[Association of chronic myelosis and cancer]. During the period between 1948-1963 a total of 3,200 tumor patients were treated in the First and Second Medical Clinics of Tg.-Mures. In these tumor patients as well as the skin cancer patients who were treated with radiotherapy the authors found in 1.5% of the patients a leukocytosis of more than 20,000. In the last ten years (1964-1974), however, in the Second Medical Clinic only, 5% of 516 tumor patients showed a leukocytosis exceeding 20,000. In the first group of patients (3,200 cases) 0.03% showed more than 50,000 leukocytes, in the other group of 516 patients 0.2% showed more than 50,000 leukocytes. These values point towards a leukemoid reaction. A shift to the left to the myelocytes or beyond in the blood picture was found in the Second Medical Clinic in 10% of patients with carcinoma during the year of 1974. In 6% of the cases erythroblasts in the peripheral blood were seen, too. This deviation occurred often independent of the total number of leukocytes and was of a temporary nature. During the same time (1949-1974) 128 patients with chronic myeloid leukemia were treated in both departments as in-patients. 6 cases (i.e., 4.6%) had a chronic myelosis simultaneous with carcinoma, in one case together with an osteosarcoma. The diagnosis was confirmed in all cases by autopsy.


The frequency, technical standard and results of endodontic therapy. The present summary and the following papers (I--VI) have been accepted in partial fulfilment of the requirements of the degree of Doctor Odontologiae at the Dental Faculty, University of Bergen. Paper I: Tooth mortality and endodontic status of a selected population group - before and after treatment in a teaching clinic. Paper II: The apical level of root fillings made by general practitioners, undergraduate students and an endodontist. Paper III: Radiographic evaluation of endodontic treatment-a methodological study. Paper IV: The quality of the seal of root fillings made by general practitioners, undergraduate students and an endodontist. Paper VI: A radiographic follow-up of endodontically retreated roots. In this summary these papers will be referred to by the above Roman numerals. Other investigations will be referred to in the conventional manner.


[Sialolithiasis in minor salivary glands. Case report]. Lithiasis of the minor salivary glands appearently occurs more frequently than hitherto presumed and should be considered as a possibility in the clinical differential diagnosis of tumors of the oral mucous membrane. The present paper refers two cases of sialolithiasis of the labial minor salivary glands. Further, a general outline of the condition is presented based on later years' increasing number of case reports.


Biological activity of catecholamines covalently linked to synthetic polymers: proof of immobilized drug theory. l-Isoproterenol was covalently coupled via an azo linkage to soluble copolypeptides of molecular weight 1500 and 10,000 containing an aromatic amine. The polymeric azo-isoproterenol derivatives were purified by gel chromatography which reduced contamination by the parent isoproterenol to undetectable levels (i.e., less than 0.01%) and by 6-aminoisoproterenol to less than 0.4%. Both polymeric isoproterenol derivatives were found to elicit positive chronotropic responses in isolated perfused guinea pig hearts. The mean effective doses (ED50S) for the 1500 and 10,000 molecular weight derivatives were within 1.3 and 2.0 orders of magnitude, respectively, of the ED50 of l-isoproterenol. The responses cannot be attributed to free isoproterenol because this drug could not be detected in our preparations. Neither can the observed biological activity be attributed to 6-aminoisoproterenol, since this compound's dose-response is shifted 3 orders of magnitude to the right of l-isoproterenol and 1-2 orders of magnitude to the right of the polymeric derivatives. Inotropic response decay times in isolated cat papillary muscles following washouts indicate that the polymer-bound drug does not diffuse into the muscle tissues. We feel that our findings demonstrate that under controlled conditions the catecholamines can retain biological activity while covalently bound to a polymeric support.


Distribution of 5-bromodeoxyuridine and thymidine in the DNA of developing chick cartilage. In order to study the mechanism of the irreversible effects of BrdUrd on the differentiation of limb bud mesenchyme to cartilage, the reannealing behavior of DNA obtained from such cells was examined. Cells incubated with [3H]thymidine ([3H]dThd) during days 1 and 2 of culture incorporated label into repetitive, moderately repetitive, and unique classes of DNA. In contrast, when 5-bromo-2'-[3H]deoxyuridine ([3H]Brd Urd) was added during the first 48 hr (in the presence of 32 muM BrdUrd), the label was preferentially incorporated into a late moderately repetitive region. Simultaneous incubation of unlabeled BrdUrd and [3H]dThd revealed a selective inhibition of [3H]dThd incorporation into moderately repetitive regions. Cultures incubated during days 3 and 4 with [3H]dThd incorporated label into all three classes of DNA; however, when [3H]dThd was present during days 3 and 4 in cultures previously incubated with BrdUrd during days 1 and 2, the [3H]dThd was incorporated preferentially in the late moderately repetitive region. The melting behavior of this reannealed DNA was identical with that of the reannealed 1-2 day [3H]BrdUrd-labeled, late moderately repetitive DNA. Turnover experiments revealed that whereas there was no loss of [3H]deoxycytidine or [3H]dThd, 37% of [3H]BrdUrd activity was lost from the DNA in 2 days after removal of the isotopes.


Intracellular forms of adenovirus DNA: integrated form of adenovirus DNA appears early in productive infection. In KB cells productively infected with adenovirus type 2, alkali-stable greater than 100S and 40-100S viral DNAs are synthesized starting 2-4 hr postinfection, i.e., before unit length (34 S) viral DNA is made. The amount of greater than 100S and 40-100S viral DNA increases when 34S viral DNA synthesis  begins, and at 16-18 hr postinfection, the 40-100S viral DNA represents 5-20% of the total intracellular viral DNA. The 40-100S viral DNA is synthesized throughout infection. Part of the 40-100S DNA synthesized 5-8 hr postinfection has a density in alkaline CsCl gradients intermediate between those of viral and cellular DNAs. This finding indicates that newly synthesized viral DNA is covalently linked to cellular DNA. Viral sequences can be excised from the cellular DNA of infected cells with the EcoRI restriction endonuclease. Fragments of viral DNA are detected in polyacrylamide-agarose gels by DNA-DNA hybridization, and these fragments correspond in size to most of the known EcoRI fragments of adenovirus 2 DNA. Viral DNA sequences in size-classes between the EcoRI-A and -C fragments are also found and probably represent viral DNA linked to cellular sequences.


Observations on polycythemia vera turning into acute or chronic granulocytic leukemia during treatment with radioactive phosphorus 32P. In a group of 172 cases of polycythemia vera treated with radioactive phosphorus acute granulocytic leukemia developed in 3 and chronic granulocytic leukemia in 6 cases. The author believes that development of acute granulocytic leukemia during this treatment may be considered with some probability as a result of the leukemia-inducing action of ionizing radiation. Transition of polycythemia vera into chronic granulocytic leukemia seems to be a natural outcome of this complex myeloproliferative syndrome in patients with survival prolonged by treatment with 32P.


New protein in human blood plasma, rich in proline, with lipid-binding properties. A protein that binds to a lecithin-stabilized triglyceride emulsion has been separated from plasma after removal of major lipoprotein classes by ultracentrifugation at density 1.21 g/ml. This protein, rich in proline, has been purified to electrophoretic and immunochemical homogeneity by subsequent gel and ion-exchange chromatography. In native plasma and after purification, it exists as a large particle exceeding 10(6) daltons, but a single component with a molecular weight of about 74,000 is found upon polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Although the purified protein contains very little bound lipid and is not present in the major lipoprotein classes from post-absorptive individuals, it is present in chylomicrons. Its concentration in plasma varies from 12 to 41 mg/dl and is significantly correlated with that of cholesterol in lipoproteins of very low and low density but not in those of high denisty.


A thermodynamic model of regulation: modulation of redox equilibria in camphor monoxygenase. Regulation of biological phenomena occurs in all types of systems, being manifested in many different reaction types, from allosteric behavior in proteins, through modulation in energy and information transfer, to the control of growth and differentiation in cells, organelles, and organisms. In this communication, a modulation in oxidation/reduction potential via ligation of substrate and protein components in the camphor 5-exo-monoxygenase system is described in terms of a four-state system using as fundamental parameters the transition free energies between equilibrium states. This approach provides a concise description of the data and is useful for describing many aspects of regulatory phenomena.


Ribonuclease H of calf thymus: substrate specificity, activation, inhibition. When the action of highly purified specimens of ribonuclease H (hybrid nuclease; RNA-DNA hybrid ribonucleotidohydrolase; EC 3.1.4.34) of calf thymus on a wide selection of homopolymer hybrids was studied, the extent, and even the occurrence, of hydrolysis was found to be governed by the interplay of several factors: the composition of the ribo strand, the length of the deoxyribo strand, and the nature of the activating metal. Mn2+ activates the enzymic cleavage of all hybrid combinations, Mg2+ only of those containing purine ribo strands, Co2+ only of poly(A) hybrids. A 1:1 hybrid of phage f1 DNA and RNA is, however, split in the presence of any of these activators. Hybrids with deoxyribo tetranucleotides can still be cleaved, but not with dinucleotides. The behavior of hybrids containing covalently linked runs of ribo and deoxyribopolynucleotides was studied with the hybrid poly(dT)-poly(A)7-(dA)X]. This hybrid is attacked by ribonuclease H so that the bulk of the resulting poly(dA) still retains one covalently linked riboadenylic acid end group, whereas a small proportion carries a ribo dinucleotide. Inhibition studies showed that ribonuclease H is inactivated irreversibly by pretreatment with S-adenosylmethionine at 35 degrees, but not at 0 degrees. S-Adenosylhomocysteine also is inhibitory, but not irreversibly; also it is essentially limited to the inhibition of the cleavage of purine ribo strands. When the enzyme is exposed simultaneously to both inhibitors, irreversible inactivation is diminished considerably.


