Evidence that fibronectin is the collagen receptor on platelet membranes. Evidence is presented that fibronectin is present on the platelet cell membrane and that it is a receptor for collagen in the platelet-collagen interaction. First, sodium dodecyl sulfate/acrylamide gel electrophoresis was performed on the proteins remaining attached to the surface of collagen after the removal of the remainder of the platelet by sonication. The material was relatively enriched in a glycoprotein that comigrated with cold-insoluble globulin (CIG), a form of fibronectin, and in other proteins which comigrated with myosin, actin, and tropomyosin. The presumptive presence of contractile proteins is consistent with the presence of microfibrillar proteins. Second, the collagen-attached material was shown to contain a protein that reacted with anti-CIG serum by immunoelectrophoresis. Third, when CIG was preincubated with fibrous collagen, the platelet-collagen interaction was inhibited. Fourth, rabbit anti-human CIG stimulated human platelets to secrete the contents of their dense granules. The stimulation was not due to antibody complexes present in the solution. Fifth, a protein was extracted from well-washed platelets and purified on affinity columns of anti-CIG antibodies. The isolated protein was found to bind to fibrous collagen.


Correlation of albumin production rates and albumin mRNA levels in livers of normal, diabetic, and insulin-treated diabetic rats. We have studied the effects of alloxan-induced diabetes and subsequent insulin replacement on albumin and total hepatic protein synthesis. Diabetes resulted in a reduction to approximately 20% of normal in albumin synthesis relative to the rate of total protein synthesis in vivo and a reduction to 10% in the absolute rate of albumin secretion by perfused livers. In contrast, the synthesis of total secretory protein and retained hepatic protein was affected to a lesser extent by diabetes. Treatment of diabetic rats with insulin restored rates of albumin and total hepatic protein synthesis to normal levels. The molecular basis of these alterations in albumin synthesis was investigated by examining albumin mRNA levels in livers of normal, diabetic, and insulin-treated diabetic animals. The level of albumin mRNA, whether assayed by cell-free translation or by hybridization to a specific complementary DNA probe, was markedly decreased in livers of diabetic animals and was restored to normal by insulin treatment. These changes occurred in parallel with changes in the rates of albumin secretion observed in perfused liver, suggesting that albumin mRNA content is the primary factor responsible for altering rates of albumin synthesis under these conditions.


Hemoglobin switching in sheep: only the gamma gene is in the active conformation in fetal liver but all the beta and gamma genes are in the active conformation in bone marrow. Differential expression of the closely linked gamma, beta(A) (or beta(B)), and beta(C) globin genes in sheep results in the production of fetal hemoglobin (Hb F, alpha(2)gamma(2)) during gestation and the adult hemoglobins (Hb A, alpha(2)beta(2) (A), and Hb B, alpha(2)beta(2) (B)) after birth. Erythropoietic stress in certain animals leads to production of Hb C (alpha(2)beta(2) (C)). The molecular mechanism of differential expression of these genes in nuclei of fetal and adult erythroid cells has been investigated by analysis of their susceptibility to digestion by DNase I (genes that are in the conformation associated with active transcription are sensitive to this nuclease). The concentration of globin gene sequences in DNA from control and DNase I-digested nuclei was determined by annealing to synthetic DNAs and analogous cDNA probes derived from recombinant plasmids containing one of the sheep globin genes. In nuclei from sheep fetal liver erythroid cells, the gamma genes but not the beta genes were digested by DNase I; the gamma locus was open but the beta(A) or beta(C) loci was closed, consistent with synthesis of only Hb F by these cells. DNase I digestion of nuclei from bone marrow of anemic sheep making only Hb C or Hb B resulted in equivalent digestion of the beta and gamma gene sequences, although gamma mRNA was not detected in these cells. Digestion by DNase I did not decrease the globin gene sequence concentration in residual DNA of spleen nuclei. As a further control, DNA from digested bone marrow and spleen nuclei were shown to anneal equally well to a cDNA prepared from liver polysomal mRNA. Differential expression of the gamma and beta globin genes in sheep fetal erythroid cell appears to be based on differences in chromatin structure. The gamma globin gene remains in the active conformation in adult erythroid cells; failure of gamma mRNA to accumulate in these cells probably reflects transcriptional or post-transcriptional regulation.


Bovine protein C: amino acid sequence of the light chain. The amino acid sequence of the light chain of bovine protein C was determined by sequenator analysis of the carboxymethylated light chain and fragments obtained by cyanogen bromide treatment, tryptic digestion after blocking of lysine residues, and cleavage with 2-(2-nitrophenylsulfenyl)-3-methyl-3-bromoindolenine (BNPS-skatole). The sequence was (in the standard one-letter code) A-N-S-F-L-X-X-L-R-P-G-N-V-X-R-X-C-S-X-X-V-C-X-F-X-X-A-R-X-I-F-Q-N-T-X-D-T-M-A-F-W-S-K-Y-S-D-G-D-Q-C-E-D-R-P-S-G-S-P-C-D-L-P-C-C-G-R-G-K-C-I-H-G-L-G-G-F-R-C-D-C-A-E-G-W-E-G-R-F-C-L-H-E-V-R-F-S-N-C-S-A-E-B-G-G-C-A-H-Y-C-M-E-E-E-G-R-R-H-C-S-C-A-P-G-Y-R-L-E-D-D-H-Q-L-C-V-S-K-V-T-F-P-C-G-R-L-G-K-R-M-E-K-K-R-K-T-L. The first eleven glutamic acid residues were carboxylated to gamma-carboxyglutamic acid (X). The NH2-terminal, vitamin K-dependent part showed an extensive homology to both prothrombin and factor X, whereas the rest of the chain showed a strong homology to factor X but little similarity to prothrombin.


Interferon action: two distinct pathways for inhibition of protein synthesis by double-stranded RNA. Double-stranded RNA inhibits protein synthesis in at least two ways. It activates a protein kinase that blocks peptide chain initiation by phosphorylating the peptide chain initiation factor eIF-2 and also activates an endonuclease that inactivates different mRNAs at different rates. The protein kinase and the endonuclease have been partially purified from interferon-treated Ehrlich ascites tumor cells. The 2',5'-oligoadenylates [pppA(2'p5'A)n], found found earlier to be mediators in the activation of the endonuclease by double-stranded RNA, are not mediators in the activation of the protein kinase by double-stranded RNA.


Altered nucleosome spacing in newly replicated chromatin from Friend leukemia cells. Chromatin from Friend leukemia cells labeled with [14C]thymidine for 24 hr followed by [3H]thymidine for 10 min is converted into nucleosomes by staphylococcal nuclease at only half the rate that total chromatin is converted. Polyacrylamide gel electrophoresis of nucleosomal DNA from cells labeled for 24 hr with [14C]thymidine followed by 10 min with [3H]thymidine demonstrates that the internucleosomal spacer of newly replicated chromatin is approximately 20 base pairs shorter than that of total chromatin. The implications of this difference for models of chromatin structure are discussed.


Isolation and characterization of a tumor cell surface antigen from spontaneously transformed BALB/c mouse fibroblasts. This work describes the detection, isolation, and partial characterization of a BALB/c mouse fibroblast cell surface antigen. This antigen migrates as a polypeptide of approximately 100,000 daltons in a discontinuous sodium dodecyl sulfate/polyacrylamide gel electrophoresis system, can be labeled by either lactoperoxidase-catalyzed cell surface 125I iodination or metabolic incorporation of [3H]glucosamine, and can be isolated by concanavalin A affinity chromatography. This cell surface glycoprotein is antigenic in BALB/c mice and has been correlated with the rejection of immunogenic tumor cells. Also, antiserum specific for Moloney leukemia virus precipitates the 100,000-dalton cell surface protein from viral and immunogenic spontaneous transformants. This virus-related antigen comigrates on sodium dodecyl sulfate gels with the major iodinated cell surface protein of these transformants. Rabbit antiserum to the purified antigen demonstrates a marked preference for the surfaces of immunogenic tumor cells as compared with normal cells and nonimmunogenic tumor cells.


Initiation of HeLa cell DNA synthesis in a subnuclear system. Mammalian cells are known to synthesize DNA in discrete stages, the first of which seems to be the formation of DNA pieces 150--200 nucleotides in length that have a s20 value of about 4 S. We have reconstructed a system derived from HeLa cell nuclei that carries out RNA-primed initiation of the synthesis of small (4S) DNA fragments. This synthesis is resistant to high concentrations of alpha-amanitin and sensitive to antibody directed against RNA polymerase I, suggesting that this enzyme may be involved in the initiation step. The formation of small DNA fragments in this system also requires DNA polymerase alpha, heat-labile nuclear factor(s), and at least one other nuclear protein.


Estrogen control of prolactin synthesis in vitro. Primary cultures of rat pituitary cells respond to estradiol-17beta by increased incorporation of radiolabeled precursors into prolactin but not into the bulk of other cellular proteins. The rate of increase in prolactin synthesis is dose dependent, reaching maximal levels in the physiological range of estradiol. At a concentration of 1 nM, estradiol, diethylstilbestrol, and estriol are stimulatory whereas androgens, progesterone, and corticosterone are without significant effect. Exposure of pituitary cells to 10 nM estradiol resulted in a 500% increase in prolactin synthesis after 7 days of culture. The results indicate that estradiol can stimulate prolactin synthesis through direct action on the pituitary.


The duplicated human alpha globin genes lie close together in cellular DNA. The organization of alpha globin genes in normal human DNA was examined by restriction endonuclease mapping, alpha globin-specific fragments in endonuclease digests of total cell DNA were identified after electrophoresis by hybridization with [32P]cDNA following the blotting procedure of Southern [(1975) J. Mol. Biol. 98, 503--517]. The data provide direct evidence for the duplication of alpha genes and further indicate that these loci are closely linked within a single restriction fragment. The HindIII sites (codons 90/91) of these duplicated genes lie approximately 3.7 kilobases apart in the physical map proposed for this region. This organization of alpha genes can be altered in DNA of individuals with alpha-thalassemia.


