Central granular-cell tumor of the jaws (the so-call granular-cell ameloblastic fibroma). Four cases of central granular-cell tumor of the jaws were evaluated to determine the clinical parameters of the lesion, and one of these cases was examined with the electron microscope to investigate the nature of the granular cells. The average age of the patients at the time of treatment was 55 years; all four patients were women. Three of the lesions originated in the mandible, and one in the maxilla. Follow-up studies revealed no recurrences. Electron microscopic examination of one case revealed that the granular cells contained many lysosome-like particles and that these cells are identical to those found in the granular-cell myoblastoma.


Peripheral odontogenic tumor with ghost-cell keratinization. A histologic, fluorescent microscopic, and ultrastructural study.


Epithelium--connective tissue interface of oral mucous membranes. The interface between the epithelium and connective tissue of mucous membranes and skin represents a tissue site that is affected by a host of diseases which alter its normal morphologic features. Many differences exist in the normal morphologic pattern of this interface between various anatomic sites. It is essential, therefore, to have a thorough understanding of these differences before a meaningful study and assessment of pathologic changes affecting the interface can be made. This study was undertaken to establish a set of morphologic standards which can be used as a basis for interpreting pathologic changes which occur at the epithelium--connective tissue interface of oral mucous membranes.


Aneurysmal bone cyst of the maxilla.

Aneurysmal bone cyst of the maxilla.


Role of preventive endodontics in maintenance of the teeth.


Cell-mediated immune response to dog pulp tissue altered by eugenol within the root canal. After pulpal extirpation of twenty teeth in each of four dogs, these animals were primarily immunized intramuscularly with the dog's own pulp (three dogs) and saline solution with pulp (one dog). A fifth dog was used as a control for skin tests. Secondary immunizations were accomplished via the root canal every 7 days over a 28-day period. Cell-mediated skin-test reactions demonstrated less of a response to the eugenol alone than when the dog's pulp was incubated with this material. In vitro analysis of cell-mediated immune response (lymphocyte proliferation) showed a marked response to the pulp altered by eugenol as compared to the saline-treated pulp (p less than 0.004). Therefore, dog's pulp tissue became antigenically altered by eugenol material, recognized by the host, and a specific cell-mediated lymphocyte proliferation resulted.


The miniaturized x-ray machines in dentistry: structural integrity and safety of the extended-anode tubes. Two different designs of the extended-anode x-ray tube were evaluated for structural stability and safety. Force-deflection curves were determined in bending and compression modes. Although the tubes experienced similar deflection characteristics, one demonstrated several design advantages. Both machines were judged adequately safe during reversed-geometry film exposures, based on the ability of the rod anode x-ray tube to rotate in its suspension arm.


The xeroradiographic appearance of simple bone cyst of the mandible.


Five molars in a mandibular quadrant.

Five molars in a mandibular quadrant.


Impacted second, third, fourth, and fifth molars.


An unusual case of unilateral periodontal disease.


Phantom body pain in paraplegics: evidence for a central "pattern generating mechanism" for pain.


Intensive care--6. Nursing care of patients on ventilators.


Aplasia and leukaemia following chloroquine therapy. Three patients with aplastic anaemia following chloroquine therapy are described. In two, chloroquine had been administered in large doses over a long period. One of them subsequently developed acute myeloblastic leukaemia. The third received only a small dose and pancytopenia with aplasia followed three weeks after ingestion of the drug. The mechanism(s) of chloroquine-induced marrow injury is not known. A parallel to chloramphenicol-induced blood dyscrasias is drawn, but remains unproved.


Electrophysiological analysis reinnervation of transplants in the anterior chamber of the eye by the autonomic ground plexus of the iris. Fetal rat hippocampus, cerebellum, and heart were homologously transplanted to the anterior chamber of the eye of adult female recipients. After the grafts were allowed to mature in oculo, ingrowing adrenergic and cholinergic fibers from the iris were activated by changing the illumination of the retina. Electrophysiological recordings from all three types of transplants showed changes similar to those reported for effects of adrenergic and and cholinergic inputs in situ. Pharmacological studies with the transplants indicated that these electrophysiological changes were caused by activation of local muscarinic cholinergic and beta-adrenergic synapses. These data suggest that the intraocular graft is able to induce functional adrenergic and cholinergic inputs from the ground plexus of the iris and support the hypothesis that target organ influences play an important role in synaptogenesis.


Autoradiographic localization of gamma-aminobutyric acid receptors in the rat central nervous system by using [3H]muscimol. Muscimol, a structural analogue and potent agonist of gamma-aminobutyric acid (GABA), was used in its tritiated form for the autoradiographic localization of GABA receptors in the rat central nervous system. [(3)H]Muscimol ([(3)H]M) was incubated with brain slices or was injected intracortically or into intraocular brain transplants. As indicated by [(3)H]M binding and autoradiographic silver grains, GABA receptors display a laminar distribution over the cerebellar cortex, cerebral cortex, and hippocampus (in order of decreasing quantity); and a nonlaminar distribution in the caudate nucleus and substantia nigra. [(3)H]M binding was not affected by brief prior treatment of brain slices with (-)nipecotic acid or guvacine, two potent inhibitors of GABA uptake, indicating receptor binding specificity. Systemic administration of unlabeled muscimol interferred with binding of [(3)H]M binding subsequently administered in vitro, indicating that muscimol or a metabolite of it traverses the blood/brain barrier and binds to receptor sites, possibly in a manner competitive with [(3)H]M. [(3)H]M binding was greatest in the cerebellum. Quantitative analyses of the distribution of autoradiographic silver grains in the cerebellar cortex and dentate nucleus showed a general distribution of GABA receptors in the neuropil: molecular layer > granular layer > cerebellar nuclei > white matter. The highest binding of [(3)H]M occurred on the Purkinje cell somatic surface, in the basket axon formation surrounding the cell body and its axon initial segment, and somewhat less on basket and stellate cell somata. Neuroglial cells of the cortex have no [(3)H]M binding capacity; some glial cells in the cerebellar nuclei do. The role of glial cells in GABA uptake, metabolism, and GABA-receptor-mediated mechanisms remains to be clarified. The distribution of GABA receptors as indicated by [(3)H]M binding differs from the distribution of [(3)H]GABA uptake and GABA synthesizing and degradative sites.


Photoperiodic regulation of the hamster testis: dependence on circadian rhythms. The testes of hamsters exposed to short days (10 hr of light per day) regress within 13 weeks. Administration of 7.5% deuterium oxide to hamsters lengthens the period of free running circadian activity rhythms by 2.2% and prevents testicular regression during short-day exposure. This consistent with predictions derived from an external coincidence model for photoperiodic time measurement: Deuterium oxide changes phase relationships between the light-dark cycle and the circadian system, the hamster's daily photosensitive phase is stimulated with light during short days, and the testes remain large. Conservation of the period of circadian rhythms within narrow limits has adaptive significance for hamster photoperiodism and for the occurrence and phasing of the annual reproductive cycle.


Inhibition of putrescine synthesis blocks development of the polychete Ophryotrocha labronica at gastrulation. Development eggs of the polychete Ophryotrocha labronica were analyzed for polyamines during the first 6 days after fertilization. The spermine content dominated initially, but gradually decreased. It was surpassed by putrescine, which rapidly increased to a maximum on the 3rd day, i.e., at the inception of grastrulation. The spermidine content was low during the entire period. Treatment of eggs with the putrescine synthesis inhibitor alpha-methylornithine from the onset of development led to developmental arrest at gastrulation and to an abnormally low content of putrescine in the treated embryos. Methylglyoxal bis(guanylhydrazone), an inhibitor of spermine and spermidine synthesis, had no visible effect of development. Our observations strongly suggest that putrescine synthesis is indispensable in early embryonic development of Ophryotrocha.


The molecular mechanism of excitation in visual transduction and bacteriorhodopsin. An electronic theory of excitation is proposed and described in terms of a three-dimensional excited/ground-state energy surface which elucidates the photochemical and excited-state dynamics of rhodopsins. In this theory the primary action of light is to produce significant electron redistribution in the retinal, thereby generating new interactions that vibrationally excite and perturb the ground-state protein conformation. Thus, light energy causes charge redistribution in the retinal and induces transient charge-density assisted bond rearrangements (such as proton translocation) in the protein structure which is stabilized by subsequent retinal structural alteration. In this theory the isoprenoid chain of the retinal is considered a structurally pliable molecular entity that can generate charge redistributions and can be subsequently achieve intermediate conformations or various isomeric states to minimize the energy of the new protein structure generated by light. Thus, the 11-cis to all trans isomerization of the retinylidene chromophore is not considered a primary mechanism of excitation. An alternate biological role for this molecular process (which is eventually completed in all photoreceptors but not in bacterial rhodopsins) is to provide the irreversibility needed for effective quantum detection on the time scale of a neural response. Finally, it will be demonstrated that this mechanism, which readily accounts for the photophysical and photochemical data, can also be restated in terms of the Monod, Wyman, and Changeux terminology suggesting that aggregates of these pigments may function allosterically.


On the formation of protein tertiary structure on a computer. In this paper we carry out computer simulation studies of some of the factors responsible for protein tertiary structure. We show that it is possible to obtain (fold) a compact globular conformation from a sequence of amino acids consisting of only glycines and alanines. Our results indicate that glycines play a central role in stabilizing globular structures by facilitating the formation of turns and by destabilizing helical structures. Using this simple two-amino-acid representation, which serves as a control experiment, we are able to obtain a conformation that resembles the native structure of pancreatic trypsin inhibitor, as closely as any obtained previously in folding studies. However, careful examination reveals that the true chain topology has not been reproduced here or in previous studies. We suggest that the discrepancies between calculated and observed structures are more significant than the similarities. The implications of these results for the validity of models for protein folding, the use of pancreatic trypsin inhibitor in folding studies, and the possible role of glycine in the evolution of protein structure are discussed.


Respective roles of short- and long-range interactions in protein folding. A lattice model of protein is studied by a Monte Carlo simulation method. The native conformation of the lattice protein molecule is stabilized by specific long-range and short-ranged interactions. By comparing results of simulation for different relative weights of the long- and short-range interactions, it is concluded that the specific long-range interactions are essential for highly cooperative stabilization of the native conformation and that the short-range interactions accelerate the folding and unfolding transitions.


