one such problem for this study. The 11 cases reported here demonstrate the insidious and subtle nature of the onset of the disease. With aggressive management, some long-standing cases of school phobia could be reversed, but not all. In a group subjected to a prophylactic regime at the onset of their malignant neoplasm, there have been no new cases of school phobia. It is important for pediatricians caring for these children to search actively for the signs of school phobia and intervene as soon as possible.


Cardiovascular responses to bladder distension in patients with spinal transection.

Arterial blood pressure, heart rate, and cutaneous volume pulses were recorded during controlled elevation of urinary bladder pressure in a group of seven patients with spinal cord transsection above vertebral level T5 and in another group of four patients below T5. Profound elevations in systolic blood pressure and pulse pressure were induced by bladder distension when the lesion was situated above T5. Lesser elevations occurred in patients with lesions below T5. Marked vasoconstriction characterized skin areas innervated by the "isolated" spinal cord, while passive dilatation occurred in areas supplied by the proximal cord. Only three of seven patients with lesions above T5 level had decreased heart rate during marked elevations in arterial blood pressure. The marked elevations in pulse pressure in patients with lesions above T5 could not be explained solelyby increased vasoconstriction and decreased heart rate, but involves also inotropic cardiac responses. These inotropic responses are mediated by cardiac sympathetic nerves which leave the spinal cord above the T5 level.


Biological effects of the metabolites of dimethyl sulfoxide.

In summary, the effects of dimethyl sulfoxide (DMSO) and its metabolites, dimethyl sulfone (DMSO2) and dimethyl sulfide (DMS), were studied in five selected systems in rats and mice. DMSO enhanced the taurine excretion and the lethality produced by such aromatic hydrocarbons as benzene and chlorobenzene in rats. In mice, DMSO decreased the toxicity such cholinesterase inhibitors as paraoxon and octamethyl pyrophosphoramide. DMSO also lowered the body temperture of rats and reduced the motor activity of mice. Although DMSO2, the major metabolite of DMSO, was not effective in increasing the lethality of solvent hydrocarbons, it seemed to be quite as effective with respect to the other effects. DMS, although quite potent with respect to lowering body temperature and reducing motor activity, was relatively ineffective otherwise. Thus each of the metabolites has a spectrum of activity different from the parent compound; DMSO has the widest spectrum and DMS the narrowest. It remains to be determined whether the therapeutic effects of DMSO are related to the experimental effects reported above in animals, and whether DMSO2 and DMS may share any of the therapeutic effects of DMSO.


Studies on the intracisternal A-type particles in mouse plasma cell tumors: induction of maturation of the particles.

Maturation of the intracisternal A-type particle found in two mouse plasma cell tumors was induced by treating the cells in culture with IDU-DMSO or with DMSO only. Morphologically, the mature particles with electron-dense nucleoids closely resembled the mature particles described in human tumor cell lines treated in a like manner. They also closely resembled the virus that has been described in guinea pig leukemias. It was not possible to demonstrate infectivity of the mature particle, as latent intracisternal A-type particles induced by IDU were found in the mouse cells presumed to be free of virus. The biochemical studies did not show distinct new peaks of virus-specific particles in sucrose density gradients when the particles in the treated cells were compared with the particles of the untreated cells. There was a difference in the density of the particles observed in the induced cells (1.2) and those of the control cells (1.185). This may reflect the difficulty of separating mature and immature particles. Analysis of the RNA present in the particles showed that the ratio of heavy-molecular-weight RNA in activated cells to the predominant species (21S) is much greater than that in control cells. Detectable levels of enzyme activity were not found in the induced particles. This could be due to too low a concentration of particles in the preparations.


The effects of dimethyl sulfoxide on neurite development in vitro.

In these studies, DMSO at concentration above 1% was shown to be a potent inhibitor of neurite maturation in vitro. The inhibition was not reversible, and occurred in both newly formed and established neurites. In the presence of DMSO, the addition of NGF resulted in a general shift of the dose-response curve. The data indicate that at levels of DMSO below 5%, DRG neurons are capable of responding to NGF stimulation. It has been suggested that DMSO blocks a specific process associated with neurite extension. These studies suggest that the inhibitory action of membranous organelles in the developing neurite, a finding consistent with previous speculation that DMSO is responsible for an increased intracellular disorganization.


Effect of dimethyl sulfoxide and hydrogen peroxide on tissue gas tensions.

Tissue gas levels were measured in experimental skin flaps in rabbits, rats, and pigs. Devascularization of the flaps led to a fall in PO2 and a rise in PCO2 levels. Application of DMSO to ischemic rabbit flaps led to a fall in PCO2, DMSO and H2O2 led to a rise in PO2, an effect that lasted up to 90 min. Neither drug had an effect on the gas levels of flaps in either rats or pigs.


Oral dimethyl sulfoxide in mental retardation. Part 1. Preliminary behavioral and psychometric data. Part 2: Preliminary medical data.

No significant side effects attributable to the drug appeared. No significant ophthalmological changes attributable to the drug occurred.


Dimethyl sulfoxide therapy in bronchiolitis.

