Evidence for pro-beta-nerve growth factor, a biosynthetic precursor to beta-nerve growth factor. The biosynthesis of beta-nerve growth factor (betaNGF) was studied in mouse submaxillary glands incubated with L-[(35)S]cystine. betaNGF was isolated from tissue extracts by the addition of antiserum against betaNGF and the washed immunoprecipitates were analyzed by sodium dodecyl sulfate gel electrophoresis. With short labeling periods (10 and 25 min) there is a major labeled species with an apparent molecular weight of 22,000 and a smaller peak comigrating with purified betaNGF chains (13,260). As time proceeds, the radioactivity in the 22,000 molecular weight peak plateaus, while the label in betaNGF continues to increase, until by 4 hr it greatly exceeds the radioactivity of the 22,000 molecular weight species. When glands incubated for 10 min are transferred to medium containing a large excess of unlabeled L-cystine, the 22,000 molecular weight peak gradually declines, and there is a corresponding increase in radioactivity at the betaNGF position. The 22,000 molecular weight species isolated from sodium dodecyl sulfate gels possesses all the cystine-containing peptides of betaNGF, and possibly two additional ones. When immunoprecipitates from submaxillary glands labeled for 25 min are incubated with the gamma subunit (a specific arginyl-esteropeptidase associated with betaNGF in the 7S NGF complex), the radioactivity in the 22,000 molecular weight species is converted to the betaNGF position. The results suggest that the 22,000 molecular weight species is a biosynthetic precursor to betaNGF, and that the gamma subunit may function as a specific protease in the processing event.


DNA packaging and the pathway of bacteriophage T4 head assembly. A cold-sensitive mutation in the structural gene for a minor phage T4 capsid protein (p20) leads to formation of heads containing p20 and cleaved head proteins and empty of DNA. Such heads can be filled with DNA and converted to active phages in vivo uponshift to high temperature. It appears that p20 has two distinct roles in head assembly: first, in construction of the prehead shell (blocked by ts and am mutation) and, second,in DNA packaging (blocked by cs mutation). The latter function is closely associated with gene 17 product, previously known to be required for DNA packagaing. Temperature shift studies of cs-ts double mutants and other observations allow determination of phage function required for DNA packaging. Contrary to previous proposals, we find that T4 DNA packaging is not directly coupled to and can follow DNA synthesis, protein cleavage, prehead core removal, and gene 21-mediated cleavage-induced increase in head volume. Our evidence suggests that an altered head assembly pathway exists and that DNA packaging is probably initiated by DNA-capsid (p20) interaction.


Isolation of an electrogenic K+/Ca2+ ionophore from an ionophoroprotein of beef heart mitochondria. A K+/Ca2+ electrogenic ionophore has been isolated from an ionophoroprotein of beef heart mitochondria and identified as a neutral peptide of molecular weight 1600. The amino acid composition and cationic specificity of the ionophore have been determined. The free ionophore was released from the ionophoroprotein as a consequence of tryptic digestion. The ionophoroprotein can be converted to an ionophoro peptide (molecular weight 5,100) by proteolysis without release of the free ionophore. The isolation of a K+/Ca2+ ionophore thus provides an introduction to the general technology of extracting ionophoro proteins and ofreleasing ionophores from these proteins by proteolytic digestion.


Antibodies to estrogen receptor: immunochemical similarity of estrophilin from various mammalian species. Immunoglobulin obtained from the serum of rabbits immunized with a highly purified preparation of estradiol-receptor complex from calf uterine nuclei has been shown to contain specific antibodies to the receptor protein (estrophilin) by four criteria: (a) precipitation of the radioactive steroid upon addition of goat antibody against rabbit gamma globulin to a mixture of the tritiated estradiol-receptor complex and the immunoglobulin, (b) adsorption of the estradiol-receptor complex by the immunoglobulin linked to Sepharose, (c) adsorption of the estradiol-receptor complex in the presence of the immunoglobulin by Staphylococcus aureus protein-A linked to Sepharose, and (d) the ability of the immunoglobulin to increase the sedimentation rate of the estradiol-receptor complex. Antibodies to calf nuclear estrophilin were shown to crossreact with the nuclear receptor of rat uterus, as well as with the extranuclear receptor of calf, rat, mouse, and guinea pig uterus and of human breast cancer. The antibodies do not react with either the nuclear or extranuclear dihydrotestosterone-receptor complexes of rat prostate or with the extranuclear progesterone-receptor complex of chick oviduct. These findings indicate an immunochemical similarity among estrophilins from several mammalian species, as well as between extranuclear and nuclear forms of the receptor, but not among receptor proteins for different steroid hormones.


Role of ribothymidine in mammalian tRNAPhe. We have previously reported that mammalian tRNAsPhe from variation tissues contain different amounts of ribothymidine and that a uridine methylase from Escherichia coli can quantitatively convert these tRNAs to species that contain their full complement ofribothymidine at position 23 from the 3' terminus. The role of ribothymidine in mammalian tRNAs has now been investigated by studying the ability of several highly purified mammalian tRNAsPhe, differing only in their ribothymidine content, to support poly(U)-directed poly(Phe) synthesis under various conditions. Our results indicate that the ribothymidine content of mammalian tRNAPhe can be correlated with the ability of these tRNAs to functionin vitro in a low-magnesium (6 mM), ribosome wash factor-dependent, poly(U)-directed poly(Phe) synthesis system from rat liver. Specifically, the effect of increasing the ribothymidine content in a class C mammalian tRNA becomes manifest in an increased apparent maximum velocity for the overall synthesis of poly(Phe), while the apparent Michaelis constant (Km) remains essentially unchanged. It is postulated that the modifiednucleoside ribothymidine might be involved in the regulation of protein synthesis at the level of translation in mammalian liver.


Primary structure of the membranous segment of cytochrome b5. The primary structure of the membranous segment of porcine liver microsomal cytochrome b5 has been determined. This polypeptide is at the COOH terminus of the cytochrome molecule and consists of 43 amino acids. It is essential for the insertion of the cytochrome into the endoplasmic reticular membrane. Automated sequence analysis of tryptic and cyanogen bromide/anhydrous heptafluorobutyric acid peptides provided data from which the following unique amino acid sequence was deduced: Ile-Ala-Lys-Pro-Ser-Glu-Thr-Leu-Ile-Thr-Thr-Val-Glu-Ser-Asn-Ser-Ser-Trp-Trp-Thr-Asn-Trp-Val-Ile-Pro-Ala-Ile-Ser-Ala-Leu-Val-Val-Ser-Leu-Met-Tyr-His-Phe-Tyr-Thr-Ser-Glu-Asn. A prediction of alpha-helices, beta-structures, and beta-turns basedon the sequence of this polypeptide is also presented.


Animal cell mutants defective in sterol metabolism: a specific selection procedure and partial characterization of defects. By using a chemically defined medium, a general and highly specific procedure was devised to select for mutant cells with less abundant or structurally altered sterol in their surface membranes. Within a certain concentration range, the polyene antibiotic filipin was shown to kill only cells with normal (as opposed to decreased) membrane sterol levels. Sterol-requiring derivatives of LM cells were isolated by chemical mutagenesis, filipin treatment, and cloning followed by replica plating in soft agar. Mutants (S1 and S2) are described which, when compared to normal cells, show decreased synthesis of demosterol in vivo from acetate and mevalonate relative to cell number or to fatty acid synthesis. When exogenous sterol is supplied, mutants S1 and S2 grow normally in suspension culture. However, when deprived of sterol supplement, mutant S1 grows slower than wild type cells and mutant S2 lyses within one to two generations. Gas/liquid chromatography revealed that the mutants contained a normal spectrum of fatty acids including unsaturated fatty acyl groups but, unlike wildtype cells, they have less abundant (mutant S1) or no (mutant S2) desmosterol in either the presence or absence of exogenous cholesterol. In vitro experiments with mevalonate as the substrate suggest that the defect in both mutants is in a demethylation reaction subsequent to lanosterol synthesis. The selection method developed here may permit the isolation of mutants with defective membrane incorporation of sterols and other polyisoprenoids as well as defective synthesis of these compounds.


Antipain and leupeptin restrict uterine DNA synthesis and function in mice. As in rats, administration of estradiol to ovariectomized mice results in a trypsin-like proteolytic activity in the uterus. After fractionation of uteri from estradiol-treated ovariectomized mice the protease activity was found in the 12,000 times g pellet and the nucleus, appearing first in the former. Further fractionation of the pellet by discontinuous sucrose gradient centrigugation resulted in sedimentation of the protease with 5'-nucleotidase, a marker enzyme for plasma membrane and separate from mitochondrial and lysosomal enzyme markers. Solubilization was best accomplished by lysis at 37 degrees. The soluble enzyme from mouse uterus had optimal activity at about 43 degrees and pH 8.3 and was inhibited by diisopropylfluorophosphate, tosylarginine methyl ester, antipain, and leupeptin, but not by soybean trypsin inhibitor. Inhibition in vitro by antipain and leupeptin, two low molecular weight peptides, prompted the study of their effect in vivo on the mouse uterus. After intact, cycling female mice received subcutaneous injections of antipain and leupeptin for 16 days, their uteri showed significant diminution in weight and total DNA when compared to untreated controls. Fertility rates were also diminished. Trypsin-like protease activity may be essential to normal uterine metabolism and function.


5'-Terminal capping of RNA by guanylyltransferase from HeLa cell nuclei. A soluble extract prepared from HeLa cell nuclei has been shown to catalyze the 5'-terminal modification of RNA and synthetic polyribonucleotides to form m7G(5')pppA-and m7G(5')-pppG- structures referred to as caps. The reaction involves the transfer of a GMP moiety from GTP to the 5' end of an RNA molecule containing at least two terminal phosphates. Significantly, neither the beta nor the gamma phosphates of GTP are transferred and polynucleotides with no 5'-terminal phosphate or only one are not acceptors. In the absence of methyl donor, G(5')pppA- and G(5')pppG- structures were synthesized, indicating that methylation is not required for guanylylation. Cap formation was considered to occur by the following mechanism:  (see article), in which AdoMet is S-adenosylmethionine, AdoHcy is S-adenosylhomocysteine, and (p)ppN- represents either the original 5' end of an RNA molecule or an internal site to which one or more phosphates were added after processing.