Model compounds for the T state of hemoglobin. O2 binding to a series of ferrous and cobaltous "picket fence" porphyrins is reported. N-Methylimidazole and covalently attached imidazoles gives O2 binding to ferrous porphyrins with deltaH degrees =-16.2 kcal/mol (-67.7 kJ/mol) and deltaS degrees =-40 eu (standard state, 1 atmosphere O2). Similar studies with cobaltous porphyrins yield deltaH degrees =- 12.8 kcal/mol (-53.5 kJ/mol) and deltaS degrees =- 39 eu. These values match well those of myoglobin and isolated subunits of hemoglobin and their cobalt reconstituted analogues. 1,2-Dimethylimidazole has been successfully used to mimic the presumed restraint of T state hemoglobin. In direct analogy to the decreased cooperativity shown by cobalt-substituted hemoglobin, model cobalt porphyrins show a smaller decrease in O2 affinity than the analogous iron porphyrins when the axial base is hindered. Thermodynamic data are presented. The molecular mechanism of cooperativity in hemoglobin is discussed.


Picosecond photodissociation and subsequent recombination processes in carbon monoxide hemoglobin. Excitation of HbCO by a single 6-psec 530-nm pulse results in photodissociation with a first-order constant of 0.89 X 10(11) sec-1. The kinetics of photodissociation, monitored by following absorbance changes in the Soret band at 440 nm, are interpreted as corresponding to predissociation followed by a corssing into a dissociative state. Subsequent recombination of CO with the porphyrin system and protein structural transformations were monitored by use of a continuous He-Cd laser beam spatially coincident with the photolysis and Soret interrogation beams at the sample. We find that the latter events take place in three distinct time regions, depending on exciation pulse energy and repetition rate. Exictation of HbCO with a single pulse (0.8--5 mJ) results in a relaxation to the ground state with an associative first-order constant of 5 X 10(3) sec-1. With a 100-pulse train (approximately 7.5 mJ), a new decay grows with a rate constant of 63 sec-1. For a pulse-train energy of 12 mJ or higher, a delay occurs at the onset of the second (slower) recombination.


Search for relationships among the hemolytic, phospholipolytic, and neurotoxic activities of snake venoms. Several snake venom neurotoxins are larger and more complex than the well-studied group of postsynaptic toxins exemplified by alpha-bungarotoxin. Several of these, exemplified by beta-bungarotoxin, show phospholipase A2 activity (phosphatide 2-acylhydrolase, EC 3.1.1.4) when tested in the presence of detergents. The high hemolytic activity of crotoxin, the neurotoxin of Crotalus durissus terrificus, in the presence of lecithin has been attributed to this activity. The phospholipase A2 activity of several snake venom proteins has now been compared under the physiological conditions of the hemolysis tests. It appears that only the basic component of crotoxin, B, is enzymatically active, and that its activity is not inhibited by component A under these conditions, or in the presence of deoxycholate. Phosphatidylserine is found to be digested more readily than egg white phosphatidylcholine; and also causes hemolysis in conjunction with much lower levels of crotoxin. In neither case is calcium required or stimulating. Phospholipase from Crotalus adamanteus, which is not neurotoxic, digests phosphatidylcholine more rapidly than does crotoxin, but phosphatidylserine more slowly; yet it is slightly less active than crotoxin in the hemolysis test with phosphatidylcholine, and much less with phosphatidylserine. The digestion of several phospholipids by either enzyme fails to release the expected protons in the absence of detergents at 37 degrees .beta-Bungarotoxin, highly neurotoxic, has negligible phospholipase A2 activity in the absence of detergents, and is almost nonhemolytic in conjunction with all phospholipids tested.Binding studies with (125)I-labeled compounds show that rabbit erythrocytes and ghosts have much greater affinity for crotoxin than for beta-bungarotoxin and do not bind Crotalus adamanteus phospholipase. The crotoxin complex is split in the course of binding, with only component B, the hemolytic component, becoming bound. It appears that the role of component A may be to diminish the nonspecific binding tendency of component B. Our data appear to be consistent with the concepts that affinity to membranes, particularly to specific sites on synaptic membranes, is the critical requirement for beta type neurotoxicity, and that this property, at least in some instances, has evolved from phospholipase A2 enzymes, but does not necessarily require retention and expression of enzymatic activity.


Analysis of the phiX DNA replication cycle by electron microscopy. We have monitored the development of intracellular phiX DNA forms during the course of a virus life cycle that duplicates as closely as possible the normal infection of individual cells by single virions. The viral DNA was isolated in a one-step purification procedure, and quantitative electron microscopy was performed on the samples, resulting in the following conclusions: (i) Early in the life cycle, when the cells accumulate duplex rings, two types of DNA replication intermediates are observed: a rolling circle with a single-stranded tail; and a novel form, a single-stranded circle that is partially duplex. Thus, duplex ring synthesis appears to occur in two asymmetric steps, with positive strand DNA first being processed from the tail of the rolling circle and circularized, before it acts as a template for negative strand synthesis. (ii) Late in the life cycle, as single-stranded circles are synthesized and virus particles are assembled, only one replicating intermediate is observed--the rolling circle with a single-stranded tail. At this stage, the number of rolling circles reaches a level of about 35 per cell. (iii) The net rate of polymerization in the rolling circle intermediates is about 200 nucleotides per sec.


On the physical basis for ambiguity in genetic coding interactions. We report the relative stabilities, in the form of complex lifetimes, of complexes between the tRNAs complementary, or nearly so, in their anticodons. The results show striking parallels with the genetic coding rules, including the wobble interaction and the role of modified nucleotides S2U and V (a 5-oxyacetic acid derivative of U). One important difference between the genetic code and the pairing rules in the tRNA-tRNA interaction is the stability in the latter of the short wobble pairs, which the wobble hypothesis excludes. We stress the potential of U for translational errors, and suggest a simple stereochemical basis for ribosome-mediated discrimination against short wobble pairs. Surprisingly, the stability of anticodon-anticodon complexes does not vary systematically on base sequence. Because of the close similarity to the genetic coding rules, it is tempting to speculate that the interaction between two RNA loops may have been part of the physical basis for the evolutionary origin of the genetic code, and that this mechanism may still be utilized by folding the mRNA on the ribosome into a loop similar to the anticodon loop.


Nucleotide sequence of an insertion element, IS1. PSM2, PSM1, and PSM15 are small plasmids derived from R100 by spontaneous deletions at either end of the insertion sequence IS1. These plasmids were used to identify regions neighboring IS1 as well as the IS1 DNA itself, by cleavage with EcoR1, HindIII, Hae III, Hpa II, Hha I, Hinf, and AIu I. The nucleotide sequencing results demonstrate that IS1 contains 768 bases. About 30 bases at the ends of IS1 were found to be repeated in an inverted order. The deletions occurring at the ends of IS1 were found to be due to illegitimate recombination. The hypothesis that RNA polymerase could play an important role in such recombination phenomena is discussed based on the nucleotide sequences surrounding the recombinational hot spots.


Two regions of the adenovirus 2 genome specify families of late polysomal RNAs containing common sequences. Late cytoplasmic RNAs specified by two regions of the adenovirus 2 genome (39.3--51.8 and 70.7--83.4 map units) were analyzed by size fractionation of poly(A)-[3H]RNA and subsequent hybridization to DNA fragments. Both regions encode RNAs whose sequence content exceeds the coding capacity of the region. These multiple transcripts are likely to function as mRNAs, because they are present on polyribosomes. The DNA segment 39.3--51.8 specifies 27S, 22S, and 18S RNAs. The genome sites specifying these three size classes were determined by hybridizations with seven different DNA fragments from this region of the genome. The 3' termini of all three size classes are specified by sequences near a common site, position 50.1. The 27S RNA includes sequences beginning near 39.3, the 22S RNA contains sequences from 41.0, and the 18S RNA includes sequences from approximately 45.3 on the unit genome. A second family of four RNAs is transcribed from 70.7--83.4. These 28S, 22S, 18S, and 16S RNAs have a relationship similar to the RNAs transcribed from 39.3--51.8. Sequences near the 5' ends of these four size classes are specified by different genome sites. However, the 3' termini of all four size classes were localized near map position 80.4. The synthesis of families of RNA may allow the translation of multiple polypeptides from a genome segment that has only one terminator site for mRNA synthesis.


Identification of precursor molecules to individual tRNA species from Bombyx mori. Short-labeled 4.5S RNA molecules isolated from the posterior silk gland of Bombyx mori can be separated by two-dimensional polyacrylamide gel electrophoresis into many discrete species, some of which are radiochemically pure by the criteria of RNA fingerprinting. One region of the gel contains two precursor RNAs, one to each of the known alanine transfer RNAs. Each precursor tRNAAla molecule contains all of the internal oligonucleotides present in the corresponding tRNAAla species plus new 5'-and 3'-terminal sequences. Precursor molecules to tRNA1Gly (which differ from each other in size) are contained in two other gel regions, and a fourth region contains a precursor to tRNA2Gly. Both of the transcription initiator purine tetraphosphate nucleosides are present in unfractionated tRNA precursor mixtures, with pppA- predominating over pppG-. Minor nucleotides are also present in B. mori tRNA precursors. No polycistronic tRNA gene transcripts were observed.


How many base-pairs per turn does DNA have in solution and in chromatin? Some theoretical calculations. Calculations on a 20-base pair segment of DNA double helix using empirical energy functions show that DNA can be bent smoothly and uniformly into a superhelix with a small enough radius (45 A) to fit the dimensions of chromatin. The variation of energy with the twist of the base pairs about the helix axis shows the straight DNA free in solution is most stable with about 10 1/2 base pairs per turn rather than 10 as observed in the solid state, whereas superhelical DNA in chromatin is most stable with about 10 base pairs per turn. This result, which has a simple physical interpretation, explains the pattern of nuclease cuts and the linkage number changes observed for DNA arranged in chromatin.


