Expression and stability of Escherichia coli F-prime factors in Proteus mirabilis. The expression and stability of Escherichia coli F-primes in Proteus mirabilis is examined. It is possible to consecutively introduce, and stably maintain, the DNA of several E. coli F-primes in P. mirabilis in the absence of selective pressure for all or some of the plasmids. Additionally, we can recover more than one F-prime from certain P. mirabilis recipient strains which carry DNA derived from several independent matings with E. coli F-prime donors.


Extra-chromosomal inheritance of rhodamine 6G resistance in Saccharomyces cerevisiae. Rhodamine 6G was found to be a specific inhibitor of aerobic growth of yeast, having no effect on fermentative growth. A single step spontaneous mutant of S. cerevisiae resistant to rhodamine 6G was isolated, which showed cross-resistance to the ATPase inhibitors venturicidin and triethyltin, to the uncoupler 1799, to bongkrekic acid and to cycloheximide, but not to oligomycin or to the inhibitors of mito chondrial protein synthesis, chloramphenicol and erythromycin. The genetic analysis of this mutant showed that both nuclear and cytoplasmic (but apparently not mitochondrial) factors may be involved in the determination of the mutation. The behaviour is discussed as a possible function for 2 micron circular (omicron) DNA.


Induction of protein synthesis in Escherichia coli following UV- or gamma-irradiation, mitomycin C treatment or tif Expression. The rate of synthesis of total cellular proteins has been studied by pulse labelling cells at various periods after irradiation with UV or gamma-rays, after treatment with mitomycin C (MMC) or after expression of the temperature sensitive mutation tif. Subsequent gel electrophoresis and autoradiography reveals changes in the rate of synthesis of several proteins. The most striking change is in a protein of molecular weight 40,000, protein X, which has been previously most extensively studied in cells treated with nalidixic acid (Gudas, 1976). Synthesis of large quantities of protein X is induced by UV, gamma-rays, MMC treatment or tif expression in rec+ but not recA cells. A feature of recA cells is that they break down their DNA excessively after irradiation or MMC treatment. However, if protein synthesis following irradiation is prohibited by chloramphenicol, post-irradiation degradation becomes excessive in recA+ cells. This inverse relationship between DNA degradation and new protein synthesis consistent with the hypothesis that an induced protein such as X is responsible for controlling DNA degradation following irradiation. Protein X is not induced in a lexB mutant following MMC treatment. In this respect the lexB mutant behaves like lexA and recA mutants in that the ability to induce protein X can be correlated with excessive DNA degradation. Studies on the induction of proteins in inf, tif and tif sfi mutants fail to reveal any correlation between induction of protein X and either the induction of prophage lambda or septation.


Manganese mutagenesis in yeast. VI. Mn2+ uptake, mitDNA replication and ER induction: comparison with other divalent cations. A medium was found in which manganese efficiently induces erythromycin-resistant mitochondrial mutations, and which is suitable for measuring Mn2+ uptake and the labelling of DNA (fig. 1). Mn2+ uptake is stimulated by glucose and slowed down by cycloheximide (Fig 2). Mg2+ competes with Mn2+ uptake much stronger than does Zn2+ (Fig. 3). All of the conditions which favour Mn2+ uptake also favour induction of erythromycin-resistant mutations (Tables 3, 4). Mn2+ strongly inhibits protein synthesis (Table 1). Nuclear DNA replication is also strongly inhibited by this cation, while mitochondrial DNA replication is only weakly inhibited during the first 3 h of labelling, but there is small if any increase of the label incorporation between the 3rd 6th h of labelling (Table 2). The relation between label incorporation into mitDNA and mutation induction by manganese is not straightforward (Table 5). From among 11 divalent cations tested, only Mn2+ was capable of inducing mitochondrial erythromycin-resistant mutations (Table 6).


Identification of an amber fragment of the beta subunit of Escherichia coli RNA polymerase: a yardstick for measuring controls on RNA polymerase subunit synthesis. An amber fragment of the beta subunit of Escherichia coli RNA polymerase has been recovered from strains carrying the rpoB12 amber mutation, indicating that the B12 mutation resides in the structural gene for the beta subunit. The fragment is readily assayed and can be used to determine the degree of  expression of a single rpoB cistron in strains haploid or diploid for this region. These studies confirm that  the bacterial mechanism, which can compensate for reduced translation of the beta message, operates by the co-ordinate induction of rpoB and rpoC. Furthermore, I show that rpo control depends upon cistron(s) located on the F' factor, KLF10, whose product(s) can act negatively in trans on rpoBC expression.


Translational fidelity in Escherichia coli: contrasting role of neaA and ramA gene products in the ribosome functioning. Strains carrying both the ramA1 and the neaA301 mutations do not exhibit the restriction of informational suppressors normally associated with resistance to neamine. Furthermore, ribosomes from such strains exhibit increased misreading in vitro with respect to particles from the neaA strain. These properties suggest that translational fidelity may be cooperatively controlled by ribosomal proteins S4 and S17, coded by ramA (rpsd) and neaA (rpsq) genes respectively.


Construction and restriction endonuclease mapping of hybrid plasmids containing Saccharomyces cerevisiae ribosomal DNA. Fragments produced by partial digestion of Saccharomyces cerevisiae ribosomal DNA (rDNA) with the restriction endonuclease EcoRI were ligated in vitro to the bacterial plasmid RSF2124. The resulting hybrid plasmids were cloned in Escherichia coli. Three hybrid plasmids which contain at least one intact repetitive unit of the multiple, tandem sequences of the yeast rDNA genes have been further characterized. These plasmids have been used to construct a map of the EcoRI, SmaI, HindII and HindIII restriction sites in the individual repetitive units of yeast rDNA.


Suppression of polarity of insertion mutations within the gal operon of E. coli. Phenotypic revertants of galOP::IS1 and galOP::IS2 mutations have been isolated after mutagenesis with nitrosoguanidine, they are probably caused by mutations in gene suA. The polarity suppressor mutations described in this study and a known mutation in gene suA isolated by D. Morse (Morse and Guertin, 1972) suppress polarity caused by IS1 more effectively than that caused by IS2 or IS4. Furthermore, suppressibility is influenced by the site and orientation of IS integration. The synthesis of the three enzymes in galOP::IS suA double mutants is constitutive and the ratio of the three enzymes is altered in comparison to the wild type. The reasons for constitutive synthesis of the galactose enzymes and for the altered ratio of enzyme synthesis are discussed.


In vitro transcription of the ribosomal RNA genes of E. coli DNA. Bacterial ribosomal RNA synthesis was studied in an in vitro system in which the presence of heparin prevented reinitiation of transcription. The number of heparin-resistant binary complexes of RNA-polymerase and E. coli DNA depended strongly on the quality of the template. High-molecular weight DNA was a much superior template than DNA prepared by conventional techniques. Using this high-molecular weight DNA as template the amount of ribosomal RNA synthetized in one round of transcription was found to be 4-5 fold higher than the amount of rDNA present. Controls have shown that the transcription probably started at the proper initiation sites and no significant read-through form distant promoters contributed to this effect. If the binary polymerase-DNA complexes were dissociated in the presence of 0.5 M KC1 prior to transcription all RNA synthesis was strongly reduced but the proportion of rRNA increased in the transcript. However, in this case the amount of rRNA did not exceed the amount of rDNA. We propose that the promoters of the rRNA genes are complex structures, able to store 4-5 molecules of RNA polymerase and of these several polymerase only one is bound in an extremely salt-resistant form.