Transfer of mannose from mannosyl retinyl phosphate to protein. Upon incubation of [14C]mannose-labeled mannosyl retinyl phosphate with a membrane fraction from rat liver, mannose was transferred to an endogenous acceptor precipitable withchloroform/methanol to the extent of about 7%. The reaction proceeded linearly with time for 120 min at a pH optimum of about 7.0. The acceptor thus labeled with mannose could be solubilized by sodium dodecyl sulfate/mercaptoethanol. More than half of this acceptor appeared in the void volume of a Sephadex G-100 column. When it was digested with Pronase, a substantial proportion of it appeared between the void and bed volumes of a Sephadex G-100 column, thus indicating that it was a glycopeptide. In high-voltage paper electrophoresis, this glycopeptide moved to the cathode at low pH and to the anode at highpH. When digested with highly purified jack bean alpha-mannosidase, the glycopeptide released almost 50% of its radioactivity as mannose. That this transfer of mannose to glycoprotein from mannosyl retinyl phosphate does not take place via dolichyl mannosyl phosphate was shown by the fact that it is Mn2+ and Mg2+ independent, it is not inhibited by the presence of a 10-fold molar excess of nonradioactive GDP-mannose, and neither 14C-labeled dolichyl mannosyl phosphate nor 14-C labeled lipid pyrophosphoryl oligosaccharide could be detected during the incubation.


3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O(2) consumption decreases exponentially to a zero value. This pattern is duplicated by subsequent additions of mitochondria. The dependence of the apparent first-order rate constant for enzyme inhibition, as well as the number of enzyme turnovers completed before inhibition, on the concentrations of 3-nitropropionate carbanion and succinate are those expected for an active site-directed and irreversible inhibitor. (ii) The inactivated enzyme is not resuscitated by centrifugation and washing of the mitochondria, in contrast to malonate-treated enzyme, and malonate protects against irreversible, inhibition. (iii) The inhibitor species is 3-nitropropionate carbanion and no external nucleophile is required for inhibition. (iv) The respiratory rates, respiratory control ratios, and ADP/O ratios obtained with NAD-linked substrates are unaffected by 3-nitropropionate carbanion. These results show that 3-nitropropionate carbanion is a highly specific, time-dependent, and irreversible inhibitor of succinate dehydrogenase. By analogy with the reaction of nitroethane with D-amino acid oxidase, the data are consistent with the hypothesis that the carbanionic inhibitor forms a covalent N-5 adduct with the active site flavin. However, the precise mechanism of inactivation, as well as mechanistic extrapolations to the oxidation of succinate, must await the elucidation of the structure of the modified enzyme. We can now explain the toxicity of plants such as Indigofera endecaphylla for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion.


Arrangement of subunits in assembled histone H4 fibers. The structure of assembled histone H4 fibers has been studied by analysis of electronmicrographs, including optical diffraction. An individual fiber has the appearance of an 80-A wide ribbon, twisted at intervals of about 330 A. Thicker fibers which have been observed seem to be bundles of ribbons. In diffraction patterns from both kinds of fiber, layer lines at axial spacings of about 1/55 A-1, 1/37 A-1, and 1/27 A-1 were most consistently observed. The possible arrangements of molecules within the twisted ribbons have been deduced and are found to be fairly closely related. The ribbons appear to consist of two parallel, unstaggered rows of repeating units, which are probably H4 dimers. The similarity between the observed layer line spacings of the H4 fibers and the spacings of the maxima in x-ray diffraction patterns from whole chromatin suggests that the H4 fibers have a structure related to that of chromatin. Since homogeneous preparations of histones H2A, H2B, and H3, or any mixture of these four histones, can form similar structures, it seems likely that the basic organization of chromatin is determined by a fibrous histone core around which the DNA is wrapped.


Ultrastructural localization of cell membrane GM1 ganglioside by cholera toxin. An immunoelectron microscopic method is described for sensitive high-resolution visualization of tissuebound cholera toxin. The principle is to incubate cells or tissue sections with toxin and then to localize the bound toxin with toxin-specific peroxidase (donor:hydrogen-peroxide oxidoreductase; EC 1.11.1.7)-conjugated antibody and enzyme substrate. Thin sections are examined for electron-opaque precipitates in a transmission electron microscope. Because of the specific binding of the toxin to membrane ganglioside G(M1), the method can be used for ultrastructural localization of this ganglioside. Semiquantitative data are obtained by titration of the limiting concentration of cholera toxin producing specific precipitates. The specificity of the method was controlled in various ways, including analyses of the correlation between the immunoelectron microscopy results and determinations of ganglioside G(M1) in tissues with different ganglioside concentrations, tissues hydrolyzed with Vibrio cholerae sialidase, tissues in which exogenous G(M1) has been incorporated, and lipid-extracted tissues. The immunoelectron microscopic method demonstrates that membrane G(M1) ganglioside is positioned on the external side exclusively. Cell-bound toxin remains in its original location on the plasma membrane surface of cells below 18 degrees , but appears to be redistributed both laterally and vertically in the membrane of cells incubated at 37 degrees for 30 min or longer. The results of this method indicate that in the central nervous system G(M1) is concentrated in the pre- and postsynaptic membranes of the synaptic terminals; a further increase in reactivity of these structures after hydrolysis of the nervous tissue with V. cholerae sialidase suggests that higher gangliosides of the same series are particularly increased in the pre- and postsynaptic junctions.


Binding of mouse interferon to polynucleotides. The polynucleotides poly(I) and poly(U), and to a lesser extent poly(G), are capable of desorbing mouse interferon from blue dextran-Sepharose columns, whereas poly(A) andpoly(C) are without effect. When covalently bound to agarose, poly(I), poly(U), and also poly(A) act as potent ligands for purification of interferon by affinity chromatography. Furthermore, poly(I) and poly(U) confer a significant degree of protection to interferon against thermal denaturation. Taken together, these observations point to a direct interaction of interferon with these polymers and suggest that interferon molecules have a polynucleotide attachment site. Possible implications for the concept of interferon induction are discussed.


Prescence of tadpole and adult globin RNA sequences in oocytes of Xenopus laevis. Complementary DNA transcribed from adult Xenopus laevis globin mRNA was used to assay ovary RNA from Xenopus for the presence of globin sequences by RNA.cDNA hybridization. These sequences are present at approximately the same concentration as the majority of poly(A)-containing ovary sequences. The sequences are also found at approximately 200,000 copies per cell in poly(A)-containing RNA extracted from mature oocytes. To rule out contamination of the oocytes with somatic cells, two additional experiments were performed. First, RNA isolated from ovulated unfertilized eggs, which are devoid of somatic cells, was also shown to contain the globin sequences. Second, globin mRNA was isolated from Xenopus tadpoles. Adult globin mRNA is free of the tadpole sequence and no homology was detected between adult and tadpoles globin RNA. The ovary was shown to contain tadpole globin RNA at nearly the same concentration as the adult sequences. Thus, the results cannot be explained by contamination with erythroid cells which should contain only the adult sequence. The swimming tadpole, which possesses an active circulatory system, was also assayed for the tadpole and adult globin sequences. Whereas the adult sequences are present at approximately the same concentration as in the mature oocyte, the concentration of the tadpole sequences increases at least 300-fold in the first 3 days following fertilization.


Temporal sequence of hormonal interactions during the prereplicative phase of quiescent cultured 3T3 fibroblasts. After addition of prostaglandin F2alpha (PGF2alpha) and insulin to quiescent cultured 3T3 fibroblasts a constant lag phase of 15 hr occurs before an increased rate of cellular exit from G1 is observed. The latter process follows first order kinetics, which can be quantified by a rate constant k. The temporal relationship of the interactions of PGF2 alpha, insulin, and hydrocortisone to produce alterations in the rate of exit from G1 was investigated. PGF2alpha establishes a constant lag phase and produces alterations in the rate constant k. These two effects can be partially separated by adding two concentrations of PGF2alpha at different times. Insulin fails to establish the lag phase but can stimulate the effect of PGF2alpha when added at any time after PGF2alpha. Hydrocortisone reduces the value of k when added between 0 and 3 hr after PGF2alpha. These results show that the lag phase can beseparated into temporal regions during which hormones can interact to produce changes in the rate of cellular exit from G1.


Succinyl concanavalin A stimulates and antimicrotubular drugs inhibit the synthesis of a brain-specific protein in rat glial cells. The relative synthesis of the brain-specific s100 protein increased as clonal rat glial cells, C6, progressed from logarithmic to stationary growth in monolayer culture. Drugs that disrupt microtubules, such as colchicine, vinblastine, Colcemid, and podophyllotoxin, inhibited the relative synthesis of S100 protein in stationary cultures. Colchicine (0.1 muM) caused a 50% inhibition of the relative synthesis of S100 protein whereas lumicolchicine,an isomer of colchicine that does not disrupt the microtubular system, had no effect. Succinylated concanavalin A (500 mug/ml) increased relative synthesis in logarithmic but not stationary cultures. These results suggest that signals inducing an increase in the relative synthesis of S100 protein in stationary cultures are transmitted intracellularly from the cell membrane by the microtubular network.


Separation and infectivity of circular and linear forms of potato spindle tuber viroid. Potato spindle tuber viroid can be separated into two fractions by polyacrylamide gelelectrophoresis in the presence of formamide and urea. One fraction contains predominantly circular molecules; the second fraction contains almost exclusively linear molecules. The purity of the fractions was estimated by electron microscopy of formaldehyde-denatured molecules. The length distributions of denatured circular and linear molecules were determined. Both circular and linear molecules were found to be infectious.


Low-molecular-weight peptide inhibits RNA synthesis in human leukemic and phytohemagglutinin-stimulated leukocytes and globin mRNA transcription in differentiating Friend cells. The RNA synthesis of human leukemic leukocytes and phytohemagglutinin-stimulated lymphocytes is markedly reduced by administration of a low-molecular-weight nonhistone peptide factor from calf thymus. Treatment with the factor strongly inhibits hemoglobin production and globin mRNA transcription in dimethyl sulfoxide-stimulated Friend cells without appreciably modifying the rate of cell growth. Evidence for specificity of these effects is provided by the lack of action of the factor on both growth rate and RNA synthesis of a number of nondifferentiating cell lines from various animal species. After removal of the compound, both human lymphocytes and Friend cells can be stimulated by phytohemagglutinin and by dimethyl sulfoxide, respectively, ruling out any toxic effect.


