Heparin prophylaxis of deep vein thrombosis in patients with a fractured neck of the femur.

A double-blind controlled clinical trial of the efficacy of the prophylactic subcutaneous administration of calcium heparin in preventing deep vein thrombosis has been conducted in 50 patients with a fractured neck of the femur. Heparin was given every eight hours in a dose of 100 international units per kilogram of body weight and was commenced as soon as possible after the patient's admission to hospital. Treatment was continued for two weeks. In the placebo group, 12 of 25 patients developed a deep venous thrombosis and in five of these patients the thrombosis propagated to the thigh. There were no deep venous thromboses in the heparin-treated group during the two weeks of treatment, but four patients developed a deep venous thrombosis within a week of stopping the heparin. The heparin regime was safe; operative blood loss was not increased, nor was there an increased incidence of wound complications as compared to the placebo group.


The value of delayed primary wound closure in colonic and rectal surgery.

The technique of delayed primary wound closure was employed in 82 out of 100 consecutive colorectal operations. Problems with wound healing occurred in seven patients, but in only three of them was it a wound infection. The value of delayed primary wound closure has been demonstrated by this low rate of wound infection (3.7%).


The spread of chloroquine-resistant falciparum malaria in Papua New Guinea.

Two cases of chloroquine-resistant Plasmodium falciparum malaria have been reported from eastern Papua New Guinea in order to alert the medical profession about the spread of resistant strains throughout that territory.


A phase II study of phenesterin (NSC-104469).

Phenesterin was evaluated in 222 patients with two different dosage regimens, one by daily treatment and the other with an intermittent schedule. Toxicity was moderate with both programs. The largest group of patients treated had breast cancer; they experienced a 10% response rate. Of interest was a higher percentage of responses in ovarian cancer (36%). An expanded study of patients with ovarian cancer would be of interest.


Increased survival in childhood acute nonlymphocytic leukemia after treatment with prednisone, cytosine arabinoside, 6-thioguanine, cyclophosphamide, and oncovin (PATCO) combination chemotherapy.

One hundred-sixty-three children with acute nonlymphocytic leukemia (ANLL) were treated with a multiple-drug induction program (PATCO) consisting of prednisone (PDN), cytosine arabinoside ((Ara-C), 6-thioguanine (6-TG), cyclophosphamide (CPM), and Oncovin (VCR). Ninety-six, 59%, obtained a remission. Remission was maintained with daily 6-TG and four-day pulses of Ara-C and CPM with a single dose of VCR every 28 days. The median duration of remission was 11.5 months. Certain prognostic factors affected induction rate and remission duration. Initial white blood count (WBC) was a significant factor in achieving a remission, whereas age, sex, and type of ANLL had no effect. Initial WBC, age, and sex had a significant effect on remission duration, but type of ANLL had no effect. Relapsing patients were treated with daunomycin and 5-azacytidine. The reinduction rate was 53% with a median second remission duration of 190 days. Overall survival for the 163 patients is 55.4% at 12 months, 31.5% at 24 months, 21.4% at 36 months, and 19% at 48 months.


Formation and early years of the AAPM.

This vignette recites significant steps leading to the formation of the AAPM and transpiring in the developments of the first decade, approximately. Persons involved, dates, and places are recognized. A table summarizes the progression of events. This recitation ends with the term of Kereiakes, the last President to be elected by the Board of Directors from its own membership, and with the move of the annual meeting time to mid-summer.


Yeast ribosomal proteins. I. Characterization of cytoplasmic ribosomal proteins by two-dimensional gel electrophoresis.

The cytoplasmic 80s ribosomal proteins from the cells of yeast Sachharomyces cerevisiae were analysed by SDS two-dimensional polyacrylamide gel electrophoresis. Seventyfour proteins were identified and consecutively numbered from 1 to 74. Upon oxidation of the 80s proteins with performic acid, ten proteins (no. 15, 20, 35, 40, 44, 46, 49, 51, 54 and 55) were dislocated on the gel without change of the total number of protein spots. Five proteins (no. 8, 14, 16, 36 and 74) were phosphorylated in vivo as seen in 32P-labelling experiments. The large and small subunits separated in low magnesium medium were analyzed by the above gel electrophoresis. At least forty-five and twenty-eight proteins were assumed to be in the large and small subunits, respectively. All proteins found in the 80s ribosomes, except for no. 3, were detected in either subunit without appearance of new spots. The acidic protein no. 3 seems to be lost during subunit dissociation.


Mini-chromosomes: plasmids which carry the E. coli replication origin.

We have isolated plasmids by linking the 5.9 MD EcoRI fragment of E. coli that carries the origin of replication to an EcoRI fragment that carries an amplicillin resistance determinant, but lacks an origin of replication. 3 plasmids of this type, pOC1, pOC2, and pOC3, are described in detail in this report. Although the plasmids have some adverse effect on the growth properties of the host strain, their existence shows that two functioning chromosomal origins can coexist in one cell. Deletions generated from this type of plasmids allow an allocation of the origin of replication of E. coli within a DNA segment less than 0.4 MD in size.


[Current status of chemotherapy of tumors of the head and neck].

The literature regarding chemotherapy of cervico-facial tumours is reviewed. Owing to its modest, short-lived results intra-arterial treatment has been largely abandoned even in the case of serious complications. It is only used in selected cases as a preparation for subsequent surgical and/or radiation therapy. General, one-drug cytostatic therapy has been given fair results with objective remissions varying from 7.5 to 58%. In recent years polychemotherapy has proved more effective with remissions of from 30 to 80%. There are too few data on the polychemotherapy-immunotherapy association to draw valid conclusions.


Yeast mutant, rna 1, affects the entry into polysomes of ribosomal RNA as well as messenger RNA.

The entry of newly labeled ribosomal subunits and mRNA into polysomes was examined in the yeast mutant rna1. The entry of both types of RNA into polysomes is inhibited rapidly at the restrictive temperature. Analysis of the labeling of the ATP pool and the kinetics of synthesis and processing of mRNA at the restrictive temperature leads to the conclusion that the primary defect in the mutant affects transport of both ribosomes and messenger across the nuclear membrane.


Restriction enzyme cleavage mapping of T7 virus early region.

DNA molecules of seven T7 mutants with overlapping deletions in the early region were cleaved by restriction enzymes HindII, HpaI and II, and HaeIII. The differences in the cleavage patterns after electrophoresis have been used to generate a cleavage map of the restriction sites of this enzyme. It covers the first 9% of the T7 DNA molecule. Cleavage points for HindII are at 0.60, 1.33, 1.59, 1.76, 5.26, 6.27, 7.4 and 8.38%; for HpaI and II at 1.36, 1.62, 4.46, 6.29, 6.62, 7.56, and 8.76%, for HaeIII at 3.85, 6.98, 7.88 and 8.26%. Some fragments have been located in the region containing the early promoters, others carry the complete sequences of gene 0.3.


A direct confirmation of the specificity of mutation frequency decline for suppressor mutations.

In a phage T7-resistand and galactose-sensitive derivative of E. coli B/r trp- it has been possible to show that MFD for UV-induced mutations is specific for Trp+ reversions (mainly of an ochre suppressor-containing type) but is without effect on galactose-resistant or D-fucose-resistant (ara Cc) forward mutations.


Reduced expression of a distal gene of the prn gene cluster in deletion mutants of Aspergillus nidulans: genetic evidence for a dicistronic messenger in an eukaryote.

The prn gene cluster involved in L-proline catabolism in Aspergillus nidulans, has the gene order prnA-prnD-regulatory region-prnB-prnC. prnB, prnD, and prnC specify proline permease, proline oxidase, and delta1-pyrroline-5-carboxylate (P5C) dehydrogenase, respectively. prnA is probably a positive regulatory gene whose product is necessary for expression of the prn activities. Proline induces proline permease and P5C dehydrogenase in prnD- mutants which lack proline oxidase, showing that proline does not have to be converted to P5C to act as inducer. Deletion mutations extending from within prnD to within prnB result in considerably reduced expression of prnC, whereas a prnD- prnB- double mutant shows normal prnC expression. This strongly suggests that the deletion mutations eliminate a promotor/initiator site for transcription of a dicistronic messenger for prnB and prnC. The fact that the deletions do not eliminate prnC expression altogether indicates that at least one other species of prnC transcript (monocistronic, tricistronic, or tetracistronic) can be made.


GABA transaminase provides an alternative route of beta-alanine synthesis in Aspergillus nidulans.

Three unlinked genes where mutation can lead to D(+)-pantothenic acid auxotrophy in Aspergillus nidulans have been identified. pantoA is probably the structural gene for pantothenate synthetase (EC 6.3.2.1) whilst pantoB and pantoC are involved in the syntheses of D-pantoic acid and beta-alanine, respectively. A pantoC- mutant is tentatively considered to be blocked in conversion of 5,6-dihydrouracil to beta-ureidopropionate. An alternative route of beta-alanine biosynthesis occurs by the transamination of malonic semialdehyde, catalysed by GABA transaminase. The possibility that beta-alanine can be replaced by certain structurally related compounds and yet nevertheless yield biologically active coenzyme A analogues is discussed.


Affinity labelling of yeast ribosomal peptidyl transferase.

Using p-nitrophenylcarbamyl-phenylalanyl-tRNA (PNPC-Phe-tRNA) and N-Iodoacetylphenylalanyl-tRNA as affinity labels we have attempted to identify the components of the aminoacyl-tRNA binding sites located in the vicinity of the peptidyl transferase centre of the yeast ribosome. Both Phe-tRNA derivatives bind to the ribosomal A-site in the presence of 20 mM Mg++ ion concentration and can be translocated to the ribosomal P-site in the presence of elongation factor. After the labels have been allowed to react covalently with ribosomes they were found associated with the large ribosomal subunit. Proteins L36, L43, L42, L29, L2, L17/18, L19/20 and proteins L26, L38, L22/23, L7/9, L4/6, L36, L11, L43, L39 were labelled in samples treated with PNPC-Phe-tRNA and N-iodoacetyl-Phe-tRNA respectively. In contrast, when only the components of the ribosomal P-site were analysed by reacting the treated particles with puromycin fewer spots were labelled, corresponding to proteins L36 and L19/20 using PNPC-Phe-tRNA and proteins L4/6, L36, and L43 using N-Iodoacetyl-Phe-tRNA.


Mechanism of the radioprotecting action of chemical compounds on Escherichia coli cells.