The action of a medicinal spray that contains anti-inflammatory and bacterio-static drugs integrated with the penetrating and potentiating agent DMSO has been evaluated clinically in 60 infants with acute respiratory obstruction. A dose of 2 ml of this spray is applied in the posterior pharynx and the tonsil region; 1 to 4 applications are made, according to the clinical evolution of the case. Two groups were chosen at random; 60 patients were paired off, and one of each pair received the treatment with DMSO spray. All the patients received ampicillin (50-100 mg/kg body weight). The following clinical results were observed. First there was an immediate recovery, after an average lapse of 30 min; improvement of sensorial involvement was observed in 80% of the cases, reduction of the intercostal retraction in 75%, reduction of polypnea in 76%, and transformation of the obstructive syndrome into a catarrhal syndrome in 80% (with fluidification of the secretions, which were expelled more easily by the upper air tracts). There was also a deferred or maintenance effect, which evaluated in comparsion with the control group that received similar treatment except for the nebulizations with DMSO spray. A sequential design, based on whether or not it was necessary to use the croupette, demonstrated the superiority of the DMSO spray over the control treatment in the bronchiolar process; in the group treated with DMSO spray it was not necessary to use the croupette. The sequential design based on the effect of this therapy on the general condition and the tabulated clinical factors permitted the inference that the therapeutic responses are more favorable in the group treated with DMSO spray than in the control group. In the sequential design, the line of significance is cut at the fifteenth pair (an error of 0.05 and P equals 0.95%). Since the application is easy, there are no toxic side effects and in view of the favorable results in the clinical evolution of the acute respiratory obstructive processes, we consider the use of this therapeutic spray very useful and beneficial in bronchiolitis.


Dimethyl sulfoxide therapy in subjective tinnitus of unknown origin.

In fifteen patients affected by essential nonvibratory tinnitus, local applications in the external auditive canal of 2 ml medicated DMSO spray were made. The spray solution contained DMSO integrated with anti-inflammatory and vasodilatory substances. This application was repeated every four days for a month. At the same time each patient was administered a daily intramuscular injection of a preparation that contained DMSO and a vasodilatory component. The therapeutic effect was evaluated through the subjective modification of the symptom and functional tests of the auditory system. Of the fifteen patients treated, the tinnitus symptom completely disappeared in nine, and did not return during a one-year observation period. The patient's symptoms diminished in two cases, and in four cases the permanent tinnitus became occasional, triggered principally by environmental cold. It is important to note that among the concomitant signs, the five patients with vertigo noted improvement. Hypacusis diminished in three of the six patients affected. Insomnia disappeared in eight and diminished in seven cases. The rise in the average tympanic membrane temperature from 36.8 degrees C before to 37.9 degrees C after treatment was noteworthy. This could indicate an improvement of the blood flow in the inner ear.


Altered mitogenic responsiveness of chronic leukemic lymphocytes and normal human lymphocytes treated with dimethyl sulfoxide.

Peripheral lymphocytes from patients with chronic lymphocytic leukemia display a delayed and lowered response to stimulation by PHA, as compared with the lymphocytes from normal donors. This response was determined by measuring the incorporation of tritiated thymidine. The addition of DMSO in concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0% (v/v) to the culture fluid of normal cell cultures that had been stimulated, with PHA elicited a 3- to 4-fold increase in the rate of incorporation of labeled thymidine at the 3-day test period. The addition of 2.0% DMSO proved to be preferentially cytotoxic to cultures of leukemic cells after 48 hours, as compared with the virtual absence of cytotoxicity for cultures of normal lymphocytes. The addition of 0.1%, 0.25%, 0.5%, and 1.0% DMSO to cultures of leukemic cells stimulated with PHA (as were normal cell cultures) resulted in a 6- to 6.5-fold increase in the rate of uptake of tritiated thymidine at 3 days.


A hypocalcemic and lympnocyte-stimulating substance isolated from thymus extracts, and its physicochemical properties.

Two kinds of active protein fraction, TP1 and TP2, were isolated from bovine thymus extracts. Both these fractions showed a single band in polyacrylamide gel disc electrophoresis. Though these two fractions showed a difference in potency, they both lowered serum calcium in rabbits and increased lymphocytes in mice. Molecular weight determination by SDS polyacrylamide gel electrophoresis gave the values of 68,000 for TP1 and 57,000 for TP2. Amino acid composition of TP1 did not show marked characteristics but was clearly different from that of bovine serum albumin. Isoelectric focusing showed the isoelectric point at pH 5.65 for TP1 and pH 5.4 for TP2. Dose-response relation in serum calcium-lowering activity was examined with a sample purified from the extracts, and a linear dependence of the response to log dose was recognized over a moderate range of doses. The time-course measurement of the hypocalcemic activity showed that the action of TP1 is somewhat different from that of calcitonin.


Albinism and auditory function in the laboratory mouse. I. Effects of single-gene substitutions on auditory physiology, audiogenic seizures, and developmental processes.

The effects of single-gene albino (c/c) mutations on auditory behavior and physiology were examined in congenic C57BL/6J mice. At 16 days of age, the c gene was additively associated with both reduced auditory functioning and lower body weight: 16-day-old c/c mice had higher auditory evoked potential (AEP) thresholds than +/c mice, which, in turn, had higher thresholds than +/+ mice; +/c mice were also intermediate with regard to body weight. Since these differences had nearly disappeared by 21 days of age, it was concluded that the c genes worked in an additive fashion to delay development during the period previously (Henry, 1967) found critical for inducing susceptibility to audiogenic seizures. At 16 days of age, albino mice (c/c) displayed susceptibility to audiogenic seizures, but nonalbino genotypes (+/c and +/+) were immune to the convulsive effects of sound. This behavior appeared to be a recessive trait at this age. But 5 days later, the behavioral phenotype exhibited incomplete dominance, with the +/c genotype displaying audiogenic seizures intermediate to those seen in the susceptible c/c and the nonsusceptible +/+ genotypes. These behaviors were compared to the thresholds and peak-to-peak amplitudes of the AEP, as seen in the input-output functions. It is suggested that differential development of the auditory systems in these genotypes is causally related to susceptibility to audiogenic seizures.


Hydroxyurea in the management of the hematologic complications of chronic granulocytic leukemia.