Translational control: recognition of the methylated 5' end and an internal sequence in eukaryotic mRNA by the initiation factor that binds methionyl-tRNAfMet. Structural analogs of the methylated 5' end (cap) of eukaryotic mRNA, such as 7-methylguanosine 5'-monophosphate, specifically inhibit both GTP-dependent binding of Met-tRNAfMet and binding of globin mRNA to eukaryotic initiation factor 2 (eIF-2). Addition of purified eIF-2 effectively relieves the cap analog-induced inhibition of globin mRNA translation. The analog competitively inhibits the function of eIF-2 and of mRNA in protein synthesis. Binding to eIF-2 of capped mRNA as well as noncapped mRNA, such as Mengo virus RNA, can be inhibited completely by free cap molecules, but much more cap is needed to inhibit binding of Mengo virus RNA. mRNA, whether or not it is capped, competitively inhibits the binding of Met-tRNAfMet to eIF-2. These results provide compelling evidence that eIF-2 recognizes mRNA. It is shown that binding of mRNA to eIF-2 is primarily at an internal sequence, and secondarily through the cap. A model for the function of eIF-2 is presented that can account for all these properties. This model can provide a molecular basis for the differential translation of mRNA species, whether or not they are capped.


Displacement-loop replication initiation sequence in animal mitochondrial DNA exists as a family of discrete lengths. The single-stranded mitochondrial DNA (mtDNA) displacement-loop initiation sequence (7S mtDNA) is hydrogen-bonded at the origin of replication in animal cell mtDNA. Analysis of 7S mtDNA from several cell sources indicates that this initiation sequence exists as a family of fragments of relatively discrete lengths. mtDNA from both mouse L cells and mouse liver has four major sizes of 7S mtDNA fragments, ranging from 500 to 580 nucleotides in length. The 5'-end region of each of these species is the same; thus, the size heterogeneity is due primarily to differences in length at the 3'-end of these molecules. By contrast, 7S mtDNA from both human KB cells and human liver exists in three major forms, ranging from 555 to 615 nucleotides in length, due to differences at both terminal regions. The mtDNA initiation sequence from Xenopus laevis oocytes also exists in at least two forms, 1350 and 1510 nucleotides in length. Thus, the maintenance of multiple forms of mtDNA initiation sequence appears to be a general phenomenon of animal cells, although the precise mechanism of synthesis or processing of these forms is variable. The sequence of 42 nucleotides at the 5'-end of 7S mtDNA from mouse L cells has been determined and found to be rich in dGuo and dThd residues, with no apparent palindromes or potential secondary structures. We thus present sequence information on the replication origin of mtDNA, as defined by the naturally occurring 7S mtDNA.


Accumulation of a slowly dissociable peptide hormone binding component by isolated target cells. The overall rate of dissociation and the fraction of bound radioiodinated human growth hormone that dissociated from hepatocytes varied with time of association. A smaller fraction of bound hormone was dissociable from isolated target cells with increased receptor occupancy and increased incubation time prior to the onset of dissociation. The inability of bound label to reequilibrate completely with the medium was demonstrated further by preincubating cells with labeled hormone prior to the initiation of saturation experiments. In such experiments, time-dependent changes in the binding properties of bound label were observed in Scatchard plots, as a result of the inability of prebound label to reequilibrate rapidly with the medium over the time course of such experiments. These data suggest that bound hormone may be distributed between at least two kinetic components. This phenomenon could be interpreted in terms of heterogeneity of sites, a slow conformational change in the receptor, or a model incorporating spatial compartmentalization of sites.


Preferential transcription of the ovalbumin gene in isolated hen oviduct nuclei by RNA polymerase B. The synthesis of ovalbumin mRNA sequences was studied in isolated nuclei from hen oviduct. Two different methods of analysis were used to distinguish in vitro synthesized from preexisting mRNA sequences: (i) Mercurated ribonucleotides were used for in vitro RNA synthesis, and the newly synthesized RNA was purified by chromatography on sulfhydryl-agarose and hybridized to radioactive ovalbumin cDNA. (ii) [3H]UTP was used to label the in vitro synthesized RNA. Hybridization to unlabeled mercurated cDNA, RNase A digestion, and subsequent purification of the hybrids on SH-agarose allowed the quantitation of newly synthesized ovalbumin mRNA sequences. Approximately 0.1% of the newly synthesized RNA was identified as ovalbumin RNA by both methods. The synthesis of ovalbumin RNA progressed during the incubation of nuclei and was sensitive to actinomycin D and low concentrations of alpha-amanitin. The preferential in vitro transcription of the ovalbumin gene (1000-fold over random transcription of the chicken genome) by RNA polymerase B (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) suggests that the specificity of in vitro RNA synthesis is retained in isolated nuclei.


Amino acid sequence of honeybee prepromelittin synthesized in vitro. Translation of melittin messenger RNA from queen bee venom glands in a cell-free system from wheat germ yielded prepromelittin. Sequence analysis of the labeled in vitro product was performed by automatic Edman degradation of the intact polypeptide as well as by analysis of some of its proteolytic fragments. Prepromelittin was shown to be composed of 70 amino acids, two of which have not been identified. The sequence of melittin is located in the COOH-terminal third of the polypeptide chain (residues 44--69). Prepromelittin starts with a very hydrophobic pre-region, probably 21 residues long, followed by a pro-part of unusual sequence, containing only alanine, proline, and acidic residues. At least three post-translational reactions are required to convert prepromelittin to mellitin.


Chromatin structure in the cellular slime mold Dictyostelium discoideum. The structure of Dictyostelium discoideum chromatin has been studied by the following techniques: electron microscopy, staphylococcal nuclease digestion, acrylamide gel electrophoresis, sucrose gradient centrifugation, and melting. The basic unit of chromatin is the nucleosome, which is a particle 98.6 A in diameter. Approximately 50% of the chromatin is protected from nuclease digestion, but this decreases when protease activity is not inhibited. The nucleosome contains 187 base pairs of DNA, including a 137-base-pair core and a 50-base-pair linker. The monomer nucleosome has an s20,w value of 11.5 S on isokinetic sucrose gradients. When the chromatin is melted, four transitions are observed, at 54.5 degrees, 66.7 degress, 74.9 degrees, and 79.7 degrees. The structure of Dictyostelium chromatin is very similar to that seen in higher eukaryotes.


Intervening sequence of DNA identified in the structural portion of a mouse beta-globin gene. The unusual electron microscopic appearance of a hybrid formed between 9S mouse beta-globin mRNA and its corresponding cloned gene segment is caused by at least one, and possibly two, intervening sequences of DNA that interrupt the mouse beta-globin gene. Such an interpretation is consistent with a paradoxical restriction site pattern previously noted in this gene and with the nucleotide sequence of that portion of the gene that spans both structural and intervening sequences. The large intervening sequence, approximately 550 base pairs in length, occurs in the structural globin sequence and immediately follows the beta-globin codon corresponding to amino acid 104. A smaller, putative intervening sequence is located close to the 5' end of the beta-globin-coding sequence but may reside beyond its initiation codon. The beta-globin gene thus appears to be encoded in two, and possibly three, discontinuous segments.


Discrete length classes of DNA depend on mode of dehydration. The length of double-stranded coliphage lambda DNA, as determined by electron microscopy using the benzyldimethylalkyl ammonium chloride technique, depends on the mode of dehydration. The freeze-dried DNA form is the longest (16.5 micron), whereas dehydration in methanol (15.9 micron) or in ethanol (three forms: 15.2 micron, 13.9 micron, and 12.4 micron) results in progressively shorter molecules. These measured lengths of the freeze-dried, methanol-dehydrated, and shortest ethanol-dehydrated forms correspond to the axial rise per nucleotide pair in the B, C, and A forms of DNA, respectively. The remaining forms of ethanol-dehydrated DNA seem to represent novel intermediary conformations of DNA. In agreement with the predicted increment, DNA exposed to ethidium bromide and freeze-dried is elongated by 39% (22.9 micron). All size classes show the same relative distribution pattern of bound Escherichia coli RNA polymerase molecules (nucleoside triphosphate:RNA nucleotidyltransferase, EC2.7.7.6), used as intramolecular markers, indicating that the dehydration-caused transitions are uniform.


Translation of rat liver fatty acid synthetase mRNA in a cell-free system derived from wheat germ. Total liver polysomes were isolated from rats that had fasted for 48 hr and that then had been re-fed a high-carbohydrate, fat-free diet for 20-24 hr. Indirect immunoprecipitation of the polysomes with purified antibody to rat liver fatty acid synthetase and deproteination on sodium dodecyl sulfate-containing sucrose gradients gave an RNA fraction which, when translated in a cell-free system derived from wheat germ, yielded a major polypeptide of apparent molecular weight 225,000 when the translation products were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The polypeptide was specifically precipitated with antibody against rat liver fatty acid synthetase and competed with unlabeled fatty acid synthetase for binding to the antibody. It was somewhat smaller than native fatty acid synthetase subunits (molecular weight 240,000). The peptide accounted for approximately 65% of the radioactive, antibody-precipitable product, the remainder being peptides in the molecular weight range 100,000-150,000. Synthesis of the polypeptide was optimized with respect to K(+), Mg(2+), and spermine concentrations. The quantity of fatty acid synthetase mRNA obtained by the above procedure and measured by translation was a function of the nutritional state of the animal. The relative activity in fasting rats compared to rats that were re-fed for 12 hr was 1:12. The data suggest that rat liver fatty acid synthetase is synthesized as intact subunits from a large mRNA molecule or molecules.


Human mitochondrial DNA: analysis of 7S DNA from the origin of replication. Heat-treated samples of human mitochondrial DNA (mtDNA) exhibited a set of three low molecular weight DNA bands in addition to the major mtDNA band when electrophoresed in polyacrylamide gels. These DNA components were seen only after heat treatment or after relaxation of the mtDNA with a restriction endonuclease. The three components were single stranded and had sizes of 550, 585, and 629 nucleotides, close to the size (600 nucleotides) estimated from contour length measurements for the 7S DNA from the D loop of human mtDNA. Hybridization of the components with restriction endonuclease fragments of known position in the mtDNA confirmed this identification. Digestion of each 7S DNA component with the restriction endonuclease Hae III produced three fragments, two of which were identical in size among the components and the third of which varied. This third fragment, shown to be from the 5' end of each component, differed in length by approximately 35 nucleotides among the components. These results suggest that human 7S mtDNA synthesis is terminated at a distinct position and that it is either initiated at one of three possible sites in the same mtDNA or that the mtDNA population consists of three subpopulations, each differing from the others by the presence or absence of a nucleotide sequence immediately adjacent to the origin of replication.