Rapid conformational changes of cytochrome P-450: effect of dimyristoyl lecithin. Binding of benzphetamine to purified microsomal cytochrome P-450 from rat liver causes a shift in the heme spin state of the protein to favor the high-spin form. This shift is strongly temperature dependent. A rapid temperature jump of a cytochrome P-450/epsilon benzphetamine mixture, monitored by changes in the Soret absorptions of the heme, reveals two relaxation processes: one in a 50-msec time range (tau(f)) and the other in a 0.3-sec time range (tau(s)). Both relaxations reflect conformational changes of the protein after the substrate binding. No bimolecular reaction of benzphetamine and the enzyme has been resolved. This indicates that there is no absorption change of the heme associated with the initial binding. In the presence of dimyristoyl lecithin, at 25 degrees C tau(f) decreases by nearly one order of magnitude whereas tau(s) decreases to one-third. The enhancement of rates by added phospholipid is both temperature- and concentration-dependent: rates are accelerated only above the gel-liquid crystalline transition temperature, and this effect saturates near the enzyme/lipid ratio of 1:20. In contrast, the lipid does not have significant effect on the equilibrium binding curve of the substrate. These results suggest that the lipid may form an envelope around the enzyme and, depending on its crystalline state, regulates the rate of the substrate-induced conformational changes of cytochrome P-450.


Protein factor that inhibits binding and promotes release of androgen-receptor complex from nuclear chromatin. A protein factor that can inhibit binding of the androgen-receptor complex to the nuclear chromatin has been isolated from the cytosol of the ventral prostate of rats. The inhibition is reversible and not caused by an irreversible destruction of the receptor or the chromatin. The inhibitor also can promote, by a temperature-dependent process, the release of steroid-receptor complex already bound to chromatin. It is conceivable that such a protein factor plays a regulatory role in the nuclear-cytoplasmic recycling or chromatin binding of the steroid hormone receptor.


Decrease in functional albumin mRNA during estrogen-induced vitellogenin biosynthesis in avian liver. Translation of rooster liver RNA in a wheat germ extract is shown to yield albumin as one of the cell-free products. Quantitation of albumin mRNA by the translation assay indicates that functional albumin mRNA represents 10% of total liver mRNA activity in control roosters. After estrogen administration, this level decreases in a continuous fashion until functional albumin mRNA represents 5% of total mRNA activity at 12 days. This decrease in functional albumin mRNA was correlated with several parameters of vitellogenin induction. Functional vitellogenin mRNA increases to a maximum at 4 days after hormone treatment and returns to control levels by 12 days. A similar pattern is seen for the hormone-stimulated increase in total mRNA activity. The decrease in functional albumin mRNA, therefore, persists after the vitellogenic response of the liver has been completed. These results suggest that the decrease in hepatic albumin synthesis after hormone treatment is due to an estrogen-mediated decrease in the content of albumin mRNA.


Phosphorylation in vivo and in vitro of human histocompatibility antigens (HLA-A and HLA-B) in the carboxy-terminal intracellular domain. HLA-A and -B antigens are phosphorylated in transformed lymphoblastoid cells and peripheral blood lymphocytes, both incubated with 32Pi. The phosphate group is attached to HLA-A and -B heavy chain (p44) as identified by immunoprecipitation with anti-beta2-microglobulin IgG, sodium dodecyl sulfate/polyacrylamide gel electrophoresis, isoelectric focusing, and susceptibility to limited proteolysis by papain and trypsin. The site(s) of phosphorylation is identified as a serine residue(s) located in the hydrophilic carboxy terminus of the p44 chain. HLA antigens are also phosphorylated in isolated membranes from transformed lymphoblastoid cells that are incubated with [gamma32P]ATP. The phosphorylation of the carboxy terminus of HLA-A and -B antigens in vivo is good evidence that this portion of the molecule is intracellular. Furthermore, this modification suggests a general way in which interactions between membrane proteins and cytoskeletal elements may be regulated.


Translation of mRNA from calf thymus in the wheat germ system: evidence for a precursor of thymosin alpha1. When translated in the wheat germ system, mRNA from fresh calf thymus stimulates incorporation of radioactive amino acids into an acid-insoluble product, and 10--20% of the total radioactivity incorporated is precipitated with antisera to active thymosin fractions. In sodium dodecyl sulfate disc gel electrophoresis, radioactivity was recovered mainly in two peptides, corresponding to 16,000 and 11,000 daltons; the latter probably represents incomplete chains. Tryptic digests of each of these peptides yielded fragments corresponding to the sequence of residues 15--19 of thymosin alpha1; these peptides were characterized by cochromatography with digests of synthetic thymosin alpha1 and by Edman degradation. Thus, the 16,000-dalton peptide synthesized in the cell-free system appears to be q precursor of thymosin alpha1 and possibly of other peptides in the fractions isolated from calf thymus. The results support the conclusion that this peptide is synthesized in the thymus gland.


Repair of O6-methylguanine in adapted Escherichia coli. Cells exposed to sublethal concentrations of simple alkylating agents develop resistance to their mutagenic effects. This results from the induction of a system that we have called the adaptive response. During exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), Escherichia coli cells induced for the adaptive response accumulate substantially less O6-methylguanine in their DNA than control cells. If O6-methylguanine does form, adapted cells possess a repair system for removing it from their DNA. The capacity of this system is limited and the system ceases to function when too much alkylation has occurred. From this point onwards O6-methylguanine starts to accumulate, and the cells begin to develop mutations at a rate directly proportional to their rate of O6-methylguanine accumulation. Our data support the idea that the O6 methylation of guanine accounts for most MNNG-induced mutagenesis.


G2 phase-specific proteins of HeLa cells. The objective of this study was to determine if HeLa cells irreversibly arrested in G2 phase of the cell cycle by a brief exposure to a nitrosourea compound were deficient in certain proteins when compared with G2-synchronized cells. Total cellular proteins of G2-synchronized, G2-arrested, and S phase-synchronized cells were compared by two-dimensional polyacrylamide gel electrophoresis. The S phase cells differed from the G2-synchronized and G2-arrested cells by the absence of about 35 and 25 protein spots, respectively, of a total of nearly 150. At least nine protein spots in the molecular weight range of 4--5 X 10(4) that were present in the G2-synchronized cells were absent in both the G2-arrested and the S phase cells. Thus, these studies suggest that the missing proteins are probably necessary for the transition of cells from G2 phase to mitosis. Supplying the missing proteins to the G2-arrested cells by fusion with G2-synchronized cells facilitated the entry of the former into mitosis.


Loss of proliferative calcium dependence: simple in vitro indicator of tumorigenicity. The proliferative activities of three lines of "normal" epithelioid rat liver cells and six tumorigenic liver cell lines in the presence of a wide range of calcium concentrations were measured by a simple colony forming assay. The proliferative activities of the normal cells and, to a lesser extent, of the cells of a marginally tumorigenic line were directly proportional to the extracellular calcium concentration. The proliferative activities of the cells of the strongly tumorigenic lines, on the other hand, were either uninfluenced by or inversely proportional to the extracellular calcium concentration. Thus, the proliferative response to the extracellular calcium concentration is a sensitive indicator of the carcinogenic potential of liver cells.


Autosomal locus regulates inverse relationship between sialic acid content and capacity of mouse erythrocytes to activate human alternative complement pathway. The observation that mouse erythrocytes (E(m)) from 21 inbred strains had variable capabilities to activate the human alternative complement pathway permitted the demonstration that membrane sialic acid content was inversely related to activating capacity and was regulated by codominant alleles of a single autosomal locus. Linear regression analysis also demonstrated a significant inverse correlation between the sialic acid content of E(m) from four inbred strains and the concentration of beta1H required for decay-dissociation of the properdin-stabilized amplification convertase on the E(m). E(m) from F(1) hybrids derived from strains with high and low alternative pathway activating capacities and from their backcrosses exhibited the alternative pathway activating capacities expected if the activity were regulated by alleles of a single autosomal locus. That this same locus predominantly regulated the sialic acid content of E(m) was established by the significant inverse correlation between the sialic acid content and the alternative pathway activating capacity of E(m) from mice of the F(1) and backcross generations. Although the fluid phase interaction of C3, B, and [unk]D continuously generates C3b in a reaction augmented by properdin, it is the covalent attachment of C3b to bystander surfaces deficient in sialic acid that activates the alternative complement pathway at that site because of impaired binding of beta1H to C3b on such surfaces. Thus, discrimination between activating and nonactivating surfaces occurs after C3b deposition, and sialic acid deficiency represents the molecular basis for our earlier finding that activating particles circumvent the regulatory actions of the control proteins of the alternative pathway.


Actinomycin D inhibits initiation of DNA replication in mammalian cells. Mammalian (Chinese hamster ovary) cells were synchronized in the division cycle and blocked at the beginning of S phase with fluorodeoxyuridine. Traces of thymidine in the medium allowed cells to enter S phase and initiate DNA replication at some origins. For many hours after the traces of thymidine were depleted new sites for DNA replication accumulated in a small fraction of the DNA. However, these potential origins became active in bidirectional replication only when cells were released by adding [3H]thymidine to the medium. Lysis at 37 degrees C released most of the pulse-labeled DNA as linear double-stranded segments larger than Okazaki fragments and smaller than the unreplicated parental DNA. Release of the newly replicated DNA involves breakage of the template chains at or near each fork. The size of the fragments increased linearly with time of pulse labeling, but the efficiency of their release decreased. The excision could be prevented by lysis at 0 degrees C. When cells were treated with actinomycin D for 3--5 min before release, the new origins failed to function, but chain growth continued from those sites at which initiation had taken place before depletion of thymidine. We interpret these results to indicate that initiation at origins requires an actinomycin D-sensitive step, presumably RNA transcription, while chain elongation, which involves the formation of Okazaki pieces, is relatively insensitive to actinomycin D during growth over long intervals.


Ten-nanometer filaments of hamster BHK-21 cells and epidermal keratin filaments have similar structures. The 10-nm filaments of baby hamster kidney (BHK-21) cells, when examined either in the form of native filament caps or polymerized in vitro, are long tubes of protein 8--10 nm in diameter. They contain about 42% alpha-helix, which, on the basis of x-ray diffraction data, is arranged in a coiled-coil conformation characteristic of proteins of the alpha type. The known structural properties such as morphology, dimensions, subunit composition, and ultrastructure of this fibrous protein are very similar to those of the mammalian epidermal keratin filament, to which it may therefore be related.