The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing peripheral leukocyte and blast counts in all cases and in reducing splenomegaly in 13 of 17 patients. The median duration of disease control was 75 days in myeloproliferative acceleration and 27 days in frank blastic transformation. Mild nausea and vomiting were experienced by most patients, but reversible bone marrow suppression occured in only three patients. The drug proved useful in 19 patients who demonstrated myeloproliferative acceleration, especially in controlling excessive leukocytosis and/or thrombocytosis. Rapid reduction of an elevated blast cell count was achieved in nine patients who presented in blastic crisis, in an attempt to eliminate the associated risk of cerebral vascular leukostasis. Five patients who required treatment for their disease following splenectomy in the chronic phase were also well controlled. Hydroxyurea appears to have a definite role in the management of these hematologic complications of CGL.


Functional and morphologic characteristics of the leukemic cells of a patient with acute monocytic leukemia: correlation with clinical features.

The clinical course of a patient with acute monocytic leukemia and prominent infiltration of the skin and testes is described. In vitro studies demonstrated that the circulating monocyte precursors were capable of adherence to nylon fibers, and phagocytosis of bacteria and latex particles. In vivo, migration of leukemic cells to skin windows was observed. Extreme nuclear folding, marked surface activity, and morphologic features suggesting nuclear and cytoplasmic maturation were seen by light and electron microscopy. The presence of morphologically and functionally more differentiated monocytic cells may account for the marked tiuuse invasion in this patient and, possibly, in other patients with monocytic leukemia.


[Sea-blue histiocytes and Gaucher-like cells. Occurrence and significance].

Sea-blue histiocytes (SBH) and Gaucher-like cells are macrophages containing a pigment related to or identical with ceroid or lipofuscin. While an occasional cell may be found in the normal bone marrow, large numbers of SBH can be observed in various conditions mainly associated with increased cellular breakdown or with disturbances of lipoid metabolism. We have examined smears and/or sections of bone marrow and spleens of 722 patients with various hematological disorders. In only four instances large numbers of SBH could be found, twice in the bone marrow, once in the spleen and once in both organs. Two of these patients were suffering from immune thrombocytopenia. Gaucher-like cells have a different morphologic appearance although the pigment shows the same cytochemical characteristics as in SBH. Gaucher-like cells are mainly found in patients with chronic myeloid leukaemia and are thought to be related to the increased breakdown of granulocytes. The exact mechanisms responsible for the formation of these pigment macrophages are not yet known. In the author's view it does not seem justifiable to speak of a special "syndrome of the blue macrophages".


Chronic granulocytic leukaemia in pregnancy.

In an era when the use of ionizing radiations for the treatment of chronic granulocytic leukaemia has largely been supplanted by therapy with busulphan or other drugs, there still exist situations where irradiation is the preferred method of initial treatment. One such situation is the unusual conjunction of chronic granulocytic leukaemia and pregnancy. Chronic granulocytic leukaemia (CGL) was diagnosed in two young women during early pregnancy as a result of routine blood examinations. Both responded satisfactorily to splenic irradiation with shielding of the uterus. The pregnancies proceeded uneventfully and each was successfully delivered of a normal and subsequently healthy baby. Both mothers later underwent elective splenectomy during a period of satisfactory haematological control: no operative or post-operative complications occurred. Although both patients have shown some thrombocytosis and peripheral blood basophilia since splenectomy, they remain well 58 and 28 months after diagnosis and 30 and 18 months after splenectomy.


Infant leukaemias and cot deaths.

Infant leukaemias differ from childhood leukaemias in ways which suggest that when haemopoietic neoplasms combine fetal origins with rapid growth rates they prevent normal development of the reticuloendothelial system and thus cause the sudden death of apparently healthy babies (stillbirths or cot deaths). Cot deaths are commoner in boys and have a peak incidence during the first half of infancy-that is, during the period most affected by the switch from passive to active immunity. Babies born from July to December, who are intensively exposed to winter conditions form 1 to 5 months of age, are also at special risk. During this period more girls and more children born form January to June die of leukaemia; and within three months of birth an exceptionally high ratio of myeloid to lymphatic leukaemias has been replaced by a low ratio, which persists throughout childhood.


Consequences of methotrexate inhibition of purine biosynthesis in L5178Y cells.

Addition of 1 muM methotrexate to cultures of L5178Y cells results in an initial inhibition of thymidine, uridine, and leucine incorporation into acid-insoluble material followed, after about 10 hr, by a partial recovery in the extent of incorporation of these precursors. Acid-soluble adenosine triphosphate and guanosine triphosphate concentrations are greatly reduced initially, but guanosine triphosphate concentrations appear to recover partially by 10 hr. Acid-soluble uridine triphosphate and cytidine triphosphate concentrations initially increase after methotrexate treatment but then, with time, they too decline. Hypoxanthine and guanine are more effective than is adenine in overcoming the methotrexate-induced inhibition of thymidine incorporation. These results suggest that, in the presence of methotrexate, guanine nucleotides become limiting for nucleic acid synthesis before adenine nucleotides do. The block of purine de novo synthesis in L5178Y cells by methotrexate is almost complete and is not reversed with time. This suggests that the additional purine nucleotides that are available for nucleic acid synthesis 8 to 10 hr after addition of methotrexate are being derived from nucleic acid breakdown. Consistent with this is the observed reduction in the number of polyribosomes and hence, presumably in messenger RNA levels.


Action of bredinin on mammalian cells.