Reconstitution of Qbeta RNA replicase from a covalently bonded elongation factor Tu-Ts complex. Escherichia coli phage Qbeta RNA replicase, an RNA-dependent RNA polymerase (RNA-dependent RNA nucleotidyltransferase), is a tetramer composed of one phage-coded polypeptide and three host-supplied polypeptides which are known to function in the biosynthesis of proteins in the uninfected host. Two of these polypeptides, protein synthesis elongation factors EF-Tu and EF-Ts, can be covalently crosslinked with dimethyl suberimidate to form a complex which lacks the ability to catalyze the known host functions catalyzed by the individual elongation factors. Using a previously developed reconstitution system we have examined the effects of crosslinking the EF-Tu-Ts complex on reconstituted replicase activity. Renaturation is significantly more efficient when exogenously added native EF-Tu-Ts is crosslinked than when it is not. Crosslinked EF-Tu-Ts can be purified from a crude crosslinked postribosomal supernatant by its ability to replace EF-Tu and EF-Ts in the renaturation of denatured Qbeta replicase. A sample of Qbeta replicase with crosslinked EF-Tu-Ts replacing the individual elongation factors was prepared. Although it lacked EF-Tu and EF-Ts activities, it could initiate transcription of both poly(C) and Qbeta RNA normally and had approximately the same specific activity as control enzyme. Denatured Qbeta replicase formed with crosslinked EF-Tu-Ts was found to renature much more rapidly than untreated enzyme and, in contrast to normal replicase, its renaturation was not inhibited by GDP. The results demonstrate that EF-Tu and EF-Ts function as complex in Qbeta replicase and do not perform their known protein biosynthetic function in the RNA synthetic reaction.


Intracellular localization of mouse DNA polymerase-alpha. Although DNA polymerase-alpha (DNA nucleotidyltransferase; deoxynucleoside triphosphate: DNA deoxynucleotidyltransferase; EC 2.7.7.7) probably functions in the nucleus, it is usually found predominantly in the nonnuclear fraction of disrupted cells. We have reexamined the intracellular location of this enzyme using cytochalasin-B-induced enucleation, a technique which avoids exposure of nuclei to extra-cellular conditions during cell fractionation. In conditions where viability of separated cell parts is high and recovery is quantitative, we find greater than 85% of total DNA polymerase-alpha (and DNA polymerase-beta) activity in the nucleated cell fragments (karyoplasts), from which we conclude that the location in vivo of DNA polymerase-alpha is either nuclear or perinuclear. On the other hand, thymidine kinase (ATP: thymidine 5'-phosphotransferase, EC 5.7.1.75) is found primarily in the enucleated cell fragments (cytoplasts). The enucleation procedure used in this work should be of general use for intracellular location studies.


Spectral differences between the alpha and beta heme groups within human deoxyhemoglobin. The contributions of the alpha and beta heme groups to the absorbance change that accompanies the aggregation of hemoglobin subunits were measured by comparing the extinction changes produced by n-butyl isocyanide binding to deoxyhemoglobin A with those produced by binding of n-butyl isocyanide to the isolated chains. Almost the entire aggregation absorbance change is associated with the unliganded alpha subunits, which exhibit a 30% increase in molar extinction at 428 nm during tetramer formation. This marked spectral change indicates a substantial perturbation of the electronic properties of the alpha heme groups in going from the high-affinity, isolated chain state to the low-affinity, tetrameric state. The lack of a significant absorbance change as sociated with the beta heme groups implies that the change in reactivity of unliganded beta subunits produced by aggregation is not the result of a change in spin or coordination geometry of the iron atom, but rather involves primarily an alteration in the protein structure near the sixth coordination position.


Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands. The isolation of an untriakontapeptide from camel pituitary extracts has been described. Its structure has been determined and shown to be identical to the sequence of carboxyl-terminal 31 amino acids of ovine beta-lipotropin. The peptide possesses very low lipotropic activity but significant opiate activity.


Hydrolytic stability of helical RNA: a selective advantage for the natural 3',5'-bond. Dodecaadenylic acid containing a single 2', 5'-linkage at a defined position was formed by the coupling of two hexamers on a poly(U) template at 2 degrees. The rate of hydrolysis of this dodecamer was compared with that of a dodecamer that contained only the natural 3', 5'-linkages. At 40 degrees, in 1 M aqueous ethylenediamine at pH 8 in the absence of poly(U), both dodecamers hydrolyzed at comparable rates, but the addition of two equivalents of poly(U) caused a 7-fold increase in the initial rate of hydrolysis of the oligomer containing the 2', 5'-bond, and a 5-fold decrease in the initial rate of hydrolysis of the natural oligomer. When the oligomers are fully constrained in helical form, the ratio of the rates of cleavage of one 2', 5'-bond to one 3', 5'-bond under these conditions is probably about 900:1. The use of the 3', 5'-bond, in combination with a right-handed helix, appears to have had a large selective advantage over the use of the 2', 5'-bond for the storage of genetic information.


Direct experimental evidence for kinetic proofreading in amino acylation of tRNAIle. Kinetic proofreading is a reaction scheme with a structure more complicated than that of Michaelis kinetics, which leads to a proofreading for errors in the recognition of a correct substrate by an enzyme. We have measured the stoichiometry between ATP hydrolysis and tRNAIle charging, using the enzyme isoleucyl-tRNA synthetase [L-isoleucine:tRNAIle ligase (AMP-forming), EC 6.1.1.5] and the amino acids isoleucine (correct) and valine (incorrect). The enzymatic deacylation of charged tRNA, which would normally prevent meaningful stoichiometry studies, was eliminated by the use of transfer factor Tu-GTP, (which binds strongly to charged tRNA) in the reaction mixture. For isoleucine, 1.5 ATP molecules are hydrolyzed per tRNA charged,  but for valine, 270. These stoichiometry ratios are fundamental to kinetic proofreading, for the energy coupling is essential and proofreading is obtained only by departing from 1:1 stoichiometry between energy coupling and product formation. Within the known reaction pathway, these ratios demonstrate that kinetic proofreading induces a reduction in errors by a factor of 1/180. An overall error rate of about 10(-4) for tRNA charging is obtained by a kinetic proofreading using a fundamental discrimination level of about 10(-2), and is compatible with the low in vivo error rate of protein synthesis.


An altered apurinic DNA endonuclease activity in group A and group D xeroderma pigmentosum fibroblasts. Endonuclease activity upon depurinated DNA was measured in extracts of cultured fibroblasts from xeroderma pigmentosum patients. Cell lines from complementation groups A, B, C, E, and the XP-variant had slightly reduced levels of activity, but cell lines from complementation group D had one-sixth of the normal activity. An altered pH dependence and a higher apparent Km for substrate in D-cell lines indicate that the remaining activity is also qualitatively different from the activity found in normal cells. A higher Km was also found in cell lines from the A-complementation group but not in cell lines from the C-complementation group. These defects in apurinic DNase might account for the neurological disorders in patients from the D- and the A-complementation groups.


mRNA-dependent synthesis of authentic precursor to human placental lactogen: conversion to its mature hormone form in ascites cell-free extracts. Messenger RNA derived from term placenta directs the synthesis of human placental lactogen (hPL, molecular weight 22,200) in an ascites 30,000 X g post-mitochondrial supernate (S-30). When the S-30 is fractionated into ribosome and cell-sap (S-100) fractions, and these are recombined for incubation, term placental mRNA directs the synthesis of a protein with a molecular weight of 25,000. This protein contains authentic hPL tryptic peptides. This suggested that during the separation of ribosomes and S-100 a component responsible for cleavage was lost. A 1.0 M sucrose cushion was used for the preparation of ribosomes and S-100 and membranous material accumulated at the sucrose interphase. When this membrane fraction was added back to the ribosome-S-100 system only hPl was formed. Cleavage was greatest when membranes were added within the first few minutes of incubation. In a run-off system composed of term polysomes, ascites S-100, and the inhibitor of initiation, pactamycin, the 25,000 molecular weight material, referred to as pre-hPL, was also synthesized. These data strongly suggest that (i) pre-hPL is an authentic percursor to hPL, (ii) cleavage of the precursor primarily occurs on nascent, ribosome-bound peptide chains, and (iii) pre-hPL is the primary gene product.


Specific release of the thioesterase component of the fatty acid synthetase multienzyme complex by limited trypsinization. Limited trypsinization of the fatty acid synthetase multienzyme complex from rat mammary gland results in the release of a protein, molecular weight 32,000, with thioesterase activity. The other components of the multienzyme complex--the acyl carrier protein, acetyl and malonyl transferases, condensing enzyme, keto reductase, dehydrase and enoyl reductase--are not affected and remain associated with the complex. The thioesterase can be isolated by ammonium sulfate precipitation and gel filtration. Extensive trypsinization of fatty acid synthetase multienzyme complex results in a loss of thioesterase activity, probably due to cleavage of the thioesterase component into inactive peptides. However, the molecular weight and specific activity of the thioesterase isolated after limited trypsinization is relatively unaffected by the severity of the conditions of proteolysis. Both the thioesterase and the residual trypsinized complex react with antibodies produced against the native multienzyme. The results demonstrate that mild trypsinization can be used to release the thioesterase component of the multienzyme with little perturbation of either the thioesterase or the other components of the complex.


Electron probe x-ray analysis of single ferritin molecules. Single molecules and groups of two or three ferritin molecules were subjected to electron probe x-ray microanalysis in a transmission electron microscope equipped with a liquid nitrogen cooled stage. Significant Fe Kalpha peaks were generated during 100-sec counts when single ferritin molecules were excited with a probe current of 0.35 nA/60 nm spot, less than the maximal current available in a thermionic gun. There was a linear relationship between the number of ferritin molecules analyzed and count rates. The experimental results are compared to the theoretically calculated Fe Kalpha yields and to the results of Isaacson and Johnson [(1975) Ultramicroscopy I, 33-52] with electron energy loss analysis. We conclude that current state of the art electron probe x-ray analysis can realize the theoretically predicted sensitivity of the method, and estimate 0.9 X 10(-19) g of Fe as the minimal mass detectable with maximal (thermionic) probe current during a 100-sec count and with 95% confidence.


Somatostatin conformation: evidence for a stable intramolecular structure from circular dichroism, diffusion, and sedimentation equilibrium. Somatostatin is a hypothalamic tetradeca peptide that inhibits the release of growth hormone insulin, and glucagon. The circular dichroism spectrum is characterized by negative extrema at 238 nm and 270 nm, and a positive extremum at 225 nm. The far ultraviolet circular dichroism spectrum is consistent with the presence of ordered secondary structure such as beta-structure, but not alpha-helix. Sedimentation equilibrium results demonstrate that somatostatin exists in its monomeric form (i.e., a molecular weight of 1610 +/- 36 was obtained) and, thus, the structure must arise from intramolecular interactions. The diffusion constant of somatostatin was estimated to be 1.66 X 10(-6) cm2/sec. These data are consistent with an ellipsoidal rather than a spherical shape. The magnitude of the ellipticity at both 225 nm and 238 nm is quite dependent on guanidinium hydrochloride concentration; the midpoint occurs at about 3 M and the transition is cooperative-like. These data strongly suggest that somatostatin has a stable conformation in aqueous solution. A model, consistent with the results of the physicochemical studies and with semi-empirical rules for secondary structure formation, is proposed for somatostatin. The proposed structure consists of a hairpin loop with several residues in an antiparallel beta-pleated sheet, is somewhat elongated, and contains a hydrophobic domain at one end and a hydrophilic domain at the other end.