Adipose conversion of 3T3 cells depends on a serum factor. The adipose conversion of 3T3-F442A cells depends on an adipogenic factor in serum. In the presence of this factor, cells grown to confluence become spherical, greatly increase the activity of their lipogenic enzymes, and accumulate triglyceride. In the absence of the adipogenic factor, the cells grow normally, but when they reach confluence they do not become spherical, do not accumulate triglyceride, and do not undergo any increase in activity of lipogenic enzymes. In cattle there is a great deal more of the adipogenic factor in the serum before birth than in the serum of grown animals. The nature of the adipogenic factor suggests that it may play an important role in the development of adipose tissue.


Control of DNA synthesis in growing BALB/c 3T3 mouse cells by a fibroblast growth regulatory factor. A cell surface component from quiescent BALB/c 3T3 mouse cells that inhibits DNA synthesis and cell division when added to a culture of growing 3T3 cells has been detected. The inhibition of DNA synthesis by this factor was dependent on concentration and time of incubation; a transient exposure of cells to the factor followed by incubation in its absence for 20 hr was sufficient to elicit its inhibitory effect. The active component appears to be protein in nature, as judged by heat inactivation and trypsin sensitivity. Extracts obtained in an identical manner from quiescent 3T3 cells that had been preincubated in situ with uridine diphosphate N-acetyl-D-glucosamine (UDP-GlcNAc) did not inhibit DNA synthesis. The effect was specific for UDP-GlcNAc: incubation with three other nucleotide sugars yielded active component. Incubation of the inactive component from UDP-GlcNAc-treated cells with purified N-acetyl-beta-D-glucosaminidase in vitro restored its inhibitory property. Extracts from growing cells failed to inhibit DNA synthesis. These results suggest that reversible glycosylation with N-acetyl-D-glucosamine residues may serve as a regulatory signal for the conversion of the active factor to its inactive form. We propose that the onset of quiescence of 3T3 cells is due to a casual relationship between depletion of growth factors in the culture medium and the presence of the active regulatory factor on the cell surface that inhibits DNA synthesis; conversion of the regulatory factor to its inactive form under favorable nutritional status may be viewed as a switch that allows DNA synthesis to resume.


Marker rescue and partial replication of bacteriophage T7 DNA. Experiments reported here show that some UV-irradiated wild-type T7 phage markers can be rescued efficiently by coinfection with T7 amber mutant phage in a permissive host. Other results show that the segments of a UV-irradiated genome that replicate efficiently are those that also are rescued efficiently during a marker rescue experiment. At higher doses, fewer markers are rescued efficiently and fewer segments of the genome replicate efficiently. The results clearly indicate that the probability of marker rescue is correlated with the ability of the DNA containing the marker to replicate. Sucrose density gradient analysis shows that UV irradiation does not produce double-strand scissions in T7 DNA at doses used here. Therefore, the partial replication and rescue of markers from the left end of the genome is not due simply to injection of only the left end of the T7 DNA.


Tumor promoter induces sister chromatid exchanges: relevance to mechanisms of carcinogenesis. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a powerful tumor promoter, is shown to induce sister chromatid exchanges (SCEs), whereas the nonpromoting derivative 4-O-methyl-TPA does not. Inhibitors of tumor promotion--antipain, leupeptin, and fluocinolone acetonide--inhibit formation of such TPA-induced SCEs. TPA is a unique agent in its induction of SCEs in the absence of DNA damage, chromosome aberrations, mutagenesis, or significant toxicity. Because TPA is known to induce several gene functions, we speculate that it might also induce enzymes involved in genetic recombination. Thus, the irreversible step in tumor promotion might be the result of an aberrant mitotic segregation event leading to the expression of carcinogen/mutagen-induced recessive genetic or epigenetic chromosomal changes.


Argininosuccinic aciduria: assignment of the argininosuccinate lyase gene to the pter to q22 region of human chromosome 7 by bioautography. Argininosuccinic aciduria, an autosomal recessive disorder of the urea cycle in humans, is associated with a deficiency of argininosuccinate lyase (ASL; L-argininosuccinate arginine-lyase, EC 4.3.2.1). ASL activity was visualized on gels after electrophoresis by a new method, termed bioautography. Bioautography involves the use of mutant bacteria to visualize the location of mammalian enzymes after zone electrophoresis. By this technique, human ASL migrated to a position different from mouse ASL, while a survey of mouse strains, tissues, and tissue culture cell extracts demonstrated the same electrophoretic form and no genetic variants of mouse ASL. Identifying human ASL, by bioautography in human-mouse somatic cell hybrids has made it possible to regionally locate the ASL gene on human chromosome 7. The human ASL phenotype segregated concordantly with the human enzyme beta-glucoronidase (GUS; beta-D-glucoronide glucuronosohydrolase, EC 3.2.1.31) in cell hybrids, but showed discordant segregation with 32 other enzyme markers representing 23 linkage groups. The gene for GUS has been assigned to chromosome 7 in humans, and cosegregation (synteny) of ASL and GUS demonstrates the assignment of ASL to chromosome 7. Regional location of ASL and GUS to the pter to q22 region of chromosome 7 was achieved in hybrids segregating a 7/9 translocation.


Effect of overall phenotypic selection on genetic change at individual loci. The selective advantage of an allele Gi (relative to the mean of alleles at this locus) is given by (formula: see text) in which Ai is the average excess of the allele on the character, X; W(X) is the fitness function; F(X) is the frequency function; W is the mean fitness; and the prime denotes differentiation. With truncation selection si = AaF(C)/w in which F(C) is the ordinate at the culling level and w is the proportion saved; this does not depend on any assumption about the distribution of F(X). If the character is normally distributed, si = AiI/sigma2, in which I is the selection differential and sigma2 is the variance of the character distribution. Finally, if the logarithm of the fitness is proportional to the squared deviation from the optimum and the character is distributed normally, si = AiK(Xop--m), in which Xop is the optimum value of the character, m is the mean value, and K is a constant determined by the variances of the fitness function and the frequency function. Truncation is the most efficient form of directional selection in the sense of producing the maximum gene frequency change for a given effect of the gene on the character, but fitness functions can depart considerably from sharp truncation without greatly reducing the efficiency.


A single base-pair change creates a Chi recombinational hotspot in bacteriophage lambda. X4+ mutations, responsible for the Chi phenotype in phage lambda, locally increase the rate of recombination promoted by the Escherichia coli recombination system (Rec). X+ mutations in the cII gene, one of a few sites in lambda at which such mutations arise, were located genetically and physically with overlapping deletions. DNA sequence analysis of the deletion segment containing the X+ C mutations showed that two independent X+ C mutations arose by the same A-T to T-A transversion. Presumably, this change creates a nucleotide sequence recognized by a protein involved in a rate-limiting step of recombination.


Comparison of cloned mouse alpha- and beta-globin genes: conservation of intervening sequence locations and extragenic homology. We have cloned and characterized a 9.7-kilobase EcoRI fragment of mouse DNA that contains an alpha-globin gene. The gene is encoded in at least three discontinous segments of DNA interrupted by two small intervening sequences that can be visualized as R-loop structures in the electron miscroscope. The size of the gene and its small intervening sequences fits well with the known size of the alpha-globin mRNA precursor, suggesting that these intervening sequences, like those of beta-globin, are transcribed. Partial sequence analysis indicates that the larger intervening sequence interrupts the alpha-globin gene at a site exactly corresponding to that interrupted by the larger intervening sequences in both the beta-globin major and minor genes. This observation suggests that these sequences were present when the alpha- and beta-globin genes diverged in early vertebrate evolution, more than 500 million years ago. Furthermore, though alpha and betamaj genes are encoded on different chromosomes, when their sequences are compared directly by visualization of heteroduplex structures, only one 150- to 200-base-pair segment of homology is recognized. These homologous sequences are located on the 3'-flanking segments of both genes, about 1.5 kilobases from each.


Idiotypic analysis of antibodies to poly(Glu60Ala30Tyr10): interstrain and interspecies idiotypic crossreactions. A common idiotype was defined by a guinea pig anti-idiotypic antiserum made against D1.LP antibodies specific to the synthetic terpolymer poly(Glu60Ala30Tyr10), referred to as GAT. This idiotype was found in the anti-GAT antibodies of all individuals of all inbred strains of mice tested. Due to its common (C) occurrence in the anti-GAT antibodies of all mouse strains, it was termed the CGAT idiotype. The presence of CGAT idiotype in mice is independent of the expression of various Ig-1, H-2, or Vg genetic markers. In contrast, antibodies produced in response to the crossreactive poly(Glu60-Ala40), termed GA, bound to the GAT ligand but did not bear the CGAT idiotype. This suggests that GAT, although bearing GA determinants, preferentially stimulates clones of CGAT idiotype. Some of the CGAT idiotypic specificities were also identified in sera of WF inbred rats after immunization with GAT. However, no significant levels of CGAT idiotype were detected in LEW rats, F344 rats, guinea pigs, or rabbits, although measurable quantities of anti-GAT antibody were present.


Binding of HLA antigen-containing liposomes to bacteria. Highly purified, detergent-solubilized HLA-A and -B antigens and HLA-D antigens were separately incorporated into liposomes. Detergent-solubilized transplantation antigens, but not papain-solubilized antigens lacking the membrane-integrated portions of the molecules, were bound to the liposomes. A considerable portion of the liposome-bound antigens displayed accessible antigenic sites, suggesting that they were oriented in the right-side-out direction. Liposomes containing the HLA-A and -B antigens or the HLA-D antigen interacted similarly with bacteria. The two types of liposomes bound efficiently to two strains of Neisseria catarrhalis (now classified as Branhamella catarrhalis) and to one strain of Haemophilus influenzae, weakly to one strain of Escherichia coli, and not at all to another strain of E. coli. The binding between the HLA antigen-containing liposomes and one strain of N. catarrhalis was abolished when Fab fragments directed against the heavy chains of HLA-A and -B antigens or against HLA-D antigens, respectively, were added. In contrast Fab fragments against beta(2)-microglobulin did not measurably impede the bacteria-liposome interaction, suggesting that, with regard to the HLA-A and -B antigens, the heavy, but not the light, chains interacted with the bacteria. Additional experiments showed that N. catarrhalis preferentially interacted with transplantation antigens when mixed with detergent-solubilized lymphocyte membrane glycoproteins. These data suggest that HLA-A and -B and HLA-D antigens may have the function of interacting with foreign antigens such as bacteria.