Growth and reactivation of single stranded DNA phage phiX174 in E. coli undergoing "thymineless death". The thymine requirement of the E. coli strain HF 4704 (uvr A-, rec A+) is thermosensitive i.e. these cells require for their growth 2 microng thymine per ml at 37 degrees C but not at 30 degrees C. Such cells when starved for thymine for 3 h at 37 degrees C are capable of sustaining growth of single stranded DNA phage phiX174 without any diminution of burst size under nonpermissive conditions. Thymine starved HF 4704 cells also reactivate UV-irradiated phiX174 by about 3fold. To test if the thymine necessary for phage growth under "thymineless" conditions was supplied by host DNA degradation products, the transfer of 32P label from the host DNA to mature progeny phages was measured by means of sucrose density gradient analysis. It was found that only about 0.7% of 32P of the host DNA was transferred to the progeny phages growing in normal cells whereas the corresponding value was 7.8% in the case of thymine starved cells.


Mechanism of conjugation and recombination in bacteria XVI: single-stranded regions in recipient deoxyribonucleic acid during conjugation in Escherichia coli K-12. The formation of mating pairs between F- and Hfr cells resulted in increased sensitivity of recipient deoxyribonucleic acid (DNA) to single-strand-specific S1 nuclease, from 3.6% to 23.5% after 30 min conjugation. A comparable amount of single strand regions in the DNA of mated wild type and recA mutant cells was detected. 10 min of conjugation resulted in almost the same amount of single-strand recipient DNA as 30 min of continuous transfer of donor DNA. Also the transfer of plasmid DNA from F+ recA strain led to the occurrence of single-strand recipient DNA. In similar experiments with Hfr tra mutant no such effect was observed. We conclude that alterations in the sechases of conjugation associated with the formation of mating pairs and/or initiation of transfer donor DNA.


Altered tetracycline resistance in pSC101 recombinant plasmids. Investigation of tetracycline resistance genetically determined by the plasmid pSC101 and several recombinants of pSC101 containing EcoRI generated DNA fragments inserted at the EcoRI site has revealed significant differences in the phenotypic expression of that resistance. The altered phenotypes of the recombinant plasmids may be the result of the location of the EcoRI site of pSC101, which has been determined to be near the genetic elements involved with tetracycline resistance.


Respiratory repression and the stability of the mitochondrial genome. The variation in sensitivity of the mitochondrial genome of Saccharomyces cerevisiae to ethidium bromide-induced petite mutation in response to changes in glucose concentration has been studied. Growth in high glucose considerably depressed the mutation rate, whilst small variations are observed in response to step-up or step-down in glucose concentration. Variations in mitochondrial DNA and respiratory activity during the mutagenic process are described. Effects of non-metabolizable sugars which repress mitochondrial biogenesis and a number of antimitochondrial drugs have been investigated. The results are discussed in terms of possible mechanisms of modulation of the mutation rates.


In vitro transcription of three different ribosomal RNA cistrons of E. coli; heterogeneity of control regions. Ribosomal RNA synthesis from three different rRNA cistrons of E. coli, located on different phage DNAs was compared and found to have the same characteristics as regards chain length, salt and temperature dependence and the effect of ppGpp. However, some clear and reproducible quantitative differences between rRNA synthesis from the different templates both in presence and absence of ppGGpp were found. Rifampicin and heparin experiments showed that these differences were located at the initiation sites. We propose that heterogeneity exists in the RNA polymerase binding regions of the rRNA prmoters in E. coli.


Chromosomal location of gene governing the trehalose utilization in Escherichia coli K12. Several mutants unable to utilize trehalose were isolated from Escherichia coli, Their genetic analysis led to determine the following gene order on the chromosomal map: pur B-dad R-tre-hem a-trp. Furthermore, the tre gene belongs to the inversion of the trp chromosomal region between E. coli and S. typhimurium.


Antimutagenic effects of spermine and guanosine in continuous cultures of Escherichia coli mutator strain mutH. In E. coli strain RH531 containing mutator gene mutH-, whose mechanism of enhanced mutability depends upon DNA replication, spermine and guanosine reduce the rates of mutation to T5R and to increased fitness.


Mutagenesis of lambda phage: 5-bromouracil and hydroxylamine. Mutagenesis by 5-bromouracil of lambda phage to clear plaque formers does not depend on the recA function of the host E. coli cell or on the red function of the phage. Pretreatment of the host cells with ultraviolet light does not affect bromouracil mutagenesis of the adsorbed phage. Mutagenesis by hydroxlamine to clear plaque formers takes place at a high level in recA- host cells, and is not changed by preirradiation of of rec+ (wild type) hosts with ultraviolet light. Thus, bromouracil and hydroxylamine appear to mutate lambda phage by a process which differs from that responsible for ultraviolet mutagenesis. Two characteristics of bromouracil mutagenesis--the nonlinear dependence of the number of mutants on bromouracil incorporation, and a high frequency of heterozygotes--fit in with Rydberg's (1977) picture of bromouracil mutagenesis as a consequence of base mispairing, with mismatch repair removing the mutations at low incorporation of the analog.


The involvement of polynucleotide ligase in the repair of UV-induced DNA damage in Escherichia coli K-12 cells. The effect of the ligts-7 mutation on cell survival and the extent of DNA repair after UV (254 nm) irradiation was determined for wild-type and uvrB5 cells of E. coli K-12 at 30 degrees and 42 degrees C. At the restrictive temperature (42 degrees C) the ligts-7 mutation resulted in (i) a decrease in the extent of repair of DNA incision breaks arising during the excision repair process, and (ii) a decrease in the extent of post-replicational repair of gaps in newly-synthesized DNA. These deficiencies in DNA repair correlated with increases in cellular sensitivity to killing by UV radiation. Thus, DNA lagase plays an important role in vivo in both the excision and post-replicational repair processes.


Identifying sites of simultaneous DNA replication in eukaryotes by N-methyl-N'-nitro-N-nitrosoguanidine multiple mutagenesis. N-methyl-N'-nitro-N-nitrosoguanidine (NG) induces certain classes of multiple mutations in yeast at high frequency. By selecting for mutation at one locus (his4 or leu1) one frequently obtains double mutants where another mutation to temperature sensitivity has also been induced. This multiple mutagenesis exhibits a considerable specificity: for mutation at one particular locus there is a high chance that another mutation will be found in the same cell at one of a restricted number of other loci. For any given locus (e.g. his4) there is a spectrum of sites at which temperature-sensitivity mutations are co-induced. This spectrum differs for different loci, such that the spectrum of sites co-mutating with leu1 differs completely from that for sites co-mutating with his4. This NG'induced co-mutation is interpreted in terms of NG acting to enhance mutagenesis at sites of simultaneous DNA replication within the cell. The results so obtained indicate a very strict control over the order and timing of gene replication in Saccharomyces cerevisiae, and it is suggested that it is now possible to use NG double mutagenesis to try and locate origins of replication in yeast.