The effect of radioprotection of indolylalkylamines (5-methoxytryptamine) and aminothiols (cysteamine) on E. coli cells is practically absent if the cells have genetic defects in the repair systems. This means that the explanation of radioprotection by scavenging of free radicals is invalid and that specific repair mechanisms may be involved. In order to explain the radioprotective mechanism it was suggested that the radioprotectors interact with the damaged sites in DNA so that they become partly screened from repairing endonucleases. Under these conditions the reduction of incision rate results in diminished enzymatic induction of lethal double-strand breaks in DNA, this being important only in wild type cells. To prove this hypothesis an experimental procedure was developed using bacterial cells carrying plasmids (ColE1). This procedure enabled to determine the in vivo rate of enzymatic incision of gamma-sites. It was found that the protectors did not change the total amount of gamma-damages in DNA but reduced the rate of enzymatic incision.


Recessive nonsense-suppression in yeast: involvement of 60S ribosomal subunit.

The ribosomal protein patterns of recessive suppressor strain and parent strain of Saccharomyces cerevisiae were analyzed by two-dimensional polyacrylamide gel electrophoresis. About 30 proteinspots were found for ribosomal proteins of small subunit for both mutant and parent strain. These patterns do not differ from each other neither in intensity of staining, nor in mobility of spots. 41 protein spots were found in electrophoregrams of 60S ribosomal proteins both from parent strain and recessive suppressor strain. The electrophoretic picture of the 60S proteins from the parent and mutant strains is similar except the intensity of staining of the L30 spot. This protein is present in 60S subunit of suppressor strain and completely absent or only weakly stained on electrophoregrams of ribosomal proteins of parent strain. The possible relationships between the content of L30 protein and the mechanism of recessive suppression in yeast are discussed.


S-adenosyl methionine requiring mutants in Saccharomyces cerevisiae: evidences for the existence of two methionine adenosyl transferases.

Mutants requiring S-adenosyl methionine (SAM) for growth have been selected in Saccharomyces cerevisiae. Two classes of mutants have been found. One class corresponds to the simultaneous occurrence of mutations at two unlinked loci SAM1 and SAM2 and presents a strict SAM requirement for growth on any medium. The second class corresponds to special single mutations in the gene SAM2 which lead to a residual growth on minimal medium but to normal growth on SAM supplemented medium or on a complex medium like YPGA not containing any SAM. These genetic data can be taken as an indication that Saccharomyces cerevisiae possesses two isoenzymatic methionine adenosyl transferases (MAT). In addition, SAM1 and SAM2 loci have been identified respectively with the ETH-10 and ETH2 loci previously described. Biochemical evidences corroborate the genetic results. Two MAT activities can be dissociated in a wild type extract (MATI and MATII) by DEAE cellulose chromatography. Mutations at the SAM1 locus lead to the absence or to the modification of MATII whereas mutations at the SAM2 locus lead to the absence or to the modification of MATI. Moreover, some of our results seem to show that MATI and MATII are associated in vivo.


Transfection and transformation of Agrobacterium tumefaciens.

The freeze thaw transfection procedure of Dityatkin et al. (1972) was adapted for the transfection and transformation of A. tumefaciens. Transfection of the strains B6S3 and B6-6 with DNA of the temperate phage PS8cc186 yielded a maximum frequency of 2 10(-7) transfectants per total recipient population. In transformation of the strain GV3100 with the P type plasmid RP4 a maximum frequency of 3.5 10(-7) transformants per total recipient population was obtained. Agrobacterium Ti-plasmids were introduced in the strain GV3100 with a maximal efficiency of 4.5 10(-8). These experiments provide further evidence that the Ti-plasmid is responsible for the oncogenic properties of A tumefaciens and for its capacity to induce "opine" synthesis in Crown-gall plant cells.


Lambda phage promoter used to enhance expression of a plasmid-cloned gene.

A 50-fold (or greater) increase in the production of phage 21 repressor was obtained by construction of a plasmid in which the 21cI (repressor) gene could be transcribed from lambdaPL. The enhancement due to increased 21cI gene copy number and transcription from lambdaPL were at least five-fold and ten-fold, respectively. The plasmid was constructed in vitro by recombination of EcoRI-generated DNA fragments. The use of the DNA fragment containing lambdaPL in obtaining expression of cloned genes is discussed.


A ribosomal RNA gene, rrnC, of Escherichia coli, mapped by specialized transducing lambdadilv and lambda drbs phages.

Specialized transducing phages carrying segments of the Escherichia coli chromosome from the rbs-ilv region including rrn genes have been isolated. These phages carry rrn transcription units coding for 16S and 23S rRNA with the direction of transcription clockwise towards the ilv operon. While one of the phages (lambdad279rbs) appears to carry the genuine rrn gene, denoted rrnC, located between rbs and ilv at 82 min on the E. coli chromosome another one isolated as an ilv transducing phage, lambda5ilv, carries a hybrid rrn gene, denoted rrnX, which has originated from a recombinational cross-over between the rrnC and one of the other rrn genes.


Effect of cI repressor level on thymineless and spontaneous induction; specificity of lambda RNA transcription.

To determine the role of the cI repressor in induction provoked by thymine deprivation, we have analyzed lambda messenger RNA made during and the effect of cI repressor levels on thymineless induction. During thymineless induction, the l- and r-strand transcription of lambda is restricted to the "early" and "delayed early" RNA. This transcriptional pattern is similar to that reported for lambda mutants defective in DNA synthesis. "Late" r-strand transcription requires the addition of thymine. A decrease (to less than 10% of 0 time) in the amount of exogenous label (3H-uridine) incorporated into total RNA by the time of maximum thymineless induction was observed. Since subsequent burst sizes are not diminished by the thymine deprivation and competition experiments show that the amount of lambda message RNA present is at least as great as that in heat induced lambda cI857 lysogens, this decrease must involve either enlarged uridine pool sizes or decreased entry of label. The introduction into the lambda lysogen of a plasmid (pKB252) carrying the lambda cI gene prevents (1) the thymineless induction of lambda (curing the plasmid restores thymineless induction) and, (2) the appearance of both spontaneously induced cells and free phage. Thus, thymineless induction is dependent on the level of cI repressor and spontaneous induction also appears to be the consequence of lowered repressor levels in lambda lysogens.


Physical mapping of genes on yeast mitochondrial DNA: localization of antibiotic resistance loci, and rRNA and tRNA genes.

We have physically mapped the loci conferring resistance to antibiotics that inhibit mitochondrial protein synthesis (erythromycin, chloramphenicol and paromomycin) or respiration (oligomycin I and II), as well as the 21s and 14s rRNA and tRNA genes on the restriction map of the mitochondrial genome of the yeast Saccharomyces cerevisiae. The mitochondrial genes were localized by hybridization of labeled RNA probes to restriction fragments of grande (strain MH41-7B) mitochondrial DNA (mtDNA) generated by endonucleases EcoRI, HpaI, BamHI, HindIII, SalI, PstI and HhaI. We have derived the HhaI restriction fragment map of MH41-7B mit DNA, to be added to our previously reported maps for the six other endonucleases. The antibiotic resistance loci (antR) were mapped by hybridization of 3H-cRNA transcribed from single marker petite mtDNA's of low kinetic complexity to grande restriction fragments. We have chosen the single Sal I site as the origin of the circular physical map and have positioned the antibiotic loci as follows: C (99.5-1.Ou)--P (27-36.Ou)--OII (58.3-62u--OI (80-84u)--E (94.4-98.4u). The 21s rRNA is localized at 94.4-99.2u, and the 14s rRNA is positioned between 36.2-39.8u. The two rRNA species are separated by 36% of the genome. Total mitochondrial tRNA labeled with 125I hybridized primarily to two regions of the genome, at 99.5-11.5u and 34-44u. A third region of hybridization was occasionally detected at 70--76u, which probably corresponds to seryl and glutamyl tRNA genes, previously located to this region by petite deletion mapping.


Restriction enzyme analysis of mitochondrial DNAs of petite mutants of yeast: classification of petites, and deletion mapping of mitochondrial genes.

We have analyzed the restriction digest patterns of the mitochondrial DNA from 41 cytoplasmic petite strains of Saccharomyces cerevisiae, that have been extensively characterized with respect to genetic markers. Each mitochondrial DNA was digested with seven restriction endonucleases (EcoRI, HPaI, HindIII, BamHI, HhaI, SalI, and PstI) which together make 41 cuts in grande mitochondrial DNA and for which we have derived fragment maps. The petite mitochondrial DNAs were also analyzed with HpaII, HaeIII, and AluI, each of which makes more than 80 cleavages in grande mitochondrial DNA. On the basis of the restriction patterns observed (i.e., only one fragment migrating differently from grande for a single deletion, and more than one for multiple deletions) and by comparing petite and grande mitochondrial DNA restriction maps, the petite clones could be classified into two main groups: (1) petites representing a single deletion of grande mitochondrial DNA and (2) petites containing multiple deletions of the grande mitochondrial DNA resulting in rearranged sequences. Single deletion petites may retain a large portion of the grande mitochondrial genome or may be of low kinetic cimplexity. Many petites which are scored as single continuous deletions by genetic criteria were later demonstrated to be internally deleted by restriction endonuclease analysis. Heterogeneous sequences, manifested by the presence of sub-stoichiometric amounts of some restriction fragments, may accompany the single or multiple deletions. Single deletions with heterogeneous sequences remain useful for mapping if the low concentration sequences represent a subset of the stoichiometric bands. Using a group of petites which retain single continuous regions of the grande mitochondrial DNA, we have physically mapped antibiotic resistance and mit- markers to regions of the grande restriction map as follows: C (99.3--1.4 map units)--OXI-1 (2.5--15.7)--OXI-2 (18.5--25)--P (28.1--34.2)--OXI-3 (32.2--61.2--OII (60--62)--COB (64.6--80.8--0I (80.4--85.7)--E (95--98.9).


A new conditional lethal mutator (dnaQ49) in Escherichia coli K12.

A conditional lethal mutator, dnaQ49, was found in Escherichia coli K12. The dnaQ49 mutation caused stimulation of rifampicin-, nalidixic acid- and streptomycin-resistant mutation frequencies 100 to 2000 fold at 30 degrees C and the frequencies were further increased 50 to 100 fold at 35 degrees C or higher temperatures. Cells carrying dnaQ49 were unable to grow in salt-free L-broth at 44.5 degrees C, and DNA synthesis but not protein synthesis of the cells was suppressed under the restrictive conditions. The dnaQ gene was located at about 5 min on the E. coli linkage map and the order of the genes residing in this region was determined to be ton A-dnaE-metD-dnaQ-pro A.