Regulation of protein synthesis in rabbit reticulocyte lysates by the heme-regulated protein kinase: inhibition of interaction of Met-tRNAfMet binding factor with another initiation factor in formation of Met-tRNAfMet.40S ribosomal subunit complexes. Protein synthesis in reticulocytes and their lysates is regulated by heme. In heme deficiency a heme-regulated translational inhibitor (HRI) that blocks initiation of polypeptide chains is activated. HRI is a protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) that specifically phosphorylates the 38,000-dalton subunit of the Met-tRNA(f) (Met) binding factor (IF), which forms a ternary complex with Met-tRNA(f) (Met) and GTP, a finding that suggests that the inhibition by HRI involves the phosphorylation of IF. We have investigated the effect of HRI in the partial reactions of protein chain initiation in which the IF-promoted binding of Met-tRNA(f) (Met) to 40S ribosomal subunits is enhanced by another initiation factor [ternary complex dissociation factor (TDF)] and AUG. The results show that HRI at very low concentrations markedly inhibits the binding of Met-tRNA(f) (Met) to 40S subunits. The inhibitory effect of HRI requires ATP. Under these conditions HRI phosphorylates only the 38,000-dalton subunit of IF. The TDF preparations not only promote the binding of the ternary complex to 40S subunits but also promote the dissociation of the ternary complex in the presence of 5 mM Mg(2+) at 0 degrees . The preincubation of purified IF alone with low concentrations of HRI and ATP does not significantly affect its capacity to form the ternary complex; however, the TDF-promoted dissociation of the ternary complex is inhibited. The nonhydrolyzable analog adenosine 5'-[beta,gamma-imido]triphosphate does not substitute for ATP. These findings suggest that phosphorylation causes a conformational modification in IF, which results in inhibition of the interaction between the ternary complex and TDF that is required for the binding of the ternary complex to 40S subunits.


Immunization of rats with polypeptide chains from torpedo acetylcholine receptor causes an autoimmune response to receptors in rat muscle. Four polypeptide chains were purified from acetylcholine receptor of Torpedo californica electric organ. Their apparent molecular weights were 64,000, 57,000, 49,500, and 38,000. Rats immunized with any of the four chains produced antibodies that crossreacted with rat muscle receptors in vivo. Specificities of anti-chain sera were evaluated in vitro by reaction with native receptor solubilized from electric organs and muscles of several species and by inhibition of this reaction with the purified polypeptide chains. The chains are immunologically distinct from one another. Antigenic determinants comparable to each chain of torpedo receptor are found in receptor from both rat and human muscle. At least part of each of these determinants is exposed on the extracellular surface of the muscle membrane. The most immunogenic determinants on native receptor are lost on denaturation to polypeptide chains. Its component peptides are much less immunogenic than native receptor, and induce antibodies of different specificity. Anti-receptor antibodies of many specificities can cause experimental autoimmune myasthenia gravis.


Construction and characterization of an Escherichia coli plasmid bearing a functional gene G of bacteriophage phiX174. In order to study the mutagenic effects of site-specific, covalent modifications of biologically active DNA, we need host cells that are permissive for any type of mutation that might be produced in vivo from the modified DNA. Specifically, we require a general, in vivo complementation system for the bacteriophage phiX174 gene G, an essential gene that we have chosen for our initial studies of chemical mutagenesis. Toward this end, we have constructed a plasmid (pphiXG) that carries a functional copy of phiX174 gene G. Three different bacterial strains that are nonpermissive for am9, a gene G amber mutant, have been transformed with pphiXG. The transformants are now permissive for this gene G mutant, but not for the gene A or E mutants that have been tested. This paper describes the construction and the biochemical characterization of this plasmid, pphiXG, and describes some of the biological properties exhibited by the pphiXG-bearing strains.


Ligand-promoted transfer of proteins between phases: spontaneous and electrically helped. A model system for the partitioning of peripheral membrane proteins into membranes by ligand binding has been examined experimentally. Both bovine serum albumin and lysozyme partition between water and 1-butanol by the addition of sodium p-toluene sulfonate at pH 2.4. The partitioning is characterized by high orders of reaction: 25 and 10, respectively. Theory indicates that these high orders of reaction need not result from cooperative ligand binding in either phase, but depend primarily upon the number N of protein sites at which the transfer-promoting ligant binds, and on the difference in free energy of formation delta F0s of the protein--ligand complexes in the two phases. From the reaction orders and the experimental values of N, 80 for albumin and 11 for lysozyme, delta F0s was calculated to be --0.5 kcal/mol (--2.1 kJ/mol) and --0.8 kcal/mol (--2.5 kJ/mol) per ligand bound, respectively. Experiments measuring the dependence on ligand concentration of the rate of protein electrophoresis across the water/butanol interface are described. These rates increase by more than two orders of magnitude as the ligand concentration approaches the critical value for partition and are inversely dependent on the number of ligant sites for the two proteins studied.


Effect of hemin on site-specific phosphorylation of eukaryotic initiation factor 2. Initiation factor 2 (eIF-2) is phosphorylated in vitro by two different cyclic nucleotide-independent protein kinases. As previously shown, a protein kinase activity that comigrates with the major casein kinase activity from rabbit reticulocytes phosphorylates eIF-2beta. In addition, a second protein kinase that specifically phosphorylates eIF-2alpha has been identified. Both protein kinase activities demonstrate cyclic nucleotide-independent activity and are not inhibited by the inhibitor protein diagnostic for cyclic AMP-regulated protein kinase activities. Phosphorylation of eIF-2alpha is almost completely inhibited by 20--35 muM hemin, whereas phosphorylation of eIF-2beta is only partially inhibited. Hemin acts by decreasing the rate of incorporation of phosphate into eIF-2alpha. The protein kinase activity that modifies eIF-2alpha has been shown to have inhibitory activity in the cell-free protein-synthesizing system, whereas the protein kinase for eIF-2beta has no effect. The identity of the former enzyme with the hemin-controlled repressor and role of hemin in the control of initiation are discussed.


Repair of depurinated DNA in vitro by enzymes purified from human lymphoblasts. Alkali-labile lesions introduced into T7 DNA by treatment with methyl methanesulfonate were removed and the DNA was repaired by incubation with DNA polymerase alpha and nuclease from a human lymphoblastoid line followed by the addition of DNA ligase. The nuclease preparation contains both apurinic endonuclease and 5'-3' exonuclease activities. Dinucleotides appear to be the first product of exonuclease action. Repair of methyl methanesulfonate-induced damage can occur by the insertion of only a few nucleotides per lesion as in vivo.


Regulation of transcription of the late genes of bacteriophage T7. The transcription program of bacteriophage T7 in vivo was analyzed by hybridizing T7 mRNAs, labeled at intervals after infection, to Hpa I restriction fragments of T7 DNA. Transcripcion of the late genes is temporally regulated: class II genes are transcribed between 4 and 16 min after infection; most class III genes are transcribed from 8 min after infection until lysis. Genes 8--10 are transcribed as both class II and class III genes. The rate of T7 RNA synthesis decreases sharply at 10 min after infection. The rapid decrease in the rate of T7 RNA synthesis and the shutoff of class II RNA synthesis were not observed in cells infected with phage defective in gene 3.5 (lysozyme). Although the decrease in the rate of T7 RNA synthesis is independent of DNA replication, the failure to shut off class II RNA synthesis normally in 3.5-- -infected cells may reflect the role of T7 lysozyme in DNA replication. In vitro, the regions of T7 DNA transcribed by the phage RNA polymerase were found to be dependent upon ionic conditions.


Thymic hormone-like restoration by human prealbumin of azathioprine sensitivity of spleen cells from thymectomized mice. Gel filtration of fresh human serum revealed that over 95% of the thymic-hormone-like activity was present in the fraction representing the total albumin and prealbumin. Further studies demonstrated that the activity resided in the prealbumin fraction; albumin was inactive. Prealbumin was isolated from Cohn fraction IV-1 of pooled human plasma by extraction  with aqueous buffer, fractionation with (NH4)2SO4, gel filtration on Sephadex G-150, and preparative disc gel electrophoresis. The final product was homogeneous by analytical gel electrophoresis was 40,000 times more active than the starting material in an azathioprine-sensitive rosette assay. Physical and chemical characterization studies showed that the isolated product was identical to authentic human plasma prealbumin. Isolation of the prealbumin fraction from sera of adult thymectomized mice revealed that the rosette activity was substantially lower than that isolated from sera of normal mice, suggesting a thymic dependence of the prealbumin activity. In vitro and in vivo bioassays of the fraction obtained prior to the final step of the purification procedure support the conclusion that prealbumin exhibits thymic hormone-like activity.


Drug-nucleic acid interactions: conformational flexibility at the intercalation site. The conformational features of the intercalation site in polynucleotides were examined. We found that, for all the crystal structures of drug-dinucleoside complexes studied thus far, two torsion angles differ from those found in A RNA (phi and chi) and that alternate sugar puckering is not a prerequisite for intercalation. This intercalation geometry, which is the basis of helix axis displacement in a polymer, would necessitate conformational changes in the adjacent nucleotides. The base-turn angle is less sensitive to the conformation of the backbone than it is to small alterations in the base-pairing geometry. We postulate that this angle is dependent on the nature of the intercalating drug.


Production a corpus luteum angiogenic factor responsible for proliferation of capillaries and neovascularization of the corpus luteum. Factors controlling the changes in the vascular pattern of the ovary that occur during the reproductive cycle have been investigated. By using the rabbit cornea, the abilities of ovarian corpus luteum and of follicles to induce neovascularization have been compared. While the corpus luteum is capable of inducing neovascularization, the follicles do not have this ability. It is therefore likely that the corpus luteum actively participates in its own neovascularization by secreting a factor that we have called "corpus leutem angiogenic factor" (CLAF).


Egg surface glycoprotein receptor for sea urchin sperm bindin. Bindin is an insoluble protein coating the sperm acrosome process and mediating the adhesion of sperm to sea urchin eggs. Milligrams of bindin have been isolated. Here we report the identification, isolation, and partial characterization of a high molecular weight, trypsin-sensitive glycoprotein fraction from the sea urchin egg surface having species-specific affinity for bindin. This glycoprotein may be the egg surface receptor for bindin. The bindin receptor was released from 125-I-labeled eggs by parthenogenetic activation of eggs with ionophore A23187 in the presence of soybean trypsin inhibitor. The receptor has an isoelectric point of 4.02 and a molecular weight in sea water greater than or equal to 5 X 10(6), suggesting that it is an aggregate. It contains 34% neutral sugars, which are galactose and mannose.