Theoretical studies on pro-leu-gly-nh2 conformation. Classical potential function calculations were carried out on the hypothalamic factor Pro-Leu-Gly-NH2. The results indicate that the proposed 10-membered, hydrogen-bonded beta-turn conformation of this tripeptide is a strongly preferred structure. Its stability appears to be inherent in the rather rigid backbone conformation of the leucine residue rather than the hydrogen bond between the carboxamide proton of glycinamide and the C=O of the proline moiety; the glycinamide has little influence on the phi-psi of the leucine backbone structure. The type II beta-turn structure of the Pro-Leu-Gly-NH2 is preferred.


Transepithelial transport in cell culture. In cell culture a kidney epithelial cell line MDCK, forms a continuous sheet of identically oriented asymmetrical cells joined by circumferential occluding junctions. The reconstructed epithelial membrane has transport and permeability qualities of in vivo transporting epithelia. The cell layer can be readily manipulated when cultured on a freely permeable membrane filter and, when placed in an Ussing chamber, electrophysiological measurements can be taken. In the absence of a chemical gradient, the cell layer generates an electrical potential of 1.42 mV, the apical surface negative. It is an effective permeability barrier and lacks significant shunting at the clamped edge, as indicated by a resistance of 84 ohms-cm2, which increased when bulk flow from basolateral to apical was induced by an osmotic gradient or electroosmosis. The MDCK cell layer is cation selective with a relative permeability ratio, PNa/PCl, of 1.7. Net water flux, apical to basolateral, was 7.3 mul cm-2 hr-1 in the absence of a chemical gradient. The morphological and functional qualities of a transporting epithelium are stable in cell culture, and the potential use of a homogeneous cell population in cell culture would enhance studies of epithelial transport at the cellular and subcellular levels.


Reversible in vitro polymerization of tubulin from a cultured cell line (rat glial cell clone C6). Tubulin from cultures of the rat glial cell clone C6 could be polymerized in vitro into intact microtubules. The polymerization was reversible and spontaneous, i.e., no addition of heterologous nucleation centers was necessary. Two cycles of polymerization/depolymerization yielded tubulin preparations of 95% purity as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electron microscopy was used to show that the microtubules assembled in vitro by two cycles of polymerization/depolymerization were morphologically intact and temperature sensitive. In contrast, tubulin from neuroblastoma cells, clone Neuro-2A, could not be polymerized in a reversible fashion. The discovery of a cell line from which tubulin can be reversibly polymerized in vitro establishes a model system for studies of cell-cycle- and cell-type-dependent regulatory mechanisms controlling the assembly of microtubules.


Clathrin: a unique protein associated with intracellular transfer of membrane by coated vesicles. Coated vesicles have been purified from brain, adrenal medulla, and a nonsecreting lymphoma cell line. A single major protein species, clathrin, with an apparent molecular weight of 180,000, forms the coat of all these vesicles. Peptide mapping suggests that the amino acid sequence of clathrin is conserved, irrespective of tissue or species studied. Coated vesicles of different sizes are found. The coats are constructed with variable numbers of clathrin subunits, arranged in closed networks of hexagons and pentagons. The amount of clathrin in lymphoma cells suggests that coated vesicles transfer substantial amounts of membrane within cells, not necessarily in association with a secretory process.


Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus. Mice were infected with the exogenous Moloney leukemia virus (M-MuLV) at two different stages of development. Either newborn mice (which can be considered as essentially fully differentiated animals) or preimplantation mouse embryos (at the 4-8 cell stage) were infected with M-MuLV. In both cases, animals that had developed an M-MuLV-induced leukemia were obtained. Two lines of evidence indicate that infection of preimplantation embryos, in contrast to infection of newborns, can lead to integration of the virus into the germ line. 1. Viremic males of the first backcross generation (N-1 generation) transmitted the virus to 50% of their offspring (N-2 generation) when mated with uninfected females. Likewise, a 50% transmission was observed from viremic N-2 and N-3  males to the next generations. 2. Molecular hybridization experiments revealed that viremic N-1 and N-2 animals carried one copy of M-MuLV per diploid mouse genome equivalent in all "non-target" organs tested. Together, both experiments indicate that the exogenous M-MuLV can be converted to an endogenous virus after infection of preimplantation embryos. The available evidence suggests that M-MuLV integrated into the germ line at one out of two possible integration sites. Thus, viremic backcross animals are heterozygous for a single Mendelian locus carrying the M-MuLV gene. During leukemogenesis an amplification of the M-MuLV from one copy to a maximum of four copies per diploid mouse genome equivalent takes place in the tumor tissues.


Influence of diet on survival of mice.

Influence of diet on survival of mice. The longevity of mice of the (NZB X NZW)F1 (B/W) strain and the DBA/2f strain of mice is dramatically prolonged by dietary restriction. B/W mice are susceptible to, and die at an early age from, immunocomplex nephritis. Mice of the DBA/2f strain are also relatively short-lived. Restriction of caloric intake prolonged life of B/W mice more than did protein restriction. DBA/2f mice showed prolongation of life when the diet was restricted only with respect to protein. Caloric restriction alone prolonged life less in DBA/2f mice than in B/W mice. These observations show that dietary manipulations have profound effects on immunity functions, including inhibition of the development of life-shortening autoimmune disease.


Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells. Treatment of young and mature mice with potent mouse interferon preparations results in a marked enhancement of the expression of histocompatibility antigens on the surface of thymocytes and splenic lymphocytes as measured by an enhanced absorption of alloantiserum. We postulate that such modifications of the cell surface may reflect an effect of interferon on lymphocyte maturation and may be relevant to the effect of interferon on lymphocyte function.


Measles virus-specific IgD antibodies in patients with subacute sclerosing panencephalitis. Indirect immunofluorescent analysis revealed that sera from five patients with subacute sclerosing panencephalitis possessed IgD antibodies directed against measles virus components in persistently infected HeLa cells. IgD levels in these sera were within the normal range. Control studies indicated that the reaction was specific for measles virus. The detection of IgD measles antibodies in these patients suggested that IgD may be involved in the pathogenesis of this viral disease.


Genetic polymorphism of IgD-like cell surface immunoglobulin in the mouse. Lymphocyte surface antigens from spleen cells of several mouse strains were studied by cell surface radioiodination, extraction with detergent incubation with various antisera, and separation of complexes using protein A-containing staphylococci as a solid phase adsorbent. Complexes were then dissociated and analyzed by polyacrylamide gel electrophoresis in the presence of sodium diodecyl sulfate. Using this technique and an alloantiserum prepared in C57BL mice against CBA spleen cells, four distinct specific peaks of radioactivity were found with CBA spleen cells. These corresponded to H-2 and Ia antigens, immunoglobulin light chain, and a heavy chain previously proposed to be the murine homolog of the human delta chain. With the same serum, B10.BR spleen cells revealed only H-2 and Ia antigens, whereas C57BL.Ige (allotype congenic) spleen cells showed only the light chain and "delta" chain peaks. Depletion of immunoglobulin from the surface-iodinated preparations resulted in removal of the light chain and "delta" chain peaks. The tissue distribution and membrane expression of this "delta" chain antigen was then studied by indirect immunofluorescence with various C57BL derived alloantisera and lymphoid cells from C57.Ige allotype congenic mice. Significant numbers of positive cells were found in spleen, lymph nodes, and Peyer's patches, whereas few if any positive were found in bone marrow or thymus. No reaction was found between this molecule and alloantisera to any of the previously described immunoglobulin allotypes. It is proposed that these alloantisera to spleen cells recognise one allelic form of the murine "delta" chain coded for by a gene locus closely linked to the known structural genes for mouse immunoglobulin heavy chains. The designation Ig-5 is proposed for this new immunoglobulin heavy chain locus.


Fluorometric assay of vasopressin and oxytocin: a general approach to the assay of peptides in tissues. A fluorometric method for the quantitative assay of vasopressin and oxytocin in individual rat pituitaries has been developed. Acid extracts of pituitaries are freed of amino acids and polyamines by passage over a copper-Sephadex column, and the peptides fraction is then labeled by reaction with fluorescamine. The resulting peptide fluorophors are separated by chromatography on a reverse-phase bonded column. Specificity of the procedure was ascertained by several criteria, including bioassay and amino-acid analysis of the eluted peptide fluorophors. The procedure serves as a model system for the assay of tissue peptides in the picomole range.


Cancer-associated isoenzyme of serum galactosyltransferase. Galactosyltransferase activity was assayed in sera from 58 patients with various types of cancer. On discontinuous polyacrylamide gel electrophoresis a slow-moving peak of galactosyltransferase activity (isoenzyme II) was found to be present in the serum of 43 of these patients in addition to the major isoenzyme I. Isoenzyme II was found in only 2 of 39 patients with various nonmalignant disorders and was not detected in the serum of 22 normal control subjects. There was no correlation between the presence of this electrophoretically distinct isoenzyme and total serum galactosyltransferase activity, alkaline phosphatase, levels of carcinoembryonic antigen, or blood type. However, patients with widespread metastases had significantly higher isoenzyme II levels than those with no metastases or with limited local spread. Further studies will be necessary to evaluate the clinical usefulness of this serum galactosyltransferase isoenzyme in the diagnosis and monitoring of patients with neoplastic disease.


Porphyria variegata and porphyria cutanea tarda in siblings: chemical and genetic aspects (addendum). A porphyria kindred in which the index case has porphyria variegata had also been shown to include a case of porphyria cutanea tarda, typical both from chemical and clinical features. The possibility that this was purely acquired rather than genetic seemed unlikely, but could not be wholly excluded. Recently, a niece of both of these cases, although asymptomatic, has been found to conform chemically with porphyria cutanea tarda, including the excretion of the isocoproporphyrin series, and thus represents the second case of this form of porphyria in this family. This strengthens the concept of genetic heterogeneity in this kindred and supports the suggestion of a double heterozygosity, as proposed in the primary paper [Watson, C.J. et al. (1975) Proc. Nat. Acad. Sci. USA 72, 5126-5129].