Replication of prophage P1 during the cell cycle of Escherichia coli. We have followed, by DNA-DNA hybridization, the variation in the number of copies of prophage P1 relative to two chromosomal markers when the doubling time of the host cells is modified by a change in carbon source. The ratio of P1/chromosome terminus undergoes a twofold decrease when the cell doubling time increases from 24 to 215 min, whereas the ratio of P1/chromosome origin increases 1.4 fold; both ratios tend towards unity at slow growth rates. This suggests that the replication of prophage P1 is not simultaneous with chromosome initiation or chromosome termination. The chromosome replication time is unaffected by the presence of P1, and remains constant over the range of doubling times studied, with a value of about 4o min. Following amino acid starvation, the P1/chromosome origin ratio increases from 0.7 to 0.9, suggesting that P1 retains the ability to replicate after chromosome initiation has stopped and in the absence of essential amino acids. The results are discussed with reference to similar studies done on F and R1.


Plasmid (pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in Escherichia coli K-12. The drug resistance plasmid pKM101 plays a mojor role in the Ames Salmonella/microsome carcinogen detecting system by enhancing chemical mutagenesis. It is shown that in Escherichia coli K-12 the plasmid pKM101 enhances both spontaneous and methyl methanesulfonate-caused reversion of an ochre mutation, bacterial survival after ultraviolet irradiation, and reactivation of ultraviolet-irradiated lambda in unirradiated cells. All these effects are shown to be dependent on the recA+ lexA+ genotype but not on the recB+ recC+ or recF+ genotypes. The recA lexA-dependence of the plasmid-mediated repair and mutagenesis suggests an interaction with the cell's inducible error-prone repair system. The presence of pKM101 is shown to cause an additional increase in methyl methanesulfonate mutagenesis in a tif mutant beyond that caused by growth at 42 degrees. The presence of the plasmid raises the level of the Weigle-reactivation curve for the raactivation of ultraviolet-irradiated lambda in E. coli and causes a shif of the maximum to a higher UV fluence. These observations suggest that pKM101 does not exert its effects by altering the regulation of the cell's error-prone repair system but rather by supplying a mechanistic component or components.


Separation of isoacceptor cysteine transfer ribonucleic acids of bakers' yeasts. Isoacceptor species of certain amino acid-specific transfer ribonucleic acids (tRNAs) were fractionated by gel permeation chromatography using Sephadex G-100. The separation is attributed to the 20% ethanol-1% NaCl solvent and to the characteristics of Sephadex. Isoacceptor tRNAs specific for cysteine, arginine, phenylalanine, and histidine were recovered from commercial tRNA of yeast by this method. Highly purified cysteine-specific tRNA, obtained by a method which would not be expected to separate isoacceptor molecules when fractionated by this procedure, was shown to contain two cysteine isoacceptor tRNAs.


Physiological modification of alkylating agent induced mutagenesis. II. Influence of the numbers of chromosome replicating forks and gene copies on the frequency of mutations induced in Escherichia coli. The frequency of reversions induced in Escherichia coli K-12 trpA58 by any of five different monofunctional alkylating agents increased as the growth rate of the organism was raised prior to mutagen treatment. The increase in mutation frequency did not correlate with growth rate-dependent changes in cell area or total cellular protein and DNA. After treatment of cells with N-methyl-N-nitrosourea (MNUA), no growth rate-dependent change was observed in the total DNA alkylation or percentage of O6-methylguanine present in the DNA extracted. The frequency of reversions induced by one mutagen, methyl methanesulphonate (MMS), increased in proportion to the average number of trpA gene copies per cell, whereas the frequency of reversions induced by the other compounds was dependent on the average number of chromosome replicating forks per cell. This difference was attributed to the different ratios of DNA base alkylation products observed, formed after treatment with MMS, an SN2-type reagent, or after treatment with the SN1-type reagents ethyl methanesulphonate (EMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), MNUA and N-ethyl-N-nitrosourea (ENUA). Possible reasons for the dependence of mutation frequency on the number of replicating forks per cell are discussed.


The evaluation of clinical predictions. A method and initial application. Clinical predictions are never certain but are inherently probablisitc. The accuracy coefficient, a measure of probabilistic accuracy based on probability assigned to outcomes that occur, was used to assess the skill of clinical rheumatologists in predicting patient outcomes. Physicians' scores correlated well with degree of clinical experience. An approach to evaluation based on the measure provides a sensitive assessment of marginal benefit of technologies such as laboratory tests, diagnostic procedures or computer consultations. Most currently used methods of computer prediction were not as accurate as the best physicians tested. By allowing measurement of ability to individualize predictions to each patient's unique characteristics, the accuracy-coefficient approach has potential use in physician assessment.


Relation between the race and economic status of patients and who performs their surgery. We evaluated the relation between race and economic status of surgical patients and their likelihood of being treated by a surgeon in training rather than by a staff surgeon. Blacks were 2.2 to 4.3 times more likely than whites to be under the care of surgeons in training (P less than 0.001). This relation has remained unchanged over the past two decades. It remained when the method of payment was via self-payment or private insurance, but disappeared when patients being paid for by Medicaid were considered. In addition, black emergency patients were more likely than white emergency patients to be cared for by surgeons in training.


Concomitant presence of tumor-specific cytotoxic and inhibitor lymphocytes in patients with osteogenic sarcoma. The lack of detectable tumor-specific cytotoxicity by the peripheral blood lymphocytes of patients with cancer may be due to a lack of cytotoxic lymphocytes or the presence of suppressor lymphocytes that inhibit cytotoxic cells. Unfractionated peripheral blood lymphocytes from 12 of 28 patients with osteogenic sarcoma were cytotoxic to osteogenic sarcoma cells in vitro (P less than 0,001). When the peripheral blood lymphocytes from patients whose lymphocytes were not cytotoxic underwent fractionation, a tumor-specific cytotoxic subpopulation was isolated from 11 of 13 patients (P less than 0.0001). Lymphocytes that inhibited cytotoxic activity of autologous tumor-specific cytotoxic lymphocytes were found in four of 10 patients with osteogenic sarcoma but not in six normal controls. Inhibitor lymphocytes form rosettes with sheep erythrocytes and adhere to nylon, whereas cytotoxic lymphocytes have a receptor for C3 but no surface immunoglobulin. The lack of tumor-specific lymphocytotoxicity in some patients can be due to inhibitor lymphocytes.


[The significance of immunology for man--intervention and change]. Classical immunological research has been mainly devoted to natural defense mechanisms against infections and to the development and action of vaccines. With the discovery of immune tolerance and following investigations on transplantation immunity, the concept of the immune response was generalized as the higher animal's ability to discriminate between "self" and "notself". Since then research has concentrated on cells and their products involved in these immune phenomena. Application of the vast knowledge in the field of modern immunology should aid greatly in the solution of many actual clinical problems and in alleviating public health hazards (parasitology, etc.) in the Third World.