Correlation between phosphorylated H1 histones and satellite DNAs in Drosophila virilis. Drosophila virilis DNA contains satellites I, II, and III. D. novamexicana DNA contains satellite I. D. virilis H1 histone contains subfractions a, b, c, d, and e; D. novamexicana H1 contains subfractions a, b, and c. Therefore, satellites II and III might be correlated with H1d and H1e. To test the validity of this correlation, the H1 histones of polytene nuclei, which contain less than 1% satellite DNA, were analyzed. Polytene nuclei of D. virilis contain substantially decreased levels of H1c and H1e and marginally decreased levels of H1d. Polytene nuclei of D. novamexicana contain decreased levels of H1c.H1c is correlated with satellite I (common to D. virilis and D. novamexicana); H1e is correlated with satellites II and III; H1d is not correlated with any satellite DNA, because its level is virtually unchanged in polytene cells lacking detectable amounts of satellite DNA. Alkaline phosphatase digestion of the H1 histones reveals that H1c is the phosphorylated form of H1b and H1e is the phosphorylated form of H1d. Therefore, the under-replication of satellite DNAs is correlated with the decreased phosphorylation of H1 histones. In vitro, D. virilis H1 histones preferentially bind D. virilis DNAs in the progression III greater than II greater than I greater than main band, whereas D. virilis core histones do not preferentially bind any D. virilis DNA. As an extension of these results, we suggest that phosphorylated H1 histones bind D. virilis satellite DNAs in vivo and are involved in the compaction of heterochromatin.


Regulation of the self-renewal probability in Hydra stem cell clones. Hydra interstitial stem cells continuously give rise to daughter stem cells as well as precursors for nerve and nematocyte differentiation. Growth of the stem cell population is controlled by the self-renewal probability (Ps): Ps is the fraction of stem cell daughters that remain stem cells in each generation. We have determined Ps for Hydra interstitial stem cells by using a novel technique based on the cell conposition of clones. Stem cell clones were grown in aggregates of nitrogen mustard-inactivated Hydra tissue. They contain several hundred cells after 14 days of growth, including stem cells, differentiating nematocytes, and differentiating nerve cells. Clone size, size variability, and the ratio of differentiating cells to stem cells are sensitive measures of Ps. We have prepared standard curves relating these parameters to Ps, using computer simulations of clone growth. Comparisoon of the experimentally observed parameter of clones to these curves indicates that Ps decreases from 0.8 in 5- to 6-day clones to 0.6 in 10- to 12-day clones. The decrease in Ps coincides with the increase in clone size and suggest that Ps may be regulated by the density of stem cells in clones. Such a mechanism could be responsible for the observed homeostasis of stem cell populations in vivo.


Growth and maintenance of HeLa cells in serum-free medium supplemented with hormones. HeLa cells grow in a nutritionally complete synthetic medium (Ham's F12) supplemented with insulin, transferrin, hydrocortisone (aldosterone), fibroblast growth factor, and epidermal growth factor. This hormone-supplemented medium supports clonal growth, long-term cultivation, and a growth rate equal to that of serum-supplemented medium. The omission of any one of the five components results in less than maximal cell growth.


EcoRI cleavage site variants of mitochondrial DNA molecules from rats. The mitochondrial DNA (mtDNA) molecules of some rats obtained from the SASCO colony contain six EcoRI-sensitive sites while the mtDNA molecules of other rats obtained from the same source contain only four EcoRI sites. By mapping the positions of the EcoRI sites on the molecules relative to the D-loop it was determined that mtDNA molecules from all rats have four EcoRI sites in common, but all the mtDNA molecules of some rats have two extra EcoRI sites. EcoRI sensitivity of mtDNA molecules was shown to be maternally inherited. Construction of heteroduplex molecules failed to reveal evidence of gross nucleotide sequence changes associated with differences in EcoRI sensitivity.


Theoretical study of genetic variability, assuming stepwise production of neutral and very slightly deleterious mutations. Mathematical treatments are presented that enable us to compute the amount of genetic variability maintained in a finite population, assuming that mutations occur in stepwise fashion and that both selectively neutral and slightly deleterious alleles are involved. Two numerical examples show that, if very slightly deleterious mutations are prevalent, the amount of genetic variability increases much more slowly as the population number increases than is the case when all the mutations are strictly neutral.


Incomplete dosage compensation in an evolving Drosophila sex chromosome. Cellular autoradiography was used to measure relative rates of chromosomal RNA synthesis and to examine the regulatory phenomenon of X-linked dosage compensation in Drosophila miranda, a species containing two distinct, nonhomologous X chromosomes (X1 and X2). The X1 chromosome was found to be dosage-compensated, since the rate of RNA synthesis along the single X1 chromosome in males equaled that of both X1 chromosomes in females. Unlike other sex chromosomes that have been studied, the more recently evolved X2 heterochromosome exhibited regional differences in transcriptional activity when males and females were compared. The distal 10% of the X2 was not dosage-compensated, whereas the majority of an interior segment, representing 30% of the X2 chromosome's length, was found to be dosage-compensated. Our data are consistent with the idea that the evolution of X2 dosage compensation has paralleled the differentiation of the X2 sex chromosome. In addition, gene rearrangement seems to have accompanied the acquisition of a dosage-compensory mechanism in the X2.


Assignment of genes to regions of mouse chromosomes. A genetic mapping procedure, called the duplication-deficiency method, is described. This method permits the genetic location of a translocation to be determined within a linkage group without the use of recombination. By utilizing the duplication-deficiency method to define the genetic breakpoints for a series of translocations involving a given chromosome and integrating this information with their cytological breakpoints, obtained by Giemsa banding, a genetic map of the chromosomes is constructed whereby groups of loci are assigned to banded regions. Duplication-deficiency mapping and Giemsa banding analysis of the T(X;7)1Ct and T(7;19)145H translocations together with information from the c25H deletion have permitted mouse chromosome 7 to be divided into six and chromosome 19 into two definable genetic regions.


Expression of human adenosine deaminase after fusion of adenosine deaminase-deficient cells with mouse fibroblasts. Two human choriocarcinoma cell lines were shown to be deficient in adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) such that they did not produce bands on starch gels after electrophoresis and histochemical staining. Radiometric assay indicated that their ADA specific activity was approximately 2% that of HeLa (human) cell controls. Subclone analysis of one of the lines indicated that this deficiency was representative of individual cells of the line. After fusion of these cells with mouse fibroblasts having high ADA activity, most independently isolated hybrid clones expressed one of two, or both, additional (to the mouse) bands of ADA activity after electrophoresis. The expression of these extra bands in hybrids was dependent upon actual fusion. The phenomenon was observed in 30 of 45 independently derived hybrid clones from four different fusion experiments involving two different parental lines from each species. The pattern of appearance of the extra bands in independent hybrid clones and the tendency of a hybrid clone to lose one of the extra bands through subsequent passages suggests that the bands were the products of human genetic material. The extra bands electrophoretically comigrated with human ADA 1 and 2 from human ADA-1-2 heterozygotes and the faster-migrating of the two extra bands comigrated with human ADA 1 from HeLa cells. Therefore, we suggest that the bands appearing in hybrids are the products of the 1 and 2 alleles of the human ADA locus. The human cells used for fusion were deficient in ADA activity but contained the genetic information for ADA 1 and 2. Fusion with mouse cells having ADA activity resulted in the activation of both human gene products coded for on separate homologous chromosomes. We conclude that the human ADA locus is under manipulatable genetic regulation.


Control of antibody heterogeneity in strain 2 guinea pigs. When Wright's strain 2 guinea pigs are immunized with 2,4-dinitrophenyl conjugates in complete Freund's adjuvant, the antibody response varies with the choice of carrier. Immunization with 2,4-dinitrophenyl-guinea pig albumin elicits a response that requires approximately 21 days to detect. The antibody produced is, according to isoelectric focusing, relatively homogeneous IgG2 having a neutral isoelectric point. On small amounts of IgG are produced. Stimulation of animals with 2,4-dinitrophenyl-keyhole Limpet hemocyanin produces a response by 14 days is similar to the peak response inititated by 2,4-dinitrophenyl-guinea pig albumin. With time, however, basic IgG2 populations are added to the response. By days 28-35, when the anti-hapten response has reached a plateau, the major subpopulation of antibody is neutral IgG2, but there exists several times as much basic IgG2 as IgG1. These data suggest that antigen-responsive cells may be ordered into groups having different thresholds of activation. Regardless of the strength of the antigenic stimulus, there is a set sequence of activation. The same cells always play the primary role, contributing most of the antibody regardless of whether secondary clones of cells are activated.


Murine complement component 3: genetic variation and linkage to H-2. Two electrophoretic variants of murine complement component 3 (C3) were detected by using high-voltage electrophoresis of fresh mouse serum in agarose gels. Most of the inbred strains tested were homozygous for the S allele (for the slow-migrating variant); only four out of 46 strains had the alternative F allele (fast variant). Pen-bred Swiss-Webster animals belonged to one of three phenotypes--S, F, or SF--and the genes responsible for this variation segregated in a strictly Mendelian manner. In three such crosses, with 5* offspring, C3 segregated with H-2 in 46 instances, corresponding to a recombination frequency of approximately equal to 0.12.


Granulocyte colony formation in chronic granulocytic leukemia during stable, accelerated and blastic disease.


Erythroid colony formation from human fetal liver. The liver of the human fetus, induced to abort by prostaglandin or by hypertonic saline, contains cells that form colonies in methylcellulose in vitro. The colonies are erythroid as identified by cellular staining of hemoglobin by benzidine. Colony formation is generally similar, with regard to number, size and time of development, to that observed in cultures of nonadherent cells from human adult marrow. The number of colonies observed increases with the concentration of erythropoietin used and with the concentration of cells plated and decreases with the time interval between intra-amniotic instillation of the inducing agent and culture. Colong number is not greatly influenced by fetal age in the period 16-20 weeks or by whether the inducing agent is prostaglandin or hypertonic saline. Prostaglandin- and hypertonic saline-induced abortuses thus provide an abundant source of human fetal erythroid tissue for morphologic and biochemical studies of erythroid development.


Radiosensitization by misonidazole (Ro 07-0582). The importance of timing and tumor concentration of sensitizer.