Bredinin, a new nucleoside antibiotic, inhibited multiplication of several mammalian cell lines in culture and had a cytotoxic effect on L5178Y cells. Growth inhibition by bredinin was prevented by guanosine 5'-monophosphate (GMP), guanosine, or guanine but not by other purine or pyrimidine nucleotides, nucleosides, or bases. Inhibition by bredinin at a low GMP; but at higher concentrations of bredinin the inhibition was not reversed even when the concentration of GMP was raised. Addition of GMP after cellular damage had occurred produced no effect on the damaged cells but it prvented further damage. Bredinin caused marked chromosomal aberrations such as breakages, translocations, and fragmentation in L5178Y cells.


The role of drug transport in resistance to nitrogen mustard and other alkylating agents in L518Y lymphoblsts.

An investigation was undertaken of the mechanism of resistance to nitrogen mustard (HN2) and other alkylating agents, with particular emphasis on the interaction between cross-resistance and drug transport mechanisms in L5178Y lymphoblasts. Dose-survival curves demonstrated that the D0 for HN2-sensitive cells (L5178Y) treated with HN2 in vitro was 9.79 ng/ml and the D0 for HN2-resistant cells (L5178Y/HN2) was 181.11 ng/ml; thus, sensitive cells were 18.5-fold more responsive than were resistant cells and the difference was highly significant (p less than 0.001). A similar evaluation of 5 additional alkylating agents, including chlorambucil, melphalan, 1,3-bis(2-chloroethyl)-l-nitrosourea, Mitomycin C, and 2,3,5-tris(ethyleneimino)-1,4-benzoquinone, revealed that L5178Y/HN2 cells were also cross-resistant, in part, to each of these compounds. Furthermore, the degree of cross-resistance was remarkably similar; for each drug, dose-survival studies showed that HN2-resistant cells were approximately 2- to 3-fold more resistant to therapy than were sensitive cells. L5178Y/HN2 cells were also cross-resistant to cyclophosphamide in vivo; after treatment with cyclophosphamide, DBA/2 female mice that were given inoculations of L5178Y cells, but not those given transplants of L5178Y/HN2 cells, showed a significant prolongation of survival time (p less than 0.01). Transport of HN2, hydrolyzed derivative of HN2 and choline by L5178Y lymphoblasts in vitro was not competitively inhibited by any of the other alkylating agents, suggesting that transport of these compounds was by an independent mechanism. These findings suggest that the mechanism whereby L5178Y/HN2 cells are cross-resistant to other alkylating agents may involve nontransport factors and that these other drugs may bypass a major portion of HN2 resistance by using independent transport systems.


[Comparative studies of the grinding methods by Jankelson and Lauritzen].

First functional analyses according to Lauritzen were performed in 10 patients and the models were ground in the Dentatus articulator.  Then the natural dentition was ground in according to Jankelson in retruded contact position.  The results of intraoral grinding-in after an average of 3--4 sessions were transferred to the Dentatus articulator by means of the split cast method and analysed.  Comparison showed that the result of intraoral grinding-in according to Jankelson was clearly inferior to that achieved in the articulator.


[Mandibular movements and joint function].

In five test persons the exact joint movements of the lower jaw in the area of the lateral teeth were tested with regard to precision of the movements and technical possiblities of balancing articulation.  The result of these measurements show that there is extreme precision of the joint movements in a non-loaded lower jaw.  With a uniformly bended compensation curve the joint movements can be compensated in sagittal direction only, and not in transversal direction.  On the basis of these findings a method for the direct formation of the sagittal compensation curve is discussed.


[Position of condyles in habitual and therapeutic occlusion].

One of the possible therapies of funcitonal disturbances in the masticatory system is finding a new intercondylar axis.  The condyles perform a movement whose direction and length can be measured.  All measuring results obtained from 51 patients are reported and in special cases the different methods of registration are compared.  It was shown that in some cases the malposition of the condyles could not be eliminated.


[Treatment of odontogenic abscesses].

Histories of 311 abscesses of odontogenic origin found in different tissue spaces were evaluated.  Location, cause, age distribution, pathogenic germs, and therapeutical measures were discussed.  The perimandibular abscess was found most frequently, the second most common was the submadibular abscess.  The parapharyngeal and paratonsillary abscesses were the rarest.  The age of the patients was mainly between 30 and 50 years.  Most often the lower molars were the starting point of the abscess.  The spectrum of pathogenic germs comprised 14 different germs.  Surgical therapy which is always necessary is performed under analgo-sedation in adults, and in ketamine anesthesia in children.  The tooth responsible for the abscess was removed seven days after the abscess incision, on the average.  If indicated, post-operative therapy should be applied after the testing of germ resistance.


[Determination of the individual-optimal occlusion height in the edentulous mouth].

Foramen ovale, foramen mandibulae and foramen mentale, as shown in lateral radiographs of human cadaver heads bisected in the median-sagittal plane, can be placed simultaneously in every position of the mandible on the logarithmic spiral line devised by M. Moss.  The individually optimal vertical dimension is that position of the mandible in which the foramina occupy the most central position on this spiral line; abduction and adduction of the mandible from this position cause a shift of the foramina to the periphery of the spiral line.  Geometrically, loss in vertical dimension due to edentia can be computed from changes of the mandibular angle.  Geometrical relationships were also shown between the distance from the foramen ovale to the foramen mandibulae, and other directly measurable distances on lateral cephaloradiographs.


[Prostaglandin F2alpha as a method of choice for interruption of pregnancy (author's transl)].

Since March 1972 we have been applying Prostaglandin F2 alpha in 6 patients between the 8th and 12th week of pregnancy, in 2 patients between the 13th and 16th week, in 16 patients from the 17th week onwards, and in 10 women at term. The intravenous and extraamniotic application of Prostaglandin for interruption of pregnancy has proved a success even in severe general diseases. No severe side effects have been observed. Antidotes are beta-sympathicomimetics as for Oxytocin, too Prostaglandin is a valuable pharmacon in the obstetrical area.