Analysis of the results of treament of lung cancer patients with BCG according to the scheme of application of the bacillus. BCG has successfuly been applied in lymphoid and in myeloid leukemia but no positive results have been demonstrated in solid tumors except malignant melanoma after intratumoral injection. The authors' approach consists in applying BCG as an only antitumor treatment, much smaller doses and in much longer intervals between them than used by other investigators. The analysis of the treatment schemes of BCG, applied to 171 lung cancer patients showed that positive responses have been obtained only in patients without peripheral dissemination of the disease and that in doses from 0.0001 mg to 0.05 mg. The results obtained depended on the frequency of BCG application: the 5 years survival rate, the mean survival period and the rate of the marked X-ray regression have been found best in patients treated once, good in patients treated in intervals longer than 30 days between the applications of the mycobacteria and worse in patients treated in intervals shorter than 20 days. A direct inverse correlation has been discovered between the mean survival period of the treated patients and the number of the applications of BCG in the first 6 months of the treatment.


Platelets and glomerulonephritis.

Platelets and glomerulonephritis. There is evidence derived from both experimental studies and from observation of human nephritis that platelets are important in the glomerular injury of chronic soluble-complex disease. It is not yet clear if platelets are involved in the events initiating endothelial damage, in perpetuating and amplifying injury, or both. Antiplatelet agents appear to have a role in the treatment of chronic forms of glomerulonephritis; but more knowledge of platelet involvement in nephritis and more readily available tests for platelet involvement are necessary before this suggestion can be tested intelligently.


[The SITAR Project. A new approach to diagnosis and surgical indication in arteriopathic patients]. The extreme variations with which atherosclerotic disease presents as regards progression index, arterial bed localization frequency, malignity and invasiveness in different ages and often as regards different anatomopathological aspects characterizing the formation and course of the primary lesion, mean that there are still many unknowns in the aetiopathogenesis, diagnosis and operative indications for this disease. Such problems are more and more important to the vascular surgeon who, with the development of atherosclerotic disease, sees the long-term results of his arterial reconstructive surgery compromised. The vascular surgeon is therefore directly involved with his colleagues in the internal medicine and pharmacological departments in problems connected with the pathogenesis of arteriosclerosis, and indeed he contributes to setting new constraints on the choice of prosthetic materials, for use in cases of bridge-work, and in the creation of new surfaces by means of thrombendarteriectomy. On the basis of such considerations, the IInd Surgical Clinic of Milan University began, in 1975, a study whose end purpose was the drafting of a clinical card designed for data computerization. Compiled by the surgeon, it is intended essentially for vascular surgeons. However, as it is personally considered that by the very nature of the disease, the atherosclerosis approach must be interdisciplinary, it also concerns physicians in the internal medicine, pharmacological and dietological departments.


Reliability of the Bacturcult system in the clinical evaluation of postpartum bacteriuria. The reliability of the Bacturcult system versus the standard calibrated loop-direct streak technic for screening bacteriuria was determined for 182 postpartum patients. Both false negative and false positive results were obtained by the Bacturcult system, therefore precluding its usefulness as a screening method. Based on these findings, therapy should not be instituted prior to performance of the standard culture technic.


The development of the placental lobular pattern in the human. Review and reinterpretation of the material. The human placental lobule is a dense mass of mostly terminal villi, with a nearly villus-free center. The villi arise from whatever stem is nearby, and branches of these stems anchor near uteroplacental arteries at the base of the loose interlobular areas. There is no one-to-one relation of lobules either to the principal villous stems, or to maternal arteries. In the first trimester the villi are nearly uniform in size and anchor over the entire palcental floor, but better vascularized villi, the later stems, can already be found to anchor near maternal arteries. Thus, a network of uteroplacental arteries with nearby anchoring stems forms on the placental floor during the second month. It becomes accentuated during the following weeks as trophoblastic destruction spares the endometrial stroma around the arteries, and thus leads to the formation of elevations of the decidua, containing arterial ostia and anchoring points of villous stems. The remaining, smaller villi lose their connection with the decidua. By the end of the second trimester, the definitive lobular pattern is complete. How the dense lobules form above the interstices of this network is not known.


Herpes gestationis. An update.

Herpes gestationis. An update. Advances in the immunopathology of blistering diseases now provide increased accuracy in the diagnosis of herpes gestationis in pregnancy. Guidelines are presented in this review to determine the presence of the disease. Exogenous corticosteroids will effectively alleviate symptoms and prevent formation of new lesions.


Clinical safety of corneal storage media. A study of the bacteriological safety of McCarey-Kaufman (M-K) media was undertaken. Twenty-five consecutive cultures of M-K media with a standard penicillin-streptomycin additive were performed at the time of keratoplasty. All cultures were negative, confirming the clinical safety of this media.


Marginal tarsorrhaphy: a technique to minimize premature eyelid separation. By using a continuous intermarginal monofilament suture, a partial tarsorrhaphy can be performed which has a minimal tendency to separate prematurely. This technique is especially useful where recovery from facial paralysis is anticipated. Surgical division of the tarsorrhaphy can be performed easily with little, if any, defect of the eyelids.


A simple and safe suture for fixation of intraocular lenses. Presented is a new simplified and safe suturing technique to prevent Binkhorst and Fyodorov II lenses from dislocating. To data, 74 lenses have been implanted by this technique. There have been no complications. Follow-up time is from three weeks to 14 months.


Introduction of the sagittal symphysotomy in the treatment of chin deformities. The management of chin problems occasionally presents a surgical problem to the clinician because of certain anatomic and clinical considerations. This article reviews and discusses some of the conventional surgical procedures in treating chin deformities. The new and versatile sagittal symphysotomy is introduced and described. Three case reports are presented.


Oral infection in immunosuppressed renal transplant patients. The most common cause of death in patients taking immunosuppressive (IS) drugs is infection. Many of the microorganisms which infect these IS patients may be found in the mouth, but the mouth has not been investigated as a potential source of lethal infection. In view of this, we studied twenty-seven IS patients taking Imuran and prednisone for 6 to 61 weeks and eighteen normal controls. The patients were followed monthly, and the incidence of oral and systemic complications was recorded. There were no deaths due to infection during the 10-month study period. Oral infection occurred as frequently as pneumonia or urinary tract infection. Systemic factors which were related to the development of dental infection were lymphocyte count and length of time on immunosuppressive drug therapy.