The radiographic spectrum of periosteal osteosarcoma. Fifteen cases of a recently described variety of osteosarcoma, periosteal osteosarcoma, were studied to define their radiographic characteristics. All the lesions were limited to the cortex that was always thickened but without invasion of the medulla cavity. The tumors presented as non-homogeneous masses of spiculated osteoid matrix progressively denser from the periphery to their cortical base. The average age was 28 and the most common location was the proximal third of the femur; all the lesions were diaphyseal in location. The spectrum of radiographic features and differential diagnosis are described in detail.


A surgical view of stable angina pectoris.


Some group practice health care facilities in Rhode Island.


FDA complicates estrogen controversy.

FDA complicates estrogen controversy.


A central aorto-pulmonary artery shunt for cyanotic neonates.


Pharmacology treatment in drug abuse.

Pharmacology treatment in drug abuse.


Group psychotherapy in Rhode Island.

Group psychotherapy in Rhode Island.


Efficacy of lithium carbonate in alcoholism: case studies.


Editorial: Prognosis in malignant melanoma.


Glassification of roentgenologic appearance of the breast.


Allogeneic articular surface and whole joint transplantation. (Experimental study on 241 dogs).


Intrafamilial levels of Streptococcus mutans and some aspects of the bacterial transmission. The number of S. mutans (S.m.) in saliva of parents and their children was studied. Thirty-six children, 4 1/2-5 years old, and their parents participated. A quantitative correlation was found between the number of S.m. in the mothers and their children. The degree of infection also seemed to reflect the caries experience of the child. When adults with different levels of S.m. in saliva contaminated metal spoons with saliva, a correlation between the salivary count of S.m. and the number of microorganisms transferred to the spoon was found. The survival of S.m. on saliva-contaminated test-plates was tested. After 7 h the number of viable S.m. had decreased considerably but a few cells could be found after 24-48 h. To study the presence of S.m. on objects in the city often touched by hands, MSB-containing agar dishes were pressed against several objects such as doorhandles. Only four out of 24 objects were found to be contaminated by S.m.


Rate of migration of oral leukocytes in patients with periodontitis. The rate of migration of leukocytes (OMR) was estimated by counts of sequential mouthrinses in 81 human subjects in order to evaluate its usefulness as a laboratory test of oral inflammation. Periodontitis was taken as a model, and neither patients nor controls had any other oral inflammation. Patients with advanced periodontitis, but with periodontal destruction of about the same level, were divided into two groups, acute phase and chronic phase. The mean number of leukocytes entering the oral cavity in 30 s was estimated in these two groups. In the same patients the difference between the cell count in the first rinse and the OMR level was estimated, to test whether it could be taken to indicate the grade of acuteness of the inflammation (GAI). OMR and GAI were assessed in the patients with periodontitis after the initial treatment and at follow-up 1 year after completion of the full treatment, which almost always included surgical procedures. The results indicate that the OMR reflects the existence of oral inflammation and can be used as a laboratory test with the same reservations as white blood cell counts for systemic inflammation. The difference in GAI between patients in the acute and chronic phases of the disease was highly significant, indicating that this test gives information about the severity of the inflammation.


Clinical, histologic and micro-radiographic study of natal, neonatal and pre-erupted teeth. A clinical, histologic and microradiographic investigation of 62 natal, neonatal and otherwise pre-erupted teeth from 51 children is presented. Such a comprehensive material has not previously been reviewed. Of the 62 teeth, 59 were mandibular incisors. A hereditary factor could be demonstrated in 12 cases. Fifty-three teeth showed more or less pronounced enamel hypoplasia. The enamel had a normal prism structure and mineralization with the exception of 22 cases where the prism structure was absent in the cervical part of the enamel. The cervical and apical dentin was atubular and in developing teeth the dentin in these regions changed to an irregularly formed hard tissue of osteodentin character, in which enclosed cells could be observed. Developing teeth often had no cementum, and in those cases where acellular cementum could be observed it was thinner than normal. In four patients atypically located carious lesions occurred.


Erythroblast kinetics in pernicious anaemia, erythroleukaemia and sideroblastic anaemia. DNA synthesis time (Ts) and 3H-thymidine labelling index (TLI) of erythroblasts have been determined in 25 patients with various types of haematologic disorders using in vitro double labelling method. No remarkable differences in both Ts and TLI were noted between haematologically normal subjects and patients with increased effective erythropoiesis (haemolytic anaemias), suggesting that the cell cycle time is not principally altered under the augmented erythropoiesis. In pernicious anaemia, Ts of basophilic erythroblasts was significantly shortened and TLI was elevated above normal. Normalization of erythropoiesis by vitamin B12 was associated with a transient increase of TLI in polychromatic erythroblasts, which was interpreted to reflect prevention of intramedullary premature death of basophilic megaloblasts. Erythroleukaemia showed a markedly prolonged Ts and lowered TLI indicating the presence of cells with prolonged cell cycle time. These findings contrasted to that of pernicious anaemia despite certain morphological as well as functional similarities. In idiopathic sideroblastic anaemia, prolongation of Ts was observed to a similar extent as erythroleukaemia, while TLI remained almost normal. In 2 cases with suspected erythroleukaemia presenting an intermediate clinical picture between erythroleukaemia and sideroblastic anaemia, Ts of basophilic erythroblasts was found to be prolonged along with modestly lowered TLI.


Isozymes of amino acid naphthylamidase in chronic meyloid leukaemia and erythroleukaemia. Isozymes of amino acid naphthylamidase were investigated in 11 patients with chronic myeloid leukaemia (CML) and 1 patient with erythroleukaemia. Two isozymes were found in all cases (isozymes A and C) which also occur in normal granulocytes. An isozyme with intermediate mobility appeared in all the patients in two main forms (isozymes BF and BS), which both differed from the isozyme B found in normal granulocytes. This may therefore support the diagnosis. In 3 patients a shift occurred between isozymes BF and BS, the possible significance of which is discussed.


Mitotic activity in myeloid leukaemias. A study of 277 cases. The proportions of myeloblasts, promyelocytes, myelocytes and promonocytes within the granulopoietic precursor pool of the bone marrow and mitotic indices (MI) of the precursor cells were determined in 277 patients with various forms of myeloid leukaemias. The MI of the leukaemic patients were significantly lower than those of 20 normals. Thus the median MI in 186 cases of acute myeloid leukaemias was 0.68%, compared with 1.0% in 85 cases of chronic leukaemias and 1.2% in the normals. Separate MI of the different leukaemic precursor cells were counted in 21 cases of acute myeloid leukaemias and these indices were lower than those of the corresponding normal cells. There were significant differences between the different groups and subtypes of leukaemias and it is suggested that mitotic countings might be of diagnostic and prognostic significance.


Acute leukemia presenting as a ruptured spleen: report of a case.


The infective complications of aggressive induction of clinical remission in adult acute non-lymphoblastic leukaemia. The infectious complications after induction of remission in 31 previously untreated adult patients with acute myeloid leukaemia are described. Clinically, most of the febrile episodes were associated with infection, and in 11 of the patients who died infection was the direct cause. In 6 out of these 11 the causal organism was diagnosed ante mortem. In 6 of the 15 patients who regenerated to clinical remission and who had fever the causal organism was isolated. The policy of management of fever in this group of patients is outlined.


Susceptibility of bacteria isolated from oral infections to nine antibiotics in vitro.


Temporomandibular pain-dysfunction and disorders of the parotid gland.


Dummy- and finger-sucking habits with special attention to their significance for facial growth and occlusion. 7. The effect of earlier dummy- and finger-sucking habit in 16-year-old children compared with children without earlier sucking habit.


Microstructure and chemical composition of noble alloys for porcelain veneering.


Neonatal asphyxia and mineralisation defects of the primary teeth. II. A histological and microradiographic study.


Histone synthesis and differentiation in murine virus-infected erythroleukemia cells. The murine virus-infected erythroleukemia cells (MELC) has been used as a useful tool to examine the regulatory mechanism of the cytodifferentiation by the genetic approach. Addition of dimethylsulfoxide (DMSO) to the MELC culture induces erythroid differentiation. A study was made to assess whether stimulation of histone synthesis is associated with DMSO-induced differentiation of MELC during 4 days of culture in vitro. The synthesis of histone increased 2-fold in the 48 hr-incubated cells while the synthesis of non-histone protein was not stimulated. The histone synthesis was maximal at 48 hr and declined by 72 hr. 3H-leucine-labeled cells treated with DMSO was mixed with an equal weight of 14C-labeled control cells. Histones were isolated and fractionated on polyacrylamide gel. A 3.6-fold increase in 3H/14C ratio occurred in histone fraction 3 and 3.4-fold in histone fraction 2b. The data indicate that the stimulation of histone synthesis is an early event following DMSO treatment of MELC cells.


Ultrasound in pre-vitrectomy assessment. Ultrasonic examination helps the surgeon to select patients for vitrectomy and enables him to plan the operative procedure. A film demonstrated the advantages of rapid B-scanning over other ultrasonic techniques of previtrectomy assessment.


A rationale for the use of liquid silicone. The fundamental problem of massive retinal retraction in the contractual stage is due to the establishment of contracting membranes, both on the surface of the retina and away from the surface. These membranes distort and immobilize the retina in a way that cannot be effectively treated by buckling alone. The injection of liquid silicone enables the membrane to be stretched to a point at which it either ruptures spontaneously, or can be ruptured at a point of weakness by a needle tip. The retina, being still elastic, is able to stretch further than the membrane. At this point the membrane is actively elevated by the injecting needle and separated from the retina aa widely as possible. Liquid silicone enables significant membranes to be easily visualized, when separated, to be divided.


Results of silicone oil injection in massive preretinal retraction. A series of 69 eyes in which silicone oil injection was used to treat retinal detachment with massive preretinal retraction was reviewed with respect to retinal re-attachment and visual function. The selection of patients for treatment with silicone oil injection was influenced by the poor prognosis with conventional methods, the high incidence of postoperative complications after silicone oil injection, and the prognosis of the fellow eye. Although silicone oil injection is not an ideal method of re-attaching the retina, it remains the only successful method in many cases of massive preretinal traction. In cases in which the fellow eye is defective or is at risk of becoming so, we believe that the injection of silicone oil is fully justified.