Pure and mixed erythroid colony formation in vitro stimulated by spleen conditioned medium with no detectable erythropoietin. Cells from CBA fetal mouse liver formed pure or mixed erythroid colonies in semisolid agarculture after stimulation by medium conditioned by pokeweed mitogen-stimulated mouse spleen cells. In general shape, the erythroid colonies resembled typical 7-day single or multiple (burst) colonies. However one-third to one-half contained, in addition to erythroid cells, macrophages and neutrophils and, less commonly, megakaryocytes or eosinophils. Culture of micro manipulated single colony-forming cells showed these erythroid colonies to be clones. Colony-forming cells declined in frequency with advancing fetal age, but low numbers were detectable in adult bone marrow. Assays of spleen conditioned medium in polycythemic mice failed to detect erythropoietin; the cloning system may detect a fetal type of erythropoietin-independent, erythropoietic cell since few were detected in adult marrow.


Intracellular distributions of mechanochemical proteins in cultured fibroblasts. We have used methods that have allowed simultaneous fluorescent staining of intracellular actin together with either myosin, filamin, or tubulin in normal rat kidney fibroblasts in monolayer culture. In the main portions of the cell body, the actin, myosin, and filamin are all present in two structures: in one, the three proteins are present in the same fiber bundles (stress fibers); in the other, there is a diffuse distribution of the three proteins. On portions of the cell periphery however-in the basal regions of microspikes, in ruffles, and in regions of cell-cell contact-actin and filamin are present, but myosin is severely depleted or absent. Microtubules are present in the cell body in a distribution independent of the stress fibers and are mostly absent from the cell periphery. Microspikes and ruffles are highly dynamic structures on the cell surface, and regions of cell-cell contact generally result from the association of ruffles on the two contacting cells. Therefore, the presence of filamin and actin but not myosin in these specialized regions on the cell surface, together with the recent demonstration [Wang, K. & Singer, S. J. (1977) Proc. Natl. Acad. Sci. USA 74, 2021-2025)] that pure filamin interacts with individual F-actin filaments in solution to form fiber bundles and sheet-like structures, suggest that in vivo filamin-actin interactions play an important role in the control of actin filament structure, in cell motility, and in the stabilization of cell-cell contacts.


Loss of growth control and differentiation in the fu-1 variant of the L8 line of rat myoblasts. A nonfusing variant, fu-1, of the L8 line of rat myoblasts was isolated and characterized with respect to its growth in vitro and developmental properties. Comparative analyses of density-dependent inhibition of growth, serum requirements, cell adhesiveness, colony formation in soft agar, and hexose transport in L8 and fu-1 cells support the conclusion that the fu-1 cells are transformed. In addition, fu-1, but not L8, cells promote the development of tumors in athymic nude mice. fu-1 cells also do not make increased levels of creatinekinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2) or myosin and they express an endogenous type-C virus. Both L8 and fu-1 cells express myokinase (ATP:AMP phosphotransferase, EC 2.7.4.3) activities in single cells. In contrast to fu-1 cells, the parent L8 line has increased creatine kinase and myosin after fusion and spontaneously contracts; expression of an endogenous virus could not be detected in these cells. These results suggest that loss of the ability to differentiate normally is associated with the loss of the normal control of cell division of myoblasts grown in vitro and in vivo.


Morphological differentiation of neuroblastoma cells in medium supplemented with delipidated serum. Neuroblastoma cells have been found to extend neurites when grown in a medium supplemented with delipidated fetal calf serum. Fetal calf sera from different commercial sources give rise to marked differences in the degree of this spontaneous morphological differentiation. The phenomenon can be prevented by the addition of certain fatty acids; oleic acid is especially effective. The serum-free conditioned medium from glial cells can quantitatively antagonize the effect of oleic acid, suggesting that glial factor activity could be due to components [lipids and/or macromolecular factors(s)] that are able to modify the properties of the neuroblastoma cell membrane.


Dissociation of tumor promoter-stimulated ornithine decarboxylase activity and DNA synthesis in mouse epidermis in vivo and in vitro by fluocinolone acetonide, a tumor-promotion inhibitor. 12-O-Tetradecanoyl phorbol-13-acetate (TPA), a tumor promoter, stimulates DNA synthesis in mouse epidermal cells in vivo and in vitro. This response appears to be mediated through polyamine metabolism because ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17)activity is markedly increased shortly after promoter exposure and this induction varies in magnitude according to dose and promoter potency of a series of phorbol esters. In vitro, exogenous putrescine (0.01-10 mM) results in a dose-related increase and prolongation of promoter-stimulated DNA DNA synthesis, a phenomenon noted in other systems of polyamine-mediated growth stimulation. The anti-inflammatory steroid fluocinolone acetonide (FA), an inhibitor of tumor promotion, prevents TPA stimulation of epidermal proliferation in vivo and in vitro. In vitro, FA most effectively prevents stimulation of DNA synthesis when applied is not required. Paradoxially, FA potentiates the increase in ornithine decarboxylase activity after TPA administeration both in vivo and in vitro. Furthermore, the inhibition of TPA-stimulated DNA synthesis by FA in vitro can be reversed by exogenous putrescine. These results suggestthat FA exerts its antipromotion effect by reducing the sensitivity of the cell to polyamines or by reducing intracellular polyamine levels.


Stable association of the human transgenome and host murine chromosomes demonstrated with trispecific microcell hybrids. Trispecific microcell hybrids were prepared by transferring limited numbers of chromosomes from a human/mouse gene-transfer cell line to a Chinese hamster recipient line. The donor cells employed were murine L-cells that stably expressed the human form of the enzyme hypoxanthine phosphoribosyltransferase. Karyotypic, zymographic, and back-selection tests of the resulting human/mouse/Chinese hamster microcell hybrids provided strong genetic evidence for a stable association of the human transgenome with host murine chromosomes in stable gene-transfer cell lines. This association, which may represent physical integration of the transgenome into the host cell genome, occurred at multiple chromosomal sites.


Rapid speciation and chromosomal evolution in mammals. To test the hypothesis that population subdivision into small demes promotes both rapid speciation and evolutionary changes in gene arrangement by inbreeding and drift, we estimated rates of speciation and rates of chromosomal evolution in 225 genera of vertebrates. Rates of speciation were estimated by considering the number of living species in each genus and the fossil record of each genus as well as information about extinction rates. Speciation rate was strongly correlated with rate of chromosomal evolution and average rates of speciation in lower vertebrate genera were one-fifth those in mammalian genera. Genera with high karyotypic diversity and rapid speciation rates may generally have small effective population size (Ne), whereas large Ne values may be associated with karyotypically uniform genera and slow rates of speciation. Speciation and chromosomal evolution seem fastest in those genera with species organized into clans or harems (e.g., some primates and horses) or with limited adult vagility and juvenile dispersal, patchy distribution, and strong individual territoriality (e.g., some rodents). This is consistent with the above hypothesis regarding the evolutionary importance of demes.


Overexpression of an unstably inherited gene in cultured mouse cells. The specific activity of hypoxanthine-guanine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) is increased up to 58-fold in unstable gene transferents produced by the transfer of cell-free chromosomal material from one mouse L cell line to another; the specific activity of this enzyme returns to normal levels when the transferred gene becomes stabilized. This phenomenon, which is not observed in comparable heterospecific transfers, may be an effect of gene dosage (multiple copies of the transferred genetic fragment in the unstable gene transferents), or it may represent an escape of the unstably inherited gene from the normal regulatory mechanisms of the recipient cell.


Heterogeneity of nephritic factor and its identification as an immunoglobulin. Complement C3 nephritic factor (NeF) produces alternative pathway-meciated C3 cleavage by binding to and stabilizing the alternative pathway C3 convertase, C3bBb. Some studies have suggested that NeF is an immunoglobulin, while others conclude that it is a distinct serum protein. The heterogeneity of NeF was evaluated by electrophoresis and isoelectric focusing of NeF-containing serum followed by hemolytic demonstration of NeF activity in agar gel. With each method, diffuse cathodal zones or multiple bands of hemolysis developed, which revealed remarkable variations in patterns from patient to patient. NeF activity was absorbed by and eluted from insolubilized antibody to Fc and Fab fragments of IgG. Immunoabsorption of six NeF-containing sera with insolubilized anti-kappa and anti-lambda light chain antisera revealed that NeF had kappa antigenic determinants in three, lambda antigenic determinants in one, and both kappa and lambda antigenic determinants in two. These data indicate that NeF is an oligoclonal immunoglobulin. Because NeF binds to the alternative pathway C3 convertase, C3bBb, we suggest that it is an antibody to a conformational antigen of the C3-factor B complex, and thereby stabilizes this complex.


Antibodies to tubulin in normal nonimmunized animals. Sera of normal nonimmunized rabbits, pigs, calves, and humans contain tubulin-reactive antibodies. Usually, low amounts of antibodies against tubulin of the IgG class (2.5-4 mg/100 ml of serum from nonimmunized animals) were isolated. Anti-tubulin antibodies were also produced by injecting pig tubulin in complete Freund's adjuvant into rabbits. Slightly higher amounts of anti-tubulin antibody were isolated from sera of immunized rabbits (7 mg/100 ml of serum). The cytoplasmic network of microtubules of Tcc 36 mouse cells in culture was not clearly stained by natural anti-tubulin antibodies, but dense staining of the centrosphere was observed. In contrast, induced anti-tubulin antibodies densely stained cytoplasmic microtubular networks. Vinblastine-induced tubulin paracrystals were equally stained by natural and induced anti-tubulin antibodies.


Inhibition of human platelet thromboxane synthetase by 9,11-azoprosta-5,13-dienoic acid. The synthetic prostaglandin analog 9,11-azoprosta-5,13-dienoic acid (azo analog I) has been found to be a potent inhibitor of human platelet thromboxane synthetase by three independent analytical methods: electron-capture gas chromatography, radioisotopic thin-layer chromatography, and radioimmunoassay. In the presence of azo analog I, human platelet aggregation induced by either the prostaglandin endoperoxide PGH2 or arachidonic acid was antagonized. The addition of azo analog I shifted the transformation of endoperoxides away from thromboxane synthesis and toward prostaglandin E2 synthesis. The specificity of azo analog I is demonstrated by its selective inhibition of the second wave of either ADP- or epinephrine-induced platelet aggregation. These data indicate that PGH2 must be converted to thromboxane A2 in order to induce human platelet aggregation.