Eel esophagus as an osmoregulatory organ. Ion and water permeabilities were measured in the isolated esophagus of the eel (Anguilla anguilla and A. japonica), and compared with those in the stomach and the intestine. The freshwater eel esophagus was impermeable both to Na+ and Cl- ions and to water, whereas permeabilities to the ions increased selectively after seawater adaptation. The ion permeabilities of both the freshwater and the seawater eel stomach were lower than in the seawater eel esophagus, although water permeability was greater than in the esophagus. Sea water enclosed in the lumen was diluted three times more efficiently in the seawater eel esophagus than in the stomach. The intestinal permeabilities were greater than those of the esophagus and the stomach, and increased after seawater adaptation. In the eel, ingested sea water seems to be diluted mainly in the esophagus by passive diffusion of the ions into the blood without addition of water. After further but less important dilution in the stomach with salt removal and with water addition, the water is absorbed by the intestine, following active absorption of the ions. Thus the eel in sea water is able to replace water lost osmotically by drinking hypertonic sea water.


Pharmacologic characterization of the Na+ ionophores in L6 myotubes. We present a pharmacologic characterization of the Na+ ionophores present in L6 myotubes in vitro. Action potentials are abolished by replacement of the external Na+ by Tris. The amplitude of the action potential is generally resistant to high concentrations of tetrodotoxin (10(-5) M) and saxitoxin (10(-6 M), but the effect of these agents is highly variable. Veratridine (10(-4 M) consistently induces, as a short-term effect, a marked prolongation of the falling phase of the action potential. As a long-term effect, veratridine consistently induces a Na+-dependent reduction in the resting potential of the cell. The effects of veratridine on the action potential are not antagonized by tetrodotoxin or saxitoxin. However, the effects of veratridine on the resting potential are strongly antagonized by tetrodotoxin (10(-5) M) and fully inhibited by saxitoxin (10(-6) M). Significantly, under conditions where saxitoxin has fully inhibited the effects of veratridine on the resting potential, the myotubes are capable of generating overshooting action potentials. In contrast to their sensitivity to veratridine, L6 myotubes are insensitive to 10(-5) M alpha-dihydro-grayanotoxin-II. These results are discussed in the contexts of developmental significance and current views about Na+ ionophores.


Rates, patterns, and effectiveness of evolution in multi-level situations. Evolution is a multi-level process. Both actual evidence and theoretical considerations suggest as a first generalization that evolution both at single levels and in series of increasingly complex levels decelerates with time. Additional evidence, the expected difference between rapid nonadaptive speciation in small populations and effective adaptation in large ones, and analysis of explosive evolution suggest further that effective adaptive evolution occurs primarily in large populations, and that segments of such evolution tend to begin slowly; accelerate, sometimes explosively; and then decelerate. The segments are irregular, and do not occur at regular intervals. However, the explosive evolution of a general adaptation pre-adapts to and is often followed by an explosive radiation of derivative lineages. This description seems to fit the origin and initial radiation of mammals, and the evolutionary history of man and man's cultures.


An experimental analysis of competitive indeterminacy in Tribolium. This report reexamines experimentally the problem of competitive indeterminacy in mixed-species populations of the flour beetles, Tribolium confusum and T. castaneum. Indeterminacy takes the form of alternative competitive outcomes: in some replicate cultures one species exterminates the other with a probability, say p, whereas in others, the opposing species wins with a complementary probability, 1-p. The conventional explanation for this is the genetic founder effect hypothesis--an explanation based on genetic stochasticity. The experiment reported here partitioned indeterminacy into founder effect and nonfounder effect components. The results implicate demographic stochasticity, not classical genetic founder effect, as a factor influencing the identity of the winning species.


Simple synthesis of a 4a-hydroperoxy adduct of a 1,5-dihydroflavine: preliminary studies of a model for bacterial luciferase. The solution chemistry of N(5)-alkyl flavinium cations and radical species formed by their le- reduction are discussed. Previously unknown, the 4a-flavine hydroperoxides are established to be formed on reaction of N(5)-alkyl flavinium cations with H2O2 or on reaction of N(5)-alkyl-1, 5-dihydroflavines with 3O2. The stability of the 4a-flavine hydroperoxide species is exemplified in the isolation and characterization of 4a-hydroperoxy-N(5)-ethyl-3-methyl-lumiflavine. 4a-Flavine hydroperoxide compounds are shown to be stronger oxidants than H2O2, and to undergo a chemiluminescent reaction in the presence of an aldehyde. Preliminary observations on the chemiluminescent reaction of 4a-flavine hydroperoxides + RCHO are provided, and these are compared to those in the literature dealing with the bioluminescence of bacterial luciferase in the presence of 3O2 and RCHO.


Hallucinogenic indoleamines: Preferential action upon presynaptic serotonin receptors. Previously, d-lysergic acid diethylamide was found to have a more powerful inhibitory action upon serotonergic (raphe) neurons than upon neurons in areas receiving an identified serotonergic input (e. g., amygdala, ventral lateral geniculate). In the present studies, using microiontophoretic techniques, the relative potencies of 3 indoleamine hallucinogens, psilocin, DMT, and bufotenine were tested upon 5HT neurons in the raphe (presynaptic neurons) and postsynaptic neurons in the ventral lateral geniculate and amygdala of the rat. Psilocin showed the greatest preferential inhibitory effect upon raphe as compared to postsynaptic neurons. DMT was intermdeiate and bufotenine had the least differential activity. This rank ordering correlates with the relative hallucinogenic potencies of these compounds: psilocin greater than DMT greater than bufotenine. The results support the hypothesis that low doses of indoleamine halluciogens act preferentially upon presynaptic serotonin receptors to inhibit raphe neurons, thus releasing postsynaptic neurons from a tonic inhibitory serotonergic influence.


[A new case of sarcomatous degeneration of the spine in Paget's disease of bone]. In referring to a personal observation the authors recall the rarity of malignant degeneration of lesions of the spine caused by Paget's disease. In the majority of cases these consist of multiple centred osteo-sarcomatosis. The lumbar spine is the most often affected. The clinical picture is essentially a syndrome of radiculomedullary compression. Rapid aggravation of the condition usually leads to a neurosurgical operation, which will confirm the existence of the osteo-sarcomatous process. The evolution is always fatal.


[The dynamic complex of the temporomandibular meniscus]. The existence of meniscocapsular insertions of the temporal, masseter and external pterygoid muscles complicates the scheme of capsulo-meniscal dynamics. Our findings do indeed agree with those of DUBECQ (Bordeaux); but we think that the insertions of the masseter and the temporal are not only fine tracts. In the embryon, the meniscus is the preglossal mekelian conjunctival blastema, which receives the 3 masticatory muscles on its anterior border. In the adult, menisco-capsulo-muscular relationships are not modified; inspite of considerable functional adaptation of the articulation to varied stimuli, the menisco-capsular apparatus seems to be triply controlled by 3 musculo-masticatory bands, owing to the anterior premeniscal tendinous lamina, in histological continuity with the meniscus and rich in corpuscles of deep sensitivity. The resultant of the tridirectional muscular traction of the masseter, external pterygoid and temporal is a force in the postero-anterior oblique direction, downwards and forwards, which allows the meniscus to stretch, as was shown by Pr Delaire, and thus to have a sub-temporal sliding pathway of 8 to 12 mm. The three muscle bundles external pterygoid, temporal and masseter constitute the dynamic complex of the meniscus.


[Bone statics of the face: the frontal-sphenoid-pterygoid bone pillars as biomechanic equivalents of the mandible]. In general biomechanics, trabecular osteo-architectonics is considered as a response to the mechanical strains present in the bone (compression or traction). The facial and cephalic skeleton is no exception to this law. The study of the bony architectionic provides the proof, since we have demonstrated in the fixed facial bone mass (at the limits of the facial skeleton and the skeleton of the base of the skull) the biomechanical equivalent of the mandible: the cranio-facial pterygo-spheno-frontal bony pillars. Paired, symmetrical and with a medio-frontal junction, they represent an embryological, anatomical and functional entity. Their ossification (mixed) may be compared to that of the mandible. They are made up of directional trabecular bone which may be analysed by stereology, electron microscope scanning and by strain gauges. Each pillar is made up of: - A part free of musculature corresponding to the supra-orbital frontal arch, which receives the four vertical pillars (naso-maxillary and maxillo-malo-frontal) of the superficial system of the face which transmit to the supra-orbital frontal arch the ascending mechanical strains of mastication registered in the spongy hard palate. The supra-orbital frontal arch is the biomechanical homologue in the fixed facial mass of the tooth bearing bony base of the mandible. - A spheno-pterygoid part, into which are inserted the alimentary muscles of the cephalic region (masticators, velar and superior pharyngeal). There is further functional homology between the ascending ramus of the mandible and the pterygoid greater wings and apophyses complex of the sphenoid. The 2 pterygo-spheno-frontal pillars also participate in the osseous statics of the orbit and the osseous statics of the temporo-mandibular joint. The basi-sphenoid plays a role of first importance in the general statics of the cephalic region. Thus the two pterygo-spheno-frontal pillars, biomechanical homologues of the mandible in the fixed facial mass, underline the functional interdependence of the osseous, dental and muscular systems of the cephalic region, a region which should be viewed as being in a stade of permanent dynamic equilibrium during growth and in the adult.


[Masticatory sysarcosis. Significance in maxillofacial surgery and pathology]. The masticatory muscles and the vertical ramus move in a closed aponeurotic lodge; sliding spaces containing cellulo-adipose formations, veritable sysarcoses, are situated between the muscles of mastication as well as between these muscles and their osteo-aponeurotic covering. Sysarcoses are embryological, anatomical and functional units. Bichat's ball must be considered as being the antero-inferior pole of these cellulo-adipose containing spaces. Apart from the mechanical role of these spaces, their value in pathology and in traumatological surgery must again be pointed out, because firstly they are the pathways of approach and fixation of fractures of the zygomamalar region. They are also of great value in reparatory surgery as knowledge of the vascularization of the fat in these spaces enables the making of flaps of fat in the surrounding area.