Tissue oxygen available as a criterion for the effectiveness of continuous positive pressure breathing. As little as 3-5 cm H2O increase in proximal airway pressure applied to normal lung reduces cardiac output. It is postulated that decreased pulmonary compliance in respiratory distress syndrome (RDS) acts as a barrier thus offsetting this effect. Since cardiac output is not routinely measured, severe reduction in it could accompany regression of disease while maintaining the same airway pressure. This study was undertaken to determine whether tissue oxygen available (O2a) could be used to detect changes in perfusion during continuous positive pressure breating (CPPB). CPPB was evaluated in 10 normal rabbits (CL = 9.5 +/- 1.8 cc/g at 25 cm H2O) and in 10 pulmonary-damaged rabbits (CL = 5.5 +/- 1.4 cc/g at 25 cm H2O) produced by subjecting them to 100% O2. Airway pressure was increased from 0-15 cm H2O in 3 cm H2O increments at 10-min intervals. O2a and PaO2 were monitored continuously. In the normal group, O2a decreased at 3 cm H2O airway pressure, reaching 22% of control at 12 cm H2O, at which pressure PaO2 decreased. Breathing 100% O2 at this airway pressure increased PaO2 to 408 mm Hg, whereas O2a returned to 45% of control. In the experimental group, O2a decreased at 9 cm H2O airway pressure, at 12 cm H2O it was 36% of control at which pressure PaO2 decreased slightly. Breathing 100% O2 at this airway pressure increased PaO2 to 316 mm Hg, and increased O2a to 200% of control. These data indicate that with excessive airway pressure, muscle hypoxia may exist during systemic hyperoxemia and that a low compliance lung exerts a protective effect on O2a. Since changes in cardiac output during CPPB are compliance dependent, and since O2a is perfusion dependent, tissue oxygen available could provide a means of selecting optimal airway pressure during CPPB.


Continuous airway pressure breathing with the head-box in the newborn lamb: effects of regional blood flows. Continuous airway pressure delivered by a head-box is an accepted means of treating clinical hyaline membrane disease. To investigate hemodynamic alterations resulting from its use, eight newborn lambs, 1 to 6 days of age, were studied at 6 and 11 mm Hg of positive pressure, while spontaneoulsy breathing room air. Organ blood flows and cardiac output were measured with 25 micron-diameter radioactive microspheres. Heart rate, left ventricular pressure, and arterial blood gases did not change during the study. Jugular venous pressures increased from 6.4 mm Hg to 18.6 and 24.2 mm Hg at 6 and 11 mm Hg, respectively (P less than .005). Cardiac output decreased approximately 20% at either intrachamber pressure setting. Renal blood flow fell 21% at 11 mm Hg. No significant changes in blood flow were found in the brain, gastrointestinal tract, spleen, heart, or liver when compared to control flows. Of particular interest was the finding of a 28% reduction in ocular blood flow at 6 mm Hg and 52% at 11 mm Hg. From these results, we conclude that substantial cardiovascular alterations may occur during the application of head-box continuous airway pressure breathing, including a significant reduction in ocular blood flow.


Radiographic findings in early onset neonatal group b streptococcal septicemia. Chest roentgenograms obtained in the first two days of life from 67 infants with respiratory distress were reviewed to determine whether the radiographic features of group B streptococcal septicemia were diagnostic or distinctive. The retrospective review contained 24 infants with proven and 14 with suspected septicemia, as well as 29 patients with other causes of respiratory distress. The films were reviewed in random order by two pediatric radiologists without their prior knowledge of clinical or laboratory data. Typical radiographic appearance of pneumonia was present in only ten of the 24 proven and two of the 14 suspected cases of group B streptococcal sepsis. The radiographic pattern of respiratory distress syndrome (RDS) was just as common among these patients. The most prominent associated radiographic feature of infants with proven septicemia was cardiomegaly which was significantly increased when compared with infants who had other causes of respiratory distress (P less than .001). X-ray recognition of neonatal group B streptococcal septicemia is limited because of superimposition of roentgen patterns probably related to associated disorders. Pediatrics, 59:1006-1011, 1977, NEWBRON, SEPTICEMIA, GROUP B STREPTOCOCCUS.


Infantile lobar hyperinflation: expectant treatment. Arterial blood gases and regional lung function, measured with a 133xenon technique, were used to evalute the physiological defects and follow the natural history of 16 infants with lobar hyperinflation ("emphysema"). Hypoxemia was due to V/Q inequality at rest. Worsening of hypoxemia (mean Pao2 delta--26 mm Hg) with crying was due to shunting as a consequence of cessation of ventilation in the involved lobe. Surgery was necessary in three patients. Two deaths were caused by bronchopulmonary dysplasia after respiratory distress syndrome (RDS). In 12 of 14 infants, lung function was normal between the ages of 5 days and 1 year. Pediatrics, 59:1012-1018, 1977, LOBAR EMPHYSEMA, BLOOD GASES, REGIONAL LUNG FUNCTION.


Vitamin E and neonatal hemolysis.

Vitamin E and neonatal hemolysis. A study was designed to determine if the presence of vitamin E deficiency during the first week of life played a contributory role in the shortened red cell life span observed in the premature infant. Carboxyhemoglobin values were used as an index of hemolysis. Ten infants received vitamin E administered intramuscularly in a total dose of 125 mg/kg during days 3 to 7 of life; ten infants served as controls. The mean percent carboxyhemoglobin level fell significantly from day 3 to day 8 in the treated group (1.08% to 0.78%) whereas the mean value remained unchanged at 0.96% in the control group. The administration of vitamin E appears to reduce but not eliminate the accelerated red cell destruction that characterizes the preterm infant. Pediatrics, 59:995-997, 1677, VITAMIN E, HEMOLYSIS, PREMATURE INFANT, CARBOXYHEMOGLOBIN.


Note upon steady visual fixation and repeated auditory stimulation in meditation and the laboratory. The techniques of steady visual fixation and repetitious auditory input are used in the laboratory for investigating perceptual phenomena and in yoga and meditation for facilitating altered states of awareness. Phenomena related to mild sensory deprivation are reported in both circumstances.


The House-Tree-Person Test as a measure of intelligence and creativity. The House-Tree-Person test and a verbal test of mental ability, the Basic Word Vocabulary Test, were administered to 23 male and 27 female, university undergraduates and to 27 boys and 38 girls in Grades 3 to 8. The drawings were given three separate and independent scorings by judges who computed intelligence scores according to the House-Person manual; rated them impressionistically on intelligence, using a forced-distribution method; or rated them impressionistically on creativity, using the same forced-distribution method. The three House-Tree-Person measures were highly intercorrelated for all groups of subjects. All three House-Tree-Person scores also correlated positively and significantly with vocabulary test scores for female university students, as did both Impressionistically derived House-Tree-Person scores for grade-school girls. Male students' and boys' vocabulary scores were unrelated to any of the House-Tree-Person scores. Results suggest that competence in graphic expression operates independently of verbal intelligence in males but validity as a nonverbal test of mental ability and that it can be scored efficiently and reliably by using a global, impressionistic method.


Spina bifida children's scores on the Wechsler Intelligence Scale for Children. An analysis of the scores of 58 cases assessed on the WISC suggested there was differential intellectual prognosis according to type of lesion, the presence of hydrocephalus, degree of physical disability and sex, with girls having the poorer outcome.


Cognitive tempo in children and their parents. An adoption study was conducted to determine if cognitive tempo (as characterized by errors and latencies on the Matching Familiar Figures Test) is more similar between parents and their biological children or between parents and their adopted children. Zero-order correlations between parents and children were not significant (regardless of familial relationship), but the results of canonical correlations for mean of parents' scores with those of biological and adopted children respectively were consonant with hypothesized values, suggesting a degree of heritability exists. A slight trend for parents' latency to be consistently related to their biological children's latency was noted, but no such trend was present for errors. The heritability of latency versus errors in cognitive tempo is discussed.