Neurophysin biosynthesis in normal rats and in rats with hereditary diabetes insipidus. When [35S]cysteine was injected adjacent to the supraoptic nucleus (SON) in rats, it was rapidly incorporated into proteins in the SON. The [35S]cysteine-labeled proteins extracted from the SON were separated by isoelectric focusing on polyacrylamide gels. Twenty minutes after the injection of [35S]cysteine, two major labeled peaks (pI = 5.4 and 6.1) were found in the SON of normal rats; Brattleboro rats had only one major labeled peak (pI = 5.4). One hour after the injection, four major radioactive peaks were found in the SON of normal animals (pI = 5.1, 5.4, 5.6, and 6.1). Animals with diabetes insipidus had only two major labeled proteins (pI = 5.1 AND 5.4). Twenty-four hours after normal rats were injected with [35S]cysteine, all of the labeled peaks described above, except for the one with pI = 5.1, had decreased markedly in size and a small amount of labeled protein with pI about 4.8 was present in the SON. After 24 hr the posterior pituitary of normal animals contained two [35S]cysteine-labeled proteins with pI = 4.6 AND 4.8. The pituitaries of Brattleboro rats had only the pI = 4.6 labeled protein. These pulse-chase data, with data we have presented elsewhere, indicate that the vasopressin- and oxytocin-neurophysins are synthesized as parts of separate precursors (pI = 6.1 and 5.4, respectively). These precursors are converted into at least two intermediates (pI = 5.6 and 5.1) which, in turn, yield the vasopressin-neurophysin (pI = 4.8) and the oxytocin-neurophysin (pI = 4.6).


Active touch exploration of extrapersonal space elicits specific electrogenesis in the right cerebral hemisphere of intact right-handed man. Language and analytic processing are currently thought to be represented in the left hemisphere, whereas spatial and holistic processing would involve primarily the right hemisphere in man. An experimental paradigm for engaging the nonlanguage hemisphere (generally the right) is described. This involves active touch exploration with the index finger to identify the orientation of a ridge with respect to the subject's body. The task is compatible with the electronic averaging of transient event-related cerebral potentials recorded from the intact scalp. A consistent positive electrogenesis of 1-5 muV and about 0.5-1.5 sec in duration was recorded over the nonlanguage hemisphere, regardless of whether the left or the right index finger performed the tactile scanning. The lateralized specific electrogenesis did not extend to the midline, and it is to be differentiated from the decision P300 component. These findings provide a new procedure for analyzing, in intact man, measurable focal potentials associated with unique processor subsystems during cognitive behavior. The method will make it possible to investigate the dynamic distribution of processing tasks between the two hemispheres in normal man in whom the commissural integration is normal, thereby adding to the data collected on patients with unilateral brain lesions or with surgical transection of the corpus callosum.


Further appraisal of antibodies to "leukemia" associated antigen in sera of plasmapheresis donors.


Effectof MgATP on stiffness measured at two frequencies in Ca2+-activated muscle fibers. The stiffness of skinned crayfish single muscle fibers was continuously monitored at two frequencies. The length of the fibers was oscillated by the sum of two sine waves (5 Hz and 100 Hz) of small amplitudes. In saline containing saturating amounts of Ca2+, the stiffness ratio (5 Hz:100Hz) was constant as the MgATP (substrate) concentration was raised from 0 to 2 mu M, then it decreased with a further increment in MgATP. The systematic decrease in the stiffness ratio in MgATP above 2 mu M indicates the presence of faster transitions in the cross-bridge cycle. This dependence of the stiffness ratio on MgATP is predictable if we use the two-state model of A. F. Huxley (1957) with a modification, in which MgATP promotes the dissociation of the attached cross-bridges.


HLA typing of leukemic cells and lymphoblastoid cell lines: effects of non-HLA antibodies in common typing sera. Several laboratories have recently observed that common HLA typing sera contain antibodies to various nonHLA antigens, including leukemia-associated antigens and normal platelet, granulocyte, or B-lymphocyte-specific alloantigens. In order to study the possible effects of these antibodies on HLA typing data in leukemia, several of these sera were adsorbed with HLA typed platelets, purified B-lymphocytes, cultured lymphoblasts, or mononuclear cells from patients with active leukemia of various types, and retested for residual activity against previously reacting cells. The results indicate that many of the reactions of leukemia cells to HLA typing sera represent reactions to nonHLA antibodies, many of which are directed against antigens common to cultured lymphoblasts, leukemia cells of several types, and normal B-cells. In the absence of family studies or prior serum adsorption, caution should be used in interpretation of all data related to HLA antigens in leukemia.


HLA and association with malignancy: a critical view.


HLA antigens on human peripheral lymphocytes and spleen of malignant lymphoma and other cancer patients.


HLA-A9 and survival in acute lymphocytic leukemia and myelocytic leukemia.


Histocompatibility antigens in adult acute leukemia.


HLA associations with acute myelogenous leukemia.


Combined therapy of osteosarcoma: preoperative irradiation, surgery, and chemotherapy. The rationale for prebiopsy and preoperative irradiation in a multimodal approach to treatment of osteosarcoma is presented. Six patients with osteosarcoma underwent preoperative irradiation, amputation, and elective chemotherapy. Five of these also received prebiopsy irradiation: three survive without metastases at 29, 36, and 56 months, with no therapy for 10, 16, and 37 months, respectively; two patients died at 6 and 19 months of pulmonary metastases which appeared at 2 and 10 months, respectively. The latter two did not receive prebiopsy irradiation. Another patient, whose pulmonary metastasis regressed at 6 months with adriamycin and was later resected, died of cardiac failure at 59 months without evident metastasis. Immunologic aspects of the disease are also discussed.


Radiotherapy-induced rib osteosarcoma after successful treatment of lung cancer. Radiation-induced osteogenic sarcoma is recognized as a long-term complication of radiation therapy. The authors report a case of rib osteosarcoma which developed after successful treatment of adenocarcinoma of the lung.


Leucocyte alkaline phosphatase elevation in human acute leukaemia derived cell lines cultured in diffusion chambers. Leucocyte alkaline phosphatase (LAP) was histochemically detected in 7 to 18% of cells in tissue culture lines derived from the peripheral blood or bone marrow of each of 5 patients with untreated acute myelogenous or monomyelogenous leukaemia and in 30% of the cells in a clonal line of a rat promyelocytic leukaemia. Following transfer to diffusion chambers intraperitoneally implanted into total body irradiated rats, LAP levels were detected in up to 92% of human and 80% of rat leucocytes. There was no associated morphologic differentiation. In rat leukaemia cells peroxidase and myeloid specific esterase also increased from tissue culture levels. Return of cells to tissue culture decreased enzymes to pre-implant levels. Addition of plasma or peritoneal fluid from irradiated rats to cells in tissue culture again induced LAP. In contrast, LAP was not increased under these conditions with cell lines derived from patients with acute lymphatic leukaemia, or Sezary cell leukaemia. These studies indicate that a humoral factor in peritoneal fluid and plasma of irradiated rats increases LAP in human as well as rat leucocytes.


Hodgkin's disease and acute leukaemia. A clinical and cytogenetic study. Three patients developing acute myeloid leukaemia after treatment for Hodgkin's disease are reported. They appeared among 153 patients treated since 1971. All three patients were treated with high-voltage radiation of large target volumes as well as multiple-drug chemotherapy. In two of the patients chromosomal analyses of the leukaemic bone marrow cells were performed by modern banding technique. Chromosome abnormalities were found in both patients. The value of cytogenetic analysis with the new staining techniques for elucidating the mechanism of leukaemogenesis in Hodgkin's disease is discussed.


Mitotic activity of the granulopoietic precursor cells in the peripheral blood in chronic myeloid leukaemia. The mitotic indices (MI) of granulopoietic precursor cells in peripheral blood and bone marrow were studied in 38 patients with typical chronic myeloid leukaemia (CML) in the chronic phase. The MI in the peripheral blood were very low, in the median 0.07%, compared to those in the bone marrow with a median of 1.07%. The blood MI were significantly increasing with raising WCC and the values of the MI above the median were combined with short survival times. The bone marrow MI were negatively correlated to the blood MI and it is suggested that this is a sign of an increased exchange of cells between bone marrow and blood.


Why SCDENPAC???!!!

Why SCDENPAC???!!!


Mission possible. Achievement through certification.


President's message.

President's message.


Treating the avulsed tooth.

Treating the avulsed tooth.


Extraction or non-extraction the active role of the general practitioner. Part 4: serial extraction.


ADA role at the local level: excellent support for the asking.


IRC notes.

IRC notes.


My personal reflections as a dental examiner.


Happy in dentistry?

Happy in dentistry?


How to motivate a patient.

How to motivate a patient.


A needed alliance--dentistry and pharmacology.


Modernize--for practice growth and increased earnings.


Effective communication between dentist and pharmacist.


Community, hospital, and research pharmacists involved in dental health problems.


Schlerochorioretinal biopsy: an approach to tissue diagnosis and study of choroidal and retinal disease.


Pars planitis.

Pars planitis.


Ocusert in Christchurch.

Ocusert in Christchurch.


Epiphora.

Epiphora.


Full-thickness eye wall resection: technique, case descriptions, and histological findings.


Facial palsy, a surgical approach.

Facial palsy, a surgical approach.


Post-herpetic neuralgia, treatment and prevention.


Pattern evoked cortical potentials employing a television pattern stimulator.


Treatment of senile disciform macular degeneration.


Diabetic maculopathy.

Diabetic maculopathy.


Vitrectomy instrumentation.

Vitrectomy instrumentation.


Pars plana vitrectomy in Auckland.

Pars plana vitrectomy in Auckland.


Experiences with vitrectomy.

Experiences with vitrectomy.


The current state of retinal surgery.

The current state of retinal surgery.


Palmerston North Low Visual Aid Clinic.

Palmerston North Low Visual Aid Clinic.


Retinitis pigmentosa--a review.

Retinitis pigmentosa--a review.


Low vision care in Christchurch.

Low vision care in Christchurch.


The pars plana approach in the treatment of anterior segment diseases.


A review of cases of congenital cataract treated surgically.


A simple method of cryoextraction for the Third World.


Simultaneous bilateral cataract extraction.


Long term results of trabeculectomy.

Long term results of trabeculectomy.


Presidential Address: retinal vein thrombosis.


Neuroleptanalgesia for cataract extraction.


Medical center teams up against cleft lip, palate.


Fraudulent insurance claims a felony.

Fraudulent insurance claims a felony.


Pseudoventricular aneurysms.

Pseudoventricular aneurysms.


Primary adenocarcinoma of the vermiform appendix: report of five new cases and review of the literature.


The diagnosis of TMJ disorders using laminographic radiography.


The need for maxillofacial prosthetic treatment.


Interest in blood pressure screening and incidence of blood pressure measurement among Virginia dentists.


Haematology in PNG revisited.