Linear arrays of intramembranous particles in pulmonary tubular myelin. Freeze-fracture preparations of tubular myelin in edematous rat lungs reveal the presence of linear arrays of intramembranous particles. The lines of particles are approximately 50 nm apart and appear to correspond to the intersections of sheets of bilayer membranes. Particles are not seen in lamellar bodies but become evident first in membranes transitional between lamellar bodies and tubular myelin. It is proposed that the particles represent a hydrophobic protein that plays a significant role in the organization of tubular myelin.


Cholesterol monohydrate growth in model bile solutions. The growth of cholesterol monohydrate from solutions of bile salt, lecithin, and small electrolytes has been studied by microscopy and with the Coulter Counter. The crystal forms found by microscopy are the same as those seen in human gallstones and in squirrel monkey cholesterol microliths. The cholesterol growth rates determined with the Coulter Counter vary slowly with cholesterol concentration at low degree of supersaturation but become exponential at higher cholesterol concentrations. Growth is accelerated by the presence of calcium and magnesium but inhibited by potassium. These results can be combined with previous measurements of cholesterol dissolution rates to give a more accurate picture of the dynamics of gallstone formation.


Neonatal suprachiasmatic nucleus ablation: absence of functional and morphological plasticity. Neonatal ablation of the suprachiasmatic nucleus in the rat has two important consequences. First, the direct projection from the retina to the suprachiasmatic nucleus fails to develop and no other retinal projection to any hypothalamic nucleus is formed. Second, circadian rhythms in drinking and spontaneous locomotor activity to not appear in these rats when they are tested as adults, and the females exhibit constant vaginal estrus. These observations indicate that the central neural mechanisms responsible for the generation and entrainment of circadian rhythmicity in the rat are not capable of either the functional or morphological plasticity characteristic of other developing neural systems.


Normal blood cells of anemic genotype in teratocarcinoma-derived mosaic mice. In allophenic (mosaic) mice produced from blastocysts injected with teratocarcinoma stem cells of the OTT 6050 transplant line, an unexpected coat phenotype led to the discovery that the tumor-lineage cells carried the steel gene (Sl(J)/+). Because steel also causes a macrocytic anemia, mosaics comprising both genetically anemic and normal (+/+) cells fortuitously provided a unique opportunity to examine in vivo the etiology of this anemia in light of previous results indicating that the lesion is extrinsic to the erythroid cells. The experiment differs from previous ones, which involved postnatal grafting, in that here hematopoietic stem cells of anemic and normal genotypes coexist throughout all developmental stages, confronted by tissues of the hematopoietic microenvironment that consist partly or solely of genetically normal cells. Therefore, the possibility exists that the anemia might be completely prevented rather than secondarily ameliorated. Moreover, variation in proportion of normal-strain cells in the hematopoietic supporting tissues could serve to "titrate" minimal requirements to promote normal erythropoiesis. Mice with mixed populations of steel- and normal-genotype cells in blood and other tissues were identified by means of independent markers specific for tumor vs. blastocyst strains of origin. The clinical blood picture of these mosaics proved to be indistinguishable from that of normal controls, even when only a small minority of cells in all tissues of one of the animals were genetically normal. Phenotypic blood normalcy was shown, by occurrence of the typical steel anemia among F(1) germ-line progeny of mosaics, not to be due to any change in the capacity of the mutant gene to elicit the anemia. The results from the mosaics thus demonstrate that the primary expression of the steel lesion is indeed in the hematopoietic microenvironment. However, they also reveal that a surprisingly small complement of normal cells there appears to be adequate to prevent this anemia permanently. The hypothesis is advanced that relatively short-range diffusible substances, produced by cells in the microenvironment and required for normal erythropoiesis, may account for the inductive effectiveness of small cell numbers.


Cell-free ring expansion of penicillin N to deacetoxycephalosporin C by Cephalosporium acremonium CW-19 and its mutants. To examine microbiological ring expansion of penicillin N to a cephalosporin, we obtained five mutants of Cephalosporium acremonium blocked in beta-lactam antibiotic biosynthesis from 2500 survivors of mutagenesis. In submerged fermentation, mutants M-0198, M-0199, and M-2351 produced no beta-lactam antibiotic (type A), whereas mutants M-1443 and M-1836 formed penicillin N but not cephalosporin C (type B). Cell-free extracts of type A mutants converted penicillin N to a cephalosporin; those of type B mutants did not. The product of the cell-free reaction was identified as deacetoxycephalosporin C by thin-layer chromatography, paper chromatography, paper electrophoresis, and enzyme tests. These data strongly support our hypothesis that penicillin N is an intermediate of cephalosporin biosynthesis.


Genetic dimorphism in influenza viruses: characterization of stably associated hemagglutinin mutants differing in antigenicity and biological properties. Influenza virus recombinant X-53 produced for use in the 1976 National Immunization Program for swine influenza was found to comprise two types of virions differing in their antigenic, replicative, and plaque-forming characteristics. One type, characteristic of X-53 and designated "L," was relatively low-yielding in chicken embryos, produced small clear plaques in Madin-Darby dog kidney cells, and was selectively inhibited by heterotypic antibody to the A/sw/Cam/39 strain of swine influenza virus. The other, X-53a or "H," was high-yielding in chicken embryos, produced large turbid plaques in dog kidney cells, and was not inhibited by concentrations of A/sw/Cam/39 antisera inhibitory to X-53. It was shown that A/NJ/11/76 (HswN1) virus, from which X-53 was derived, and five other swine influenza virus isolates from humans and pigs were dimorphic mixtures of the two types of virus. Segregation of the hemagglutinin genes of L and H variants by further recombination demonstrated that their different properties were pleiotropic phenotypes of mutation in the hemagglutinin gene. Under selective conditions suppressive to the L mutant, mutation of cloned L to H virus was observed. This observation, as well as the apparent ubiquity of the two mutants in nature, suggests that this is another example of viral dimorphism-the stable association of two allelic mutants. Of special significance is the indication that antigenic variants may be selected by selection for properties other than antigenicity, and therefore may represent mutants with pathogenic effects determined by factors other than lesser modulation by host antibody.


"Dark-active" rat transformed into "light-active" rat by destruction of 24-hr clock: function of 24-hr clock and synchronizers. In alternating 12-hr periods of light and dark the rat is active mainly in the dark. Its activity in the dark (beginning at 1800) depends exclusively on release of activity by the 24-hr clock. In the light (beginning at 0600) the 24-hr clock inhibits activity; the normal rat becomes totally inactive in the light except for activity resulting from external stimulation. After section of the connections between the optic chiasma and the hypothalamus, some rats become totally and permanently inactive in the dark. This sectioning destroys the 24-hr clock. After destruction of the clock removes inhibition of activity in the light period, the rat becomes active promptly at start of the light period--i.e., becomes a "light-active" animal. In the normal rat, activity becomes synchronized to start of the dark (by the electric clock at 1800), regardless of the amounts of activity. Destruction of the 24-hr clock eliminates the synchronizer at 1800. However, almost at once, activity, eating, and drinking are kept together by a second synchronizer, start of the light (by the electric clock at 0600). This may explain the ability of the rat to survive after destruction of the 24-hr clock.


Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine. The antihistamine [3H]mepyramine binds to H1 histamine receptors in mammalian brain membranes. Potencies of H1 antihistamines at the binding sites correlate with their pharmacological antihistamine effects in the guinea pig ileum. Specific [3H]mepyramine binding is saturable with a dissociation constant of about 4 nM in both equilibrium and kinetic experiments and a density of 10 pmol per gram of whole kinetic experiments and a density of 10 pmol per gram of whole brain. Some tricyclic antidepressants are potent inhibitors of specific [3H]mepyramine binding. Regional variations of [3H]mepyramine binding do not correlate with variations in endogeneous histamine and histidine decarboxylase activity.


In vitro segregation of different cell lines with neuronal and glial properties from a stem cell line of rat neurotumor RT4. A clonal stem cell line, RT4-AC, of the rat peripheral neurotumor RT4 differentiates in culture into morphologically distinct cell types RT4-B, RT4-D, and RT4-E (cell type conversion). The multipotential stem cell type RT4-AC and cell type RT4-D produce a glial marker, S100 protein, but RT4-B and RT4-E do not. The stem cells also show a small but significant response to veratridine on voltage-dependent Na+ influx. Cell types RT4-B and RT4-E show a clear response of voltage-dependent Na+ influx to veratridine, typical of neuronal cells, whereas cell type RT4-D is completely negative. These results indicate that (i) the stem cell type RT4-AC shows both neuronal and glial properties, (ii) cell types RT4-B and RT4-E have a neuronal property, and (iii) cell type RT4-D has a glial property. Therefore, cell type conversion of stem cell RT4-AC to RT4-B and RT4-E cells seems to result in differentiation towards neuronal cell types, and cell type conversion of RT4-AC to RT4-D results in differentiation towards a glial type in culture.


Ionic factors in release of 45Ca2+ from chicken cerebral tissue by electromagnetic fields. Electrical stimulation with radiofrequency fields amplitude-modulated at brain wave frequencies increased 45Ca2+ efflux from isolated chicken cerebral tissue. The response was not sensitive to variations of the calcium concentration (0-4.16 mM) in the bathing solution but was enhanced by addition of H+ (0.108 mM HCl) and inhibited in the absence of normal bicarbonate levels (2.4 mM). Addition of lanthanum to the bicarbonate-free solution restored electrical responsiveness, but the stimulus decreased instead of increasing 45Ca2+ efflux. It is suggested that low-frequency, weak, extracellular electric gradients may be transduced in a specific class of extracellular negative binding sites normally occupied by Ca2+ and susceptible to competitive H+ binding.


Localization of cholecystokinin-like immunoreactivity in isolated nerve terminals. Subcellular fractionation of the rat cerebral cortex demonstrated the presence of immunoreactive cholecystokinin in the pellet identified by electron microscopy as containing a high proportion of synaptic vesicles. The recovery in this pellet of 40% of the total immunoreactivity in the initial cortical extract is quite comparable to the recovery of other peptides such as vasoactive intestinal polypeptide and somatostatin, which are also located in synaptosomes and for which roles as neuroregulators or transmitters have been suggested. The evidence of concentration of cholecystokinin-like peptides in the synaptosomal pellet is consistent with our earlier demonstration by immunohistochemical techniques of cholecystokinin's presence in rabbit cerebral cortical neurons. These observations and the evidence for diminished concentration of cholecystokinin-like peptides in the brains of hyperphagic mice are consistent with cholecystolinin's suggested role as a neuroregulator for appetite.