Requirement of protein and RNA synthesis for lambda repressor inactivation by tif-1: effects of chloramphenicol, neomycin and rifampicin.

The inactivation of lambda repressor was followed by the specific DNA binding assay during the course of lysogenic induction provoked by incubation at 42 degrees C of an E. coli tif-1 lysogenic strain. The presence of up to 400 microgram/ml chloramphenicol during the inducing treatment did not impair the loss of repressor binding activity, whilst concentrations of 200 microgram/ml neomycin and 100 microgram/ml rifampicin effectively inhibited the inactivation of lambda repressor. Residual protein synthesis in the presence of chloramphenicol, neomycin and rifampicin was 5%, 5% and 27% respectively of that observed in the drug-free control. This residual synthesis did not appear to involve amplification of the X-protein. These results suggest that tif-mediated inactivation of the lambda repressor requires the activation of some specific gene(s), the translation of which appears to be resistant to chloramphenicol.


The expression of tetracycline resistance after insertion of foreign DNA fragments between the EcoRI and HindIII sites of the plasmid cloning vector pBR 322.

In vitro recombination techniques were used to construct hybrid plasmids between pBR 322 and different DNA fragments derived from pML 21 and the E. coli chromosome. Some of the resulting hybrid plasmids express the tetracycline resistance gene of pBR 322, depending on the DNA fragment which has been ligated into the HindIII-site of pBR 322. From these studies we could conclude the direction of transcription of the kanamycin resistance gene in plasmid pML 21 with respect to the SalI, SmaI, HincII, KpnI, EcoRI and HindIII restriction sites. The replacement of the small HindIII-EcoRI-fragment in pBR 322 by other DNA fragments from the E. coli chromosome and selection for tcr-phenotypes showed that this system may be very useful for screening and analysis of promotor-containing DNA fragments.


Induced mutagenesis in dam- mutants of Escherichia coli: a role for 6-methyladenine residues in mutation avoidance.

E. coli strains carrying the dam-3 and dam-4 mutations resulting in reduced levels of 6-methyladenine in the DNA have been found to be more sensitive to base analogue mutagenesis than dam+ strains. Mutagenesis by EMS was also found to be enhanced in dam- strains. Dam- mutants however were not found to be hypermutable by UV light. It is concluded that the dam- strains are deficient in the correct repair of mispairing lesions. The data are consistent with the hypothesis that 6-methyladenine residues in the DNA are involved in strand discrimination during mismatch correction.


Circular mitochondrial DNA molecules from petite mutants of Saccharomyces cerevisiae: resolution by polyacrylamide gel electrophoresis.

Mitochondrial DNA (mtDNA) from petite strain K45 of Saccharomyces cerevisiae contains about 7% circular DNA molecules which comprise a simple oligomeric series based on a monomeric size of 1.7 kilobase pairs. Electrophoresis of K45 mtDNA on a polyacrylamide-agarose slab gel fractionates the mtDNA into a major band (containing linear DNA) and several faster running minor bands each containing particular size class of circular DNA molecules. From study of mtDNA from K45 and two other simple petites it was found that the mobility of circles is inversely proportional to the logarithm of the circle size. Polyacrylamide gel electrophoresis thus permits the separation of circular mtDNA from the linear mtDNA of simple petites, and physically resolves circles of different size from one another.


"Maturation" of DNA duplexes.

Reassociation of typical single-copy DNAs, like E. coli DNA, even when performed at relatively low temperatures, results in the formation of perfect duplexes with thermal stability very close to that of the native DNA. In contrast, duplexes of mouse repeated DNA as well as duplexes of Streptomyces DNA prepared under the same conditions, show a low thermal stability and undergo post-reassociation changes upon prolonged incubation. These changes, called "maturation" of the DNA duplexes, result in increasing of their thermal stability. Some of the factors affecting the rate of "maturation" are studied. The implication of the "maturation" process in reassociation analysis and in characterization of the heterogeneity of DNA is discussed.


Dissociability of free and peptidyl-tRNA bound ribosomes.

The influence of peptidyl-tRNA on the dissociation of yeast 80 S ribosomes into subunits was studied. For this purpose temperature-sensitive (ts) suppressor strain of yeast Saccharomyces cervisiae carrying a defect in peptide chain termination was used. It was found that peptidyl-tRNA did not influence the dissociation of ribosomes either at high salt concentration or in the presence of dissociation factor (DF) from yeast. After dissociation of yeast ribosomes in 0.5 M KCl, peptidyl-tRNA remains bound to the 60 S subunit. Some characteristics of the termination process and release of nascent polypeptides from yeast ribosomes are discussed.


Altered mitochondrial ribosomes in a cold-sensitive mutant of Saccharomyces cerevisiae.

A mutation at a new locus denoted tsr1 which lies very close to the ery1 locus and 21S rRNA gene in mitochondrial DNA of Saccharomyces cerevisiae, confers conditional respiratory deficiency on cells grown at low temperature, namely 18 degrees. Studies on mitochondria isolated from a strain carrying the mutatated tsr1 locus demonstrate that the rate of mitochondrial protein synthesis is cold-senitive at 18 degrees. The large subunit of the mitochondrial ribosomes isolated from the mutant strain is unstable during extraction and the isolated ribosomes are shown to be defective in catalyzing the poly U-directed synthesis of polyphenylalanine. It is concluded that the tsr1 locus is involved in the determination of the properties of the large subunit of the mitochondrial ribosome.


[Conversion of nucleoside triphosphates in an RNA polymerase system].

The behavior of nucleoside triphosphates (NTP) in the RNA-polymerase system from E. coli was studied. The conversion of NTP to the corresponding nucleoside diphosphate (NDP) was observed. This phenomenon was accounted for a contaminating enzyme activity in the RNA-polymerase preparations. The possibility to remove such a contamination was demonstrated, the best technique being the DNA-cellulose affinity chromatography. The purified enzyme does not catalyze the intermediate formation of NDP's from NTP's during RNA synthesis with poly(U) and poly(dG)-poly(dC) as templates.


[Role of ribonucleic acids in organizing the structure of Escherichia coli ribosomes].

The paper summarizes recent data on the secondary and tertiary structure of RNA in ribosomes. The participation of RNA in intraribosomal interactions and the role of these interactions in organization of ribosomal subunits are discussed. The following conclusions are made: 1) the structure of ribosomal subunits is predominantly created with their RNA components; 2) RNA molecules in ribosomal subunits have a very compact structure; the formation of this structure is followed by the rearrangement of the secondary structure of RNA; 3) the small group of ribosomal proteins plays an important role in the folding of RNA in the compact conformation: they not only stabilize intraribosomal RNA conformation but probably induce new RNA-RNA contacts.


[The depressive child (author's transl)].

Depressive states in childhood often remain unrecognized and so are either handled wrongly or not at all. Some 2--3% of all children with abnormal behaviour are moderately to severely depressed, and a further 6--8% mildly so. The diagnosis of neurotic, constitutional, endogenous and exogenous depression is more difficult in children than in adults, because the depressive symptomes alter with its development. In small children the condition usually presents with psychosomatic complaints, whereas in schoolchildren it produces mixed psychological and psychosomatic manifestations, and in adolescents predominantly psychological depressive symptoms. From the point of view of the child psychiatrist, childhood depression is regarded as "primary" depression, characterized by atypical symptoms; typical adult depressions are "secondary", and masked depression in these age-groups a "regressive" form. Treatment of depressive conditions in children is directed both at the causative factors and the symptoms. Environmentally induced and constitutional depressions mainly need psychotherapy and remedial training, sometimes in conjunction with antidepressant medication. Management of exogenous depression is directed towards the underlying organic disorder. The endogenous phasic depressive illnesses, very rare in children, are a matter for treatment with psychotropic drugs.


[The aggressive child (author's transl)].

In children a "normal" aggressiveness should be distinguished from "hostile" and "inhibited" aggression; the latter usually become apparent as heteroaggressive or autoaggressive behaviour. Autoaggression is more common with younger children. Different hypotheses about the origin of aggressiveness are discussed. In the younger child nail biting, trichotillomania, rocking, an intensified phase of contrariness and enkopresis may have components of aggressiveness. In older children and adolescents dissocial forms of development, drug taking, attempted suicid, and anorexia nervosa may be parts of aggressive behaviour. Minimal brain dysfunction, autism, and postencephalitic syndromes predominate amongst organic alterations of the brain as causes for aggressive behaviour. Particularly the Lesch-Nyhan-syndrome, but equally the Cornelia de Lange-syndrome show autoaggressive tendencies.


[Psychological care in pediatric oncology: patients, family, and personnel (author's transl)].

The improved outlook in many pediatric tumour and leukemia patients has brought about new psychological problems: we no longer have to focus our attention only on death and its implications, but also on the impact of aggressive multimodal therapy, of remission and relapse, of permanent cure alas sometimes paid for by lasting physical defects. There are relatively few "hard" physical data, based on controlled studies, concerning the reactions of the patients themselves and of their environment to the different phases of cancer in children, but certain empirical findings, based on clinical observations and the work of some interested psychologists, allow a number of conclusions to be drawn. The reactions of children to a life-threatening disease and to the possibility of death are mostly age-dependent; parents' reactions, as a rule, follow certain typical patterns superimposed by individual particularities (initial shock, non-acceptance and escape; finally, ways of coping) which ought to be taken into account by the medical and nursing team. The ability to convey hope and trust, competence, self-confidence, emotional stability and continuous personal engagement of those who treat such children are of paramount importance in minimizing psychological damage. Organized group discussions may sometimes be of additional help.


[Electrophoretic study of the acid soluble proteins of Saccharomyces cerevisiae yeast chromatin].

Fractionation of acid-soluble proteins from yeast Saccharomyces cerevisiae chromatin by gel electrophoresis suggested the existence of four histonestone fractions--H2a, H2b, H3, H4 and histone H1-like protein. The latter was isolated according to the second method of Johns and extracted with 5% HClO4. Amino acid analysis of the histone H1-like protein showed a moderately high content of basic amino acids, but a much lower ratio of lysine: arginine (approximately 3) than that of the hisone H1 from higher eukaryotes. In addition to histone H1-like protein a protein X was also extracted with 5% HC1O4. The sequence of the electrophoretic mobilities of histone fractions from yeast coincides with those of histone fractions from plants--H4 greater than H3 greater than H2a greater than H2b greater than H1.


["Killer" plasmid in natural strains of Saccharomyces].