Haematology in PNG revisited.


A review of 700 bone marrow aspirations in Papua New Guinea. A retrospective survey of 700 marrow examinations in Papua New Guinea in a 2 1/2 year period has been carried out. Over half of the total came from the Port Moresby General Hospital. Anaemia and splenomegaly were the commonest indications. A disturbing proportion of the specimens were unsatisfactory for interpretation. Hypercellular marrows with erythroid hyperplasia were very common. Iron stores were absent or nearly absent in almost half of the evaluable specimens; this proportion rose to over 95% amongst pregnant or post-partum women with anaemia. Other relatively frequent findings included: a combination of features consistent with hypersplenism; mild degrees of eosinophilia and/or plasmacytosis; and mild degrees of megaloblastic changes. Haematological malignancies were found in over 10% of evaluable specimens. Of 611 assessable marrows from Melanesians, only 11 (1.8%) were entirely normal, but another 151 (24.7%) contained only minor abnormalities.


Potentially dangerous group O blood: incidence of anti-A and anti-B haemolysins in group O blood in Port Moresby. Samples of serum from 322 group O donors taken at random at Port Moresby, were examined within 24 hours of collection of blood by a simple screening test for haemolysins; 101 (35.31%) of 286 Papua New Guinean (PNG) group O sera and 16 (44.44%) of 36 European sera containing either anti-A or anti-B haemolysins. There were no differences in the extent to which A or B cells from Europeans or Papua New Guineans were lysed by these sera.


Hereditary ovalocytosis in Melanesians.

Hereditary ovalocytosis in Melanesians. A distinctive type of hereditary ovalocytosis has been found in Papua New Guinea and a few areas of Southeast Asia. Its main features include a high incidence among tropical lowland dwellers, autosomal recessive inheritance, specific depression of a number of red cell antigens, a characteristic morphology in blood films, and an effect on the erythrocyte sedimentation rate. Speculation has occurred as to whether the high incidence of ovalocytosis in malarious areas may be related to a selective advantage possessed by ovalocytics with regard to severe malaria. Preliminary data tend to support this hypothesis, but the evidence is not conclusive and much further work is needed.


Splenectomy: follow-up of patients in the Solomon Islands. The case histories of 19 splenectomy patients are discussed. Of these, four have died, five have had subsequent attacks of malaria, and the remainder have enjoyed good health, although only two patients have been taking regular malaria prophylaxis in this malaria endemic area. The roles of the reticulo-endothelial system and the spleen are discussed in relation to the effects of splenectomy.


Regarding cyanophilic bodies, toxoplasma cysts and ferruginous bodies.


Sputum fixatives.

Sputum fixatives.


Carcinoma of the common bile duct diagnosis by cytologic examination of T-tube drainage contents.


The false negative smear: an instrumental error?


A method for the collection and examination of the exfoliative cytology of the human female reproductive tract from menstrual blood flow-Case reports: cervical dysplasia.


The morphology of cells in effusions settled on glass. The cells of human body cavity fluids were examined by light microscopy and with a scanning electron microscope after settling on the surface of glass. Some differences in behavior of various cell types were noticed. The histiocytes, a few minutes after settling, began to spread, and thin processes later extended from their cytoplasm. Extension of mesothelial cells was observed a few hours after settling, and was not proceeded by flattening. The flattening of neutrophils occurred soon after settling, and was not followed by extension. The other cells encountered in effusion, both benign and malignant, did not change their shape even up to 12 hours after the time of settling. The differences in behavior after the settling of various cell types encountered in human effusions is discussed in relation to their biological properties.


Cytological studies in women using copper intrauterine devices.


Fiberoptic bronchoscopy in the diagnosis of lung cancer comparison of pre-and post-bronchoscopy sputa, washings, bruchings and biopsies. Fiberoptic bronchoscopy (brushings, washings and biopsies) was performed and pre- and post-bronchoscopy sputum cytologies obtained on 70 patients with histopathologically proven lung cancer. Bronchoscopy, with its associated procedures performed in 52 patients with primary bronchogenic carcinoma, was diagnostic in 41 (79%). Of all the various methods of obtaining specimens, bronchial brushing and bronchial biopsy gave the highest percentage yield (67%). However, since brush specimens could be obtained from peripheral lesions under fluoroscopic guidance, a greater number of positive specimens were obtained by this procedure (34) than by forceps biopsy (25), making brushing more useful. Pre- and post-bronchoscopy sputa were positive and thus of value in two cases when brushing and biopsy were both negative. Bronchial washing did not add significantly to the yield of positives and could therefore be eliminated as an unnecessary cost-and time-consuming procedure. Fiberoptic bronchoscopy was not helpful in diagnosing mediastinal tumors (5), lung metastases (7) and bronchial adenomas (6).


Differential diagnosis between follicular adenoma and follicular carcinoma of the thyroid by nuclear DNA determination. Distinction between follicular adenomas and follicular carcinomas of the thyroid using fine needle aspiration cytology presents a problem. We investigated whether Feulgen photometric nucear DNA determination could offer additional, usable information for differential diagnosis. Since both diploid carcinomas and polyploid, widely scattered adenomas and nodular colloid goiter are seen, we found that nuclear DNA determinations proved useful in differential diagnosis only for occasional special cases.


The accuracy and consistency of the cytologic classification of squamous lesions of the uterine cervix. The slides of 60 cases of cervical lesions in the five categories of benign inflammatory change, mild to moderate dysplasia, severe dysplasia, squamous carcinoma in situ, and invasive squamous carcinoma were reviewed on two separate occasions by two cytopathologists, nine cytotechnologists, and four cytotechnology students. Their overall concurrence of the cytologic with the tissue diagnoses was 78 per cent and was slightly higher for the cytotechnology students than for the more experienced observers. In 44 per cent of the invasive carcinomas and in 38 per cent of carcinomas in situ, there was considerable disagreement between cytologic and tissue classification partly due to the presence of inadequate material on the cytologic slides which had been selected consecutively based on the subsequent tissue diagnosis. The pathologists reproduced their own cytologic classification within one category variance in 94 per cent of the cases as compared to 92 per cent for the cytotechnologist and 86 per cent for the students. The study emphasizes the need for evaluation of laboratory performance based on routine diagnostic material in considering the accuracy and reproducibility of the procedure and in establishing quality control programs.


Microinterferometric measurement of dry weight of blood lymphocytes in hematologically normal patients and in patients with chronic lymphocytic leukemia. Lymphocytes from the peripheral blood of 20 patients with nonhematologic disorders (HN patients) and 13 patients with chronic lymphocytic leukemia (CLL) were studied. A scanning and integrating microinterferometer was used for calculation of dry weight of cells. In HN patients dry weight of lymphocytes was found to be 38.09 +/- 11.11 pg. The HN patients could be divided into three groups according to their lymphocytes' mund to be 29.79 +/- 7.99 pg. This population was uniform and resembled the "light" group of lymphocytes in HN patients. A study of the kinetics of PHA transformation of lymphocytes from both HN and CLL patients revealed a good correlation between the morphological evaluation and dry weight calculations.


Psammoma bodies of benign endometrial origin in cervicovaginal cytology. This case report illustrates a benign endometrial condition associated with a combination oral contraceptive agent in which psammoma bodies were produced. Additionally, it reemphasizes the fact that nonmalignant processes are capable of forming such structures. The presence of psammoma bodies in cervicovaginal material is uncommon and may be associated with the presence of a malignant tumor.  However, a variety of benign conditions are capable of forming these laminated, calcified bodies.  A case is reported in a 46-year-old woman who had been taking oral contraceptives for 3 years.  An ovary had been removed earlier for a benign cyst.  A psammoma body was identified in a cervical smear.  An acute inflammatory cellular exudate was present.  Also, embedded within the stroma were other psammoma bodies and dense, amorphous calcified structures.  No cellular dysplasia was noted.  These endometrial changes are thought to have been caused by the use of a combination oral contraceptive agent.  Microscopic findings are illustrated.


Primary papillary carcinoma of the prostate: report of a histopathologic, cytologic and electron microscopic study on one case. An unusual type of prostatic carcinoma is described. Histopathologic examination showed a papillary and acinar appearance. Aspiration cytology showed papillary fragments and sheets of malignant cells. The ultrastructural features of this tumor were similar to those reported for prostatic carcinoma rather than endometrial carcinoma supporting a prostatic orgin for this tumor.


Sarcoma of the vagina an unusual cytologic diagnosis. The reported case, exceptional in our oncological material, illustrates the cytologica features of sarcoma of the vagina. We believe that the diagnosis of sarcoma of the cervix or other parts of the female genital system is not difficult providing that the tumor is exfoliating cells. Sarcomatous cells should not be mistaken either with those from keratininzing epitheliomas with desquamated fiber cells or snake cells. Such differentiation should not be a problem for an experienced cytologst. In spite of the low frequency of this malignancy, the microscopical appearance of the cells is so different from the cells of routine gynecological material that when present we should, at least, suspect a sarcoma.


Mechanisms of chromatid breakage in human lymphocyte cultures. G2 banding of human peripheral blood cultures with actinomycin D and tetracycline produced chromatid breakage in lightly stained Giemsa bands, and the number of such breaks tended to increase with fixation time. Chromatid breakage due to 3H-thymidine incorporation into DNA was also localized in light bands, but the number of these breaks did not increase with fixation time. These findings suggest that modification of chromosomal protein as a result of exposure to AMD or other chemicals following DNA synthesis can result in fixative-dependent chromatid breakage of susceptible chromosomal regions, unlike breakage due to 3H-thymidine which primarily affects DNA and is not affected by fixation. Thus, chromatid breakage observed in short-term lymphocyte cultures is not necessarily evidence of mutagenicity involving DNA, but rather may be due to toxic effects on synthesis or attachment of chromosomal proteins.


Cytogenetic studies of human endometrial carcinomas by means of tissue culture. The cytogenetic studies of human endometrial carcinomas were performed using a tissue culture technique. Seventeen cases or 40.5 per cent out of 42 trials for culture could be analyzed. The mode of chromosome number was found at the diploid range in all cases, and the exact counting of the modal range revealed that the peak of the number was 46 in 75 per cent of the analyzed cases. The distributions were even both in the hypo- and hyperdiploid areas. The karyotype analyses showed that the majority of the endometrial carcinomas presented pseudo-diploid chromosomes, revealing irregular numerical alterations of each group constitution and scattered variant chromosomes with minor structural changes. Only four cases were noted to have an unclassified chromosome with marked structural aberrations. A marker chromosome was identified in only one case, whereas no common specific chromosome was noted and the histologic findings did not correlate with chromosome aberration. From our tissue culture study, carcinomas of human corpus uteri consist mainly of the cells with a pseudodiploid chromosomal constitution. It is suggested that a culture method would be a desirable procedure for the cytogenetic study.