Acute myelogenous leukaemia occurring at the same time in husband and wife. Acute myelogenous leukaemia was diagnosed within a 1 week's interval in a married couple without consanguinity. The husband had acute myelomonocytic leukaemia whereas the wife had acute myelogenous leukaemia of the classical type. Neither the histories nor findings contributed to an understanding of leukaemogenesis. The calculated risk that a husband and wife should develop acute myelogenous leukaemia within the same year is approximately 1:400 millions.


Non-randomness in complex translocations of chronic myeloid leukaemia. A new case of chronic myeloid leukaemia with a complex translocation involving chromosomes No. 1, 9 and 22 is reported. The striking similarity of this case with another previously reported case and the involvement of band 9q34 in chromosome rearrangements in CML patients indicates clearly a non-randomness of chromosome abnormalities in this blood disease, even when the translocation is different from the usual t(9;22) one. The usefulness of R-banding techniques is emphasized in these cases.


Platelet volume, density and 5 HT organelles (mepacrine test) in acute leukaemia. Qualitative platelet parameters (volume, 5 hydroxy-tryptamine (5 HT) organelles studied by the mepacrine test, and density) were evaluated in 31 patients with acute leukaemia: 11 myelomonocytic (AML), 8 lymphoblastic (ALL), 12 granulocytic (AGL). Macrothrombocytosis was observed in most of the cases of AML, was rare in AGL and was never found in ALL. The 5 HT organelles/volume ratio was normal in AGL and ALL but was significantly decreased in AML. In contrast, platelet density distribution was always abnormal whatever the platelet volume and 5 HT organelle concentration. Thus, using simple new methods, convenient even in cases of thrombocytopenia, we demonstrate that qualitative platelet abnormalities are a constant feature in acue leukaemia and that they are more severe in AML.


Epidemiologic investigations of styrene-butadiene rubber production and reinforced plastics production. The United States National Institute for Occupational Safety and Health (NIOSH) began an epidemiologic study of workers employed in the styrene-butadiene rubber (SBR) industry during 1976. This study was prompted by reports of relatively high numbers of leukemia deaths occurring within SBR production work populations. Simultaneous with the initiation of this investigation, the University of North Carolina released a report associating an excess risk of death due to hematopoietic and lymphatic malignancies among workers producing several synthetic rubbers, including SBR. This report  presents NIOSH's preliminary mortality observations and a discussion of progress made on the analyses of contaminants found in two SBR production facilities. Currently, NIOSH is determining the feasibility of doing an epidemiologic study in the reinforced plastics industry. Interest in this study developed as part of an effort to determine health hazards associated with occupational exposure to styrene. Most of the technology for the reinforced plastics industry developed in the 1950s, and therefore this process represents a relatively new industry. This report also includes information on environmental conditions observed in the reinforced plastics industry and enumerates some of the complicating characteristics of this industry which increase the complexity of this study.


[Partial denture in periodontitis: treatment and discussion of a case]. Case report on the use of a partial denture in the treatment of a periodontal case. The results of the presented case are excellent after ten years and the prognosis remains extremely favourable. It seems very interesting to compare decisions of yesteryear in the light of new experience and knowledge. The choice of conservative treatment for diseased organs must take into consideration the patient's attitude, the possibilities of technical realization, and intuitively, the chances of a valid result.


[Is the reason for a decrease in dental caries after fluoridation in Basle the delay in tooth eruption?]. In several previous reports it was shown that water fluoridation in Basel has significantly reduced caries frequency in 7--15 year-old schoolchildren. This reduction is only for a small part caused by certain time differences in the eruption of the teeth. Neither can it be explained by instruction and motivation for better nutrition and home care, because mouth hygiene of the Basel schoolchildren has not improved over the last decade. Also, a reduction in sugar consumption could not be observed. Therefore, the conclusion seems justified that water fluoridation is mainly responsible for the reduction of caries.


[Changes in the masticatory system in myasthenia gravis]. Myastenia gravis causes by a hypofunction of the striated musculature a variable motor dyscoordination, which was examined in 106 patients. Hypofunction alone does not have any periodontal consequences, caries intensity however was obvious. Incoordination caused by hypofunction often is the cause for TMJ damage. The increase in mouth opening and of masticating force by Tensilon therapy is a characteristic and diagnostically useful test for myasthenia patients.


[The marginal periodontium of impacted upper canines. Evaluation following various methods of surgical approach and orthodontic procedures]. The marginal periodontium of 29 impacted upper canines and several aspects of their treatment have been studied. The situation has been analysed after treatment according to 3 methods of surgery and orthodontics: a) excision and active eruption, b) excision and passive eruption and c) replaced flap and active eruption. Many aspects regarding the choice and course of treatment depend primarily on individual data of the patient and on the location of impaction. With surgical exposure by excision some mucogingival problems seem to appear, especially for vestibular impactions. In those cases the surgical techniques using replaced or deplaced flaps seem to be more indicated to preserve the periodontal tissues.


[Acceptable compromises for the incisor positions with standard points AS and BS]. The cephalometric points A and B after Downs are criticized and on the angle ANB their selective replacement by "standard-AS and BS points along with the angles ASNB and ASNBS is suggested. With 55 ideal cases of the permanent dentition it was proven by the t-test that the mean values of the latter angles vary only very little from the angle ANB. Steiner's "acceptable compromises" are compared with a new combination of "flowing norm values" using AS and BS. The correlation coefficients are considerably higher than Steiner's (r = 0.47--0.66). They are between r = 0.75 and 0.93. Also the mean deductive mistakes of the incisal parameters keep within relatively small limits. Steiner's expected relations of the ANB angle (reduction of same to one half of the original measure) seem doubtful. Probably it is mainly dependent upon the type of anomaly and the method of treatment, further upon the type of growth and age.


[The shape of the ideal arcogrammetric dental arch]. On 48 arcograms of 24 cases with ideal occlusion polynomes of the form y = bo + b1x + b2x2 + b3x3 ... + b8x8 were established by the method of least squares. By means of a stepwise polynomal regression the coefficients up to the 8th degree were tested on significance. Finally polynomes of 4th degree were chosen to describe the anterior dental arch from 6 mesial to mesial 6 of the arcogram. Resulting error expressed as mean of the residuals of values observed--values calculated was 0.08 +/- approximately 0.6 mm (mean +/- 1 SD).


Acute renal failure in McArdle's disease. A case of reversible acute renal failure in an adult with myophosphorylase deficiency (McArdle's disease) is described. Myoglobinuria, possibly abetted by intravenous urography, was incriminated as the cause of impairment of renal function.A muscle biopsy specimen contained necrotic fibers and no histochemically demonstrable phosphorylase activity. Ultrastructurally, nonspecific degenerative changes were observed.


Involvement of descending inhibition in the effect of acupuncture on the splanchnically evoked potential in the orbital cortex of cat. The possible involvement of descending inhibition in the effect of acupuncture on the transmission of visceral afferent impulses has been investigated. Averaged splanchnically evoked potentials were recorded in the orbital cortex of the unanesthetized immobilized cat. The evoked orbital potentials could be inhibited by electroacupuncture. Section of the descending inhibitory pathway which is known to be located in the dorsolateral funiculi of the spinal cord produced marked diminution of the acupuncture inhibitory effect on the evoked cortical potentials with needles either inserted in the hindlimb or in the forelimb. Since the afferent impulses from the forelimb entered the cord above the level of section (T3-4), the ascending pathway for acupuncture signals to the supraspinal structure was thus left intact. Destruction of the pontobulbar reticular formation including mainly the nucleus raphe magnus produced the same diminution of the acupuncture effect. The results indicate that the ascending visceral afferent impulses are blocked at the level of the spinal cord by the acupuncture-induced descending impulses from the supraspinal center, probably the nucleus raphe magnus.


[Fissure sealing with Evicrol in animal experiments]. The preventive effect of fissure sealing with the composite material Evicrol was tested in a programmed standardized caries experiment on Wistar rats. The results obtained indicate that Evicrol is not suited for fissure sealing.


[Disinfection of the oral mucosa before intraoral injections]. It is reported of the suitability of a 0.2% peracetic acid solution with ethanol. Considerable bacterial count reduction was achieved in 200 patients by applying the solution once to the site of injection, without previous drying, and allowing it to react for five seconds. The procedure is recommended for routine use in everyday practice.


[Biostatistical proof of retarded tooth eruption in the permanent dentition of patients with clefts]. It is evidenced biostatistically that the eruption of the permanent teeth is retarded in cleft patients. This retardation concerns both the maxillary and mandibular teeth. Both sexes are involved. In female cleft patients the change to the permanent dentition occurs earlier than in male cleft patients. There is no sidedness.


[Comparative clinical and exfoliative cytological studies on the use of occlusive dressings]. Among the variety of surgical packs described in the literature, zinc oxide-based packs have proved especially useful. Two types still currently used are the zinc oxide-eugenol pack according to Büchs and Walter and the pack modified by Behlke which contains Peruvian balsam in place of eugenol. Of 27 patients who had undergone a periodontal-surgical intervention, 6 were treated with a zinc oxide-eugenol pack, and 21 with a pack modified by Behlke. Clinical and cytological examinations were performed before intervention, at each change of pack (on the 5th, 8th and 14th days after intervention) and 4 weeks after intervention. The comparison of the results obtained shows the superiority of the pack modified by Behlke over the zinc oxide-eugenol pack.


[Suction technic and suction method in dental practice]. By way of introduction the authors deal with the necessity for suction as an important component of ergonomic work organization in dental practice. The technical pre-conditions (suction technique) are indicated. Principles are formulated for their beneficial application in the sense of systematic suction methodics.


[Incidence and distribution of tumors of the mouth cavity. 30 year's experience at the Clinic of Maxillofacial Surgery, Budapest]. The present paper deals with the qualitative and quantitative distribution of tumour patients treated at the Budapest Clinic Maxillofacial Surgery in the east 30 years. These patients suffered from: odontogenic tumours, 135 cases: non-odontogenic benign tumours, 1219; and malignant tumours, 1238. Compared to previous data, the present findings evidence the upward trend of the frequency of tumours and of the malignant ones among them.


[A rare case of hyperodontia].

[A rare case of hyperodontia]. A rare case of hyperdontia is described to demonstrate that under favourable conditions supernumerary, normally formed teeth must not be extracted, but can be fully included in the planning of orthodontic treatment.