Double stranded RNA's of thirteen wine strains of Saccharomyces belonging to different species and exhibiting killing activity were studied. Two strains of Oxford genetic stocks were used for control. All these strains have four different spectra of killer activity and contain two double stranded RNAs, L and M. All strains regardless of the type of killer activity have the same electrophoretic mobility of L. The mobility of M varies in different strains but is not connected with the spectrum of killing activity. All strains can be cured by cycloheximide. Cured variants have no M. Certain cured strains contain small portions of double stranded RNAs with electrophoretical mobility faster than of M.


[Analysis of the thermostability of the hybrid DNA molecules of microorganisms as a means of increasing the resolution of the molecular hybridization technic].

A comparative study of termostability of microorganisms DNA was performed in order to increase the resolution of the method of molecular hybridization. Molecular hybridization was carried out and the curve of hybrid DNA duplexes distribution, acccording to termostability of two groups of microorganisms, related to strains Echerichia coli B1 and Vibrio cholerae eltor 18647, were obtained. It was determined that the form of the curves is specie specific for the microorganisms investigated but there exists a similarity between the closely related strains which can not be distinguished by the percent of homology.


Amelioration of bronchopulmonary dysplasia after vitamin E administration. A preliminary report.

We studied the effect of vitamin E on the development of bronchopulmonary dysplasis in neonates with respiratory-distress syndrome. Twenty infants received vitamin E administered intramuscularly during the acute phase of the syndrome, and 20 infants served as controls. Administration of vitamin E significantly increased the serum vitamin E concentration. Nine vitamin-treated and 13 control patients required supplemental oxygen for longer than 250 hours; all were treated with positive-pressure ventilation and endotracheal continuous distending airway pressure. Six of those 13 controls had x-ray changes consistent with bronchopulmonary dysplasia, and four died. None of the nine vitamin-treated patients had changes characteristic of bronchopulmonary dysplasia (P = 0.046), and all survived. Administration of vitamin E during the acute phase of the respiratory-distress syndrome appears to modify the development of bronchopulmonary dysplasis.


[X-ray structural analysis of pepsin. V. Conformation of the main chain of the enzyme].

A detailed description of structural investigations of pepsin from 3.5 to 2.7 A resolution are given. The main attention is drawn to the conformation of the polypeptide backbone of the enzyme. The numbers of amino acid residues involved in the formation of various structural elements are listed. The structure of pepsin is similar to that of acid proteases isolated from lower organisms. The two domain structure of all acid proteases has a periodicity in the sequence of beta-segments and helices and a very specific symmetrical structure of each domain. This makes it possible to describe the structure of acid proteases in simple terms.


Efficacy of chest physiotherapy and intermittent positive-pressure breathing in the resolution of pneumonia.

We undertook a randomized clinical trial to evaluate the efficacy of chest physiotherapy and intermittent positive-pressure breathing in the treatment of pneumonia. The diagnosis of pneumonia required a compatible clinical history and x-ray confirmation. A total of 54 patients were assigned to treatment and control groups and were similar in age, smoking history, underlying lung disease and prior antibiotic treatment. Antibiotic therapy, guided by Gram stain and sputum and blood cultures, was similar in both groups. Chest physiotherapy, consisting of postural drainage, percussion and vibration, was given concurrently with intermittent positive-pressure breathing with use of racemic epinephrine every four hours. There was no statistically significant difference in duration of fever, extent of radiographic clearing, duration of hospital stay and mortality between the control and treated groups. Chest physiotherapy and intermittent positive-pressure breathing do not hasten the resolution of pneumonia.


The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial. Survey of 71 "negative" trials.

Seventy-one "negative" randomized control trials were re-examined to determine if the investigators had studied large enough samples to give a high probability (greater than 0.90) of detecting a 25 per cent and 50 per cent therapeutic improvement in the response. Sixty-seven of the trials had a greater than 10 per cent risk of missing a true 25 per cent therapeutic improvement, and with the same risk, 50 of the trials could have missed a 50 per cent improvement. Estimates of 90 per cent confidence intervals for the true improvement in each trial showed that in 57 of these "negative" trials, a potential 25 per cent improvement was possible, and 34 of the trials showed a potential 50 per cent improvement. Many of the therapies labeled as "no different from control" in trials using inadequate samples have not received a fair test. Concern for the probability of missing an important therapeutic improvement because of small sample sizes deserves more attention in the planning of clinical trials.


Cellular sensitivity to collagen in rheumatoid arthritis.

We examined patients with rheumatoid arthritis for cellular sansitivity to native human Types I, II and III collagens. Mononuclear cells from 50 patients with rheumatoid arthritis, 21 with other inflammatory arthritides, 20 with osteoarthritis and 20 normal subjects were evaluated for the in vitro production of leukocyte inhibitory factor in response to collagen and a control antigen, streptokinase-streptodornase. By this assay, cells from 37 (74 per cent) and 39 (78 per cent) of the patients with rheumatoid arthritis responded to Types II and III collagens, respectively. In contrast, cells from the 41 patients with other kinds of arthritis and the normal group did not produce this lymphokine to collagens. There was no response to Type I collagen or to denatured alpha chains of these collagens. All four groups responded equivalently to streptokinase-streptodornase. These data demonstrate that most patients with rheumatoid arthritis exhibit cellular sensitivity to Types II and III collagens.


QB DNA-containing hybrid plasmids giving rise to QB phage formation in the bacterial host.

Hybrid plasmids consisting of PCRI and a complete DNA copy of the RNA genome of coli.phage QB, inserted in either orientation, elicit the formation of phage QB when introduced into Escherichia coli


DNA sequence for a low-level promoter of the lac repressor gene and an 'up' promoter mutation.

The promoter for a weakly expressed constitutive gene, the lactose repressor gene (lacI), has been sequenced, along with an 'up' promoter mutation Iq. The 10-fold enhancement in I expression found in Iq is the result of a single base change at position -35. To facilitate the sequencing, the lacI gene was cloned in a small plasmid.


Sequence of the lacI gene.

The structural gene for the lac repressor of Escherichia coli, the lacI gene has been sequenced. This 1,080 base pair region of the E. coli chromosome codes for the lac repressor protein of 360 amino acids. The DNA sequence largely confirms but extends the previously reported protein sequence and allows a structural analysis of genetic phenomena.


Correlation of nonsense sites in the lacI gene with specific codons in the nucleotide sequence.

Nonsense mutations derived from 90 different codons in the lacI gene of Escherichia coli have been correlated with the I gene nucleotide sequence. In over 80 cases the specific codon which generates the nonsense mutation can be identified. The sequence shows that 14-16 sites arise through tandem double base changes.


Molecular basis of base substitution hotspots in Escherichia coli.

In the lacI gene of Escherichia coli spontaneous base substituion hotspots occur at 5-methylcytosine residues. The hotspots disappear when the respective cytosines are not methylated. We suggest that the hotspots may result from the spontaneous deamination of 5-methylcytosine to thymine, which is not excised by the enzyme DNA-uracil glycosidase.


Heterogeneity of pepsin-solubilized human glomerular basement membrane collagen.

The collagen component of isolated glomerular basement membrane ws solubilized by limited pepsin digestion and further purified. The amino acid and carbohydrate composition of the final material was very similar to that described for the alpha1-chains of type IV collagen. However, the presence of several components was detected when the material was analyzed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis either without or after reduction. The molecular weights of the major components in the reduced material were about 140,000, 100,000, 80,000 and less than 65,000 (in the case of five components). The data thus do not support the previous suggestion that the human glomerular basement membrane contains only one type of collagen polypeptide chain. However, part of the heterogeneity may be due to the presence of more than one collagenous part in a procollagen-type polypeptide chain, and an additional reason may lie in a partial degradation of collagenous portions during pepsin digestion.


The quantitative assessment of lipofuscin pigment, cytoplasmic RNA and nucleolar volume in senile dementia.

Treatment of patients suffering from senile dementia with meclofenoxate has been reported to result in an improvement in mental performance. Furthermore meclofenoxate reduces the amount of lipofuscin pigment in nerve cells. We have shown that, although nerve cells in a group of demented patients have decreased amounts of cytoplasmic RNA and reduced nucleolar volume, they contain no more pigment than do cells of a control group. It seems, therefore, unlikely that removal of lipofuscin, per se, has any bearing on this reported improvement in intellectual capability, nor is it implicated in the aetiology of senile dementia.


[Comparison of EMG tracings obtained by means of computer analysis and by routine quantitative method].

The purpose of the present work was to compare EMG tracings obtained by the automatic method using the computer ANOPS and by the method of quantitative electromyography. The measurements of the automatic method were found to be reliable and reproducible permitting to distinguish normal from pathological tracing, and in the pathological tracing to discriminate between the so called primary muscular and the neurogenic changes. The automatic method permits a much larger number of potentials to be evaluated, besides it is less time consuming and more objective since it rules out subjective selection of potentials which is a drawback in the conventional method.


The treatment of intracranial aneurysms by injection with a tissue adhesive.

The authors have developed a technique of occluding intracranial aneurysms by the direct injection of a tissue adhesive. Previous work in our laboratory had revealed the unusual intravascular characteristics and physiological properties of isobutyl-2-cyanoacrylate (IBC). These findings had indicated the feasibility of utilizing IBC in the treatment of intracranial aneurysms by its direct injection. We have now treated twenty patients by this method. Eighteen aneurysms were injected during open craniotomy and two were treated by closed stereotactic injection utilizing electronic radiography. Follow-up data, ranging from 1 to 6 years after operation, are available on these patients. Sixteen patients (80% of the series) have had good to excellent results. Our experience and the application of this technique as a potential tool in the treatment of intracranial aneurysms are discussed.


Neurosurgery and the anatomy of reading: a practical review.

Tumors and vascular malformations in the posterior parts of the dominant hemisphere are frequently associated with preoperative alexias, and surgical maneuvers in these areas may cause the appearance of this neurobehavioral deficit as an operative complication. Lesions of the dominant (left) angular gyrus are associated with the syndromes of alexia with agraphia. Alexia without agraphia results from lesions of the pathways which conduct visual information from the calcarine areas to the left angular gyrus (splenium of the corpus callosum, left lingual and fusiform gyri, left transverse and vertical occipital fasciculi). A brief bedside examination (outlined in the text) provides useful pre- and postoperative localizing information. Fresh cadaver studies of the brain in situ have shown that the approximate center of the left angular gyrus area is found by first locating a point 9 cm forward along the midline from the inion and then moving 4 1/4 cm laterally. These measurements define a point which is a few centimeters medial and posterior to the center of the parietal eminence.


A technical modification of Cloward's posterior lumbar interbody fusion.