Ultrastructure of acute myeloid leukemia arising in multiple myeloma.

Bone marrow from a case of multiple myeloma in which acute myeloid leukemia supervened four years after diagnosis was examined with the electron microscope. Two distinct populations of neoplastic cells, one plasmacytoid and the other myeloid, were identified in the marrow. It is concluded that the acute leukemia that developed in this patient was a distinctly new neoplasm arising from the myeloid series of cells. Since in nearly all previously reported cases, and in our patient, alkylating agents had been administered, it is thought that this may have been a factor in the development of acute myeloid leukemia.


Chromosome examination of newborn children: purpose and ethical aspects.

The purpose of making chromosome investigations of newborn children as well as ethical problems in such studies and in follow-up studies of children with chromosome abnormalities is discussed, and a survey of 6 chromosome studies from a total of 47 145 newborn children is presented. It is stressed that more chromosome studies of newborn children are needed for several reasons, but one of the main reasons is to study the development of children with different chromosome abnormalities, especially those with sex-chromosome abnormalities and compare them with controls.


Chromosomal polymorphism in Nucella lapillus.

A technique for the examination of chromosomes in testicular material in Nucella lapillus is described. The diploid chromosome number varies between 26 and 36. Eight pairs of meatcentric chromosomes are always present and range in size from 9mu to 4mu. Additionally, 10 pairs of acrocentric chromosomes (4mu to 1mu) are present in the 2n equal 36 form and correspond to five pairs of metacentric chromosomes in the 2n equal 26 form. Trivalents occur in individuals heterozygous for chromosome arrangements; this is consistent with the interpretation that the polymorphism is Robertsonian in nature. The southern British distribution of the chromosome polymorphism in Nucella is described. The polymorphism occurs regularly only in bay's in the south-west; elsewhere the populations are monomorphic 2n equal 26. Two areas where the polymorphism occurs have been examined in detail. In each of these the frequency of acrocentrics is negatively associated with increasing wave force, but there is some variation suggesting that other factors relating to water movement (tidal currents and range) are important also. It is pointed out that the overall distribution of the polymorphism can be explained on the assumption that a high chromosome frequency is favoured where total water movement is least.


An empirical method of grouping genotypes based on a linear function of the genotype-environment interaction.

The regression approach for analysing genotype-environmental interaction is extended to include the grouping of genotypes. An unweighted pair-group cluster analysis was applied to a special dissimilarly index, derived from the test statistic for differences among regressions. The resulting groups reflect the general pattern of response to the various environments. The data of Yates and Cochran (1938) were used to illustrate the clustering process.


Absence of crossing-over in female butterflies (Heliconius).

Absence of recombination between linked markers in female Heliconius is suggested by coupling backcross broods in H. erato, by a repulsion F2 in H. melpomene, and by other crosses with this species. No recombinants have been found in the offspring of doubly heterozygous females in either species. This supports the contention that the absence of chiasmata at oogenesis in these bufferflies prevents genetic crossing-over. Chiasmata are absent in all the female Lepidoptera examined by Suomalainen and others, but Ephestia seems to show the absence of chiasmata but the presence of genetic recombination in the female, and therefore would repay further study.


A continuous selective model for an X-linked locus.

Neglecting age-structure, but taking into account matings with differential fertility in Mendelian reproduction, a continuous selective model is formulated for a single X-linked locus with an arbitrary number of alleles. Without restricting the mating system, differential equations are derived for the genotypic and allelic frequencies. Assuming random mating, no selection, and constant fertilities and mortalities, these differential equations are solved explicitly. For this case, in contrast to the corresponding phenomenon in the usual model with discrete, non-overlapping generation, the difference between the frequencies of any allele in males and females approaches zero without oscillation.


Coronally repositioned periodontal flap. Clinical evaluation after one year.

After increasing the width of the attached gingiva by free palatal mucosa transplants, 20 procedures with coronal flap repositioning were performed on 41 teeth with gingival recessions in 13 young adults. The amount of gingival recession and the clinical gingival sulcus depth were measured pre-operatively and 1, 6 and 12 months after surgery; the amount of osseous dehiscence was measured during surgery. No significant differences were found among reduction values of gingival recession by reattachment 1, 6 and 12 months post-operatively. Although a significant correlation was found between the degree of gingival recession preoperatively and 1 month post-operatively, non was found between the amount of alveolar bone dehiscence and gingival recession 1 month post-operatively.


Gingival vasculature around erupting deciduous teeth of dogs and cats.

The presence of plaque and of overt inflammation, occurring with eruption of deciduous teeth in dogs and cats 2-14 weeks old, were related to the concomitant gingival vascular morphology, using vital microscopy, perfusion and histological techniques. Although localised, acute inflammation accompanied plaque formation at the time of weaning, it seldom developed into chronic inflammation. The onset of overt chronic inflammation was not related to tooth eruption or to events associated with formation of the gingiva. Infiltration of gingival tissue by chronic inflammatory cells occurred in only a few specimens and was associated with increased plaque and replacement of the gingival vessel network by loop paterns.


Periodontal changes during chronic benign granulocytopenia in childhood. A case report.

The report describes two children with chronic benign granulocytopenia, suffering from gingivitis and marginal periodontitis in the deciduous dentition. The radicular areas of the attached gingiva were well delineated against the alveolar and papillary mucosa.


The role of occlusion for the stability of fixed bridges in patients with reduced periodontal tissue support.