[Parotidectomy in Sjogren-Houwers-Gougerot syndrome]. The authors report two cases of Sjögren's syndrome which fulfilled the diagnostic criteria and which were accompanied by voluminous parotid hypertrophy. In a 42 year old woman, bilateral parotid hypertrophy, in addition to the aesthetic problem, also had major psychological repercussions. In a 59 year old woman, parotid hypertrophy was limited on the right but voluminous on the left, with frequent episodes of parotiditis. Total parotidectomy with conservation of the facial nerve, followed by filling of the post-operative cavity by a strip of sterno-mastoid, bilateral in the first case and unilateral in the second, gave excellent results, diminishing the real degree of infirmity which rendered these patients extremely unhappy and the complications related to the parotid hypertrophy of Sjögren's syndrome.


Hypotheses on the role of chromosomal changes in leukemias. Application of the Weibull distribution function. Investigations were carried out in 38 patients with acute leukemias or with chronic myeloid leukemias in the blast phase and a correlation was made between the cytogenetic aspect and the survival time. The interpretation of results was made by the Weibull distribution function. It was mathematically demonstrated that in the leukemic patients with chromosomal aberrations there is a preclinical period of over 40 months necessary for the formation of these anomalies. Chromosomal aberrations, the absence of mitoses and age over 70 proved to be aggravating factors in the diseases investigated.


[Radioisotopic examination and diagnosis of dryness of the mouth]. The clinical and sialographic opposition between true xerostomia (with continuous disorders) and paradoxical asialia (with inter-prandial disturbance, but sparing mealtime) led the authors to analyze these patient's scintigraphic scannings. A kinetic study of excretion was carried out with gamma-camera recording of intensity and glandular activity: the information thus obtained was set down in a numerical integration block and dealt with by computer. A graph of activity was plotted for each gland showing: - a phase of ascending concentration followed by a plateau corresponding to excretion at rest; - a phase of excretion provoked by a gustatory stimulus (physiological) with a very rapidly descending graph. It is possible to establish a ratio of glandular activity/blood activity at maximum concentration and maximum excretion. From the graphs thus obtained it is possible to perfectly differentiate true xerostomia (no excretion even with stimulation) from paradoxical asialia (no plateau of excretion at rest, but stimulus effective). A better knowledge of "dryness of the mouth" should enable better adapted therapy.


[Kahler's disease manifesting mandibular localization]. The authors present a case of multiple myeloma, the diagnosis of which was made at the time of the appearance of a mandibular tumour following the extraction of a tooth.


[Calcifying odontogenic cyst: apropos of 5 cases]. With reference to 5 personal cases involving the mandible 3 times and the lower gum twice, the authors recall the principal characteristics of calcified odontogenic cysts: very little clinical manifestation frequently limited to simple tumefaction, well bounded radiological image with low density, cyst with an epithelial border comprized of calcification and ghost cells. Calcified odontogenic cysts which have a definite morphological likeness to Malherbe's epithelioma, also have the same benigh course as the latter.


[Migrating or ectopic teeth].

[Migrating or ectopic teeth]. These three cases are examples of ectopia related to tumor formations which they may have precipitated or of which they are the consequence. Here it is not a question of explaining the phenomenon, but only of showing some cases of migration or of relatively exceptional ectopia with the specific pathways of approach.


Neutrophil dysfunction and granulomatosis in the preleukemic state. A 40-year-old male had periods of fever, sore throat and anemia for 14 months before acute myeloblastic leukemia could be diagnosed from hematological findings. During the preleukemic state, impaired bactericidal capacity of the granulocytes was repeatedly demonstrated and multiple hepatosplenic and skin granulomas occurred. Results of granulocyte function studies may prove to be of significant aid in the diagnosis of the preleukemic state of acute myeloblastic leukemia.


[The value of Schüller's temporomandibular joint radiography for the diagnosis of joint related malocclusion]. A tentative diagnosis of the supposed position of the condyle in its glenoid fossa was made for 150 temporomandibular joints only be means of Schuller radiographs. To determine the value of the radiographs for diagnosis of occlusion the radiologic diagnosis of each joint was then compared with the real diagnosis based upon instrumental functional analysis of the occlusion, clinical findings and individually projected radiographs of the joint. Radiologic diagnosis and real diagnosis coincided to a relatively high degree provided that the radiographs were readable. Very high correspondence was found for anterior and posterior displacement of the condyle whereas supperior, inferior and lateral displacement showed considerably less coincidence. By the Schuller technique 30 of the 150 joints were not represented readably and better projection by a different angulation of the central X-ray beam was possible for half of those only. Posterior displacement of the condyle was found to be the most frequent malposition of the joint in this study.


[Statistical study of dental caries in children aged 5 1/2 to 6 1/2 years of geneva in 1973. Study of 614 children following administration of fluoride tablets, in collaboration with the Geneva Youth Dental Clinic]. By this study it was possible to evaluate dental health in children of Geneva aged 5 1/2 and 6 1/2 years old. Of 614 children, 28.1% of the 5 1/2 year old and 18.2% of the 6 1/2 year old are without caries or fillings. The DMF factor is of 3.34 (t), 4.40 (s) and 5.57 (t), 8.02 (s) respectively. About one fifth of the children shows an irreproachable mouth hygiene. These children with mediocre or bad hygiene. 7.0% and 5.4% respectively show green or black stain. Children receiving fluorine tablets have more resistant deciduoud teeth than others of the same age from unfluoridated regions.


Lysergic acid diethylamide- and mescaline-induced attenuation of the effect of punishment in the rat. At a dose as low as 1 microgram per kilogram of body weight, lysergic acid diethylamide (LSD) significantly decreased the suppressive effect of electric shock on licking behavior of the rat. Attenuation of punishment was also obtained with mescaline, but neither dimethyltryptamine nor delta9-tetrahydrocannabinol was active in this test. Cyproheptadine and alpha-propyldopacetamide, drugs that interfere with the function of neurons that contain serotonin, have a behavioral effect similar to that of LSD and mescaline, which suggests that the attenuation of punishment produced by these hallucinogens may result from decreased activity of such neurons.


Acute blastic transformation in patients with chronic granulocytic leukaemia and myelofibrosis. A retrospective study of 21 patients with acute transformation of chronic granulocytic leukaemia (CGL) and myelofibrosis was undertaken. The patients were divided into 3 groups according to whether transformation had occurred in pre-existing CGL (11 patients), myelofibrosis (6 patients) or in patients who presented with acute leukaemia and significant marrow fibrosis--acute myelofibrosis (4 patients). In an attempt to investigate some recent reports that during the acute blastic crisis there is conversion to the haemopoietic stem cell, the morphology of the blast cell and the response to therapy were assessed. The blast cell morphology was reviewed in 17 of the 21 patients studied. Three patients had blast cells which morphologically resembled lymphoblasts. The mortality in these patients was similar to that in patients in whom the blast cell morphology was myeloblastic. The response to treatment in the acute phase was poor. However, some patients who received therapy with thioguanine, daunorubicin, cytosine arabinoside, methotrexate, prednisone, cyclophosphamide and vincristine (TRAMPCO) appeared to do better. in most patients, splenectomy was performed for advanced diseases. Acute blastic transformation supervened within 4 months in 3 of 4 patients with CGL who underwent splenectomy. In 3 of 5 patients with myelofibrosis, splenectomy was followed by an increase of primitive cells in the peripheral blood and rapid liver enlargement. Although they had improved symptomatically the patients died within 10 months of the splenectomy. The indications for and timing of splenectomy remain controversial.


Surgical aspects of airway management in infants and children. The surgical management of the upper airway in infants and children varies in many important details from the principles of airway management usually applied to adults. Recent technical adaptations and innovations have improved our ability to deal with upper airway obstruction effectively. Advances in respiratory support for sick infants have saved thousands of lives and at the same time produced a new spectrum of airway problems which must be dealt with effectively. The surgeon who takes on such problems should be specially trained and dedicated to the unique requirements of infants and children.


Evaluation of splenectomy in chronic myelogenous leukemia. Splenectomy was performed in 45 patients with chronic myelogenous leukemia; 23 were in the chronic phase and 22 in the acute phase. Indications for operation included inability to control the disease by chemotherapy or radiation therapy, severe thrombocytopenia, frequent need for blood transfusion and extensive splenomegaly causing discomfort. Median survival time for these patients was better than survival time of other reported groups of patients who did not have a splenectomy. According to our criteria, splenectomy was beneficial to 15 patients in the chronic phase as well as to eight in the acute phase of chronic myelogenous leukemia. Median survival time after splenectomy was higher in patients who had splenectomy within two years of the diagnosis as compared with those who had the operation after two years. Splenectomy did not prevent the future onset of fatal blastic crisis. Although significant abnormalities in coagulation studies were seen in 37 of the patients, intraoperative hemorrhage was not a major problem. Considering the poor general condition, inadequate healing and susceptibility to infection, the postoperative mortality and complication rates were comparable with those reported in series in which splenectomy was performed for other diseases. It seems that splenectomy benefits a selected group of patients with chronic myelogenous leukemia; however, a randomized series would furnish better data upon which to make decisions.


[Combined treatment of patients with osteogenic sarcoma]. The results of the combined treatment in 30 patients with osteogenic sarcoma (preoperative radiotherapy after the method of large fractionation, using the dosage up to 4000 rad with subsequent amputation or exarticulation of the extremities) are reported. An average survival in patients with osteogenic sarcoma was 15.2 months following the operation.


[Preclinical form of blast leukosis].

[Preclinical form of blast leukosis]. The problem of the early diagnosis "acute" leukosis is of a great practical and theoretical interest. Lately many authors speak of "pre-leukemic syndrome" or of "pre-leukemia". In that sense the notion "acute" leukosis appears to be inaccurate and its substitution for the term "blast" leukosis is more expedient. A woman-patient with an early form of blast leukosis is described in the paper, diagnosed by a sternal puncture 18 months before the typical clinical and cytomorphological manifestations of the disease. The total pre-leukemic "stage" lasted three years, manifested with persisting anemia, acceleated RES, granulocytopenia, monocytosis. Exitus followed after the fifth month of the blast eucosis clinical manifestation.


[Autoimmune thrombocytopenia in the course of hemoblastosis]. The results of an investigation on platelet antibodies by thromboagglutination and antiglobulin consumption test (AGCT) in 51 patients with different types of hemoblastoses (acute and chronic leukemias, Hodgkin disease, lymphosarcoma) are reported. Complete and/or incomplete antibodies were found in 50,9% of the cases, with lymphoid forms showing the highest frequency. Although a constant relation between thrombocytopenia and platelet antibodies is by no means demonstrable, four fully descirbed cases clearly show and the onset of autoimmune thrombocytopenia in the course of hemoblastoses. Two chronic myeloid leukemia cases treated with Myleran and one chronic lymphoid leukemia case presented thrombocytopenic purpura and normal number of megakaryocytes. One case of lymphosarcoma presented thrombocytopenia and autoimmune hemolytic anemia with bone marrow aplasia. Steroid therapy had been partially effective only in two cases. The pathogenetic relationship between platelet immunization and hemoblastoses and cytostatic therapy is discussed.