The concept of interbody (intercorporal) fusion as a useful treatment for intervertebral disc disease in the cervical area has been well received. Thirty-two years have passed since Cloward first introduced his technique of posterior lumbar intervertebral fusion. The author believes that the delayed acceptance of this procedure is due to fear of technical difficulties. A technical modification of Cloward's posterior lumbar interbody fusion is introduced. It entails better technique in controlling epidural bleeding by careful positioning of the patient and the use of oxidized cellulose as a tampon in the epidural space. The integrity of the facet is preserved through a more limited interlaminal approach. Osteosynthesis of the grafts is assured by multiple perforations of the cortical plate in accordance with Robinson's principle utilized in cervical interbody fusion. The author believes that the modification simplifies the Cloward posterior lumbar interbody fusion. It also assures better stability after surgery by retention of the facet and lessening the dangers of settlement of the graft by preservation of the cortical plate. In a series of 75 cases, tomograms made 4 months after operation have shown a viable graft with active osteosynthesis between the graft and the adjoining vertebral bodies in 94%.


The development of modern intracranial aneurysm surgery.

This history of the steps leading to the modern surgical treatment of intracranial aneurysms begins some 200 years ago when it was found that cervical carotid artery ligations (for trauma) could be tolerated. This discovery led, early in the 1800's to the use of carotid ligation for the treatment of carotid-cavernous fistulas and eventually for the treatment of intracranial saccular aneurysms. The era of modern intracranial surgery for aneurysms began after Moniz introduced cerebral angiography in 1927. The first trapping procedure (for a carotid-cavernous fistula) was performed in 1932, and the first successful planned intracranial operation for a saccular aneurysm was reported in 1933. Subsequent developments are chronologically cited, together with mention of methods now obsolete.


Respiratory problems associated with head trauma.

Respiratory problems occur commonly in association with severe head injury. Seven easily measured parameters for the diagnosis of respiratory insufficiency are outlined. Certain central and peripheral causes of insufficient ventilation are analyzed, including head trauma and drug overdose as central sources and aspiration, pulmonary edema, disseminated intravascular coagulopathy, fat embolism, chest trauma and iatrogenic complications as peripheral causes. Establishment of the diagnosis and management of the problems within each category are discussed.


Spinal dysraphism: a comprehensive diagnostic approach.

Twelve patients with the clinical findings of spinal dysraphism form the basis for this report. In eight patients, physical findings, plain x-rays, and unenhanced spinal computed tomography allowed for precise diagnosis and subsequent therapy, without contrast myelography. All patients in the study had intravenous pyelography, and this revealed evidence of renal deterioration in two. The other 10 patients had radiographically normal upper urinary tracts. Urodynamic assessment was performed in seven; three were normal and four were abnormal. The pattern of the abnormal studies (three "flaccid type" with an adequate urethral pressure profile and one with detrusor-sphincter dyssynergia) allowed for appropriate therapy to be employed for bladder emptying and continence. Both spinal computed tomography and urodynamic testing serve as noninvasive studies that can be employed in the follow-up and management of patients with spinal dysraphism.


[Acute hepatic failure and renal damage. Experimental and clinical studies].

Renal damage in acute hepatic failure induced in the pig by means of an hepatic state, temporary or permanent devascularisation Amanita phalloides poisoning or orthotopic liver transplant proved of slight degree, particularly in animals treated with replacement therapy. In the cases of animals that died in acute hepatic coma, on the other hand, renal cortex ischaemia and marked medullary congestion were constant. Histologically, the damage consisted of slight tubular nephrosis; this was more apparent in the proximal tubules. Evaluation of renal damage in 38 patients with acute hepatic failure was more complicated owing to the variety of clinical conditions (level of coma, hypovolaemia, intensive care and hepatic assistance). Nevertheless, a clear relation was established between the degree of liver damage and blood creatinine and creatinine clearance values. All patients who died presented liver cell necrosis of over 75%, blood creatinine values of more than 2 mg/100 ml, and less than 50 ml/min clearance. Tubular nephrosis was the predominant lesion. It appeared that renal damage was primarily pre-renal. No signs of a true hepatorenal syndrome could be made out.


[The significance of cryoglobulins and cryohemagglutinins. Immunological and clinical study of 39 cases].

In about 5 years of clinical and immunological research, 39 cases of cryoplasmopathies (5 with cryoglobulinaemia and 34 with cryohaemoagglutinaemia) were identified on the basis of immunological typing studies (immunoelectrophoresis, immunodiffusion, identification and isolation of cryoantibodies, cryocrit, titration, identificcation of antibody specificity). Discussion and physiopathological interpretation of possibly associated cases and diseases are conducted on the basis of personal immunological data and the most recent literature on matters of clinical immunohaematology.


The amyloidosis.

The clinical and pathological features of amyloidosis are examined in the light of a classification based on anatomical models of amyloid distribution: 1) generalised amyloidosis, including primary and secondary sporadic forms, hereditary and familial amyloidosis, and senile amyloidosis; 2) local amyloidosis, including amyloid tumours, neoplasia with amyloid stroma, and other forms. The nature of amyloid is described. Morphological, ultrastructural, biochemical and immunochemical research has shown that: 1) amyloid is a fibrillar protein with a typical EM and X-ray diffraction appearance; 2) two main types of amyloid proteins exist, one related to Ig light chains and found in primary forms and in association with myeloma, the other (called AA proteins) being the main component of secondary forms and certain types of familial amyloidosis; 3) serum proteins structurally related to the AA proteins may be used as amyloid precursors. The cause and mechanisms of amyloid production are becoming clearer. In particular, a relation with the production of Igs has been established. Improved methods for the diagnosis and treatment of the disease will throw more light and the nature of amyloid and its protein precursors.


[Preliminary results of treatment with Tagamet (cimetidine SK and F) in gastric and duodenal ulcers].

Following 3x200 mg Tagament (cymetidine SK & F) tablets at meals and 2 in the evening (5 per day) for an average of 31 days, complete endoscopic cure was obtained after 29 days (duodenal patients) and 35 days (gastric patients) in 26/27 subjects with slow healing histories (17 with duodenal and 10 with gastric ulcer). Rapid regression of pain and dyspepsia was observed form the outset and there was a marked reduction in the consumption of antacid preparation. Its marked efficacy and good tolerance make Tagamet a drug of choice in the treatment of peptic, duodenal and gastric ulcers.


Naproxen in the treatment of rheumatoid arthritis.

Naproxen, a new nonsteroidal anti-inflammatory analgesic drug was found to be better than placebo and as effective as indomethacin in the treatment of rheumatoid arthritis. The drug was well tolerated, and appears to be a useful alternative to more established medication such as aspirin.


Effects of bromocriptine mesylate on the composition of the mammary secretion in non-breast-feeding women.

A double-blind trial was performed on 26 women, who had elected not to breast-feed their infants, to determine the effect of bromocriptine mesylate (2.5 mg twice daily for 14 days postpartum) on the composition of the mammary secretion during lactogenesis. Mammary secretion (less than 5.0 ml) was collected from each breast of each woman at daily intervals during the 14-day treatment period and the progressive changes in the concentration of the milk constituents, lactose, alpha-lactalbumin, serum albumin, total protein, lactoferin, IgA, IgG, sodium and potassium were determined. The degree of milk leakage and breast engorgement were also assessed. Both the subjective assessments and the changes in the concentration of the milk constituents demonstrated that lactogenesis occurred between about Day 2 and Day 5 postpartum in the placebo group (in the absence of the suckling stimulus) but was suppressed in the bromocriptine-treated group.


Puerperal infection due to group A beta hemolytic streptococcus.

A cluster of 5 patients with puerperal infection due to group A beta hemolytic streptococcus (GABHS) is described. The most striking clinical signs included the early onset of uterine tenderness followed by an abrupt temperature elevation to greater than or equal to 102 F. At the time of uterine tenderness (Day 2, postpartum), 4 of 5 patients had gram-stained lochial smears showing a predominance of gram-positive cocci. The cluster of cases occurred with no source of the infection identified after 365 culture attempts. Therapy was rapidly successful with intravenous penicillin.


Low-dose carbenicillin prophylaxis for vaginal and abdominal hysterectomy.

A double-blind prospective study of 99 patients undergoing vaginal and abdominal hysterectomy was performed at North Carolina Baptist Hospital of the Bowman Gray School of Medicine at Wake Forest University. The study indicated that low-dose intravenous carbenicillin begun preoperatively and continued for 24 hours resulted in decreased febrile morbidity, postoperative infection rate, and shortened hospital stay in patients undergoing both vaginal and abdominal hysterectomy. The indications for operation, clinical characteristics of patients, and operative and postoperative management were similar for the control and study groups. For the vaginal hysterectomy group, febrile morbidity was reduced from 34.6% in the control group to 7.7% in the group receiving carbenicillin. For patients undergoing abdominal hysterectomy, febrile morbidity was reduced from 54.1% in the control group to 4.0% in the group receiving prophylactic carbenicillin. Similar reductions for the carbenicillin study group in fever index and average total hospital stay were also noted. Urinary tract infections were determined to be present more commonly in the group of patients with febrile morbidity receiving no prophylactic antibiotics. The incidence of pelvic infections were reduced in both carbenicillin-treated groups. This investigation suggests that low-dose carbenicillin prophylaxis is beneficial in reduction of morbidity following both vaginal and abdominal hysterectomy.


Progressive necrotizing wound infections in postirradiated patients.

Five cases of postoperative progressive gangrenous wound infection are described in patients who had received whole pelvis irradiation prior to surgery for genital tract cancer. The syndrome described as distinct from Meleney Type I and II ulcers. Predicated on the experience derived, a scheme for its management is proposed.


Pituitary gonadotropin response to LHRH in human pregnancy.

The effect of synthetic LHRH on serum levels of FSH, LH, and hCG was determined during early and midgestation. Eight healthy volunteers were studied during the first (8--9 weeks) and second (15--20 weeks) trimesters of pregnancy with 4 patients in each group. Serum samples, obtained before and 15, 30, 45, 90, 120, 150, and 180 minutes after an intravenous bolus of 100 microgram LHRH, were assayed for LH, FSH, and hCG by specific radioimmunoassays. Serum levels of estradiol, progesterone, and 17 alphahydroxyprogesterone were also measured in samples obtained prior to and 3 hours after LHRH injection. The serum levels of LH and FSH were undetectable in all samples, and no increase was observed after administration of LHRH. Levels of chorionic gonadadotropin, estradiol, progesterone, and 17alpha-hydroxyprogesterone did show slight fluctuations, but there was no significant effect from LHRH administration. These results support the concept that pituitary gonadotropic function is markedly suppressed during early human pregnancy.