The present investigation reports how occlusion may be utilized to establish and maintain stability of fixed bridges in patients with markedly reduced periodontal tissue support. The material consisted of 20 adult patients, aged 27-69, with advanced periodontal breakdown, often in combination with extensive loss of teeth. After periodontal treatment, the patients were rehabilitated with fixed bridges, whose stability was evaluated once a year for 2 to 6 years. The results show that permanent stability of bridgework can be obtained in patients where there is a minimum of remaining periodontal tissue support, even in combination with marked hypermobility of individual abutment teeth. The stability was achieved by proper treatment of the diseased periodontal tissues, and by establishment of stable occlusion in the intercuspal position. When there was a risk of bridge mobility on excursive movements of the mandible, balancing contacts were established for the prevention of migration, tilting and increasing mobility. The study also shows that cantilever pontics can be used to achieve and maintain the stability of fixed bridgework.


The effect of plaque control and surgical pocket elimination on the establishment and maintenance of periodontal health. A longitudinal study of periodontal therapy in cases of advanced disease.

The present clinical study was initiated in 1969 to test the hypothesis that microbial plaque is the cause of periodontal disease and that hence even advanced cases of periodontitis can be cured in patients willing to exercise optimal plaque control. The material consisted of 75 patients with severe destruction of the periodontal tissues. The patients were selected for the study because of their ability to maintain plaque-free dentition. Following an initial examination, a preliminary treatment plan was presented to the patients. This plan included detailed instructions in plaque control measures, scaling, root planning and emergency dental care, including endodontic therapy and extractions. Three to six months after the termination of the so-called presurgical treatment, surgical elimination of pathologically deepened pockets was performed. The patients were recalled every 3 to 6 months after the end of the treatment. At these reexaminations the following parameters were assessed: Plaque Index, Gingival Index, Pocket Depths, Marginal alveolar bone topography and height. The results demonstrate that it is possible to treat periodontal disease successfully, even in advanced stages, in patients willing to maintain plaque-free dentition.


Follow-up studies of free gingival grafts.

Vestibuloplasties with free gingival grafts were performed on 42 teeth in 12 patients exhibiting gingival recession. The tendency toward recurrence was studied after postoperative intervals of 1, 6 and 12 months. The extensions (vestibuloplasties), which were always wider than the transplant, recurred up to the transplantation margin. The transplant itself underwent shrinkage averaging 25 per cent. The vestibular depth, which had been increased by the operation, showed a 25 per cent reduction within 1 month, but then had a tendency to deepen again from 1 to 12 months postoperatively. The marginal free gingiva and sulcus depth were not influenced by the operation.


An in vivo evaluation of interface media used with the electric pulp tester.

Four interface media were tested with an electric pulp tester to determine whether the amount of current needed to elicit a response varies with the material. Each material was tested on the facial and linqual surfaces of anterior teeth. Clinical results showed no appreciable difference between the materials used, provided they were water or petroleum based. Facial and lingual readings were the same in about half the tests, and lingual readings were slightly lower than facial readings in 40% of the tests.


Hand, foot, and mouth disease: a viral disease of importance to dentists.

Hand, foot, and mouth disease is a disease of viral origin that produces characteristic lesions in the mouth and on the hands and feet. Knowledge of the disease is important to dentists since the oral vesicular and ulcerative lesions are usually the first clinical signs of the disease, and the epidemiclike patterns of the disease make it likely that the dentist will contract the disease himself or possibly become a carrier of the virus. The lesions of hand, foot, and mouth disease usually regress in two to three weeks, and complications are rare. Treatment is basically palliative to reduce the pain and irritation. Differential diagnosis of the disease must include consideration of herpes simplex, herpangina, recurrent aphthae, erythema multiforme, and animal foot and mouth disease. A case involving a dentist and his family is reported.


Aspirin-induced oral lesion: report of case.

Aspirin is one of the most extensively used medications and has many beneficial effects. However, its injudicious use can produced local as well as systemic undesirable effects. A case of aspirin burn of the oral mucosa is presented. The lesion was in an unusual location. However, the history and the successful results from discontinuance of the drug supported the provisional diagnosis.


Professional opinions in the identification of dental manpower shortage areas.

A study was initiated by the Minnesota Dental Association to identify criteria that dental practitioners use in defining a dental manpower shortage area and to determine the perceived effectiveness and acceptability of solutions to the manpower shortage problem. This report from the association presents the study findings. The five factors, in order of importance, that should be considered in a definition of a manpower shortage area are the public's "dental IQ," the ratio of dentists to population, the availability of dental appointment times, the age and productivity of practicing dentists in the area, and the distance patients must travel to the dentist. Minnesota dentists perceived dental placement techniques to be more effective and acceptable than financial incentives or the use of auxiliary personnel in solving the dental manpower shortage problem.


Patterns of dental practice in the United States: solo vs group practice.

This overview of selected characteristics of group and solo practices provides baseline information on the dimensions and structures of two general practice types in the United States. It appears that although a dentist spends no more hours or sees no more patients on the average in a group practice, the structure in terms of use of auxiliaries, appointment flexibility, and structured programs provides the dentist in a group practice more opportunity to participate in other professional activities and generate a higher income. Further analysis on the interrelation of these variables will provide a more conclusive comparison of group and solo practices. Also, more conclusive research on variations among different types of group arrangements is needed to appreciate differences in partnerships, groups, and incorporations.


Long term ridge augmentation with rib graft.

Results of ten cases are reported to indicate the bone augmentation that may be expected in three to six years using transoral rib grafting. Some augmentation was present in all cases. This is an improvement over the continued resorption that would have taken place in these already thin mandibles. Function was improved in all cases. This modality falls short of the ideal aid to these patients, but is an available holding procedure.


A study of biological chemistry on the nature of jaw cysts. On the maintainance of homoeostasis in jaw cyst fluid.