Validation of graphoanalysis by "global" or "holistic" method. Graphoanalysis is the most systematically developed and best researched of all methods of handwriting analysis (genetically called graphology). This is a projective expressive movement that is neither better nor more poorly validated than most projective techniques as a means of personality assessment, which is inadequate because their subjectivity makes statistical study difficult. With all projective techniques "sign" or trait validation has been minimal, and the best validation has come from "global" or "holistic" methods. The present study presents a paradigm for the latter type of approach to handwriting analysis, using a matching technique with probabilities of 1/5, wherein five subjects were matched by people who knew them to one of five blind Graphoanalyses of the subjects' writing. This design is herein replicated five times, with total data significantly different from chance expectation (p less than .001), supporting the hypothesis that it is possible to evaluate personality through analysis of handwriting.


An Aeromonas species implicated in ulcer-disease of the cod (Gadus morhua). Vibrio anguillarum is the most frequently isolated bacterial species involved in ulcer disease in salt water fish. However, an Aeromonas species was very often incriminated in ulcers and septicaemia in cods (Gadus morhua) in Danish coastal areas. These Aeromonas strains were very uniform in their biochemical activities only differing in growth on Simmons citrate agar, and the mean value for the guanine + cytosine content of DNA was 59 per cent with a standard deviation of 0.4. Primary serological investigations demonstrated a possible identity to O and K antigens. The most characteristic biochemical features of these strains were a gas production from glycerol but not from glucose. They were positive in lysine decarboxylase, did not produce indole, and had a typical fermentation pattern of the glycosides. Negative results were found in H2S production, phosphatase and in the utilization of NH4+ and glucose as the only source of N and C. The evident differences from the species described and subspecies of Aeromonas elucidate the weakness of the existing systems of biotyping. A broader conception of the biochemical spectrum for the individual species of Aeromonas combined with serotyping would seem to be a better system for identification, and also for an epidemiological purpose.


Studies of the pathogenesis of enteric E. coli infections in weaned pigs: bacteriological and immunofluorescent studies. Qualitative and quantitative, bacteriological studies were performed on spontaneous cases of post weaning E. coli diarrhoea (PWD). The pigs derived from a herd, D, in which the disease had persisted for a period of almost 2 years. Orally vaccinated healthy pigs from herd D and from herds A and M without the disease were also examined. The results showed that haemolytic E. coli were frequently isolated from faecal samples which had been collected 5--7 days after weaning but seldom from samples from the same pigs collected before weaning. Haemolytic E. coli dominated the aerobic intestinal flora at 3--5 days after weaning in pigs from herd D with PWD. Oral vaccination using a formalinized vaccine delayed and suppressed the occurrence of haemolytic E. coli in pigs from herd D (Table I). Intestinal counts of the bacteria showed that the number of haemolytic E. coli present in the anterior portion of the jejunum was 10(-3)--10(-5) times higher in pigs which suffered from PWD than in weaned pigs of the same age which did not show symptoms of the disease (Table II). The lowest bacterial counts in various portions of the intestine were consistently observed in the sections obtained from the orally vaccinated healthy pigs. Pure cultures of K88-negative enteropathogenic E. coli serotype O149:K91 were consistently isolated from all the diseased pigs. Fluorescent antibody studies showed that the specific strain of bacteria adhered to the villous epithelium of the jejunum in a layer which covered the villi from the tip to the base and sometimes continued down into the crypts (Figure 1). The bacterial adhesion coincided with an intensive colonization of the jejunum with the homologous E. coli serotype and was nerve observed in apparently healthy pigs which did not have symptoms of PWD. It was concluded that characteristic intestinal colonization by adhesion may occur with enteropathogenic strains of E. coli O149:K91 which lack the K88 antigen (Figure 2).


An epizootic of Mycobacterium intracellulare, serotype 8 infection in swine. Eight strains of mycobacteria isolated from tuberculous lymph nodes of swine were identified as Mycobacterium intracellulare, serotype 8. The infected swine were borne in a large breeding herd and as 8 weeks old piglets distributed to a number of farms for fattening. Autopsy material from the breeding herd, incriminated as the primary source of M. intracellulare, serotype 8 infection, has not been available for bacteriological examination, but none of a number of sows slaughtered showed any visible lesions. The organism, however, was isolated from sawdust-bedding and dust collected in pigpens. Eight samples of water collected from the well and several pipelines and taps of the automatic watering system in the infected pigpens all turned out negative. Results of medical examination of 7 farmworkers from farm G excluded the possibility of a human source of infection. Altogether 799 out of about 2000 piglets raised at farm G. and distributed for fattening to 7 different farms were detained for tuberculosis-like lesions when slaughtered some three months later. In none of the seven farms did spread of the infection occur, and despite no special measures of segregation and disinfection were taken, the M. intracellulare infection left the premises with the last pig from farm G. Neither in sow herd G. animal to animal infection seemed important. Following a rigid practice of cleaning and disinfection of the sow pens in between each litter, the infection which apparently had persisted in the environment for about nine months, disappeared and the sow herd could be saved.


Differential requirements for polypeptide chain initiation complex formation at the three bacteriophage R17 initiator regions. The initiation specificity of washed E. coli ribosomes in the presence and absence of purified initiation factors and/or S1 protein has been examined in protection experiments using 32P-labelled R17 RNA. We find that the three bacteriophage initiator regions do not exhibit equal requirements for either of these components during initiation complex formation. Specifically, both factors and S1 stimulate ribosome binding to the beginnings of the coat and replicase cistrons to a greater extent than they promote recognition of the A protein initiation site. The differential effects are therefore inversely correlated with the degree of mRNA-16S rRNA complementarity exhibited by the three initiator regions. We also observe that S1 suppresses ribosome binding to spurious sites in the R17 RNA.


Requirement of chain initiation factor 3 and ribosomal protein S1 in translation of synthetic and natural messenger RNA. Amino acid incorporation directed by poly(A), poly(U) or R17 RNA has been examined in S1-depleted protein synthesizing systems. We observe that the translation of either synthetic or natural messenger RNA is strictly dependent on the presence of chain initiation factor 3 and ribosomal protein S1. With poly(A) or poly(U) both IF-3 and S1 stimulate amino acid incorporation at least 25-fold, and with R17 RNA the stimulation is approximately 15-fold. More than one copy of S1 per ribosome decreases amino acid incorporation directed by poly(U) or R17 RNA. Initiation complex formation with R17 RNA is also stimulated optimally by the addition of one copy of S1 per ribosome. The function of IF-3 and S1 in protein synthesis is considered.


The iminoproton NMR spectrum of yeast tRNA-Phe predicted from crystal coordinates. The ring current effects on the base paired iminoprotons in yeast tRNA-Phe have been calculated from crystal coordinates. The results in conjunction with independently determined intrinsic positions of the iminoprotons in various base pairs enable us to predict the low field NMR spectrum of yeast tRNA-Phe. It turns out that the calculated NMR spectra are very sensitive to slight changes in structure. Moreover the crystal and solution structure are identical as far as the present methods go.