A quick method for concentrating and processing cancer cells from serous fluids and fine-needle nodule aspirates. A quick method of concentrating cancer cells and the preparation of cytological slides from body fluids and aspirates is described, using a single Ficoll gradient and cytocentrifuge. The method eliminates the disadvantages of conventional techniques, i.e., excess contamination by red (erythrocytes) or white (leukocytes) blood cells and a scarcity of cancer cells. Because the technique is simple and requires only standard cytotechnological equipment, it can be easily adopted as an aid to diagnostic routine in cancer cytology.


Quantification of protein thiols in normal and pathological cells of the epithelium of the portio uteri.


Surface ultrastructural response of the human uterine lining epithelium to hormonal environment. A scanning electron microscopic study.


McArdle's syndrome. Fine structural changes in muscle. Two cases of McArdle's syndrome are reported. One is a "classical" example; the other is unusual because of the in vitro presence of muscle phosphorylase activity. In the latter case, the electronmicroscopic investigation confirmed the diagnosis. The fine structural changes characteristic of this disease are summarized and it is concluded that histochemical studies alone are insufficient to exclude the diagnosis of McArdl's myopathy.


The pathophysiology and methods of treatment of climacteric disorders.


Pharmacokinetic and pharmacodynamic studies on oestradiol valerianate administered orally to postmenopausal women. Peripheral plasma from four postmenopausal women was analysed for oestrone (E1) and oestradiol (E2) during 48 hours after oral intake of a single tablet of 2 mg Progynon (oestradiol valerianate). Plasma levels of E1, E2 and d-norgestrel were analysed daily in five postmenopausal women during treatment with tablet Cyclabil (oestradiol valerianate in a biphasic preparation with dl-norgestrel) in 21 dyas. Radioimmunoassay (RIA) was utilized for the quantifications. Pretreatment plasma levels of E1 were about 20 pg/ml and E2 about 12 pg/ml. It is concluded that oestradiol valerianate is rapidly absorbed from the gastrointestinal tract and converted to E1. This is reflected by plasma levels of E1 considerably higher than those of E2. The E2 levels found were in the range of those in ovulatory women, while the oestrone levels were higher.


Coagulation and fibrinolytic studies on 17-beta-estradiol and synthetic estrogens.


The prevention and management of post-menopausal osteoporosis. In 6 groups of peri- and post-menopausal women, there was an inverse relation between the urinary sediment smear maturation value and the fasting urinary hydroxyproline/creatinine ratio. Administration of ethinyloestradiol and Progynova both reduced urinary hydroxyproline into the pre-menopausal range, the fall being proportional to the starting value. Oestrogen therapy also produced a significant fall in plasma ionised calcium. In a prospective trial, oestrogen therapy prevented post-menopausal bone loss but calcium therapy was less effective. It is suggested that a high fasting urinary hydroxyproline/creatinine ratio might be taken as an indication for oestrogen therapy in post-menopausal women. In established post-menopausal osteoporosis, pre-disposing risk factors appear to be low calcium intake, malabsorption of calcium and low oestrogen status. These patients appear to represent the fast bone-losers in the post-menopausal population. The accelerated bone loss can be wholly or partially corrected by hormone replacement therapy and by calcium supplements given to those with normal absorption only. These therapies also prevent loss of height due to further crush fractures. The malabsorption of calcium is very resistant to vitamin D therapy but responds to 1alpha-OHD3. Balance data suggest that the most effective therapy may be a combination of 1alpha-OHD3 with oestrogen.


The perception of menopause in five ethnic groups in Israel. An investigation was made into the menopausal symptoms and attitudes of 1, 148 Israeli women of five different ethnic origins. The results show that, while some of the somatic menopausal symptoms are independent of ethnic origin, psychic and psychosomatic symptoms are more closely associated with this variable. Similarly, attitudes to the climacteric vary across cultural origins, especially with regard to husband-wife relationships. This study underlines the necessity of a multi-factorial, biological, sociological, psychological and anthropological approach to problems of menopause.


Epidemiology and pathophysiology of corpus carcinoma.


Endometrial hyperplasia and carcinoma: histopathology and hormonal factors.


Methods of diagnosis and staging of corpus carcinoma.


The effects of cyclical oestrogen therapy and sequential oestrogen/progestogen therapy on the endometrium of postmenopausal women.


Pregnancy in the young teenage woman.

Pregnancy in the young teenage woman. Since 1967 the number of delivered young teenage women has gradually decreased. During the same period the number of therapeutic abortions among these young women has increased, probably to a sufficient extent to explain the decreased nativity. There is no evidence in this study of any effect of more extended sex and contraceptive education in schools.


The effect of oxytocin on hypertonic saline abortion. Oxytocin was infused in 22 randomly selected pregnant women after extraamniotic hypertonic saline instillation. In another 24 pregnant women no oxytocin was infused at midtrimester abortion. There was no difference between the two groups in mean time from saline injection to expulsion of the fetus.


Dysgerminomas (seminomas) in genetic males with female phenotype. One case of gonadal dysgenesis and gonadoblastoma and one of testicular feminization. Gonadal tumors in patients with somatosexual ambiguity are rare but of considerable clinical and pathological interest. Two patients with dysgerminomas and abnormal sexual differentiation were recently treated at the Department of Gynecologic Oncology. One (Case 1) was an 18-year old girl and the other (Case 2) an unmarried woman of 58 years. In spite of their female phenotype both showed a male genotype, 46, XY. In Case 1 the dysgerminoma (or rather seminoma) originated in a gonadoblastoma in one of two dysgenetic testes but in Case 2 in one of two "feminizing testes". The clinico-pathological features of both cases will be reported and commented and the relation between the germ cell tumors, gonadal dysgenesis and the Y-chromosome will be discussed.


The influence of the bony pelvis in persistent occiput posterior position. Roentgenologic pelvimetry has been performed in 68 consecutive cases of occiput posterior position. The results point to an influence from a transverse narrowing of the pelvis or a tendency towards large dimensions. In many cases, however, no clear correlation to pelvic dimensions is found. A significant difference exists in the rate of obstetrical complications between nulliparous and parous women. The reasons for this and for the persistent OP position are discussed.


Transcutaneous monitoring of PO2 in different skin areas in the neonate and in the scalp of the fetus during labor - methodological and physiological observations. The reliability and physiological significance of continuous non-invasive PO2 recording by means of skin electrodes was studied by comparing simultaneous tracings from different skin areas in a series of 40 newborns with normal labor and birth. A new measuring equipment - the Radiometer prototype unit TPM 1 - was used. In addition, the applicability of the method to the fetus was tested in a primary series of 11 labor cases. Certain technical and physiological factors that can influence the tracings were identified.


Efficacy of primary radiation in carcinoma of the endometrium. Five-year follow up of unselected material from a specific region in the north of Sweden. A case material from the northern part of Sweden comprising all known cases of carcinoma of the endometrium during the years 1963-1969 is presented. A clinical experiment has been carried out in which 320 patients with carcinoma of the endometrium have been uniformly treated. The patients have been given primary radiation treatment, mostly with radium packing according to a modified Heyman method. About two thirds of the patients have had a prophylactic operation with total removal of the uterus and the adnexa about six weeks after the radiation treatment. Patients with contraindications to surgery have had a curettage three months after radiation treatment. The primary cure rate and the complications have been reported in a previous paper. The five-year survival rate in stage I in cases treated with radiation and surgery was 92%. The survival rate corrected for intercurrent death was 93%. The survival rate in cases treated with radiation only was 71%. The survival rate corrected for intercurrent death was 88%. The total survival rate in stage I was 85% and the survival rate corrected for intercurrent death in Stage 2 was 92%. The total survival rate in the whole case material including all stages was 75.3% and the survival rate corrected for intercurrent death in the total material was 82.8%.


Fever and parturition. An experimental study in rabbits. The hyperthermic effect of purified lipopolysaccharides (Pyrexal, Wander) was tested and analyzed in pregnant rabbits. The fever produced premature deliveries - probably caused by oxytocin, released from the posterior pituitary - in 50% of 40 tested rabbits on the 31st day of gestation. Injections of Syntocinon had a roughly equally strong effect. In control animals injection of saline did not accelerate delivery. The offspring of several animals, in which hyperthermia had been induced, were born dead. Fever during pregnancy thus can result in premature delivery and in injury to the fetus. Fever and febrile conditions occurring during pregnancy should therefore be treated as promptly and as effectively as possible.


The concept of pressure in biology and pressure transducers.


Cervical cancer. Mass screening, incidence and mortality in Finland. Since mass screenings were started in Finland, the incidence of cervical cancer has dropped by about 50 per cent. In the age groups 25-60 the decrease has been two thirds. Moreover, there has been a similar decrease in mortality in the younger age groups, in particular. All risk groups are not covered by the screening program, however. Cervical carcinoma is still a socio-medical and clinical problem particularly among elderly women.


Mass screening in Sweden for cancer of the uterine cervix. Results and epidemiologic effect. The mass screening program in Sweden for cancer of the uterine cervix, which was started in 1964, is now almost nation-wide. Approximately a quarter of a million women are screened every year. The attendance varies between 55 and 90%. Approximately two per cent of the screened female population is invited to further examination or treatment. The yield through the mass screening program varies between 3.5 and 10 positive cases per 1000 examined women. The incidence of cancer of cervix is decreasing. This is most evident in those counties, which have been carrying out the screening program for about ten years. The stage distribution in cancer of the cervix has not been changed by the screening program. Mortality in cancer of the cervix is unchanged. There has been an enormous increase in the number of diagnosis of cancer in situ of the cervix, which is a difficult practical problem.


Legg-Calvé-Perthes' disease. Radiological results of treatment and their late clinical consequences.


Microvascular supply of skeletal muscle fibres. A microangiographic, histochemical and intravital microscopic study of hind limb muscles in the rat, rabbit and cat.


Direct analysis of volatile organic compounds produced by fungi. A gas chromatographic head-space technique has been developed for the analysis of volatile organic compounds produced by fungi. The method described is useful for establishing the pattern of volatile compounds emitted by an organism and for following the time course of production of volatile metabolites. Many of these volatile products are physiologically active and influence the growth and development of the same or other organisms.