[Optimal dental radiography by means of expert film processing]. The processing of the dental radiographic films in the darkroom is decisive of the optimal information content of dental radiographs. Proper storage of the films, darkroom lighting according to regulations and standardized film developing are the basic conditions for stable film quality. The indications given are above all intended for aiding the stomatological nurse in taking dental radiographs.


[Impacted wisdom tooth 48].

[Impacted wisdom tooth 48]. To illustrate the great variety of wisdom teeth impactions, the authors report a case where a vertically impacted 48 projected with its apex over the mandibular border by almost 2 mm. Possible causes of impaction and their consideration in the surgical removal of such teeth are mentioned.


[The healing of periapical periodontitis after root canal filling with diaket]. A clinical and radiological study was performed to test the utility of Diaket in the conservative treatment of chronic periapical periodontitis. 86% of the treatments were successful with a follow-up of 12 months.


[Clinical, radiological and histological results after vital treatment of exposed pulps]. The authors present the clinical and radiological results of their long-time controls of 210 permanent teeth after direct capping of the exposed pulp and describe some histological findings. The over-all evaluation of the results permits to conclude that the method of direct pulp capping is more successful only if the indication is established discriminately. The patient's age is of no or minor importance to the choice of treatment.


[Comparative studies of the oral flora in patients with cancer and precancerous lesions  of the mouth mucosa]. Bacteriological smears were taken from various regions of the oral cavities of a total of 100 subjects (patients with carcinoma, non-specific ulcer or leucoplakia, and patients without pathological oral findings). The preparations were stained by the Gram procedure and differentiated according to germ count, morphology and ability to combine with dyes. Gram positive cocci prevailed in all groups. The total germ counts were greater in patients with carcinoma than in those with nonspecific ulcer and in normal subjects.


[Personal method for the surgical treatment of recessed gingiva]. The authors report their experience with a personal technique for the surgical treatment of gingival recessions. Their experience is based on operations upon 35 teeth. To avoid recurrences, the authors perform, on principle, the necessary vestibuloplasty, covering the wound surface with a full-thickness skin graft taken from the cheek, three weeks after the first intervention. The good results obtained permit to recommend this method.


[Bilateral synalgias].

[Bilateral synalgias]. Total pulpitis leads in most cases to unilateral synalgia. Bilateral synalgiae are considerably rarer, but theoretically possible, in which pain radiates to the non-affected half of the jaw or face. Case reports illustrate the symptomatology, cause and therapy.


[The use of Ornipressin in dental local anesthesia]. Blood-pressure and pulse-rate measurements, sensibility tests and tissue clearance measurements were performed in juvenile patients aged from 12 to 18 years to evaluate the clinical effects and side-effects of the new vasoconstrictor POR 8 (ornipressin) in ambulatory dental treatments. There were no significant differences in efficiency compared to adrenaline. Indications for the use of POR 8 are mentioned.


[Technic and evaluation of effectiveness of infraorbital anesthesia using the approach along the axis of the 2d premolar]. The method of infraorbital anaesthesia along the axis of the second premolar, which has been inaugurated by Jorgensen, is described and critically evaluated in the light of results from morphological, anatomical and clinical studies. Considering the sufficient depth of anaesthesia achieved with this technique, the author regards its simple and safe execution and the avoidance of complications as decided advantages over the conventional technique are recommends it for use in practice.


[Median superior diastema--definition, etiology, symptoms]. The definitions, aetiology, and symptomatology of the diastema mediale superior are discussed in the present study on the basis of personal experience and reports in the literature, special attention being paid to the verbal evaluation of "genuine" or "spurious".


[Dental local anesthesia in patients with diabetes mellitus]. In 51 tooth extractions in medicinally controlled diabetics, adrenaline and noradrenaline (used as vasoconstricting additives to the local anaesthetic) did not differ in their effects on the blood-sugar level. A clinically important or lasting disturbance of the carbohydrate metabolism was observed in no case. The general preference given to noradrenaline as a vasoconstrictor in diabetics is not supported by the present study.


[An unusual care--results of replantation]. In the course of the regular ambulatory supervision of orally rehabilitated patients, the author reexamined in a patient the molars 16 and 17 which had been replanted 22 years ago. The problems related to replantation are discussed.


Leukaemia in Papua New Guinea.

Leukaemia in Papua New Guinea. All cases of leukaemia diagnosed between 1968 and 1976 in the Melanesian population of Papua New Guinea have been analysed, and comparisons made with an earlier series from this country and with findings reported from elsewhere. The major findings were: a low overall incidence (0.79/100,000), absence of a childhood or old age peak in incidence, a relatively lower proportion of acute lymphoblastic leukaemia in childhood, more than the expected proportion of cases of chronic granulocytic leukaemia under 20 years of age, and the rarity of chronic lymphocytic leukaemia.


The cytology of the retained IUD with relation to the mechanism of action. Cellular reactions to 82 IUDs retained for different periods of time have been examined using the "loopal smear" method. The smears were divided according to periods of retention and degree of inflammatory reaction. In 47 cases the inflammatory reaction was graded as moderate to severe, while in 35 cases the reaction was graded as mild. Since contraception was effective also in those cases presenting with mild reactions, it must be concluded that factors other than inflammation play a role in the contraceptive mechanism. Cells obtained from 15 IUD washings were incubated with Staphylococcus albus in order to identify macrophages. In none of these cases were macrophages identified, thus rendering questionable the hypothesis that the contraceptive effect of the IUD is based on phagocytosis of spermatozoa.


Point, minute and small cancers of the stomach at the early developmental stage detected by improved chymotrypsin lavage method for diagnostic cytology. The improved selective chymotrypsin lavage method under fluoroscopy for cytologic detection led to the discovery of 12 point or minute gastric cancer lesions of less than one cm maximum diameter among 420 patients. It is reported herein how tiny cancers of the stomach can be found by the method, and how valuable it is to employ morphologic criteria for correct identification of the individual atypical cells in these tiny gastric cancers.


Tissue culture of cells in serous effusions. Evaluation as an adjunct to cytology. Cell pellets from peritoneal, pleural and pericardial effusions from thirty-six patients were incubated in tissue culture medium. Both the culture supernatants and the cell monolayers in the flasks were examined for malignant cells. Of the ten cases diagnosed as positive for malignant cells by the conventional cytologic smears, eight were positive on examination of the tissue culture supernatants and only six were positive by analysis of the monolayers. All the cases diagnosed as positive from the culture supernatants and from the monolayers were also positive by the conventional smear method. Hence, tissue culture of cells in serous effusions is not helpful as an adjunct to routine diagnostic cytology techniques.


Significant hormonal changes in patterns of lipid granules in vaginal exfoliated cells. In vaginal exfoliative cytology, the routine Papanicolaou and Shorr's staining procedures do not reliably indicate the post-ovulatory phase. An experimental study of 100 female albino rats and a clinical study of 190 women was initiated to establish an easier method for identifying the post-ovulatory phase. It was found that the appearance of intracytoplasmic lipid granules in vaginal cells stained by Oil Red 0 may serve as a sensitive indicator of the post-ovulatory phase.


Binucleate cell recognition in automated gynecologic cytopathology. Medium resolution two dimensional image analysis techniques were applied to a large number of abnormal and binucleate cells from the uterine cervix. Techniques were developed for the extraction of nuclear boundary information from fluorescence images and two new nuclear shape descriptors were applied to the binucleate cell recognition problem. The descriptors were a contextual measure of concavity location and size on the nuclear boundary, and mean area of the two largest concavities. These features were superior both to total convex deficiency and to ratio of perimeter squared to area when applied to binucleate cell recognition. Classification based on the second feature, mean convex deficiency, provided lowest error rates. These were approximately 10% false positive and false negative single cells, and occurred with an effective two micron spot size. Higher false negative rates were observed with a one micron spot size.


Psammoma bodies in cervico-vaginal smears. Case report and review of the literature. A case is reported in which psammoma bodies were present in a cervico-vaginal smear. No malignancy was found upon hysterectomy. Both this case and a review of the literature emphasize the non-specificity of psammoma bodies in the diagnosis of malignancies.


Banding analysis of three primary cancers. Chromosomes of a breast cancer and two colonic cancers were studied with banding methods. An intracystic papillary carcinoma of breast had the following constitution: 46, XX, -1, +3, -20, +i(1q), +i(1q), +t(1;20)(p13;p13). The second tumor, a well-differentiated adenocarcinoma of the colon had several autosomal trisomies and del(3)(p14). There was karyotype stability in both tumors. The third tumor, an undifferentiated colonic cancer, had a pseudodiploid stemline, namely 46, XX, -1, +(1q), and four sidelines with additional numerical changes.


Cytologic diagnosis of malignant melanoma metastatic to the endometrium. A case of cytologically diagnosed malignant melanoma metastatic to the endometrium is presented. The literature on extragenital malignant neoplasms metastatic to the uterus was reviewed to document the rarity of this entity. The cytologic features of metastatic malignant melanoma are described along with a differential diagnosis of other lesions having pigmented cells such as primary pigmented lesions of the endometrium, primary malignant vaginal melanomas, benign pigmented lesions of the cervix and vagina, and pigmented conditions other than melanoma.


Circulating mitotic cells in the newborn infant. The preparation of karyotypes without prior cell culture. A method is described which permits the rapid chromosome analysis, without prior culturing, of newborn infants suspected of having chromosomal abnormalities. This was accomplished by the direct preparation of karyotypable slides from in vivo circulating mitotic cells taken from  placental cord blood immediately after delivery.


Adenovirus infection and cytopathic alterations of human cervical epithelial cells in vitro. The effect of adenovirus infection was studied in monolayer cultures of human ecto- and endocervical epithelial cells. In both types of cultures adenovirus type 1 resulted in a slowly progressing lytic infection with persistent production of infectious virus, viral antigens and of cytopathic alterations in a fraction of cells. The changes were similar in ecto- and endocervical epithelial cells. Although many of the alterations detected may represent unspecific lesions, nuclear changes consisting of lobulated nuclear inclusion bodies seemed to be characteristic. These alterations differ from those observed during infection with the herpes group of viruses and may serve as indicators of cervical adenovirus infection in cytologic screening.