Jaw cyst lining cells have an active transporting mechanism for Na+ ion and K+ion, a secreting mechanism and a selecting mechanism, and they allow permeation of electrolytes, lipids and protein into cysts. The components within the cysts have a controlling metabolism, and keep the system stable. Tumour wall cells of cystic ameloblastoma have only a passive transporting mechanism for various substances. Their nature differs from that of jaw cyst lining cells.


Some findings in patients with uraemic stomatitis.

Uraemic stomatitis may occur in patients with advanced renal failure. Thirteen patients with severe oral lesions due to their uraemic state are discussed. The stomatitis became manifest after a few days of severe renal failure (blood urea level was at least 20 mnol./1) and persisted for 2-3 weeks even when the urea concentration had decreased.


Vertical osteotomy of the ascending rami in mandibular retrognathism.

The authors present their experience and conclusions regarding surgical lengthening of the mandible in retrognathism due to bone hypo-development. Thus, in hypotrophies of the ascending ramus, especially in temporo-mandibular ankylosis, they use a longitudinal osteotomy (Popescu 1949); various technical adaptations of this method, in different situations, are described, as well as their association with osteoplasty, utilizing iliac bone grafts or the hypertrophic chin prominence. In retrognathism due to hypo-development of the mandible, when the ascending rami have a good conformation, sagittal osteotomy (Obwegeser 1957, Dal Pont 1961) is preferred.


A longitudinal study on electrical pulp testing following Le Fort type osteotomy and Le Fort type fracture.

A longitudinal study of electrical pulp testing was carried out in 27 cases, or 53 maxillary halves following Le Fort type fractures and Le Fort type osteotomies. On the average, most teeth required positive responses around 7 months or around 11 months afterwards. The central and lateral incisor teeth demonstrated poor results; only 8 percent and 36 percent responded positively at 8 months, and at 14 months, 23 per cent  and 50 per cent, respectively. The overall percentage of responsive teeth was 29 percent at 6 months and 85 percent at 14 months. These results are discussed and compared with those of segmental maxillary osteotomy, together with the value of pulp testing in the diagnosis in fracture and osteotomy.


Experimental animal research into segmental alveolar movement after corticotomy.

Experiments with beagle dogs show that groups of teeth can be rearranged by orthodontic appliances, within a  few days when bone is weakened by corticotomy. The rapid movement does not damage the vascular supply of the pulp. This is demonstrated by intravascular injections of Plastoid. If the marginal bone is not impinged upon by the ostoetomy saw, only vascular changes in the free gingival mucosa indicate slight reactions of the parodontal membrane.


Intraoral closure of subcutaneous clefts of lip.

A new method for the closure of subcutaneous clefts of lip has been presented. The operation was achieved from an incision in the oral mucosa, without skin incision in the white portion of the lip. The muscle stumps of the orbicularis oris are freed from their false insertion and re-united. In addition, the musculature is separated from the skin In this manner, the shortness of the white portion of the lip, which is due to the elevation of the musculature, is largely eliminated. The lip on the cleft side thus attains the same length as that of the healthy side. The muscular pull gives rise to a conspicuous philtrum pit and ridge, without external scar on the lip. This principle of separating the musculature can also be used in the repair of incomplete and complete clefts of lip, and in all reoperations of the lip.


Trigonometric method of analysis of the upper part of the mouth cavity.

A method of analysis of a cast of the upper part of the mouth cavity which allows a comparison of various forms thereof, by the use of five parameters is described. For their calculation, only five measurements between four pre-determined points are needed. With the great accuracy which the method ensures, it is possible to follow, at short time intervals, the changes brought about by jaw-orthopaedic and surgical procedures. Numerical and schematic graphical comparison permits a rapid evaluation of results achieved in the treatment of clefts. The character of the parameters elucidates the morphogenesis of clefts and indicates the most rational therapy.


Pharyngoplasty through cross palatopharyngeal flaps.

A surgical technique is presented which is a development of Orticochea's pharyngoplasty, which permits the establishment of a dynamic velopharyngeal closure, using the palatopharyngeal muscles by intercrossing and introducing them into a surgical pocket. This technique obtains a new relationship by changes in the direction of anter-posterior action of the palatopharyngeal muscles (longitudinal portion), which are transformed into an oblique force by crossing them, It may be done prior to the palatal closure (previous or prophylactic pharyngoplasty), simultaneously or later, to correct any deficiency that may remain. This technique avoids the pushback and a good functional result is obtained.


The neuropathological findings in irreversible coma. A critque of the "respirator".

1. Postmortem examinations were made on 240 of the 459 cases succumbing (52 percent of the deaths) in the Collaborative Study on Cerebral Survival; the central nervous system was examined in 226 cases. 2. The autopsy was performed on an average of 15.3 hours after death. 3. The mean weight of the brains was 1450 plus or minus 196 grams; the mean weight of the brains of patients on whom resuscitation was stopped, presumably on the basis of "cerebral death," was greater than that of the patients succumbing to cardiac failure. There was a tendency for the brain to increase in weight about 24 hours after the initiation of resuscitative measures. At that time, swelling, discoloration, softening, congestion, and brain herniations also became more prominent. 4. On the basis of a survey of American neuropathologists and the data from this study, the entity commonly termed "respirator brain" may be confirmed. This is a dynamic process that is complicated by concurrent postmortem changes. The respirator brain requires time (approximately 24 hours) for maturation; many patients die a cardiac death during the metamorphosis. If the patient survives for 3 to 4 days, the percentage dying with typical respirator brains is less, and more patients have electroencephalograms with biological activity. 5. The following clinical factors tend to be associated with an increased number of respirator brains: A. Cerebral trauma B. Subnormal body timperature C. Low systolic blood pressure D. Dilated pupils E. Pupils unresponsive to light F. Absence of cephalic reflexes G. Electrocerebral Silence (ECS) 6. The following factors have no apparent effect on the number of respirator brains or tend to be associated with fewer respirator brains: A. Severe drug intoxications B. Small reacting pupils C. Medications D. Presence of spinal reflexes E. Presence of biological activity (BA) in the electroencephalogram 7. A set of common criteria for a respirator brain was used to test the following: A. The local and consultant neuropathologist's diagnosis of respirator brain B. The significance of critical perfusion pressure and critical oxygen tension in respirator brain C. The role of cardiac output in the production of a respirator brain 8. Since a respirator brain is an imperfectly defined entity, an exact correlation with any combination of clinical and EEG findings could not be expected. The use of a standardized measurement of CBF seems a logical and promising confirmatory test for respirator brain.