[Treatment of monocytic blast leukosis with vinblastine]. Monocytic blast leukosis progresses very aggressively, with severe complications--hemorrhages, infections, tumors, severe anemia and rapidly comes to a lethal end. The therapeutic remedies are limited for that type of blast leukosis. The present communication covers 20 patients with monocytic blast leukosis, treated with vinblastin. In five of them--a complete remission was observed and in two--not complete. The first remissions lasted at an average of 3-5 months with a total duration of living up to seven months. The results are satisfactory for that hard to cure clinicohematological form of blast leukosis.


[Local reaction to the intradermal injection of PHA in healthy persons and in chronic lympholeukosis patients]. Phytohemagglutinin (PHA) that stimulates the lymphocytes to blast transformation in conditions of cellular cultures provokes local skin reaction, when applied intradermally. At the beginning that reaction is manifested with hypermia at the place of the application and later an infiltration is formed. In healthy subjects the infliltration reaches maximal dimensions on the 48th to the 72nd hour post PHA injection. The presence of lymphocytes was established with the cytologic examination of the material from that infilitration at the 24th hour, lymphoblasts and hyperbasophilic blast cells at the 48th and 72nd hour and single reactive lymphocytes were observed at the 96th hour. The infiltration appears later in patients with quiet development of chronic leukosis, only after the 96th hour and is with smaller demensions. Negligible infiltration is observed in malignant leukosis, its progress in time does not differ from that in healthy subjects. However, skin reaction in intraderma injection of PHA gives a certain orientation about the immune organism reactivity and in case of 1 chronic leaukosis--about the form and severity of the disease.


[Changes in plasma and whole blood viscosity during starvation (author's transl)]. More than 6000 parameters were collected during a 21-day period of starvation in 51 obese patients aged 17 to 65 years and stored as data bank on a CDC CYBER 74 at the calculating centre of the University of Technology in Vienna. Samples for multiple linear regression were obtained on the basis of various selective criteria. The essential results of this analysis are the depression of plasma viscosity, which correlates positively with the decrease in blood lipids and the reduction of overweight, as well as the unexpected increase in whole blood viscosity. The latter can probably be explained by an altered erythrocytic fluidity due to the metabolic changes which take place during a longer period of starvation.


[Tracheal dimensions and shape in healthy subjects and in patients with chronic obstructive lung disease (author's transl)]. Normal data for tracheal shape and dimensions were obtained by the investigation of a group of 90 men and women aged 50 years or over with normal pulmonary function. Significant differences were found between the sexes in regard to tracheal shape and cross sectional area. Another group of 90 men and women with pulmonary function data indicative of severe chronic obstructive lung disease was also investigated and the tracheal findings were compared with those of the control group. It was demonstrated that patients with chronic cough and chronic bronchitis exhibit a tendency to intrathoracic coronal narrowing and sagittal widening i.c. "saber-sheath" deformity. Mechanisms responsible for this alteration in tracheal shape are discussed. No definite correlation was demonstrable between age, total lung capacity, residual volume and tracheal shape. The relatively unknown, but fairly characteristic radiological appearance of the "saber-sheath" trachea is described and the importance of routine X-ray of the trachea in patients with chronic obstructive lung disease is stressed.


[The personality of obese persons in psychological tests with special consideration on latent obesity]. The results of psychological tests of the obese are inconsistent and no characteristic personality structure of the obese can be deduced from them. Investigations in childhood obesity failed to establish a general psychogenetic model of obesity. Yet overweight and ideal weight-subjects differ in spontaneous eating behaviour. Appetite and satiety of obese subjects are controlled by external stimuli to a far greater extent than in nonobese. From a behavioural scientific viewpoint it is proposed that learning experiences during childhood socialisation generate the disposition for obesity which can manifest itself later, after interaction with a special environment. At this stage, however, individual reactions to starting overweight are insolved; this process is strongly influenced by individual personality structures: an inadequate conflict management favours obesity; by cognitive control normal weight can be preserved in spite of the acquired disposition for obesity. Taking these "latently obese" as an example the role of personality structure and wrong eating habits is discussed and related to possible therapeutic strategies. A model of the psychogenetic basis of obesity is proposed. In this model eating-related learning experience is attributed a primary role and individual personality structure a secondary role in the psychogenesis of obesity.


Pulmonary hamartomas: cytologic appearances of fine needle aspiration biopsy. The cytologic findings in specimens obtained from pulmonary hamartomas by fine needle aspiration biopsy are presented. The following are the main characteristics: 1. In spite of the fact that the lesions are usually hard and cartilaginous, find needle aspiration is possible and can obtain diagnostic material. 2. The material obtained usually has few cells. 3. The cells aspirated include columnar ciliated cells, lymphocytes, histiocytes as well as fragments of cartilage which are quite characteristic. 4. The differential diagnosis is discussed.


Urothelial neoplasms of the upper urinary tract. A correlation between cytologic and histologic findings in 43 patients with urothelial neoplasms of the renal pelvis or ureter. The present study elucidates the possibilities to diagnose and classify urothelial tumors of the upper urinary tract by means of exfoliative cytology on voided urine using a membrane filter method. In a series of 30 patients with renal pelvic tumors and 13 patients with ureteral tumors an overall agreement between cytology and histopathology was obtained in 25 cases (58%). None of the Grade 1 tumors or of the non-invasive Grade 2 tumors were regarded as positive by cytology whilst two out of five invasive Grade 2 tumors had positive cytologic reports. The series included 24 patients with poorly differentiated or anaplastic tumors, 17 of whom had positive cytology (71%). By excluding from the series 13 patients with obstructed urinary passages or radiologically non-functioning kidneys on the tumor side an agreement between cytology and pathology was reached in 83 per cent of the cases, regardless of tumor grade, and in 17 out of 18 patients with Grade 3-4 tumors (94%).


Cytopathology of intra-hepatic bile as component of integrated procedure ("minilap") for hepatobiliary disorders. Twenty patients with hepatobiliary disorders were prospectively studied by means of minilaparotomy. The study included cytologic evaluation of intra-hepatic bile obtained at trans-hepatic cholangiography. The yield of malignancy identified was increased one third by the cytologic studies.


Cytophotomeric DNA-analysis of aspirated cells from prostatic carcinoma. In the present study material obtained from prostatic lesions by transrectal aspiration biopsy was subjected to a comparative morphologic and cytophotometric DNA analysis. Based on the morphologic pattern, the clinical material was divided into benign lesions (prostatic hyperplasia), suspected prostatic malignancy and highly, moderately and poorly differentiated prostatic carcinoma. The cytochemical analysis, based on quantitative cytophotometric measurements of Feulgen stained nuclei, showed that cell nuclei from benign lesions (prostatic hyperplasia) exhibited the normal diploid amount of DNA. Contrary to this, cell populations from prostatic malignancies, were characterized by various degrees of heteroploidy, i.e. the existence of cells with nuclear DNA quantities increased above the normal diploid level. A general correlation between degree of heteroploidy (frequency of heteroploid cells) and degree of clinical malignancy seemed to exist; high grade malignant prostatic carcinoma (poorly differentiated) exhibited a pronounced degree of heteroploidy with more or less distinct aneuploid stemlines, whereas low-grade prostatic carcinomas (highly differentiated) were more similar to benign cell populations, in showing a large proportion of cells with a diploid DNA quantity suggesting the existence of diploid or near diploid stemlines. Cases morphologically classified as moderately differentiated prostatic carcinoma, which previously have been shown to exhibit individual variations in degree of clinical malignancy, also showed large individual variations in degree of hetyroploidy. Approximately half of these cases had cytochemical DNA characteristics similar to that of highly differentiated prostatic carcinoma in showing a modal DNA value in the diploid region, while the other half showed cytochemical characteristics similar to that of poorly differentiated prostatic carcinoma, i.e. aneuploid DNA distributions. However, no morphologiifferentiated prostatic carcinoma. In conclusion it can be stated that the present investigation suggests the possibility that quantitative cytochemical DNA analysis may be used in combination with, and offer additional information to, morphologic analysis in the malignancy grading of prostatic carcinoma. A future clinical follow-up, now in progress, will hopefully give a more definite answer to that idea.


Aspiration biopsy of salivary gland tumors. VI. Morphologic studies on smears and histologic sections from mucoepidermoid carcinoma. The cytologic findings in fine-needle aspiration biopsy of 24 primary mucoepidermoid carcinomas of salivary glands are reviewed. The morphologic details which permit recognition of this tumor in smears of the aspirate are described.


Impedance and spontaneous electrical activity as a localizing method in percutaneous spinal surgery. Simultaneous recording of impedance and spontaneous electrical activity of the spinal cord was accomplished by use of a roving electrode. The method for this double monitoring in cats and in human surgery is described. The impedance method revealed a significant and well-delineated difference between the gray and white matter of the spinal cord which can be seen clearly on the recording. Well-localized high electrical activity was observed in the anterior horn.


Fluoride and dental age.

Fluoride and dental age. The dental ages of 149 children born and grown up in a district with naturally occurring fluoride in the drinking water (maximum level 2.0 mg/l) were compared with those of 181 control children born and grown up in a neighbouring low-fluoride district (less than or equal to 0.1 mg/l). The children were 9--12 years old. In neither group did the dental ages prove to differ from normality. It is concluded that concentrations below the highest recommended level fluoride occurring naturally in the drinking water do not seem to have any long-term effect on the individual physiologic maturation, as judged from the dental age of the growing child.


The nuclear dry weight of liver cells from patients with virus hepatitis and from controls. Interferometric investigations were performed at liver cell nuclei isolated in 70 per cent glycerol. In 11 patients with virus hepatitis and seven patients without liver disease the nuclear dry weight of liver cells obtained by liver biopsy was determined by interferometry. The average nuclear dry weight of diploid liver cells from controls was 39.9 pg while an average value of 45.4 pg was found for patients with hepatitis. The corresponding nuclear volumes were 241 and 274mu3 respectively. The dry mass and volume of tetraploid nuclei was twice as big as that of diploid nuclei in both materials. The nuclear water content was neither significantly different between diploid and tetraploid nuclei nor significantly different between nuclei from controls and patients with hepatitis.