Gradient separation of normal and malignant cells. II. Application to in vivo tumor diagnosis. Data were obtained concerning the usefulness of discontinuous Ficoll and Isopaque-Ficoll gradients in separating malignant from non-malignant cells from a variety of sources. Most of the material was from effusions, but there is no theoretical restriction of the methods to effusions. Animal and human material were studied, utilizing non-malignant as well as malignant material, the former acting as controls. In the discontinuous Ficoll gradient, concentration of malignant cells at a specific interface was mainly a function of cell density. Thus, while most malignant cells banded in the last two fractions, adenocarcinomas, especially those high in mucus (which decreases total cell density) banded higher in the gradient. The Isopaque-Ficoll technique also proved useful in concentrating malignant cells. The advantage of the discontinuous Ficoll gradient was its ability to separate cells from small specimens (1-10 X 10(6) cells). Contrarily, the Isopaque-Ficoll gradient was preferable for processing specimens of larger volumes.


[Treatment of leukemic infiltrations of the central nervous system. Preliminary communication]. In a group of 39 patients with acute leukaemias lumbar taps with intrathecal administration of drugs were done. In 20 cases lumbar tap was done at the time of development of neurological signs. In 19 cases one prophylactic intrathecal drug administration was done. In the treatment of leukaemic infiltrations in the central nervous system three methods were used administering intrathecally methotrexate in the first schedule, methotrexate and cytosine arabinoside in the second schedule, and cytosine arabinoside with Ultracorten in the third schedule. These methods caused usually disappearance of most clinical signs and changes in the cerebrospinal fluid. In 7 cases side effects appeared due to chemical irritation of the meninges but disappeared after several days.


Osteosarcoma. A multifactorial clinical and histopathological study with special regard to therapy and survival. A multifactorial analysis was performed on all 153 unequivocal cases of genuine osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968. Cases of so-called parosteal osteosarcoma, soft-tissue osteosarcoma and osteosarcoma secondary to Paget's disease of bone were not included. The osteosarcomas were subclassified as follows: osteoblastic (69 per cent), chondroblastic (19 per cent) and fibroblastic (12 per cent). The overall 5-year survival rate was 22 per cent; 55 per cent for those who had undergone amputation above the joint proximal to the involved skeletal part, 22 per cent for those amputated on the involved skeletal part, 11 per cent for those treated with local extirpation of the tumor, and 1 per cent in cases in which the lesion was not radically removed. Tumors of the femur, humerus and scapula were as malignant as axial tumors. The former carried a 5-year survival rate of 13 per cent, regardless of whether the patients had been treated with exarticulation or amputation on the involved skeletal part. Patients with axial tumors showed a 5-year survival rate of 15 per cent. These survival data suggest that proximal amputation alone might suffice for lesions situated distally to the knee and elbow joints, while tumors in the humerus and femur should be treated with amputation combined with multicytostatic treatment or immunotherapy and axial tumors with local resection and multicytostatic or immunologic treatment.


Telangiectatic osteosarcoma.

Telangiectatic osteosarcoma. Of the 242 cases of osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968 only one was found to represent telangiectatic osteosarcoma. Another case was recently diagnosed in our department. The characteristic morphologic features of these neoplasms were anaplastic stroma, high mitotic activity, osteoid-formation, widely anastomosing blood spaces, and alkaline phosphatase activity. The experience gathered indicates that telangiectatic osteosarcoma constitutes a histopathologic variant of genuine osteosarcoma with a serious prognosis, necessitating the same kind of treatment as for the genuine tumour.


Hematogenous development of rat mature granulocytic leukemia--distribution of leukemic foci in vertebral bodies. The oral administration of N,N'-2,7-fluorenylenebisacetamide (2,7-FAA) induces leukemia, especially mature granulocytic leukemia, in rats. We compared the distribution of nodular foci of 2,7-FAA-induced mature granulocytic leukemia with that of transplanted leukemia for the purpose of proving hematogenous development of leukemia. The bone marrow of the vertebral bodies was examined in the cases of scattered lesion of 2,7-FAA-induced and transplanted leukemia. The leukemic nodular foci were most frequently located around the center of the craniocaudal axis of the vertebral bodies in both leukemias. On the other hand, they were evenly distributed along the dorso-ventral axis in both leukemias. The similarity of the distribution of nodular foci between 2,7-FAA-induced and transplanted leukemia may be an evidence for the hypothesis that the former is spread by hematogenous metastasis.


Oxazepam in the treatment of anxiety in children and the elderly. The nature of anxiety, particularly in the young and the elderly, is described. The difficulty of treating anxiety occurring at the extremes of age is emphasized. Oxazepam is exceptionally well tolerated by these patients and is considered to be the benzodiazepine of choice for paediatric and geriatric anxiety. Metabolic and pharmacokinetic factors may account for this distinction.


The abuse potential of benzodiazepines with special reference to oxazepam. Extensive use of oxazepam, particularly in the abuse-prone population of alcoholic patients, has shown that the dependence-producing potential of this drug is remarkably low, only four cases of dependence having been encountered over many years. Even abrupt withdrawal of oxazepam does not normally precipitate an abstinence syndrome. A computerized literature search retrieved 68 papers on benzodiazepine abuse and/or dependence, only 4 (6%) being concerned with oxazepam. Three reasons are proposed to account for the exceptionally low abuse-potential of oxazepam, the first being considered to be the most important: its onset of central nervous system activity is gradual, so there is no sudden 'intoxication' effect; it tends to cause dizziness at high dosages, discouraging the patient to increase the dose; and because it has a short half-life and no major active metabolites, intermittent therapy (which many patients now practise with all benzodiazepines), periodically allows the complete elimination of the drug from the body.


Benzodiazepine receptor in brain.

Benzodiazepine receptor in brain. The evidence that the brain possesses specific receptors for benzodiazepines is summarized. Further we present a series of brain lesion experiments in rats showing that specific neuronal destructions by 6-hydroxydopamine, kainic acid in the striatum, X-ray irradiation of the hippocampus, intraperitoneal 3-acetyl-pyridine or hemisection at the thalamic level do not reduce the level of benzodiazepine receptors in striatum, hippocampus, cortex or cerebellum. These results show that the benzodiazepines are not positioned on dopamine or noradrenaline terminals, cholergic or GABA-ergic neurons in the striatum, granular cells in the hippocampus or climbing fibers in the cerebellum.


The pharmacokinetic profile of oxazepam. Oxazepam has the shortest half life of the benzodiazepines and does not form any active metabolites. Its pharmacokinetic properties in healthy volunteers, uremic patients and dogs are reviewed. In normal man half lives between 6 and 25 hours are obtained. The drug is completely absorbed and steady state concentrations develop after multiple doses. In uremic patients the terminal half life of oxazepam in plasma was prolonged to 24-91 hours. However the clearance of oxazepam was not significantly decreased in this patient group and similar doses as in normal subjects are recommended. There was a marked retention of the water soluble oxazepam conjugate in the uremic patients but no pharmacological effect could be detected. In the uremic patients, as in dogs, secondary plasma concentration peaks were seen after single doses. In uremic patients, fecal excretion of oxazepam was increased. In the dog one third of a single intravenous dose was recovered in the bile. Thus enterohepatic cycling may occur in the dog and in uremic patients.


Pharmacokinetics of oxazepam given during labour. The transfer across the placenta and the maternal and neonatal kinetics of oxazepam and its conjugate was studied in 12 patients and their newborns. Oxazepam was readily absorbed and peak plasma concentrations were similar to those in healthy non-pregnant volunteers. When meperidine was given within one hour of the dose of oxazepam the absorption was delayed but the bioavailability did not decrease. In the newborns the umbilical vein plasma concentration of oxazepam usually exceeded that of the conjugate. The reverse was true for all subsequent plasma samples from the newborn. The half-life of oxazepam in the newborn averaged 22 hours as compared to 6.5 hours in the mothers. A significant rise of the plasma concentration of oxazepam conjugate was noted in three newborns during the first 6-10 hours of extrauterine life. This shows that the newborn is able to conjugate oxazepam. The Apgar score values were normal.


The episodic nature of anxiety and its treatment with oxazepam. The presentation of anxiety in clinical practice is examined, and it is concluded that many patients, perhaps a majority, experience fluctuating levels of anxiety. It is therefore suggested that therapy should be intermittent, according to this waxing and waning of symptoms. Most benzodiazepines are long-acting, and are therefore unsuitable for this type of therapy, but oxazepam, which is short-acting and has no active metabolites, is ideal for this purpose. It is proposed that such a regimen would minimize the problems of over-sedation, psychological habituation, and a reluctance, due to a permanently tranquillized state, to deal with the root causes of the anxiety.


Interferon therapy in neoplastic disease. A preliminary report. The treatment of 10 patients having neoplastic disease with exogenous i.m. interferon therapy is described. The interferon given is partially purified interferon produced from human leukocytes. Sendai virus is used as interferon inductor. The patients reported in this paper have been on treatment for periods of 2-28 months. Apart from initial periods of fever, no side-effects have been recorded. Patients suffering from bladder papillomas have shown partial regression after a few months of therapy. The other cases treated are too few to warrant any conclusions, but the therapy does seem to have been beneficial.


Interferon and spontaneous cytotoxicity in man. II. Studies in patients receiving exogenous leukocyte interferon. The spontaneous cytotoxicity of peripheral lymphoid cells from five tumor patients was measured before and at various times after the first injection of human leukocyte interferon (IF). Four of the patients' lymphocytes exhibited cytotoxicity before the IF injection. After injection of IF there was an initial decrease in cytotoxicity, followed by an increase to 1.5-5 times above the preinjection level, the peak being reached at 12 hours. Thereafter the spontaneous cytotoxicity decreased but usually remained elevated for 24 hours after the injection. The lymphocytes of the fifth patient had very low spontaneous cytotoxicity before the injection of IF, and this did not markedly change afterwards. The proportion of E-rosette forming cells seemed to decrease slightly in all patients after the injection, followed by a normalization at 24-48 hours.


Accurate determination of serum ASAT isoenzymes. An improved electrophoretic modification for measuring aspartate aminotransferase (ASAT) isoenzymes is presented. This method fulfils the clinical requirements for sensitivity and allows the detection of 1 U/l mitochondria ASAT activity at 25 degree C. The procedure is relatively simple, requiring about one hour for a series of 8 determinations. Mitochondrial ASAT activity was found in all patients suffering from acute myocardial infarction pathological activity was observed for several days longer than that of total serum ASAT enzyme. None of the 25 healthy people studied had mitochondrial ASAT in their serum.