Rationale and techniques of closed vitrectomy. The three indications for vitrectomy are opacity causing severe visual deficit, vitreo-retinal traction causing or threatening retinal detachment, and displacement of the vitreous from its normal position. The types of pathology which cause opacity and/or traction and which are amenable to treatment by closed vitrectomy are lens changes or lens/iris remnants, opaque vitreous gel, ochre membranes, transgel traction bands, posterior hyaloid membranes, and epiretinal membranes. Closed vitrectomy has superseded the open sky method because the integrity of the cornea is preserved, the crystalline lens can be preserved, the intraocular pressure can be regulated, and the visualization and access to the posterior segment are good. More than 200 closed vitrectomies have been carried out at this hospital since 1974, using the Machemer VISC VII, the Douvas Rotoextractor, and the Peyman Vitrophage. The techniques which have been evolved as a result of experience with these instruments are demonstrated in a film.


Mechanical problems associated with the cutting of vitreous. The properties of the vitreous are considered from the standpoint of the physicist and engineer and the difficulties of its cutting and manipulation considered. The principles underlying existing instruments for use in the vitreous cavity are examined and a series of new instruments is described and illustrated.


Results of closed vitrectomy.

Results of closed vitrectomy. The results of 101 closed vitrectomy operations are reported. The cases were classified on morphological grounds, and analysis showed that eyes with anterior segment or pure gel pathology responded favourably to surgery, while those with associated retinal disease had a poorer prognosis.


Vitrectomy in the management of the injured eye.


Vitrectomy. Present problems and future aspirations.


Experience with 194 posterior chamber lenses in 20 months. The author describes his experience with 194 posterior chamber lenses, mainly of the Pearce tripod variety. The surgical technique and complications peculiar to this type of prosthesis are considered. It was found that 75 per cent of eyes saw 6/9 or better and that the visual results compared favourably with figures given by other workers using different types of implants. The tripod posterior chamber lens is free of some of the problems associated with other intraocular lenses, especially pupil block glaucoma, hyphaemata, and the contact with plastics of the corneal endothelium. It is felt that the posterior chamber deserves further consideration as the correct place for an intraocular lens, because it provides a more "normal" eye than any other prosthesis.


Effect of intraocular lenses on the corneal endothelium. Methacrylate surfaces adhere to corneal endothelial cell membranes and appear to tear off the cell membranes as they separate. This adhesion appears to cause much of the massive cell damage seen at the time of intraocular lens insertion even in the hands of several groups of very experienced implant surgeons. The damage appears correlated with the incidence of endothelial touch, and may be avoidable both by avoiding contact, even for a brief period, between the endothelium and the intraocular lens during insertion, and by increasing the safety of such lenses through a hydrophilic protective coating which would give a surface similar to human lens epithelium or soft contact lens material which does not damage the endothelium. It is possible that similar damage also plays a role in causing abdominal adhesions through contact with rubber gloves, as well as venous thromboses and urethral strictures.


Prevention of postoperative ocular hypertension by prostaglandin inhibitors. The Pneumatonometer of Langham was used to monitor intraocular pressure in the operating theatre and in the early postoperative period after cataract surgery. Both indomethacin and aspirin were shown to prodcue a significant reduction in the acute ocular hypertension which can be expected to follow 6 hours after routine cataract surgery. It is suggested that the inhibition of prostaglandin synthesis by these drugs is probably responsible for this effect.


Treatment of rhegmatogenous detachment without apparent holes. In a series of cases of retinal detachment without visible holes, failure was not associated with local procedures but, as in all cases of retinal detachment, with membrane formation and retinal fibrosis. In total detachments with no localizing signs we favoured the encirclement procedure. In this group of thirty cases of retinal detachment in which no hole could be found we achieved the surprisingly high success rate of 87 per cent, but in as many as seventeen of the thirty cases a local buckle was applied to the most likely site of the tear. We therefore feel that the principle of performing the least traumatic procedure, i.e. a local procedure, can still be followed in a considerable number of these challenging cases.


Thrombotic glaucoma. Prophylaxis and management.


Vascular insufficiency (neovascular) glaucoma. An integrating pathogenetic concept.


Role of debridement in the treatment of herpetic keratitis.


Optimal usage of exogenous human interferon for prevention or therapy of herpetic keratitis.


Antivirals for the therapy of herpetic eye disease.


Corticosteroids in the management of herpetic eye disease. The discriminate use of topically applied corticosteroids to modify or abolish the inflammatory response in herpetic stromal keratitis, has, as its objectives, the prevention of visual loss from corneal scarring and disorganization and a lessening of the morbidity associated with this disese. Steroids may be expected to have a profound anti-inflammatory effect in antibody-complement mediated inflammation and are effective in delayed hypersensitivity as in homograft rejection. The equally profound effect of pharmacological vasoconstriction may enable steroids to impede both afferent and efferent pathways in an immunological reflex arc, and they may be expected to reduce inflammation of nonimmunogenic origin. The adverse effects of the misapplication of these potent drugs in herpetic keratitis, in terms of an increase in the rate of complications and in the severity and morbidity of the disease, should be emphasized again.


Prospects of prevention of recurrent herpetic eye disease. Various theories of recurrence of herpetic disease are outlined to indicate the potential role that interferon, interferon-inducers, or a hypothetical perfect synthetic antiviral may have in preventing recurrences, and the possibilities of minimizing trigger effects are considered. Attention is drawn to certain aspects of the management of herpetic eye disease that have a direct bearing on the incidence of subsequent recurrence. There is a need to initiate a movement to mobibize ophthalmologists everywhere to educate general practitioners in order to restrain them from harmfully using steroids in undiagnosed red eyes.


Updating biological depression.

Updating biological depression.


Implications of therapeutic 'failure' with tricyclic antidepressants.


Suture entrapment of femoral nerve as a complication of inguinal herniorrhaphy: a case report.


Microcirculatory reactions to local pressure induced ischemia. A vital microscopic study in hamster cheek pouch and a pilot study in man.


Deoxyribonucleoside triphosphate metabolism of leukemic cells.


The function and clinical significance of DNA polymerases in human hematopoietic cells.


Values and limitations of exercise testing after myocardial infarction, with special reference to quantitative criteria.


Penetration of ions from silicate cement restorations into Copalite--covered cavity walls. This study aimed to asses the effect of silicate cement on Copalite -covered cavity walls in extracted human teeth. Class V cavities were prepared in 24 premolars and filled with silicate cement (Bio-Trey). Four cavities were unlined, the rest of the cavities were lined with 1 or 2 layers of Copalite before insertion of the restorations. After 6 months, 70-100 microns thick longitudinal sections of the teeth were studied by polarized light microscopy, microradiography and electron probe microanalysis. When imbibed in water or quinoline, a subsurface zone of altered birefringence was noticed in nearly all cavity walls. Nearly half of the cavity walls in the experimental groups showed a surface zone of increased radiopacity. In a few instances a subsurface radiolucent zone was present. By electron probe microanalysis F (0,4-3% by weight), Zn (1-4%) and Al (0,2-6%) were measured in the outer 10-60 microns of the cavity walls. The study shows that even with a double layer of Copalite, known to prevent microleakage, a desirable uptake of F and Al from silicate restorations into cavity walls can take place. Copalite does not prevent a phosphoric acid effect on the cavity walls.


Chewing efficiency and state of dentition. A methodologic study. Chewing efficiency, defined as the ability to grind a certain portion of a test food during a given time, was tested in 139 Skolt Lapps, ages 14-65. 94 persons had natural teeth and the remaining 45 wore dentures (partial and/or complete). The test food was almonds. Number of chewing strokes, swallowings and chewing time was denoted. The chewing efficiency was classified after a scale from 1 to 5 where 1 meant very good and 5 very poor ability to reduce the particle size of the test food. Clear associations were found between chewing efficiency and dental state. Number of occluding pairs of teeth was closely correlated with chewing efficiency and individuals with less than 20 teeth had a higher index score than those with more than 20 teeth. The values noted for number of chewing strokes, swallowings and chewing time were smaller for those with a good chewing efficiency, but the variation was not linear and not always significant. Denture wearers had statistically significantly higher chewing efficiency score than those with natural teeth, without dentures, and needed more chewing time before swallowing.


Stress/strain behavior of some dental luting cements. The compressive strength, modulus of elasticity and the plastic strain at fracture have been studied for several dental luting cements. Stress/strain diagrams of cylindrical specimens using two different crosshead speeds (2 mm/min and 0.1 mm/min) at 23 degrees and 37 degrees C showed that large differences existed between various luting cements. A zinc phosphate cement exihibited high strength, high modulus of elasticity and a small plastic strain at fracture. A resin cement also had high strength, but elastic and plastic strains were high. A polycarboxylate and an EBA-cement both showed low values of strength and modulus of elasticity combined with a high degree of plastic deformation at fracture. Testing with low strain rate at 37 degrees C accentuated the differences between these two materials and the zinc phosphate cement.


Organization and function of the sympathetic innervation.


The adrenergic innervation of the pituitary of the eel, Anguilla anguilla, with special reference to the control of the pars intermedia.


Influence of sympathetic nerves, amine receptors and anti-adrenergic drugs on follicular contractility and ovulation.


5-Hydroxytryptamine-containing enterochromaffin cells: storage site of substance P.


Distribution of 14C-5,6-dihydroxytryptamine in the CNS of the rat.


On the relation between central noradrenaline and serotonin nerve terminals and postsynaptic receptors during ontogeny.


Species differences in serotoninergic in innervation and secretory activity of rat, gerbil, mouse and rabbit subcommissural organ.


Subcortical afferents to the prefrontal cortex: organization of mesencephalic dopaminergic and mediodorsal thalamic projections.


The origin of substance P and acetylcholine projections to the ventral tegmental area and interpeduncular nucleus in the rat.


Destruction of amine accumulating neurons in rabbit and goldfish retina.


A catecholaminergic neuron connecting optic neuropiles of crayfish.


Influence of the cerebrovascular sympathetic innervation on blood-brain barrier function.


Changes in sensitivity of cerebral vessels to noradrenaline and 5-hydroxytryptamine in the presence of subarachnoid blood.


Histochemical, ultrastructural and functional evidence for a neurogenic control of cerebrospinal fluid production from the choroid plexus. Histochemical studies have shown that the rabbit choroid plexus receives a well-developed adrenergic and cholinergic nerve supply. The adrenergic innervation, which orginates almost entirely from the superior cervical sympathetic ganglia, begins to develop around birth and is fully established 3 weeks later. Electron microscopy has shown that the nerve terminals innervate both the plexus arterioles and its secretory epithelium. The sympathetic fibres have been shown to influence the plexus epithelium, as reflected by their effect on its carbonic anhydrase activity. They appear to have an inhibitory effect on the bulk CSF production, as revealed by electrical nerve stimulation and denervation experiments. The control seems to be excerted primarily on the plexus epithelium, though some of the effect may also be associated with alteration in choroid plexus blood flow.