Intake system using glass ampoules for gas chromatographic analysis of volatile compounds of biological origin. A gas chromatographic intake system using 1 ml glass ampoules is described. Examples of analyses of gases and volatile organic compounds produced by soil and soil organisms incubated in the ampoules are given. The gas chromatographic system was used to analyze permanent gases produced by germinating Fusarium conidia and by an agricultural soil as well as to study the respiration of Panagrellus nematodes. A comparison of the gas chromatograms of volatile organic compounds present in a beech forest soil and an agricultural soil indicates that the chromatograms represent "finger prints" of the two soils. Results obtained with the intake system described are compared to those obtained using a conventional head space technique.


Pyrolysis gas chromatography -- a potential technique for characterization of complex organic material. A pyrolysis gas chromatography (PGC) technique is described and various pyrolysers discussed. Results from analyses of synthetic polymers and organic salts are given. The influence of temperature rise time, pyrolysis temperature, pyrolysis time and sample size is considered. Pyrolysis studies on microorganisms are described various ways of improving the technique are considered.


Pyrolysis gas chromatography of microorganisms. Influence of various pyrolysis parameters on the yield of volatile organic products. Bacteroides fragilis was analysed by pyrolysis gas chromatography (PGC). The influence of temperature rise time, pyrolysis temperature and pyrolysis time on the yield of volatile organic pyrolysis products was studied. The use of short pyrolysis time (8 msec) and a high pyrolysis end temperature (1300 degrees C) was found to provide a high yield. In consecutive analyses of the test organism, under the pyrolysis conditions indicated, the standard deviation of the total yield of volatile organic products was +/- 7%. The pyrolysis technique described suggests that few secondary reactions of the pyrolysis fragments occur.


High-pressure liquid chromatography as a tool for determination of antibiotics in biological fluids. The toxicity of some antibiotics used today necessitates rapid, specific and accurate determinations of antibiotic concentrations in biological fluids. Microbiological assays do not fulfill these needs and new procedures have recently been developed, for instance, fluorimetric assays, radioimmunoassays and radioenzymatic assays. However, these techniques have not been generally applicable to various antimicrobial agents. - The technique for high-pressure liquid chromatography (HPLC) has recently been applied to determination of antibiotics in biological fluids. The methods involve extraction of drug from the biological samples, separation by HPLC and detection by ultraviolet spectrophotometry of fluorimetry. Results obtained with tetracycline, amphotericin B, and cephalothin show that this procedure meets the demands for rapid, specific and accurate monitoring of antibiotic concentrations in body fluids. Because of its versatility, the HPLC technique seems to be applicable to the determination of a variety of antibiotics and other drugs in clinical and experimental medicine.


Cancer in Malmö 1958-1969. An autopsy study.


Local sympathetic reflex mechanism in regulation of blood flow in human subcutaneous adipose tissue.


3H-TDR labelling of osteoprogenitor cells after 226RA incorporation in mice. The time course of 3H-TDR labelling index of osteoprogenitor cells and the doses in endosteum of lumbar vertebra and distal femoral epiphysis were autoradiographically determined in young female mice after single injections of 19.7 and 55.9 micronCi/kg body weight of 226Ra. The selected bone areas were examined in animals killed 2 hours to 28 days after the injection of nuclide. It was ascertained that changes in the relative labelling index are depending on the absorbed doses of alpha radiation. The possible relevance of these experimental findings for the explanation of the osteosarcoma induction and localization is discussed.


Animal disease information processing. Epidemiologic analyses of the feline urological syndrome.


Ethics in dental practice: doctor and patient.


Stress in dental practice: a personal account.


Dental treatment of cerebral palsied patients.


Endodontic treatment and the risk of subacute bacterial endocarditis.


Dentistry as a later career choice.

Dentistry as a later career choice.


Ethics of the dental profession: the profession and the public.


Our Brazilian adventure.

Our Brazilian adventure.


Dental auxiliary education.

Dental auxiliary education.


The bookshelf.

The bookshelf.


A world of contrast and transition: Papua New Guinea.


Hand-mirror cell leukemia, a new clinical and morphological variant.


Blast crisis of chronic granulocytic leukemia. Morphologic variants and therapeutic implications. Chronic granulocytic leukemia (CGL) terminates in a disease similar to acute leukemia. Except for a study indicating an increased response rate to the drugs, vincristine and prednisone, therapy of this terminal phase has been universally disappointing. We have studied the bone marrows and clinical courses of 67 patients in the terminal phase of CGL to discern if any parameters were associated with an increased response rate or survival. The results of this study indicate that patients who have a lymphoblastic morphology or hypodiploid cytogenetics in the terminal phase respond better to treatment with the combination of vincristine and prednisone than those with myeloblastic morphology or hyperdiploid cytogenetics. Response rate and survival are significantly increased in those with lymphoblastic morphology. Recognition of the heterogeneity of the terminal phase of CGL may dictate specific therapeutic modalities.


A balanced smile--a most important treatment objective.


Autogeneic and allogeneic tooth transplants in the treatment of malocclusion.


A photographic study of the soft-tissue profile of the Negro population. The present investigation was undertaken to compare the Ricketts, Steiner, and Holdaway soft-tissue values to the Negro individual. The study involved the photographs of more than 1,000 North American Negroes, (500 males and 500 females). One-hundred of the most attractive were selected by a group of judges of different social status levels. In this group fifty male and fifty female soft-tissue profile analyses were performed. The analyses considered were Ricketts' esthetic plane, Holdaway's H line, and Steiner's S line, because they are the most often used and widely accepted. The results of the investigation showed that the black individual was more protrusive in soft-tissue profile and that the standards for white persons established by Ricketts, Steiner, and Holdaway are not applicable to the black individual. Black males were reported to be more protrusive than black females. The study utilized a line drawn from soft-tissue nasion to soft-tissue pogonion. Measurements were made from this line to evaluate the soft-tissue profile. The use of this line suggests a method for measuring the profile in millimeters.


A vertical cephalometric analysis of the human craniofacial complex. A vertical analysis involving ten linear measurements was developed to localize skeletal and dentoalveolar dysplasias. The measurements are of biologic relevance, reflecting the amount of growth harmony or disharmony to the examination and record-taking time. The vertical dimensional analysis uses the age- and sex-related University of Michigan mean values for comparative data for each measurement. Ratios were computed for a five-unit proportional analysis. Both analyses were applied to assess the vertical problems of three female patients. The analyses detected specific areas of dysplasia for each patient.


A behavioristic approach to oral hygiene.


Tip-back mechanics.

Tip-back mechanics.


Temporomandibular dysfunction in pretreatment adolescent patients.


On the reliability of cephalometric measurements and predictions.


An orthodontic dilemma: practitioner increases, patient decreases.


The practice of dentistry and the 'fourth party".


A simple method of diverting anaesthetic waste gases and vapours from the Engström ECS-2000 ventilator. A simple method of diverting anaesthetic waste gases from the Engström ECS-2000 ventilator is described. Unless special precautions are taken the digital volume measurement may be influenced; the simple solution of this problem is given.


Treatment or care.

Treatment or care.


The President's corner: a time for component action.


Dental practice.

Dental practice.


Gilles de la Tourette's syndrome. Familial occurrence and precipitation by methylphenidate therapy. Gilles de la Tourette's syndrome was independently ascertained in two male cousins once removed. Previous studies have shown familial clustering of individuals with tics, but no consistent pattern of inheritance of Tourette's syndrome has been apparent. The onset and later exacerbation of symptoms in our younger patient were associated with the administration of CNS stimulants given for excessive motor activity. The adverse effects of methylphenidate and dextroamphetamine therapy on Tourette's syndrome supports the hypothesis that this condition results from a relative excess of CNS catecholaminergic activity. Physicians prescribing these agents should inquire about the presence of tics in patients and their families.


Treatment of chronic gastric ulcer a study of the treatment recived by 135 gastric ulcer patients in a western community. A study was made of the treatment received by 135 gastric ulcer patients within one month and within six months of diagnosis. The treatment was divided into three types. Effective measures included surgery and those measures that have been shown favourably to influence the initial healing rate of chronic gastric ulcer (i.e. hospital admission and carbenoxolone sodium). Ineffective measures included those that have been shown convincingly not to accelerate ulcer healing--diet, antacids, sedatives and no treatmen at all. Anticholinergic drugs were included in the third group where the evidence is conflicting. The patient's therapeutic status was assessed one month and six months after diagnosis. Within six months of diagnosis only 32% of patients received treatment that clinical trials have shown favourably to influence the course of gastric ulcer and approximately half received treatment that has never been shown favourably to influence the course of gastric ulcer. The social class of the patients and whether they were seen by a consultant physicians or family doctor made no difference to the form of therapy received.


Who and what should be monitored?

Who and what should be monitored?


Monitoring under intravenous sedation, complications encountered and how they were treated.


The nephrotic syndrome in Papua New Guinea: aetiological, pathological and immunological findings.


Approval mechanisms for continuing education courses in pain and anxiety control.


A cheap oral therapy for Paget's disease of bone. Nine patients with painful Paget's disease of bone were treated for 200 days with a drug combination designed to elevated plasma calcium, hence stimulating the production of endogenous calcitoning and suppressing that of parathyroid hormone. This combination was oral calcium, a thiazide diuretic, a low phosphorus diet and aluminium hydroxide. Eight of the nine patients experienced sustained pain relief after 20--70 days. The mean plasma alkaline phosphatase (expressed as a percentage of the pre-treatment level) commenced to fall after 30 days of treatment and at 120 days was 58% of the pre-treatment level; this fall was sustained at 200 days. There was a mean rise of 0-08 mmol/l in plasma calcium; there was no significant change in plasma inorganic phosphorus or plasma creatinine. In view of the extremely low cost of this drug combination and its lack of side-effects, it is suggested it be considered as a treatment for Paget's disease of bone.


A comparison of oral theophylline and oral salbutamol in exercise-induced asthma. Ten patients with exercise-induced asthma were premedicated with oral salbutamol and oral theophylline on separate occasions before performing a standardised exercise test. Although both agents produced bronchodilatation, reflected by increases in peak expiratory flow rates (PEFR) at rest, they were generally ineffective in preventing an abnormal post-exercise fall in PEFR. Only one patient was afforded protection by salbutamol and another two patients by theophylline.