Creatine kinase isoenzymes in the confirmation of acute myocardial infarction. Serum MB isoenzyme of creatine kinase is the most specific and sensitive indicator of myocardial infarction. Despite these virtues, its clinical use is handicapped by rapid normalization after the onset of myocardial injury. In patients suffering brain accidents, the increase of serum CK-MB isoenzymes indicates stimultaneous myocardial damage and means poor prognosis.


Left ventricular function after myocardial infarction: relation between systolic time intervals and quantitative ischaemic ECG changes. Twentyfour male patients with sustained myocardial infarction (MI) were studied with 12-lead ECG and systolic time intervals (STI) 5 months after the acute episode. From the ECGs were calculated the summed voltages of the R wave (sigma R), the Q wave (sigma Q), and the ST segment deviation (sigma ST). These ischaemic ECG variables were correlated with the STI parameters of left ventricular function: LVETI, PEP and PEP/LVET. Statistically significant regression equations relating the ECG changes to the STI variables were found in anterior MI, for sigma ST in the entire series, but not in inferior MI. Thus a simple and rapid inspection of the resting 12-lead ECG gives an indirect but reliable quantitative estimate of left ventricular function in patients with a sustained myocardial infarction.


Haemodynamic and endocrinological profile of essential hypertension. In this study the results are presented of the haemodynamic and endocrinological inventarisation of 207 patients with essential hypertension. After establishing the relations of the various parameters with age (part IIA), interrelations between these variables are described (part IIB). The general finding is an increase in total peripheral vascular resistance early in the course of essential hypertension. In particular, this rise in resistance is found in the renal vasculature. In part III emphasis is given to the natural history of essential hypertension on the basis of a follow-up study. Again a rise in renal vascular resistance is found. As pointed out in the discussion (part IV) the cause of the abnormal resistance remains unknown. Emphasis is given to the renin-angiotensin system, which plays only a minor role. Here the factors regulating long-term renin secretion are discussed in favour of the baroreceptor theory.


Leukemia in radiation-treated patients: cytogenetic studies in eight cases. Abnormal chromosomes have been found in various clinical settings and in cancer patients. Eight patients developed leukemia several years after the diagnosis and treatment of a primary malignant disease. All the patients were being treated with irradiation, and five of them also received chemotherapy, notably, alkylating agents. The type of leukemias and the interval between irradiation and leukemia parallel very well with those reported from the atomic bomb casualties. Chromosomal abnormalities were seen in all the patients. These abnormalities have been reported in irradiated normal persons without developed leukemias. These findings suggest that the development of clinical cancer or leukemia may depend, not only on the presence of abnormal cells, but also on other factors. Perhaps the environment that allowed the original cancer to develop in our patients is capable of allowing the radiation-induced abnormal cells to be expressed as clinical leukemia.


Effective adjuvant treatments. A brief review of U.S. clinical trials. A variety of adjuvant trials performed in the United States for osteogenic sarcoma, breast, lung, and colon cancer have achieved encouraging results and are briefly summarized. Trials in osteogenic sarcoma are reporting 2-year disease-free survival rates of 50%. However, they have only been evaluated against historical controls and there is some evidence that other factors might have greatly improved the disease-free survival in the absence of adjuvant therapy. The NSABP breast cancer trial only shows significant improvement for women under 50 years of age with 1 to 3 positive axillary nodes. A very promising trial using intrapleural BCG immunotherapy for squamous cell lung cancer is described. Also, two trials of 5-fluorouracil for colo-rectal cancer, both showing trends suggesting slight improvement among treated patients, are presented. Proper care in the design of adjuvant trials with sufficient attention paid to prognostic variables is urged.


Current trends and prospects in surgical adjuvant trials. New concepts and treatments currently available for adjuvant studies are illustrated by a review of ongoing studies sponsored by the National Cancer Institute. More thorough information is needed on immunotherapeutic agents to allow more rationale in the use of these agents. Solid bases to properly select drugs or drug combinations for adjuvant purposes are being established. However, dose-schedule and duration of treatment are still to be defined. Strategies directed at prolonging the benefit of surgical adjuvant chemotherapy remain to be planned. Progress continuously achieved with immunotherapy and chemotherapy should rapidly broaden the spectrum of tumour types to be included in adjuvant studies.


Acute stomatitis medicamentosa. Two case reports. Two cases of acute drug reaction with oral mucosal lesions and problems of diagnosis in the absence of specific clinical and histopathological findings are presented.


Dental implications of narcotic addiction. The nature of dental problems peculiar to narcotic addicts is discussed. A high caries rate and severe periodontal disease are common and can be attributed to a combination of dietary considerations and oral neglect. Loss of customary accompanying analgesia may complicate an attempted withdrawal programme. An approach to dental treatment of the narcotic addict is suggested. This should aim primarily at relief of pain and be carried out in consultation with the drug treatment centre. The risk posed by these patients of transmission of Hepatitis B is emphasized.


The effect of irradiation and heat on the content of adrenaline in commercially manufactured local anaesthetic solutions--a pilot study. Carpules of commercially available local anaesthetic solutions containing adrenaline have been exposed to varying conditions of heat, ultra-violet and infra-red light over a period of two months. The adrenaline content in the solutions was assessed by fluorometric assay both at the commencement of study and at regular intervals over the period of exposure. Infra-red light appeared to have little or no effect on the concentration of adrenaline, while ultra-violet light, either alone or in combination with infra-red light, caused the adrenaline levels to diminish rapidly. The results suggest that the ultra-violet component of light is probably responsible for the breakdown of catecholamines in local anaesthetic solutions when these solution are stored in areas exposed to sunlight.


Furcation involvement--a suggested rationale for treatment. Furcation involvement is classified and methods of treatment discussed. Evidence is presented to indicate that altered plaque elimination techniques are essential in the furcation region.


In vitro studies on the use of cetylpyridinium chloride as a bacterial plaque control agent. Studies have shown that cetylpyridinium chloride (CPC) containing mouthwash may in vitro inhibit artificial bacterial plaque accumulation under certain conditions. These studies, together with the findings of clinical trials, suggest that the clinical activity of CPC in partially limiting plaque accumulation depends on its adherence to cleaned enamel surfaces rather than its penetration in performed plaque.


Removing broken roots--a simple method.

Removing broken roots--a simple method. A simple technique has been outlined for the removal of fractured root fragments. It can be applied to a number of situations and employs instruments which are readily available in the dental surgery.


The expectations of the dental graduate. The young dental graduate expects to deliver a certain standard of health care to the community. It is likely that both the standard of care required by the Australian people and the proportion of the population seeking treatment will increase in the coming decades. The dental profession has a responsibility to meet these demands. Although dentists should expect adequate monetary return for their activities, it would be improper to limit entry into the profession solely on the grounds of seeking to maintain some present datum line of "economic viability" of practice.


Dendritic crystallization.

Dendritic crystallization. The fundamentals of dendritic crystallization are presented. Examples illustrating the processes and structures involved have been obtained by the metallurgical examination of specimens of the base metal partial denture casting alloys.


The prognostic value of the HV interval in patients with acute myocardial infarction and bundle branch block. HV intervals were measured in 42 of 119 patients in the acute phase of myocardial infarction associated with bundle branch block (BBB). The mean HV intervals of patients with right, left and incomplete bilateral BBB were similar. The hospital and subsequent mortality of patients with prolonged HV intervals did not differ significantly from that of patients with normal HV intervals. The HV interval appeared to remain stable over the following months in most patients in whom it was remeasured. We conclude that the HV interval cannot be used to select patients who might benefit from prophylactic long term pacing.


Thromboembolic complications of mitral valve disease. Five hundred and eighty-eight patients with mitral valve disease were studied. The incidence of systemic emboli was found to be higher in patients with pure mitral stenosis (16.6%) and mixed mitral stenosis and incompetence (19.4%) than in patients with mitral incompetence (3.1%). The patients with mitral stenosis who had episodes of systemic emboli tended to be older than 40 years, with moderate or severe valve lesions, atrial fibrillation and moderate or gross enlargement of the left atrial appendage or left atrium. The following factors were found to be unrelated to systemic embolism---associated aortic valve disease, sex, smoking habit, history of rheumatism, parity, haemoglobin, blood urea, pulmonary hypertension, duration of antifailure treatment, presence of heart failure, and cardiothoracic ratio.


Electrophysiology of disopyramide in man. The electrophysiological effects of an intravenous dose of disopyramide phosphate (2 mg per kg body weight) were studied in 17 patients. Studies were performed with the patients fasting, unpremedicated, and off all medication for three days. Blood samples for estimation of serum levels of disopyramide were collected in 15 of these patients. The effects of intravenous disopyramide were maximal at five minutes, less marked at 20 minutes, and largely gone by 30 minutes after administration of the drug. Sinus cycle length and corrected sinus node recovery time were shortened significantly. No index of atrioventricular nodal function was significantly changed. Both atrial and ventricular effective refractory periods were significantly prolonged. Further impairment of intraventricular conduction occurred in six patients with bundle branch block on electrocardiogram or prolonged HV interval. In one of two patients with Wolff-Parkinson-White syndrome, the bypass effective refractory period was prolonged. These electrophysiological changes are similar to quinidine and quinidine like drugs. It is recommended that disopyramide should be used cautiously in patients with evidence of His Purkinje system disease since it may lead to higher degrees of intraventricular block.


Gentamicin and amikacin---an in vitro comparison using 1000 clinical isolates. The in vitro antimicrobial activities of gentamicin and amikacin against 1000 bacterial isolates from clinical material were compared. The minimum inhibitory concentrations were determined by an agar dilution technique. Both of these aminoglycoside antibiotics had a similar spectrum of activity, being highly active against most species of aerobic Gram negative bacilli. Gentamicin was more active than amikacin against most species of enterobacteria, Haemophilus influenzae and Staphylococcus aureus but amikacin was more active against a proportion of Klebsiella and Providencia isolates. For most isolates, the differences in activity between gentamicin and amikacin were small, however, amikacin achieves higher serum levels. Most resistant isolates in this survey did not influence patient mortality.


Social factors and clinical disease: a checklist data base for correlative analysis. The adequate care of a patient entails consideration of his social and psychological problems in addition to the relevant medical data. To facilitate this integrated approach, a Social Work Indices Checklist (SWIC) is described, and its use in practice is illustrated. A narrative report is generated from a possible 3095 items of information recorded in SWIC.