What function have cholinergic nerves in the smooth muscle of the male genital tract?


Electron microscopy of adrenergic, cholinergic, and "P-type" nerves in the myometrium, and a special kind of synaptic contacts with the smooth muscle cells.


Electrophoretic properties of esterases in chronic granulocytic leukemia. Granulocytes were obtained from samples of peripheral blood of five patients who had untreated chronic granulocytic leukemia, and polymorphonuclear leukocytes were isolated from peripheral blood of three normal persons. Specific and nonspecific esterases were extracted from leukocyte preparations with cetyltrimethylammonium bromide and with lysolecithin, and subjected to polyacrylamide disk electrophoresis. In samples from both patients and normal persons, electrophoretic patterns of nonspecific esterase activity using alpha-naphthyl acetate and alpha-naphthyl butyrate were similar, and the esterase bands were weakly inhibited by fluoride. Lysolecithin extracts of specific esterase showed similar electrophoretic patterns for patients and normal subjects. However in cetyltrimethylammonium bromide extracts of specific esterase, 11 bands were seen in preparations from all of the patients with chronic granulocytic leukemia. In preparations of normal polymorphonuclear leukocytes, only eight bands were visualized. The results are consistent with an interpretation that these fast-moving components of specific esterase in chronic granulocytic leukemia granulocytes are present in normal polymorphonuclear leukocytes, but in quantities too small to be visualized with the technics used. Alternatively, the apparent "additional" bands of specific esterase may reflect abnormal metabolism of malignant granulocytes in chronic granulocytic leukemia.


Prevention of ventilator hazards.

Prevention of ventilator hazards.


Vocal cord closure. A cause of upper airway obstruction during controlled ventilation. Studies of vocal cord function were undertaken in a quadriplegic patient requiring ventilatory assistance, and in 2 normal subjects during controlled ventilation in a tank-type respirator. When the patient and the normal subjects relaxed and made no conscious effort to assist the respirator, the vocal cords were observed to close during inspiration and a large pressure gradient (12 to 19 cm H2O) developed across the cords. When the subjects made a slight inspiratory effort ("assist" mode), the cords opened widely during inspiration. There were large increases in flow and tidal volume in the "assist" mode compared with passive ventilation. Measurements of transdiaphragmatic pressure and esophageal pressure showed that these variables did not increase with the slight assist. Thus, increase in ventilation during the "assist" mode appeared to be due to alleviation of inspiratory obstruction at the level of the vocal cords. The same phenomenon was observed in the patient during phrenic nerve pacing. A pacemaker was designed to be triggered by the electromyographic impulse from an accessory muscle of respiration. In this manner, vocal cord opening could be coordinated with the mechanical assist given by the phrenic nerve pacer.


Characterization of respirator adsorbent filters by means of penetration curve parameters--II. Effect of relative humidity.


Acquired hemoglobin H in refractor sideroblastic anemia. A preleukemic marker. Two patients with idiopathic refractory sideroblastic anemia (IRSA) were found to have acquired hemoglobin H. Both developed leukemic syndromes. Six other patients with IRSA had normal hemoglobin electrpohoretic patterns, and none has developed acute leukemia in up to five years. We suggest that hemoglobin electrphoresis be performed routinely in IRSA. The finding of hemoglobin H in this population may be a relatively frequent occurrence and may serve to distinguish the preleukemic patients from those not destined to develop leukemia.


Therapeutic angiography. Its value to the surgical patient. Standard angiographic techniques formerly used exclusively as diagnostic modalities have been modified to serve as definitive or adjunctive therapeutic measured. The techniques include transcatheter embolization; infusion of vasoactive drugs, chemotherapeutic agents and radioactive particles; tamponade of bleeding arteries and balloon catheters; extraction of vascular foreign bodies and retained biliary tract stones and transluminal arterial dilation. These techniques have been proved effective and safe when used judiciously.


The polar lipids of Actinomyces viscosus.


Charged particle analysis of fluorine distributions in the surface of human tooth enamel.


The ultrastructure of tissues at the epithelial-messenchymal interface in developing rat incisors.


Scanning electron microscopy of the neonatal line in human enamel.


Prevalence and survival of microbial contaminants in heated nebulizers. Over a 2-year period, 600 cultures of fluid in heated nebulizers in use by patients in the Peter Bent Brigham Hospital were performed. The most commonly isolated microorganisms were Pseudomonas and Alcaligenes species. Pseudomonas aeruginosa was never isolated. Three types of heated nebulizers were in use, and their contamination rate was significantly different (45 percent, 21 percent, and 8 percent, respectively; p less than 0.001). In the course of the study, the overall contamination rate decreased from 47 percent to 10 percent. This was mainly due to elmination of the type of heated nebulizer that was most prone to contamination. Five types of currently available large-reservoir nebulizers were inculated with various organisms and growth patterns studied. The various nebulizing equiment differed in its ability to inhibit or eliminate microbial growth; 1 of the heated nebulizers appeared to enhance growth of some of the inoculated bacteria.


The transfilter transmission of [3H]-proline labelled material in cultured rat tooth germs.


Water-induced resistance in disposable respiratory-circuit bacterial filters.


Characterisation of antigens extracted from cells and culture fluids of Streptococcus mutans serotype c.


The future of general surgery in Australasia.


Hyperthermia and cancer.

Hyperthermia and cancer. The effects of heat and its possible significance in cance therapy have been documented for more than a century. Hyperthermia has been widely investigated as an alternative or adjuvant to conventional therapies such as surgery, radiation, and chemotherapy. The clinical reports are interesting, notwithstanding some harmful side effects and other complications which, however, may be attributable to an advanced stage of the disease at the time of treatment. In view of the extreme difficulty in matching suitable controls for cancer patients undertaking such therapy, it is essential to extend knowledge of the effects of hyperthermia on normal and neoplastic tissue by experimental studies. Further, the different methods of utilizing heat therapy have need for substantial technological improvements. To stimulate interest in this area, we have gathered together in this review some of the more pertinent reports on the application of hyperthermia to neoplastic and normal tissues as observed clinically and in the laboratory.


The combined approach to cancer therapy in cancer centres. In the complex field of cancer therapy the cancer centre approach may be seen more clearly by division of its structure into vertical and horizontal components. Vertically, there are numerous special consultative clinics in types of cancer usually associated with a body region (lung, breast, melanoma, etc.). Horizontally, there are teams of specialists (surgeons, radiotherapists, solid tumour chemotherapists), in some clinics supplemented by haematologists, immunologists, and endocrinologists, providing a wide therapeutic spectrum. Working together in a particular consultative team, the specialists are clinical oncologists, but without the summed wisdom and expertise of the group, the members are more accurately designated individually as specialists in the field from which they spring, for example, thoracic surgeon, haematologist, radiotherapist, and so on. The team approach lends itself to full exploitation of all the centralized sophisticated cancer machinery, be it in the form of equipment like cell-trifuges and linear accelerators, a range and depth of cancer monitoring aids, or a medical record system aligned to a computer, with consequent immediate and long-term therapeutic gain to patients. For the State there is greater efficiency and hence economy. In teaching, the aggregation of all matters relating to cancer therapy presents enhanced opportunities for training of technicians and scientists and nurses as well as doctors, for postgraduate instruction, and for continuing education. For progress in understanding cancer, it is clear that clinical research in conjunction with the combined approach in cancer centres can be conducted with sufficient numbers of patients to give statistical credence to clinical trials.


Surgical adjuvant therapy for potentially curable cancer: the rationale of adjuvant chemotherapy and anticoagulant therapy.


The consultant surgeon and mammography.

The consultant surgeon and mammography. It is important that the mounting wave of criticism of mammography in breast screening programmes should not obscure the fact that it remains the most accurate method of diagnosing breast cancer short of biopsy. Furthermore, breast cancer may be diagnosed by mammography at an early stage before it has spread to regional lymph nodes, at a time when the prognosis is better. At this time it may be beneficial to outline the role of mammography as an aid to the consultant surgeon in the management of patients referred with breast problems.


Psychosocial aspects of head and neck cancer surgery. Thirty-six patients who underwent major surgical excision and reconstruction for head and neck cancer were subjected to a psychosocial assessment in hospital and, later, in their home environments. The information gained from the survey is discussed, with particular reference to those factors which can be used by the head and neck surgical team to improve the quality of the patients' existence.


Gliomas of the optic nerve and chiasm in children. This paper reviews the clinical features, management, and prognosis of patients with gliomas of the optic nerves and chiasm who have received treatment at the Royal Children's Hospital, Melbourne, between 1954 and 1977. The relationship of this tumour to other neoplasms in the region is discussed, and emphasis is placed on the natural history of the disease. The controversy concerning the exact nature of this lesion is summarized, and an attempt is made, in the light of this evidence and from the reviewed series, to formulate an appropriate overall plan of management of these patients.


The cavernous sinus: an anatomical survey. An anatomical survey of the cavernous sinus in 16 adult cadavera has been made, based on serial sections cut at 15 micron in the coronal and sagittal planes. Certain aspects of the survey are of particular interest: (1) the oculomotor, trochlear, and ophthalmic nerves do not run in the lateral dural wall of the cavernous sinus; (2) venous sinuses of the cavernous sinus flow freely in a medial direction both anterior and posterior to the dorsum sellae; (3) trabeculae in the form of collections of fine areolar tissue extend between the vascular and neural elements. The amount present is variable; (4) the horizontal section of the internal carotid artery within the cavernous sinus runs a variable course in relation to the hypophysis and the lateral dural wall; (5) the oculomotor nerve lies within a meningeal envelope as far anteriorly as the tip of the anterior clinoid process; (6) the ophthalmic nerve communicates with the oculomotor, trochlear, and abducent nerves in the anterior part of the cavernous sinus; (7) the abducent nerve may lie within a meningeal envelope in the posterior part of the cavernous sinus; (8) the greater part of the sympathetic nerve plexus around the vertical part of the internal carotid artery passes into the abducent and ophthalmic nerves. Sympathetic fibres pass into the sheaths surrounding the oculomotor and trochlear nerves. Sympathetic ganglia are suspended from the ophthalmic nerve.