Antimicrobial effect of amniotic fluid.

The antimicrobial effect of amniotic fluid (AF) obtained during the first (AF1) and second (AF2) trimesters was compared with the third (AF3) against anaerobic bacteria, such as Bacteroides fragilis ss. fragilis (6 strains), Eubacterium lentum (3 strains), and Peptostreptococcus anaerobius (4 strains). Escherichia coli (5 strains) served as a positive control. AF1 supported the growth of all 4 anaerobes (except B fragilis for 4 hours) for the entire 24-hour period tested. AF2 supported the growth of E coli and B fragilis for 24 hours but temporarily inhibited P anaerobius and E lentum. In contrast, AF3 inhibited all bacteria tested for 8 hours or more. It is concluded that AF1 is the least inhibitory, AF3 the most, and AF2 intermediate for the organisms tested. Lack of antimicrobial effect of AF on anaerobic bacteria may be one explanation for the higher incidence of anaerobic infections during absortion than during the prenatal period.


Cervicofacial abcesses of unknown origin. A survey of eighty-one cases.

A survey of eighty-one patients with cervicofacial abscesses of unknown origin is presented. The salient clinical features and the treatment of the abscesses are described. Mainly affected were children under 4 years of age, and the submandibular and submental regions were the most common sites of involvement. Staphylococcus aureus was the predominant pathogenic organism, and epidemic strains were implicated in some cases. A high incidence of resistance to penicillin was noted. The nasal vestibule is postulated to be reservoir of the organisms, and the possible relationship between infection, malnutrition, and a mild degree of anemia is examined.


Evaluation of preoperative ibuprofen for postoperative pain after removal of third molars.

An evaluation of the analgesic effects of preoperatively administered ibuprofen on prospective pain after the surgical removal of impacted third molar was undertaken in 100 patients in a double-blind parallel treatment trial. The pretreatment with ibuprofen delayed the mean time of onset of postoperative pain more than 100 minutes, as compared to pretreatment with placebo. The severity of pain initially experienced postoperatively was less in the pretreated group. There was no detectable interaction between the pretreatment and the analgesics administered postoperatively. The results of this study suggest that it is possible to delay the onset and lessen the severity of postoperative pain by preoperative administration of a nonsteroidal, antiinflammatory analgesic, such as ibuprofen.


Betamethasone-17-benzoate in the treatment of recurrent aphthous ulcers.

A double-blind study of the effectiveness of betamethasone-17-benzoate in the treatment of recurrent aphothous ulcers (RAU) was concucted. The drug was found to be effective in reducing symptoms and shortening healing time but not in preventing recurrences. Evaluation of the medical histories and laboratory studies suggests that multiple factors may be involved in the etiology of RAU, as reported by others.


The bactericidal potential of various endodontic materials for primary teeth.

An in vitro study of the bactericidal or bacteriostatic effects of several pulp therapy compounds and their components on selected bacterial commonly isolated from infected primary teeth was undertaken. It was determined that zinc oxide had no inhibitory effects on E. coli, Staph. aureus, and Strep. viridans; however, the addition of  eugenol to this system retarded the growth of only the grampositive organisms. The inclusion of zinc acetate as a setting accelerator inhibited both gram-positive and gram-negative bacteria. Also the inhibitory effects on these three organisms could be greatly enhanced by the addition of formocresol or paraformaldehyde to the zinc oxide--eugenol--zinc acetate system. It was also noted that Sargenti's N-2 paste was apparently no more effective in retarding growth of these organisms than the mixtures. Only the lead tetroxide and hydorcortisone present in the N-2 paste was toxic to the Staph. aureus but not to E. coli or to Strep. viridans. The other heavy metals in N-2 apparently have no antibacterial activity in the manner in which they were tested. This evidence suggests, but is not conclusive, that zinc oxide--eugenol--zinc acetate, with or without formaldehyde-containing compounds, may be effective in the elimination of bacteria from pulpotomized primary teeth. Therefore, the addition of highly cytotoxic chemicals which will remain sealed in a root canal and be active for extended periods of time may not be necessary for successful treatment.


Submergence of roots for alveolar bone preservation. II. Reimplanted endodontically treated roots.

Root canal therapy was accomplished on the mandibular premolars of four dogs. These premolars were then extracted, contoured, reimplanted, and submerged. Resorption occurred up to 60 days; healing progressed satisfactorily, with some evidence of coronal osseous regeneration. Root canal sealer was expressed out the coronal orifice after the roots were submerged. This sealer appeared to affect normal healing over the coronal surface of the roots.


Myxoedema coma. A review.

Myxoedema coma is a rare emergency needing prompt recognition and urgent treatment before diagnostic confirmation. The pathyphysiology, clinical features, differential diagnosis, investigations and treatment are described. Triiodothyronine in small doses intravenously with continuous cardiac monitoring is suggested. Slow rewarming, care of the airway and prompt treatment of hypoventilation by assisted ventilation, the use of hydrocortisone and the avoidance of sedatives, vasopressors and overloading are also discussed, as is prevention. This emergency occurs in elderly people often with co-existent disease and thus only close attention to detail will be rewarded with improving results and falling mortality figures.


Lipoid nephrosis and focal glomerulosclerosis.

Forty-one renal biopsies from 34 patients presenting over a 7-year period with the nephrotic syndrome or significant proteinuria and considered initially to be cases of lipoid nephrosis have been reviewed, and the results correlated with clinical findings. Lipoid nephrosis was confirmed in 25 of the patients (20 males, 5 females) 6 of whom showed a small proportion of completely sclerosed glomeruli. Twenty-two of these patients were in remission at the time of review. Nine of the patients (4 males, 5 females) showed features typical of focal glomerulosclerosis; only 4 of these were in remission, 4 showed continuing proteinuria, and one had died. The study emphasizes the importance and problems of distinguishing lipoid nephrosis from focal glomerulosclerosis.


Lymph node and splenic imprints: their value in diagnosis.

Comparison was made of the value of information obtained from imprints and from histological sections of lymph nodes from 100 biopsies on patients with mainly haematological disorders and 55 spleens removed surgically. The sections provided the definitive diagnosis. It was seldom possible to make a definite diagnosis from imprints, but they provide additional information useful in interpreting the histology of sections.


[On the hypotensive activity of carrageenan iota in the rat (author's transl)].

1. Carrageenan iota and dextran sulfate deplete the plasmatic stores of kininogens in the Rat. 2. A slow intravenous infusion of carrageenan iota in the anaesthetized Rat produces a lowering of blood pressure which is only transient because of the development of tachyphylaxy. At this stage the cardio-vascular system which fails to respond to carrageenan iota injection is also refractory to ellagic acid administration. After depletion of the plasmatic stores of kininogens by dextran sulfate, glandular kallikreins or ellagic acid, carrageenan iota has lost its hypotensive properties. It is concluded that the cardio-vascular effects of carrageenan iota are mainly due to activation of the kininogenskinins system. 3. Indomethacin curtails the hypotensive effects of kinins by inhibition of the release of prostaglandins by these polypeptides. It also reduces the duration of the hypotensive response to carrageenan. Carrageenan iota is neither a histamine nor a 5-hydroxytryptamine liberator.


The longevity of Clonorchis sinensis.

The persistence of Clonorchis sinensis infestation of the bile duct for a period of at least 26 years without neoplasia supervening is reported in a Chinese immigrant to Australia.


[Hodgkin's disease. T lymphocyte defect in patients in complete remission (author's transl)].

11 patients with Hodgkin's disease in remission, including 7 patients with an initial stage III-IV, off treatment for at least 6 months, were tested for blood T lymphocyte functions. All were completely re-evaluated at the end of treatment to assess complete remission. The number of peripheral blood lymphocytes was below 1,200/cu mm 5/11 patients. Absolute numbers of E-rosette-forming T lymphocytes were decreased in 8 patients, whereas active rosettes were normal in 4/6. A slightly increased percentage of EAC rosettes, a marker for B lymphocytes, was found in only 2 patients. In vitro lymphocyte reactivity to a sub-optimal dose of PHA was studied in 9 patients. A statistically significant defect of lymphocyte transformation was observed in the patient group T lymphocytes. A membrane change is suggested rather than a true depletion. The persistance of such abnormalities long after treatment may raise the question of a complementary immunostimulating treatment in these patients.


Computerized system for the selection of the most HLA-compatible kidney recipient (France-Transplant).

The RITRAN program is applied to renal transplantation and operates within the framework of France Transplant. It makes it possible to choose the most compatible kidney recipient within the ABO blood group system and within the major histocompatibility system in man (HLA). The file presently comprises the data stored on tape concerning 1800 dialysis patients who are awaiting grafts. It is managed by UNIVAC 1108 computer. More than 25 medical-surgical transplant teams from France, Switzerland, Holland and Spain are connected with the computer. It was five years ago that the first interrogation system began operating in real time 20 hours out of 24, using a telex line, and it continues to provide complete satisfaction. The updating of the data is done by the RITREC system, also using a telex machine. An adaptation of the programs applied for choosing blood and platelet donors is in the process of being realized.


A micromethod for measuring neutrophil candidacidal activity in neonates.

We developed a micromethod, requiring but a few drops of blood, for measuring the ability of neutrophils to kill ingested Candida albicans. The neutrophils of 10 normal adults killed 26.2 +/- 9.5% of ingested C. albicans in 2.5 hr in a standard fungicidal assay, and 21.4 +/- 6.5% in our new micromodification. Neutrophils from 14 full term, healthy 30- to 40-hr-old infants, studied with the micromethod, killed 23.2 +/- 6.0% of ingested C. albicans. We conclude that the neutrophils of normal neonates are competent in this sphere of antimicrobial activity.


The stimulus secretion coupling of glucose-induced insulin release. XXVII. Effect of glucose on K+ fluxes in isolated islets.

The effect of glucose upon the handling of K+ by islets of Langerhans removed from normal rats was investigated by measuring both the net uptake of 86Rb+ and its efflux from prelabelled islets. The inflow of K+ into islet cells is mediated, in part at least, by an ouabain-sensitive pump. Glucose fails to affect the inflow rate of K+, but it apparently decreases the permeability of islet cells plasma membrane to effuent K+. The glucose-induced change in permeability is a rapid and rapidly reversible phenomenon. Under steady-state conditions, it leads to an increase in the islet cells K+ pool and a decrease of its fractional turnover rate.


A diffractometer using a lateral effect photodiode for the rapid determination of sarcomere length changes in cross-striated muscle.