Proton magnetic resonance spectra of tRNA-Met-f from Thermus thermophilus. 220 MHz proton magnetic resonance spectra of tRNAs in bulk and tRNA-Met-f from Thermus thermophilus have been measured and compared with those of tRNAs from E. coli. Temperature dependences and chemical shift positions of the bulk tRNAs are well explained by the difference in their GC contents. It is known that the base sequence of the double helical regions in the cloverleaf structure of T. thermophilus tRNA-Met-f is different from that of E. coli tRNA-Met-f only at two positions in TpsiCarm; one more C:G pair is contained instead of a U:G pair of E. coli tRNA-Met-f and a C:G pair of E. coli is replaced by a G:C pair. In spite of the resembrance in the base sequences, nmr patterns around 13 ppm are fairly different from each other. The difference is discussed in relation with their tertiary structures and with the origin of chemical shift displacements.


On the binding of aminoalkyl adenylates to isoleucyl-tRNA synthetase from Escherichia coli MRE 600. The binding of nine aminoalkyl adenylates to isoleucyl-tRNA synthetase from Escherichia coli MRE 600 was measured and compared with the binding of the cognate amino acids. It was found that they bind rather tightly to the enzyme, the Kd's ranging from 3.1.10(-4) M with glycinol-AMP ester to 3.7.10(-9) M with L-isoleucinol-AMP ester. The binding is not affected by magnesium. It is shown that the free energies of binding of the esters can be calculated adding a constant contribution of the AMP-moiety of about - 4.1 (- 17) kcal/mole (kJ/mole) to the free energies of binding of the cognate amino acids, which we have reported earlier (19, 25, 26).


Synthesis of oligonucleotides with sequences identical with or analogous to the 3'-end of 16S ribosomal RNA of Escherichia coli: preparation of m-6-2-A-C-C-U-C-C and A-C-C-U-C-m-4-2C via phosphotriester intermediates. The synthesis of two fully-protected hexanucleotides (11a and 11b) via a phosphotriester approach, which is based on the use of two types of protecting groups for the internucleotide linkages, i.e. one 2,2,2-tribromo-ethyl at the 5'-terminus and four 2-chlorophenyl groups for the remaining linkages, is reported. The hexanucleotides 11a and 11b, assembled via a block-wise two-step phosphotriester method, can be deblocked conveniently to give the two hexamers 12a and 12b containing only 3'leads to5' internucleotide linkages.


DNA-synthesis with methylated poly(dA-dT) templates: possible role of O4-methylthymine as a pro-mutagenic base. The alternating copolymer poly(dA-dT) has been methylated with either dimethyl sulphate (DMS) or N-methyl-N-nitrosourea (MNU) and the levels of the various methylation products determined. In addition to the methylated adenines formed by both methylating agents, MNU resulted also in the formation of 3-methylthymine, O4-methylthymine and phosphotriesters. The methylated polymers have been ution of complementary and non-complementary nucleotides determined. With the DMS methylated template no wrong nucleotide incorporation was detectable, but with the MNU methylated polymer the incorporation of dGMP was observed. The amount of dGMP incorporated correlated with the level of O4-methylthymine in the template over the range of methylation studied. The results indicate that O4-methylthymine is capable of miscoding on a one-to-one basis while the products of DMS methylation (1-, 3- and 7-methyladenines), and also possibly the phosphotriesters, do not lead to any misincorporation.


The sequence specificity of a mammalian DNA methylase. The sequence specificity of an extensively purified DNA methylase preparation from Krebs II mouse ascites cells has been examined. The enzyme appears to be highly sequence dependent. Moreover the sequence distribution of cytosine residues that are methylated, bears a very close resemblance to the sequence distribution of 5'-methyl cytosine found in vivo in a wide range of vertebrate cells and is consistent with methylation of cytosines in the sequence R-Yn-C-R.


Synthesis of oligonucleotides with sequences identical with or analogous to the 3'-end of 16S ribosomal RNA of Escherichia coli: preparation of A-C-C-U-C-C via the modified phosphotriester method. A combination of two different methods for the synthesis of oligoribonucleotides, i.e. the two-step phosphotriester method with 2-chlorophenyl phosphate as bifunctional phosphate source and the modified triester method with 2,2,2-trichloroethyl 2-chlorophenyl phosphorochloridate as monofunctional phosphate source, is applied for the synthesis of the fully-protected hexaribonucleotide A-C-C-U-C-C. The two-step method is used for the synthesis of the required dinucleotide monophosphates 9, 10 and 11. Application of the modified triester method for the coupling of the oligonucleotide blocks results in the formation of the fully-protected hexamer 15. Furthermore, attention is paid to 2,4,6-triisopropylbenzenesulphonyl 4-nitroimidazolide as a new condensing agent for the coupling of larger oligonucleotide blocks.


Specific cleavage of ribosomal RNA caused by alpha sarcin. Alpha sarcin causes the specific cleavage of RNA from 80S ribosomes and 60S subunits of yeast, but not from the 40S subunits to produce a small RNA fragment. The fragment was also produced on treatment of the 60S subunits of wheat germ ribosomes. The fragment has a molecular weight of 100,000 and is a cleavage product of the large RNA species in the 60S subunits. The fragment is not derived from the 5'end of the yeast 25S RNA nor does it bind to 5.8S RNA and we propose that the fragment represents the 3' terminal 320 nucleotides of 25S rRNA. The ability to produce fragment could not be separated from the ability of alpha sarcin to inhibit protein synthesis. Alpha sarcin also causes the specific cleavage of the 23S RNA of the E. coli subunit to produce a smaller fragment of RNA than that produced from eukaryote ribosomes.


Transcription in vitro of bacteriophage lambda 4S RNA: studies on termination and rho protein. When bacteriophage lambdapga18 DNA is transcribed in a purified in vitro system by E. coli RNA polymerase (nucleoside triphosphate: RNA nucleotidyl-transferase, EC 2.7.7.6), several major transcripts are synthesized. We have investigated transcriptional termination of one of these transcripts, the 4S, or "oop" RNA. Analysis by two-dimensional "fingerprinting" of T1 oligonucleotides reveals that transcription of the 4S RNA terminates at a specific site on the lambdapga18 DNA template, t-L with an efficiency of approximately 80%, i.e. 20% of transcripts are extended into larger RNAs. Addition of the E. coli protein rho to our transcription reactions has two effects: a) the efficiency of termination at the t-L site is increased to 100%; b) the number of 4S transcripts synthesized is increased by greater than 5-fold. Rho appears to stimulate 4S RNA synthesis by facilitating more rapid release of RNA polymerase from the t-L' termination site.


The presence of RNase II in high salt washed E. coli ribosomes: effect on circular dichroism of ribosomal complexes. Traces of the exonuclease RNAse II are retained by E. coli ribosomes purified by conventional high salt washing. The residual activity can give rise to serious artifacts, especially in physical studies.