Influence of stone mixing agents, impression materials and lubricants on surface hardness and dimension of a dental stone die material. The influence of different stone mixing agents, impression materials and lubrication methods on the surface hardness of a stone die material has been evaluated. For one impression material the dimensional effect of the mixing agents and lubrication on the dies was also studied. The stone die material was mixed with water or a gypsum hardener and allowed to set on surfaces of glass, agar-agar, polyether, polysulfide and silicone impression materials. The lubrication methods for the stone were mineral oil, water soluble lubricant and mineral oil followed by water soluble lubricant. The surface hardness was measured according to the Brinell test. The Brinell test was chosen after a comparative study of the Brinell, Vickers and Knoop hardness test methods. The results showed that gypsum hardener was preferable to distilled water. The impression materials appear to have influence on the surface hardness of stone. The effect differed on water mixed and hardener mixed stone which emphasizes the importance of the mixing agent. All lubrication decreased the surface hardness of stone. With hardener mixed stone the combination of mineral oil followed by water soluble lubricant seemed preferable. Neither the gypsum hardener nor the lubrication influenced the dimension of the stone die material.


Cytologic findings in stilbestrol exposed females with emphasis on detection of vaginal adenosis. This prospective study of 271 females believed to have had prenatal exposure to stilbestrol documents the cytologic findings in separate vaginal and cervical preparations. In 233 patients, direct circumferential scrapings of the upper vaginal wall were taken after potentially contaminating mucous secretions had been removed. These specimens were considered evaluable for the cytologic detection of vaginal adenosis. Cellular evidence of vaginal adenosis was observed in 105 (45%) of these patients as determined by the identification of columnar cells and/or metaplastic squamous cells in the vaginal samples. Columnar cells were observed in 87 (37%) of the 233 patients. Metaplastic squamous cells accompanied the columnar cells in 54 cases. In an additional 18 patients (8%) metaplastic squamous cells were the only cytologic evidence of adenosis. Similar cellular changes were observed in 88 per cent of the vaginal samples from 25 patients with biopsy-proven vaginal adenosis. Malignant cells were not found in any of the cytologic or histologic specimens. Dysplastic squamous cells, however, were present in cytosmears from four patients. Biopsies from two of these patients confirmed the diagnosis of squamous dysplasia. Dysplasia also was identified by biopsy in four others. We believe cytology is a valuable aid in the evaluation of patients with a history of intrauterine exposure to stilbestrol. Vaginal adenosis as well as neoplastic and dysplastic lesions can be reflected in properly obtained cellular specimens.


Effect on plaque of a xylitol-containing chewing-gum. A pilot study. The effects on plaque induced by the use of xylitol- and sucrose-containing chewing-gums were studied on ten test-persons with neglected oral hygiene during two three-day periods. The chewing of three, as well as of ten pieces per day of a xylitol chewing-gum resulted in a significantly reduction in the amount of plaque and in the decrease of activity of invertase-like enzymes in plaque extracellular phase, when compared to corresponding conditions where a sucrose-containing chewing-gum was used.


Immediate diagnosis in vaginal cytology using interference contrast microscopy (Nomarski). Studying fresh aspiration material from the posterior fornix and cervix, by Interference Contrast Microscopy (Nomarski) is a good method of cytologic examination. It is shown how most cell types can be observed, just as they can be by the classical Papanicolaou staining. Normal and abnormal, even dysplastic and malignant cells can be recognized. This method is also very useful for identifying parasites, fungi and bacteria, by morphology and active movements. While encoraging the use of this method, it is advisable to compare the results with slides examined later by the Papanicolaou technique, for maximum safety of the patient.


Frequency of sex chromatin in the buccal smear of newborn females and their mothers during first six days after delivery. The frequencies of sex chromatin in the buccal smear of the newborn females and their mothers were low on the first post-partum day and it increased gradually during the second and third day. By the fourth and fifth day it stabilized and the incidence of sex chromatin both in the mothers and the children became similar, although the frequency on the first day was significantly lower in the newborn. The incidences of pyknotic cells in the buccal smears of the newborns and their mothers were highest on day one and these declined rapidly in the following days. The significance of these findings have been discussed.


Effect on plaque of a xylitol-containing chewing-gum. A clinical and biochemical study. The effects on plaque induced by single or repeated use of xylitol- and sucrose-containing chewing-gums were studied on twenty subjects refraining from tooth-brushing for three days. Mechanical removal of plaque by chewing during a single period was shown to yield no significant differences between gravimetric values obtained before and after chewing. Daily use of a xylitol-containing chewing-gum reduced by 47% the weight of plaque formed in comparison to a sucrose-containing product, and by 20--41% in comparison to conditions when no chewing-gum was used. The use of a xylitol chewing-gum induced a lower invertase-like activity in plaque extra cellular phase. Results at variance with the gravimetric data were obtained by using a stained plaque scoring system; the eventual inadequacy of such plaque scoring systems was discussed.


Measurement of fine structures in roentgenograms. III. Studies on root canals of teeth. A study of the projection of root canals of natural teeth on dental roentgenograms was carried out as a sequel to an earlier phantom study. The material consisted of extracted teeth and teeth in situ in jaw preparations. The same radiation source and focus-film distance were used throughout, but the exposure times and tube voltages were varied. The roentgenographic images of the root canals were analysed densitometrically and compared with measurements of the actual object dimensions. The root were sectioned at the level studied and their cross sections were traced and measured with the aid of a profile projector. There was good agreement between the true breadth of the canal and that projected on the film. The maximum contrast in the image of the canal and the densitometrically measured difference in substance, expressed in metal equivalents, were proportional to the depth of the canal in the direction of radiation. The breadth of the canal in the plane of the film was the same regardless of whether the tube voltage was 50, 60 or 90 kV. On the other hand, the tube voltage affected the photographic density differences between the canal and the dentine walls. Changing the voltage from 50 to 60 kV did not affect the results, but there was a highly significant difference between 90 and 50 or 60 kV. The clinical significance of tube voltage and exposure time is discussed.


Nose morphology in individuals with Angle Class I, Class II or Class III occlusions. The intention of this work was to describe the nose morphology in individuals with different craniofacial patterns which dentally were characterized by Angle Class I, Class II div. 1, and Class III occlusions. The material comprised male adults (age 20--30 years), and the results are based on measurements on tracings of lateral cephalograms. Generally, the inclination of the nose in relation to the nasion-sella-line was similar in all groups, and so was the nose length as well. The depth of the nose, when related to the hard and soft tissue facial planes was, however, significantly different, apparently due to the different sagittal position of the chin.


Prognostic value of mitotic studies in myeloid leukaemias. Seven patients with various forms of myeloid leukaemia have been studied by repeated sternal punctures during the course of illness. None of the patients received cytostatics before or during the study. The mitotic indices declined with time and there was a significant relation between the slopes of the mitotic curves and survival time. Repeated mitotic counts seem to serve as a diagnostic and prognostic tool in myeloid leukaemias.


Chronic granulocytic leukemia without the Philadelphia chromosome. Cytogenetic studies of bone marrow were performed in 230 consecutive cases of patients with chronic granulocytic leukemia (CGL) admitted to the National Cancer Institute since 1961. Twenty patients lacked the Philadelphia (Ph1) chromosome. All were previously untreated. When compared with Ph1-positive patients, CGL patients with Ph1-negative disease had a higher median age (60 compared with 42 years) and were diagnosed at lower median leukocyte (75,000) and platelet counts (170,000). Their response to chemotherapy was generally poor, with a median survival of 15 months compared with 44 months for the Ph1-positive group. Four patients survived more than 5 years and two, more than 10 years. Thirty-five per cent of the Ph1-negative patients had aneuploid cell lines of various percentages. Absence of the Ph1 chromosome in patients with the hematologic characteristics of CGL is a bad prognostic sign.


Prediction of orthodontic tooth movement. Orthodontics is rapidly advancing from the stage of fortuitous success to one of planned success. When appliance design is based on simple concepts of equilibrium, prediction of desirable and undesirable tooth movement becomes possible. The flow chart that has been presented allows the clinician to systematically treat dental discrepancies more effectively in potentially less treatment time, since the number of desirable and undesirable side effects can be known in advance and managed accordingly. Simple laws of equilibrium, based on a knowledge of the force systems required for specific tooth movement, also permit the design of proper preactivation bends for an appliance. The procedure may be enlarged to include treatment of each arch since, once the teeth are ideally positioned and rigidly held within each segment, each arch can be considered to consist of three "large, multirooted teeth."


The effects of orthopedic forces on the craniofacial complex utilizing cervical and headgear appliances. 1. A three-dimensional anatomic model of a human skull was produced with birefringent materials for photoelastic analysis. By means of photoelastic techniques during application of high-pull and cervical extraoral traction, stresses were visualized within the model. 2. Extraoral anchorage affected the position of the maxillary molar and its resulting alveolar development. Cervical headgear had a much greater tipping effect on the maxillary molar than did the high-pull headgear. Both appliances examined could produce stresses which may be transmitted to distant eraniofacial sutures. As opposed to high-pull traction, cervical pull in general stressed more areas and to a much greater degree. 4. The pterygoid plates of the sphenoid bone, the zygomatic arches, the junction of the maxilla with the lacrimal bone and the ethmoid, and the maxillary teeth were affected by both types of headgear. 5. Only cervical traction produced stresses at the frontal process of the maxilla and the Zygomaticofrontal suture. 6. There were two findings which had not been previously reported: First, cervical traction tended to open the palate in the posterior region. Second, high-pull traction produced compressive stresses at the junction of the right and left maxillae inferior to the anterior nasal spine.


[Artificial ventilation with the servo-ventilator 900 (author's transl)]. The use of artificial ventilation in the treatment of seriously ill or severely injured patients demands extensive knowledge on the part of the physician of the physiological and pathological effects of ventilation. In addition, it is required that the manufacturers develop ventilators able to meet there special demands. During the last two years the Servo-Ventilator 900 has been in use in our intensive care unit. During this period we were very impressed by its versatile applicability. The use of this apparatus however more than ever before requires the knowledge of breathing mechanisms and their pathophysiological consequences. The various flow- and breathing-rate-patterns combined with the exact electronic control of the respiratory make possible subtle adjustments--to the required ventilation pattern.