A simple method is devised to record rapid sarcomere length changes of muscle fibres using a lateral effect diode. In the standard position the diffractometer records length changes between 1.65 and 3.8 micron, the output being linear 1 V/micron with a frequency response of -3 dB at 1.2 kHz. The absolute error is less than 0.05 micron between 1.65 and 2.80 micron and less than 0.1 micron between 2.81 and 3.30 micron. The resolution of length changes is less than 0.005 micron over the whole range. By varying the detector position the length range can be extended to either side, and spatial resolution can be improved at the expense of length range.


Standardized fixation of human lung for radiology and morphometry; Description of a "two chamber"-system with formaldehyde vapor inflation.

In order to obtain optimal preservation of lungs for histology, morphometry and radiology a two-chamber system of lung fixation with hot formaldehyde vapor is introduced. Compared with other procedures this system offers small dead space and ensures quick and thorough fixation by imitating "inspiration" and "expiration". Volume- and pressure-regulated "breathing" enables fixation in a stage of the respiration cycle, which can be chosen. This procedure can be used routinely in the autopsy room. The only serious drawback seems to be air pollution, if the chambers are not absolutely insulated.


[Resistance of yeast cells to plastics and elastics].

For the investigation of plastics and elastics several sensitive biological methods are in use. In the Pharmacopeia of GDR, 2nd edition, a safety-test on isolated frogheart is prescribed for plastics and a safety-test on daphnia magna for elastics. Ionescu-Stoian had recommended a test using saccharomyces cerevisiae. We found a good conformity of the result given by this test with the results of the daphnia-test. On the other hand, the saccharomyces cerevisiae-test is much more sensitive than the test with isolated frogheart.


[Complex pneumoconiosis in dental laboratory technicians].

Five cases of complex pneumoconiosis are described in dental prosthesis makers. The histo-spectrographic analysis with Castaing's microprobe of the lung fragment obtained by surgical biopsy revealed a complex disease associating silicosis of cobalt pneumoconiosis.


Pretransplant assays of alloimmunity in predicting renal graft outcome.

Forty-one renal allograft recipients were studied for evidence of specific antidonor alloimmunity prior to transplantation. Pretransplant evidence of antibody to the donor as detected by ADCC correlated with the occurrence of early graft loss. This suggests that the ADCC may serve as a useful pretransplant corssmatching procedure.


Long-term results of renal transplantation in children.

Of 81 children at risk for 5 to 11 yrs following an initial renal allograft, 62 (77%) are alive and 54 (67%) have a functioning allograft. Growth retardation remains a significant problem following transplantation in children; however, rehabilitation is excellent with 94% of recipients surviving with a functioning allograft engaged in age appropriate activities.


Renal transplantation in systemic lupus erythematosus.

Patients with end-stage renal disease secondary to SLE with or without preceding nonrenal disease manifestations, should have dialysis and/or transplantation offered to them. There is no increased risk of allograft rejection. Neither does there appear to be excessive risk of recrudescence of SLE disease activity.


Mechanism of ultraviolet-induced mutagenesis: extent and fidelity of in vitro DNA synthesis on irradiated templates.

The effect of UV irradiation on the extent and fidelity of DNA synthesis in vitro was studied by using homopolymers and primed single-stranded varphiX174 phage DNA as substrates. Unfractionated and fractionated cell-free extracts from Escherichia coli pol(+) and polA1 mutants as well as purified DNA polymerase I were used as sources of enzymatic activity. (DNA polymerases, as used here, refer to deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7.) The extent of inhibition of DNA synthesis on UV-irradiated varphiX174 DNA suggested that pyrimidine dimers act as an absolute block for chain elongation by DNA polymerases I and III. Experiments with an irradiated poly(dC) template failed to detect incorporation of noncomplementary bases due to pyrimidine dimers. A large increase in the turnover of nucleoside triphosphates to free monophosphates during synthesis by DNA polymerase I on irradiated varphiX174 DNA has been observed. We propose that this nucleotide turnover is due to idling by DNA polymerase (i.e., incorporation and subsequent excision of nucleotides opposite UV photolesions, by the 3'-->5' "proofreading" exonuclease) thus preventing replication past pyrimidine dimers and the potentially mutagenic event that should result. In support of this hypothesis, DNA synthesis by DNA polymerase from avian myeloblastosis virus and by mammalian DNA polymerase alpha, both of which are devoid of any exonuclease activity, was found to be only partially inhibited, but not blocked, by UV irradiation of the template and accompanied by an increased incorporation of noncomplementary nucleotides. It is suggested that UV mutagenesis in bacteria requires an induced modification of the cellular DNA replication machinery, possibly an inhibition of the 3'-->5' exonuclease activity associated with DNA polymerases.


Functional covalent complex between elongation factor Tu and an analog of lysyl-tRNA.

Complex formation between elongation factor Tu, GTP, and Nepsilon-bromoacetyl-Lys-tRNA results in the cross-linking of the protein and the modified Lys-tRNA. The efficiency of affinity labeling is greater than 50%. In the presence of unmodified Lys-tRNA, the amount of crosslinking is greatly decreased. There is no covalent reaction with elongation factor Tu in the absence of complex formation. Substantial purification of the crosslinked ternary complex can be achieved by gel filtration at low Mg2+ concentration and passage through nitrocellulose filters. The crosslinked complex exhibits message-dependent binding to ribosomes which is accompanied by the hydrolysis of the associated GTP, as shown by both filter assays and gel filtration profiles. The crosslinked complex therefore appears to function normally except for its inability to dissociate. These experiments demonstrate that the ternary complex is the true intermediate in the binding of aminoacyl-tRNA to the ribosomes.


ATP-induced conformational changes in the restriction endonuclease from Escherichia coli K-12.

ATP induces a conformational change in the Escherichia coli K-12 restriction enzyme that allows it to discriminate between unmodified and modified DNA recognition sequences. This conformational change does not require ATP hydrolysis. However, ATP hydrolysis is a requirement for DNA cleavage.


Direct demonstration of duplicate tuf genes in enteric bacteria.

Radioactive tuf mRNA was used to detect the tuf gene in bacterial DNA that had been digested by various restriction endonucleases. Both the K-12 and the B strains of Escherichia coli contain two tuf genes, but no more than two. Salmonella typhimurium also contains duplicate tuf genes.


Evaluation of the partitioning of bound inorganic phosphate during medium and intermediate phosphate in equilibrium water oxygen exchange reactions of yeast inorganic pyrophosphatase.

During the rapid exchange of oxygens of Pi with water catalyzed by yeast inorganic pyrophosphatase, Pi at the catalytic site may either dissociate or undergo reversible loss of an oxygen to water. The effective partitioning of bound Pi during exchange starting with medium Pi containing 18O in all four oxygens has been evaluated by mass spectral analysis of the change in the distribution of Pi species containing zero to four 18O oxygens per Pi. This analysis indicates that the rate of Pi release from the enzyme is only 1.4 times faster than the rate of reformation of the anhydrous intermediate. A similar partitioning of bound Pi is observed during PPi hydrolysis, indicating that hydrolysis and medium exchange have common intermediates. The approach should be applicable to study of related phosphate oxygen exchanges.


Visualization of the intracellular development of bacteriophage lambda, with special reference to DNA packaging.

To reveal intermediates in lambda DNA packaging, infected cells were osmotically ruptured and the cell lysates were deposited on electron microscope grids by sedimentation through a sucrose/formalin cushion. A fixation procedure that crosslinks head-related structures to DNA allowed us to study successive stages in the process of head filling. Three types of head-related structures can be distinguished: (i) empty heads (petit lambda), less angular in outline than complete lambda heads; (ii) heads partially filled with DNA (partially filled heads), having a roundish outline; and (iii) particles tightly packed with DNA (full heads), having a hexagonal outline. DNA-head complexes were bound either at the terminal end of a DNA thread or at a point intermediate along the thread. The terminal complexes were more abundant. No head-related structures could be found in an induced lambda mutant lysogen blocked in the synthesis of petit lambda (amber in lambda gene E). One type of mutant blocked in DNA packaging (amber in gene A) produces empty heads and free tails, whereas another (amber in gene D) produces partially filled heads in addition. Our data suggest that a DNA-petit lambda complex may be an early intermediate in packaging and that the lambda DNA substrate can be a cohesive-ended concatemer or a concatemer with double-stranded cohesive site sequences.


Identification of the structural proteins of an ATP-driven potassium transport system in Escherichia coli.

The three structural proteins of the ATP-driven Kdp potassium transport system of Escherichia coli [Rhoads, D. B., Waters, F. B. & Epstein, W. (1976) J. Gen. Physiol. 67, 325-341] have been identified and found to be located in the inner membrane. The high-affinity repressible Kdp system in one of four potassium transport systems in E. coli. The Kdp proteins were identified both in growing cells as well as in heavily UV-irradiated cells infected with transducing phages carrying the kdp operon. Although all previously identified ATP-driven transport systems of Gram-negative bacteria have been shown to contain a periplasmic protein component, no evidence was found for such a component or for an outer membrane component of the Kdp system. The molecular weights of the three inner membrane proteins, KdpA, KdpB, and KdpC, were determined to be 47,000, 90,000 and 22,000, respectively.


Novel template requirements of N4 virion RNA polymerase.

A DNA-dependent RNA polymerase has been purified from disrupted virions of the Escherichia coli bacteriophage N4. The RNA polymerase is phage-coded and is required for class I N4 RNA synthesis, which is defined as RNA synthesized in vivo in the absence of post-infection protein synthesis. A polypeptide of molecular weight 350,000 is detected when the purified enzyme is analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. N4 RNA polymerase requires denatured DNA as a template in vitro and shows a strong preference for denatured N4 DNA. With this template, transcription is asymmetric. The RNA product is complementary to only the H strand of N4 DNA. Furthermore, only class I N4 RNA is synthesized. In vivo transcription by the N4 virion RNA polymerase is inhibited by coumermycin. This result suggests that the activity of E. coli DNA gyrase, an enzyme that introduces negative supertwists into DNA, is required for N4 transcription.


Reconstitution of purified detergent-soluble HLA-A and HLA-B antigens into phospholipid vesicles.