Myocardial ouabain content and susceptibility to ouabain cardiotoxicity associated with circulatory volume overload in the dog. The influence of circulatory volume overload on the myocardial uptake of ouabain and on cardiotoxicity was studied in the unanaesthetised dog with aorto-caval fistula. One hour after tritiated ouabain (0-02 mg/kg IV) both ventricles and atria contained more ouabain than did those of normal dogs (left ventricle (LV), 166+/-23 (SD) ng/g vs. 97+/-19 ng/g, P less than 0-001) while concentrations in skeletal muscle, liver, kidney and plasma were not different in the two groups. In other experiments ouabain was infused to cardiotoxicity (7-5 microgram/kg followed by 3 microgram/kg/min). Cardiotoxicity occurred earlier in dogs with fistula than in normals (16-5+/-2-7 min vs. 24-1+/-2-4 min, P less than 0-001). Ouabain concentrations in myocardium were not different (LV, 434+/-58 ng/g, vs. 442+/-42 ng/g) while concentrations in liver and kidney were less in those with fistula (181+/-35 ng/g vs. 278+/-69 ng/g, P less than 0-001; 1422+/-189 ng/g vs. 2747+/-479 ng/g, P less than 0-001). Average content of skeletal muscle was also less, in proportion to administered dose. The increment in myicardial ouabain content associated with aorto-caval fistula appears to be physiologically active and hence is presumably specifically bound to the digitalis receptor. The observations in this model suggest the possibility of augmented cardiac glycoside uptake in some clinical cardiac diseases.


The use of non-activated prothrombin concentrate in the management of haemophilia A with factor VIII antibodies. Three children with haemophilia and antibodies to factor VIII were treated with a non-activated prothrombin concentrate (Prothrombinex) for 12 bleeding episodes. There was clear clinical response and joint aspirations were performed after infusions of phothrombinex in a dose of 30--50 factor IX units/kg body weight and there was no clinical evidence of thrombosis or febrile reactions. There was a significant shortening of the activated partial thromboplastin time (PTT) at one and four hours after the initial infusion with a return to pre-infusion levels 9--24 hours after infusion. The shortening in the PTT was less marked in subsequent infusions. There were no changes in the level of factor VIII procoagulant activity, factor VIII related antigen or factor VIII antibodies after the infusion. In two patients platelet function studies were unaltered by the infusion and in one patient procoagulant levels of factor II, IX and X were no greater than expected from the infusion. We conclude that infusions of non-activated prothrombin concentrates are clinically effective in the treatment of children with haemophilia and factor VIII antibodies but the mechanism of action is unknown.


Erythromycin jaundice: diagnosis by an in vitro challenge test. A 53-year-old housewife who had developed severe cholestatic hepatitis following the administration of erythromycin estolate therapy two-and-a-half years previously, was studied by an in vitro "challenge" test in which peripheral venous lymphocytes were cultured in the presence of erythromycin estolate, erythromycin stearate and erythromycin base. Evidence of blastogenesis was observed in response to erythromycin estolate, but not to erythromycin stearate of erythromycin base. This test thus provided evidence that the patient was "sensitized" to erythromycin estolate without exposing her to the risk of in vivo challenge. Furthermore, in contrast to previous studies, the findings provide evidence that erythromycin estolate jaundice is mediated by immunological mechanisms.


The pyloric septum: acquired or congenital? Pyloric septa are occacionally found on radiographic or endoscopic examination of the upper gastrointestinal tract. Their frequent association with peptic ulcer disease has supported an acquired etiology. The exact pathogenesis of this unusual anomaly, however, remains unclear and its natural history is unknown.


The Laurence-Moon-Biedl syndrome in a Singhalese family. The first published occurrence of the Laurence-Moon-Biedl Syndrome in a Singhalese family is reported. Three members of a family of six with first cousin non-affected parents are described along with studies to indicate that the hypogonadism in this family can be ascribed to hypogonadotrophism. The high incidence of congenital heart disease and genito-urinary abnormalities noted by other is confirmed.


Landry-Guillain-Barré-Strohl syndrome in typhoid fever. A case is described of a 15-year-old girl who developed Landry-Guillain-Barré-Strohl Syndrome (LGBSS) on the ninth day of typhoid fever. In the absence of other known cause or association of LGBSS Salmonella typhi is believed to be aetiologically related. The patient recovered uneventfully from her neurological illness in about ten weeks from onset of symptoms.


Werner syndrome.

Werner syndrome. A case of Werner syndrome is reported. The patient was prematurely old, had skin atrophy, characteristic posterior subcapsular cataracts and prepubertal primary hypogonadism. Additional ocular features compatible with premature ageing included presbyopia, arcus seniles and diminished tear flow. Diabetes mellitus, poliosis, baldness and beak-like nose were not present.


Fertility and the physician.

Fertility and the physician. Gonadal function in both sexes is under the synergistic control of the pituitary gonadotrophins, follicle stimulating hormone (FSH) and luteinising hormone (LH) which are in turn influenced both by the hypothalamus (via the gonadotrophin releasing hormone) and by feedback signals from the gonads. There is good evidence that such feedback is mediated by steroid hormones and by a product of the germinal epithelium, termed inhibin. A logical approach to reproductive disorders involves the localization of the primary disturbance either to the hypothalamo-pituitary unit or to the gonad, on the basis of history, physical findings and the results of hormone assays. In men, the majority of disorders leading to infertility are of unknown aetiology and cannot, therefore, be treated specifically. In women, anovulation is usually readily treatable and recent studies have emphasised the usefulness of prolactin assays and of specific treatment for hyperprolactinaemia in restoring ferility. Increased understanding of the mechanisms leading to infertility may provide valuable new approaches to fertility control.


Microsurgery: a rapidly expanding field.


The College and rehabilitation.

The College and rehabilitation.


Microlymphaticovenous surgery for obstructive lymphoedema.


The vascular complications of digital replantation. A report on a series of 18 digital replantations is presented. The overall survival of digits was 13 (72%). All but one of the crush and avulsion amputations developed vascular complications. Venous insufficiency was much more commonly seen than arterial. Substantial blood loss was the rule in all digits which developed further vascular problems. A conservative approach is advocated for the majority of these complications.


Microsurgical vasovasostomy: a reliable vasectomy reversal. Optimal results of repair of a severed tube can be expected when a meticulous atraumatic microsurgical technique is based on a detailed knowledge of the anatomy and function of the tube. A reliable vas repair after vasectomy involves the avoidance of leakage or scarring in a tube of which the ends differ in internal diameter from 1 mm to 0-2 mm and in which the inner mucosal layer is difficult of access because of its solid muscular core surround. In addition, the healing will only occur without massive scarring and the nerve supply will only return if the blood supply can be retained as close as possible to the anastomosis. The technique described was first researched in the Macaque monkey and requires considerable microsurgical expertise. It has proved reliable in that 98% of the first 50 patients showed sperms in their ejaculates three months after operation, with a 62% pregnancy rate after an operation on one side only. The vasectomies had been performed up to 13 years before, and one can only conclude that a routine scrotal vasectomy should not be considered irreversible.


Vascular compression of lower cranial nerves: observations using microsurgery, with particular reference to trigeminal neuralgia. A new finding made possible by the use of the operating microscope in neurosurgery is discussed. Nineteen patients with trigeminal neuralgia have been explored, and in 14 of these vascular compression of the fifth nerve at its entry zone to the pons has been found. Relief of this vascular compression has caused cessation of pain in all these patients. In addition, one patient with hemifacial spasm, and one patient with glosso pharyngeal neuralgia, are reported; each of these also had vascular compression of the appropriate nerve causing the symptoms.


Ergonomics applied to the practice of microsurgery. Microsurgery presents special problems of visual information and fine manipulation, including tremor control. These problems can be studied usefully through ergonomics, the science of man at work, already used widely in industry. This paper presents factors affecting visual feedback, normal hand tremor, and instrument design, and refers to the process of skill acquisition and the care of surgical instruments.


The catheter team: an essential service for rehabilitating neurogenic bladders. A carefully controlled programme of intermittent catheterization provides substantially better care of the bladder than indwelling catheters during the initial period after acute spinal cord injury. It is very difficult to maintain a programme of intermittent catheterization around the clock without a small team of nursing personnel highly skilled in the technique of aseptic catheterization. the practical details of setting up a catheter team are described. Some of the results that have been associated with the establishment of such a team at the Rehabilitation Branch of the Royal Perth Hospital are presented.


Orthopaedic surgery and rehabilitation in rheumatoid arthritis. Orthopaedic surgical procedures are episodes in the continuing management and rehabilitation of the patient with rheumatoid arthritis. Well-chosen procedures give excellent relief of symptoms and deformity, and successful management is a prime example of rehabilitation requiring considerable team work from physician, surgeon, therapists, social workers and nursing staff. Team work enables the rheumatologist to be in charge of the overall management of the patient through the clinic with responsibility for general medical care, while the surgeon can take charge during periods in hospital for surgery and the immediate postoperative outpatient care. Cooperation between physician and surgeon eases each of some of the clinical burden that is at present provided by this disease.


Complete remission of metastatic malignant melanoma following immunotherapy with Bacillus Calmette-Guerin (BCG): report of a case. A complete response to BCG is described in a case of recurrent melanoma. In a woman aged 38 years, intracutaneous metastatic deposits confined to the limb of origin had occurred after excision of a malignant melanoma from the ankle, and elective groin dissection had shown two lymph nodes infiltrated with melanoma. BCG vaccine was applied to the buttock, initially by scarification and later by a multiple puncture gun. All metastases slowly regressed, and biopsy of a metastatic site at six months showed no tumour cells. The patient remains free of detectable disease 36 months after the commencement of therapy. It is inferred that BCG may facilitate remission of melanoma, perhaps by reason of antigenic cross-reactivity between BCG and surface components of human melanoma cells.


Hepatic metastases from colorectal carcinoma: an analysis of survival rates and histopathology. Out of 338 patients undergoing laparotomy and resection of a primary colorectal carcinoma, 49 (14-5%) were folnd to have liver metastases. The average age was 70 years. The median period of survival was 11-4 months. The histological grade of malignancy of the primary tumour did not appear to influence the survival rate. Compared with similar tumours in patients without hepatic metastases, the primary growth showed a significantly increased incidence of venous invasion, a higher grade of malignancy, and a more frequent origin from the right colon. When the local spread of the primary tumours was investigated it was found that one-third of them had not progressed beyond Stage Dukes A or B.


Total scapulectomy for hydatid disease.

Total scapulectomy for hydatid disease.


Osteoma involving multiple paranasal sinuses.


Comments on the histological staging of melanoma.


Malignant melanoma in situ.

Malignant melanoma in situ.