[Comparative studies on the efficiency of ventilation by engström-respirator ER 300 (author's transl)]. The efficiency of ventilation provided by the Engstrom-Respirator ER 300 was examined in 35 patients under general anaesthesia and relaxation during normoventilation and hyperventilation of 15% and 30%. For criteria the acid-base-status of arterial blood was used. There was a tendency to acidosis in all kinds of ventilation, probably as a consequence of surgical effects. During normoventilation the acid-base-status showed changes of low hyperventilation which are desired for security. During hyperventilation of 15% and 30%, arterial pCO2 was reduced to 30 and 27 Torr. Both situations showed no advantage over normoventilation. Using the Engstron-Respirator, normoventilation should be preferred during general anesthesia. Higher degrees of hyperventilation should be avoided because of their effects in lowering cerebral blood flow.


[Acute erythremic myelosis as a terminal phase of polycythemia rubra vera]. A male, 66, developed Acute Erythremic Myelosis in the course of Polycythemia Vera. The time of onset of Polycythemia Vera could not be determined, his first symptoms being vascular complications. He received treatment with Phlebotomies and Myleran. Five years later he became ill with malaise, fever, splenomegaly; in the peripheral blood profound pancytopoenia with immature, bizzare erythro-and megaloblasts have been found. Bone marrow was full of atypical megaloblasts, some of them having two or more nuclei. The number of mitoses was increased. Chromosomal abnormalities consisted of ane-uploid cells, chromatid  breakes and translocations (G to A-1). The therapy with B12, Cytosin-Arabinoside, Oncovin and Blood transfusions was unsuccessful. He died 21 days after being admitted to the Hospital.


Demonstration of cellular immunity in chronic myeloid leukaemia using leucocyte migration inhibition assay. Peripheral blood leucocytes from chronic myeloid leukaemia patients in remission were tested for inhibition of migration in presence of solubilized membrane antigens from leukaemic cells in 15 cases. Eight out of 9 autochthonous combinations (88-8%) and 35/49 allogenic combinations (71-4%) showed inhibition of migration. Antigens prepared from relapse leukaemic cell samples in 4 cases showed inhibition of migration of autochthonous as well as allogeneic remission leucocytes. The same batch of CML antigens inhibited migration of normal leucocytes at the level of 22-2%. The difference between inhibition of migration shown by remission leucocytes and normal leucocytes in presence of CML antigens was statistically significant. Solubilized antigens, similarly prepared from normal leucocytes, showed inhibition of migration of remission leucocytes to the extent of 15% only. The difference between the reactivity of CML remission leucocytes to normal and CML antigens was also statistically significant. No enhancement of migration of remission leucocytes was seen with CML antigens.


Adenosine deaminase activity in peripheral blood cells of patients with haematological malignancies. Adenosine deaminase (EC 3.5.4.4, ADA) has been assayed in lymphocytes, granulocytes and erythrocytes from 45 patients with haematological malignancies. Activities were uniformly low in lymphocytes from patients with chronic lymphocytic leukaemia. Variable, but abnormal activities were frequently found in multiple myeloma, untreated lymphoma and leukaemic reticuloendotheliosis. High values were observed in lymphocytes from patients with lymphoma during intensive combination chemotherapy. ADA levels in lymphocytes were not correlated with levels in granulocytes or erythrocytes. ADA was elevated in blasts of patients with acute lymphocytic and myelogenous leukaemias but the ranges of activities per cell were so similar that ADA assay is unlikely to be of major help in distinguishing the two diseases.


Diagnostic and prognostic significance of peripheral blood cultural characteristics in adult acute leukaemia. A simple liquid culture technique has been used to study peripheral blood from patients with acute myelogenous leukaemia. Evidence is presented that cells from morphologically identical types of leukaemia have differing capacity for "differentiation" from free floating blast cells into plastic-adherent phagocytic, trypsin-resistant macrophage-like cells with Fc and C3 receptors. Preliminary analysis suggests that patients whose cells have the greatest capacity for "differentiation" have a better chance of achieving complete remission.


Lack of prognostic value of lymphoblast size in acute lymphoblastic leukaemia. There are conflicting reports about the relationship of cell size and type to prognosis in acute lymphoblastic leukaemia (ALL). For this reason, bone marrows at diagnosis and first relapse were studied in 56 children with ALL treated on the same protocol. Lymphoblasts greater than 12 mmu in diameter were called macrolymphoblasts (MLB). Forty-one of 56 initial bone marrows had less than 20% MLB(group A), and 15 had greater than 20% MLB (group B). Median survival, complete remission rate, first remission duration, and the distribution of CNS leukaemia were similar in both groups. First relapse marrows were examined from 50 patients and a significant increase in MLB compared to initial pre-treatment bone marrows (18% vs 8%) was found.


Analysis of treatment in childhood leukaemia. II. Timing and the toxicity of combined 6-mercaptopurine and methotrexate maintenance therapy. The first and second Medical Research Council UKALL trials have shown that alteration in the timing of methotrexate and 6-mercaptopurine maintenance therapy for the treatment of acute lymphoblastic leukaemia can markedly change drug induced toxicity. Maintenance chemotherapy in both trials used a similar total dosage of these drugs but the timing of their administration was different in the two schedules.


Erythrocyte membrane modification in malignant diseases of myeloid and lymphoreticular tissues. I. Tn-polyagglutination in acute myelocytic leukaemia. Tn polyagglutination (persistent mixed-field polyagglutination) occurring in a patient with an acute myelocytic leukemia is described. The association of this RBC membrane change, thought to be due to somatic mutation at stem cell level, with a myeloproliferative disorder, has not been previously reported.


Erythrocyte membrane modification in malignant disease of myeloid and lymphoreticular tissues. II. Erythrocyte "mosaicism" in acute erythroleukaemia. A case of acute erythroleukaemia is described. The patient's RBC, which at first appeared to be a mixture of groups B and O, were shown in fact to be a mixture of normal B and very weak B.


Influence of humoral regulators on proliferation and maturation of normal and leukemic cells. Factors that influence the proliferation of marrow elements can be detected in sera. To determine the function and to compare the effect of these factors, cells were obtained from patients with normal and leukemic bone marrows. The effects of drug-induced stimulatory and inhibitory sera and leukemic pretreatment sera over time (0 to 6 days) on proliferation and granulocytic morphology of normal and leukemic bone marrow cells in culture were evaluated. Increased proliferation was associated with stimulatory sera, while inhibitory and leukemic pretreatment sera retarded proliferation of both normal and malignant cells. Exposure of normal proliferative cells to inhibitory or leukemic pretreatment sera yielded the greatest increase in mature granulocyte forms. In contrast, although the proliferative response of leukemic cells to these sera was similar to normal, maturation was minimal. These data suggest that leukemic pretreatment sera are similar to inhibitory sera and are not leukemogenic. Both retard proliferation of normal and leukemic bone marrow cells while enhancing maturation of normal cells. Leukemic myeloblasts, however, cannot be made to mature by these humoral regulators.


Isoenzyme pattern of phosphorylase in white blood cells and fibroblasts from patients with liver phosphorylase deficiency. Isoenzyme patterns of phosphorylase in white blood cells and cultured fibroblasts of a patient affected with liver-type phosphorylase deficiency were studied. Three bands were observed with electrofocusing of white blood cells and liver from controls. In the white blood cells of the patient only two bands were observed. Patient and control fibroblasts showed two bands, probably identical to the two bands observed in the patient's white blood cells. These results indicate that the liver-type phosphorylase is not expressed in the cultured fibroblasts.


Comparisons of caries prevalence of children with different daily toothbrushing frequencies. Clinical caries examinations, supplemented by bite-wing radiographs, were conducted on 290 schoolchildren. The children ranged from 12 to 15 years of age and were residents of a fluoride-deficient community in New York State. The children were divided into two groups based upon their stated daily toothbrushing frequency, namely, those brushing once or less/day and those brushing twice or more/day. Mean DMFS and DMFT scores were recorded for children in both categories. A trend was noted that more frequent brushing was associated with less caries activity. For females and male-females combined the differences in mean DMFS and DMFT scores between those children brushing once a day or less. The caries scores for males in these two brushing groups were marginally significant (P less than .05). Ninety percent of the children used fluoride-containing dentifrices. The inverse relationship between brushing frequency and caries activity may be related to the more frequent fluoride contact when the children brush.


A study of 8 years' domestic salt fluoridation for prevention of caries. The author reports on an 8-year study with 250 mg F/kg domestic salt fluoridation. During this period the dmft index in the 2-6 years age range decreased by 41%, the DMFT index in the 7-11 year age range decreased by 58%, and in the 12-14 year age range decreased by 36%. The proportion of cariesfree children also improved significantly, from 23% to 60%, from 4.8% to 41%, and from 2.7% to 8.4%, respectively. Urinary fluoride tests performed showed that with the concentration used, enough fluoride could not be ingested to reduce caries to the level anticipated with water fluoridation, but even so the caries reduction was significant. Experiments are now continuing with 200 mg F/kg and 350 mg F/kg domestic salt mixtures.


Enamel mottling in a non-fluoride community in England. In 1974--75 an assessment of mottling in incisor teeth was carried out on a random sample of 13- to 14-year-old children in Liverpool, England. The number of children examined was 463. All of these children were born and had lived in Liverpool when the fluoride content of the water supply had averaged 0.12 parts/10(6). The mouth prevalence of mottling was 42.5%. The tooth prevalence of mottling was 9.6%. There was no sex difference. The data obtained was compared with those of other authors and confirmed that a considerable proportion of mottling observed in fluoride and non-fluoride communities was caused by factors other than ingested fluoride.


An epidemiologic study of occlusal anomalies in relation to development of the dentition in Icelandic children. The purpose of the investigation was to determine the prevalence of occlusal anomalies in relation to dental stages (DS) in Icelandic schoolchildren, and to compare it with results from other Scandinavian countries and Ireland found on the basis of the same method. The material consisted of 1,641 randomly selected children, 791 boys and 850 girls, corresponding to 9.5% of the total primary and secondary school population of Reykjavík. A significant sex difference was only recorded in the frequencies of of two of the single morphologic traits of occlusal anomalies, the boys showing higher frequencies in deep bite and in scissors-bite. Significant differences in the occurrence of occlusal anomalies in Iceland and Denmark were only found in two out of 108 pairs of frequencies.