Purified detergent-soluble human histocmpatibility antigens (HLA-A and HLA-B) were reconstituted into phospholipid vesicles by mixing the protein and lipid together in the presence of either octylglucoside (octyl-beta-D-glucopyranoside) or deoxycholate and removing the detergent by dialysis. The resulting preparation consisted of lipid vesicles containing all or most of the added protein. The protein in the vesicles was antigenically active, as demonstrated by specific binding to anti-beta2-microglobulin IgG-Sepharose beads and by specific inhibition of alloantibody and complement-mediated cytotoxicity. Protein incorporated into vesicles at a protein/phospholipid ratio of 1:10 showed an asymmetric distribution of the HLA-A and HLA-B molecules, with virtually all of the antigens oriented facing the external medium. Cleavage experiments with proteases showed that the molecule was attached to the vesicle membrane via the COOH terminus, consistent with its proposed structure in intact cellular plasma membranes. Electron micrographs of the vesicles showed 50-60 A knobs on the outer surface similar to structures observed for other membrane proteins. HLA-A and HLA-B could also be incoporated into vesicles together with Semliki Forest virus membrane proteins. The resulting preparations should be useful in defining the molecular interactions involving HLA-A and HLA-B antigens in the immune response.


Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431.

The binding and internalization of epidermal growth factor (EGF) in human epithelioid carcinoma cells (A-431), which have approximately 2.6 X 10(6) receptors per cell, has been followed with 125I-labeled EGF and by fluorescence microscopy. We have prepared a fluorescent derivative of EGF that is biologically active and retains substantial binding affinity for cell receptors. After binding of this derivative to cells at 6 degrees, the cellular borders were prominently stained and the fluorescence on the remainder of the membrane was uniform. Upon warming of these cells to 37 degrees for 10 min, the surface fluorescence diminished and randomly distributed endocytotic vesicles appeared in the cytoplasm. After 20 min at 37 degrees these fluorescent vesicles formed a perinuclear ring. The binding of EGF to the surface of these cells was also visualized by immunofluorescence using rabbit antibodies to EGF and rhodamine-labeled goat anti-rabbit antibodies. We did not detect large fluorescent clusters or cap formation in these experiments. These data provide direct confirmation of the previous biochemical data that suggested that cell membrane-bound EGF is rapidly internalized.


Transport of long-chain fatty acids by Escherichia coli: mapping and characterization of mutants in the fadL gene.

A new locus (fadL) that is required for the utilization of long-chain fatty acids has been mapped and partially characterized in an Escherichia coli mutant. The fadL locus has been mapped at 50 min on the chromosome. A mutant bearing a defect in this locus cannot utilize long-chain fatty acids as a sole carbon source. Derivatives of this mutant that can grow on decanoate (termed fadR) are capable of growth on medium-chain but not long-chain fatty acids. It is believed that the fadL mutants is defective in the transport of long-chain fatty acids into the cell for the following reasons: (i) fadR fadL strains can oxidize in vivo decanoate but not oleate; (ii) neither fadL nor fadR fadL strains can incorporate oleate into their membrane  lipids; (iii) the activity of the acyl-CoA synthetase (EC 6.2.1.3) in fadR fadL strains is comparable to the acyl-CoA synthetase activity in fadR fadL+ strains; and (iv) in vitro extracts from fadR fadL+ strains. If the above hypothesis is correct, the uptake of long-chain fatty acids by E. coli requires at least two gene products.


Enhancement of the neonate's nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant.

N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) and certain derivatives that are structural analogs of part of the bacterial peptidoglycan monomer have been shown to be adjuvant active and to enhance the nonspecific immunity of adult mice infected by Klebsiella pneumoniae. In the present study muramyl dipeptide and two other synthetic analogs were found to be active in newborn mice. This activity could be demonstrated after administration by subcutaneous or even by oral route. In contrast to what was observed after treatment by lipopolysaccharide, 8-day-old mice were definitively protected against bacterial challenge by these glycopeptides. Therefore such molecules could have a great value in view of studying and correcting the neonate's unresponsiveness.


Interspecies transmission of Creutzfeldt-Jakob disease to Syrian hamsters with reference to clinical syndromes and strains of agent.

Experimental Creutzfeldt-Jakob disease was serially transmitted from guinea pigs to Syrian hamsters with 100% incidence, morbidity, and mortality. All animals developed a subacute spongiform virus encephalopathy with neuronal destruction and concomitant astrocytic changes. In the first passage three different clinical syndromes were recorded, each with widely variant incubation times; these results suggested there may be different strains of the Creutzfeldt-Jakob agent, some of which may be partially separated when the agent is passaged from one species to another. Accumulations of neurofilaments in neuronal perikarya and processes and increased lipofuscin were suggestive of changes seen in senility and aging.


Coronary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with prostacyclin and other prostanoids.

The effects of a recently synthesized, stable prostacyclin (PGI2) analog, 13,14-dehydro-PGI2 methyl ester, and authentic PGI2 and several other prostanoids on the coronary circulation were investigated in the intact dog by using a new technique to measure coronary sinus blood flow. The PGI2 analog, PGI2, and prostaglandin (PG) E2 and D2 each increased coronary sinus blood flow in a dose-related fashion when injected into the left coronary artery. The analog and PGE2 had similar vasodilator activity while PGI2 was slightly more potent. PGD2 was a moderately active coronary vasodilator whereas PGF2alpha was inactive. The coronary vasodilator effects of PGI2, its analog, PGE2, and PGD2 occurred at doses that had little effect on aortic pressure, left ventricular pressure and its first derivative, or on cardiac output and heart rate. The prostaglandin precursor arachidonic acid and the endoperoxide intermediate PGH2 both increased coronary sinus blood flow in a dose-dependent manner. The effects of arachidonic acid were inhibited by indomethacin. These data show that PGE2, PGI2, and a stable PGI2 analog are potent vasodilators in the canine coronary vascular bed and suggest that the vasodilator effects of arachidonic acid and PGH2 may be due to the formation of PGE2, PGD2, or PGI2 in the dog heart.


The cytochrome P-450 reaction mechanism--kinetic aspects.

The reviewed kinetic investigations at the experimentally accessible partial reactions of the reaction sequence clearly evidence that the P-450 system represents a complex reaction system, the main control points of which are shown in Scheme 3: As can be seen, control elements are the substrate, the cytochrome species (P-450/448), the reducing agent, the reductase, phospholipid and parts of the b5 system as well. Formula (see text): All of these steps can be rate limiting (rate interfering), depending on the distinct substrate and oxygen donor. The ternary complex evidently has a key position however in that is structural specificities determine rate and product distribution of the respective substrate conversion. But unfortunately the ternary complex decay (including the e2 transfer) is kinetically unresolved till now.


Patient compliance: practical implications for physical therapists. A review of the literature.

Patients do not always follow medical advice. This literature review describes the extent to which patients fail to comply, methods of measuring compliance, factors affecting compliance, and programs to obtain maximal compliance. Although most of the literature on patient compliance stems from drug studies, physical therapists can gain valuable information from these studies. Some of the practical implications for physical therapists are presented.


Ego vicissitudes in response to replacement or loss of body parts. Certain analogies to events during psychoanalytic treatment.

A comparison is made between the analytic experience and two distinct kinds of surgery, i.e., organ transplant operations and more traditional surgical procedures. Basically, the first add new parts, while the latter remove old parts. This fundamental difference influences patients' response to the surgical intervention. Similarly, in analysis one can identify phases when the patient is troubled over the possibility of acquiring new parts of the self, and other phases, usually later in treatment, when he mourns the loss of old and familiar parts. These generalizations bear on the problem of resistance to change during analysis and patients' fears about permitting themselves to be influenced by analytic treatment.


Neurotic and narcissistic transferences in Freud's relationship with Josef Popper.

An analysis of Freud's avoidance of meeting with Josef Popper is offered which suggests that Freud's idealization of Popper was related to an unconscious fear of being attacked by him. This view is compared and contrasted with the concept that Freud had a "mirror transference" to Popper, as proposed by Wolf and Trosman (1974). The choice of focusing on either narcissistic or neurotic mechanisms in this psychobiographical inquiry is discussed and related to similar choices that commonly occur in clinical work.


Treatment of hypertension with biofeedback and relaxation techniques.

The present study describes a 16-week trial of the use of a combination of biofeedback and relaxation techniques for the treatment of hypertension. Twenty-two hypertensive patients were randomly allocated to one of three groups: (1) diastolic blood pressure feedback, electromyographic feedback, and verbal relaxation; (2) sham blood pressure feedback; and (3) no treatment. For the 14 patients completing active treatment during an initial or crossover period, the average changes in blood pressure as measured outside the laboratory were minimal (0/-1 and +1/0 mm Hg, supine and standing, respectively). Average blood pressure reduction in the laboratory was no greater with active than with sham blood pressure feedback (-3/-2 vs. -5/-2 mm Hg). One subject, however, after showing no change in blood pressure during sham feedback, achieved pronounced and prolonged improvement following active treatment. Overall results do not support the usefulness of these techniques as primary therapy in most hypertensives.


Nonpharmacologic control of essential hypertension in man: a critical review of the experimental literature.

Many nonpharmacologic (behavioral) techniques are being proposed for the therapy of essential hypertension. The research in this area is reviewed and divided roughly into two categories: the biofeedback and relaxation methodologies. While feedback can be used to lower pressures during laboratory training sessions, studies designed to alter basal blood pressure levels with biofeedback have not yet been reported. The absence of evidence for such changes through biofeedback limits the usefulness of this technique in hypertension control. The various relaxation methods, such as yoga, transcendental meditation, progressive muscle relaxation, and others have shown more promise. With varying degrees of experimental vigor, many of these techniques have been associated with long-lasting changes in blood pressure. The strengths and weaknesses of the various authors' research designs, data and conclusions are discussed, and suggestions for further experimentation are offered.


Patterning of cognitive and somatic processes in the self-regulation of anxiety: effects of meditation versus exercise.

Davidson and Schwartz (1) have proposed a psychobiological analysis of anxiety that emphasizes the patterning of multiple processes in the generation and self-regulation of this state. The present article specifically reviews recent research on cognitive and somatic components of anxiety. A dual component scale which separately assesses cognitive and somatic trait anxiety is described and applied to the study of the differential effects of a somatic (physical exercise) and a cognitive (meditation) relaxation procedure. A total of 77 subjects was employed; 44 regularly practiced physical exercise and 33 regularly practiced meditation for comparable periods of time. As predicted, subjects practicing physical exercise reported relatively less somatic and more cognitive anxiety than meditators. These data suggest that specific subcomponents of anxiety may be differentially associated with relaxation techniques engaging primarily cognitive versus somatic subsystems. It is proposed that relaxation consists of (1) a generalized reduction to multiple physiological systems (termed the relaxation response by Benson) and (2) a more specific pattern of changes superimposed upon this general reduction, which is elicited by the particular techniques employed. The data from this retrospective study need to be followed up by prospective studies to establish the precise mechanisms for these effects.