Lymphocytotosicity for gingival epithelial cells in periodontal disease.

An immune pathogenesis has been implicated in periodontal disease. Lymphocytotoxicity assays utilizing a suspension of peripheral blood lymphocytes incubated with allogeneic trypsinized gingival epithelium were performed. The results demonstrate a significant in vitro lymphocytotoxicity for gingival epithelial target cells when the aggressor lymphocytes are from patients with destructive periodontal disease (high PDI). No significant lymphocytotoxicity was demonstrated with lymphocytes for periodontal disease-free (low PDI) patients. We conclude that there is a significant reduction in gingival epithelial cell survival after an 18-hour incubation with aggressor lymphocytes obtained frompatients who have destructive periodontal disease, and suggest there is a pathologic relationship between the patient's lymphocytes and the disease process.


A histologic examination of a free osseous autograft. Case report.

Twenty-eight months following free osseous autograft therapy, a block section was taken for histologic examination. (2) Microscopically, the periodontal structures were reconstructed with new alveolar bone, periodontal ligament, and cementum. (3) A 'separation artifact' was present between new and old cementum. This defect is probably an artifact of histologic processing.


Ultrastructural studies of human gingiva. V. Microfibrils of elastic nature and their direct penetration of the basal lamina in chronic periodontitis.

In this study, microfibrils widely distributed in the connective tissue of the gingival wall of periodontal pockets were examined by electron microscopy, Theirdistribution, ultrastructural characteristics, close association with fibroblasts and direct communication with the basal lamina were shown. The microfibrils in our specimens were observed in three different groupings (Types A, B, and C). They were believedto represent different stages of maturation of elastic fibera. There was a striking ultrastructural resemblance between oxytalan microfibrils, and the immature or imcompletetype of elastic fiber shown in this report.


Myofascial pain dysfunction syndrome involving tumor metastasis. Case report.

This report is an example of tumor metastasis to the temporomandibular joint and its effect on pain, restriction of jaw movement, and the subsequent inability of the patient to function normally. Neoplasm is not the usual etiology of myofascial pain dysfunctionsyndrome and the muscle sparm component of this patient's jaw dysfunction was emphasizedby the relief of symptoms from the use of symptomatic reversible type therapy (tranquilizer, muscle relaxant, and heat). There was an overlay of stress-tension factors in this case history that contributed to the muscle spasm symptoms of the patient. There canbe other etiological factors in jaw dysfunction associated with TMJ pathology such asdevelopmental anomalies, trauma, arthritis, and neoplasm, but as a group they comprise only about 5% of TMJ dysfunction problems (D.M. Laskin, personal communication).


Acute nonlymphocytic leukemia. An adult cluster.

Between 1970 and 1973, seven cases of acute nonlymphocytic leukemia were diagnosed in the village of Elmwood, Wis, and the surrounding area. The patients ranged in age from 14 to 97 years. Interpersonal relationships were noted among all patients in the group. This cluster of cases represents a greater than 20-fold increase in the expected incidence of this disease for this population. Morphologic similarities in the blast cells were seen in all cases. This cluster of cases may bear a relationship to bovine leukemia since the town was located in dairy farming country and because a number of the patients had either worked at or lived near the town creamery.


Effects of central-nervous-system irradiation on neuropsychologic functioning of children with acute lymphocytic leukemia.

Two neuropsychologic studies were performed to determine the long-term effects of "prophylactic" cranial or craniospinal irradiation on the psychologic and neurologic functions of children with acute lymphocytic leukemia. In a prospective study, 34 patients with leukemia who received either craniospinal irradiation or cranial irradiation combined with intrathecal methotrexate were evaluated by standardized neurologic and psychologic examinations before and after irradiation. Their performance was compared with that of 27 controls who received irradiation to parts of the body other than the cranium. In a retrospective study, 11 patients with leukemia receiving prophylactic craniospinal irradiation and 12 controls with the disease not receiving such therapy were followed from the second year after either irradiation or the initial hematologic remission. Eighteen months after irradiation in the prospective study and four years after irradiation in the retrospective study, no noteworthy neurologic or psychologic differences were found between subjects and controls.


Post-neonatal infant deaths in the Auckland Hospital Board area 1972.

A study has been made of the final, and contributory, causes of post-neonatal deaths in the Auckland Hospital Board area for 1972. There was a high rate of deaths from infection. Maori infants died from pneumonia at a rate 28 times that of european infants. Prevention of these infant deaths will need improvement in parent recognition of illness, medical practitioner availability and training, and hospital facilities.


Industrial hand injuries in Pacific Island immigrants.

There is a disturbingly high incidence of heavy machinery, industrial hand mutilation, involving recent Pacific Island immigrants many of whom have a poor comprehension of English. A survey of cases admitted to the Hutt Hospital during eight monts of 1973, showed a proportionately greater incidence of severe injuries amongst these immigrants, and indicates that one causative factor is unsuitable selection of works for this dangerous machinery, coupled with inadequate instruction in its use and safety precautions.