Effect of salt on the transcription of T7 DNA by RNA polymerase from T4 phage-infected E.coli. Transcription of T7 DNA by T4 core enzyme with host sigma is more sensitive to KCI than that by host core enzyme with host sigma. When salt is added after initiation of RNA chains has occurred, it is not inhibitory. Salt affects the binding of T4 enzyme to T7  DNA to the same degree as the binding of host enzyme. Active preinitiation complex formation is inhibited more by salt with the T4 enzyme and the inhibition is temperature-dependent.


The status of community health nursing research. Community health nursing research studies and methodology articles published in English in journals during the years 1972-1976 are reviewed. The subjects studied, the investigators, and the methodology employed are discussed with recommendations for improved research methodology and utilization.


Research in the field of psychiatric nursing: 1952-1977. This review and assessment of research in the area of psychiatric nursing discusses guiding assumptions which have provided the underpinnings for research in the field, a chronological view of the research with comments on the methods of the times, and a discussion of trends and future directions.


Sizing acute myocardial infarcts: present limitations and potential approaches. It is now possible by scintigraphic imaging to identify the presence of acute transmural or nontransmural myocardial infarcts by noninvasive techniques and to localize acute transmural infarcts. Radionuclide blood-pool scintigraphy allows assessment of the impact of old and new myocardial damage on left ventricular function.


[Molecular weight and several features of the structure of yeast polysaccharides possessing antiviral properties]. By the methods of biogel R-10, R-30, R-60 and R-200 gel filtration, sedimentation analysis and IR-spectroscopy polysaccharides isolated from yeast Candida tropicalis 3b, C. arborea KAM-1 and a commercial yeast extract (Merck) were investigated. The effect of the preparations on TMV was also studied. Polysaccharides consisted primarily of glucanes with a molecular weight of 10000-16500. The yeast extract preparation also included mannane with a molecular weight of 48000. IV-spectra of the purified preparations were in the main identical and were typical of polysaccharides. The mannane containing preparation inhibited TMV more significantly that glucane containing preparations. The interaction between physical parameters, structure and biological activity of the biopolymers tested is discussed.


Affinity of intact Escherichia coli for hydrophobic membrane probes is a function of the physiological state of the cells. The fluorescence parameters of several common membrane probes in the presence of whole E. coli have been examined. The probes included electrically neutral lipophilic molecules N-phenyl-1-naphthylamine, pyrene, and 1,6-diphenyl-1,3,5-hexatriene as well as the negatively charged molecule 8-anilino-1-naphthalene sulfonate. It is demonstrated in each case that certain fluorescence parameters are a function of the state of energization of the cells. All the probes appear to monitor structural changes in the E. coli envelope which accompany the energization and de-energization of the cells. tthe phenomenon is completely reversible as demonstrated by re-energizing anoxic cells by the addition of oxygen, or starved cells by the addition of substrate. All the results are qualitatively consistent with an increased binding of probe by de-energized cells and a subsequent expulsion of probe when the cells are re-energized. A pyrene substituted with a photosensitive group, 1-azidopyrene, has been synthesized. Photolysis in the presence of a suspension of energized E. coli reveals a relatively small amount of probe irreversibly bound to the cells. However, in the presence of cells that have been de-energized the amount of irreversibly bound probe is dramatically increased. This molecule should be useful for localizing the regions of the bacterial envelope that are involved in the structural changes being monitored in these experiments.


Chromosomal location of a structural gene for the RNA polymerase sigma factor in Escherichia coli. A set of F' strains of Escherichia coli K-12 partially diploid for various chromosomal segments has been examined for possible gene dosage effects in the synthesis of sigma factor of the DNA-dependent RNA polymerase (RNA nucleotidyltransferase; nucleoside-triphosphate:RNA nucleoti-dyltransferase, EC 2.7.7.6). It was found that all F' strains diploid for the dnaG region synthesize sigma at rates two to three times higher than other F' or F- strains. Moreover, strains of Salmonella typhimurium harboring these F' plasmids produce E. coli sigma in addition to Salmonella sigma. This has been shown on the basis of the finding that Salmonella sigma can be precipitated with antiserum against E. coli RNA polymerase but is distinguishable from E. coli sigma in its mobility in sodium dodecyl sulfate/polyacrylamide gel electrophoresis. E. coli sigma polypeptides thus produced seem to be stable in cells of S. typhimurium. These results indicate that a structural gene for sigma (rpoD) is located at the metC-argG region, probably near the dnaG locus (66 min on the current genetic map of E. coli).


A gene from Escherichia coli affecting the sigma subunit of RNA polymerase. The RNA polymerase sigma subunits of Escherichia coli K, E. coli C, and Salmonella typhimurium can be resolved by electrophoresis. Using this technique, we have analyzed Salmonella strains carrying F' plasmids from E. coli K in order to map the gene for the sigma factor. Partial diploid analyses show the location of the sigma gene at 62-66 min on the E. coli genetic map. This gene is cotransducible with toIC and dnaG, at 66 min.


Microenvironment of the binding site in the lac carrier protein. Studies with a homologous series of (N-dansyl)aminoalkyl-1-thio-beta-D-galactopyranosides containing two to six methylene carbons bridging the galactosyl and dansyl ends of the molecules are described. The compounds were utilized in radioactive and nonradioactive form, and binding of each homologue to membrane vesicles isolated from Escherichia coli ML 308-225 was measured directly by flow dialysis in the presence of D-lactate. The results are compared with the D-lactate-induced fluorescence enhancement observed with each dansylgalactoside and with the ability of N-methylpicolinium perchlorate to quench the fluorescence of the bound homologues. The binding affinity of the lac carrier protein for the probes varies directly with the length of the alkyl linkage, and the same number of binding sites is observed with each homologue. In contrast, however, the increase in fluorescence observed upon binding varies dramatically as the alkyl chain is increased in length, with the fluorescence exhibiting maximal values at two and six methylene carbons and a minimum at four methylene carbons. Furthermore, quenching by N-methylpicolinium perchlorate exhibits an inverse relationship and maximum quenching is observed with the 4 carbon homologue. Possible reasons for this behavior are discussed.


Origin of replication of colicin E1 plasmid DNA. Cleavage maps of colicin E1 plasmid DNA and its smaller derivative, pNT1 DNA, were constructed by using restriction endonucleases. The nucleotide sequence of a region that contains the orgin of replication was determined. The site of the nucleotide from which DNA replication is initiated was determined with 6S L-fragments, the DNA fragment first made on colicin E1 plasmid DNA. The fragments were labeled with [gamma-32P]ATP and polynucleotide 5'-hydroxyl-kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) at the 5'-OH groups which were uncovered by alkali treatment. The site is one of three consecutive nucleotides, dA, dA, and dC, located at a unique position. One or a few rA residues were found to be attached to some of the DNA molecules. The transition from the primer RNA to DNA occurs in a region consisting of a segment of five A residues. Both sides of this segment are rich in G and C.


Albumin synthesis in mouse uterus in response to liver mRNA. Messenger RNA was isolated, by means of its attachment to poly(A), from calf liver and the livers of mice, rats, and chickens. When injected into the uterine lumen of immature or spayed mice, both mouse albumin and the albumins characteristic of the species donating the mRNA were synthesized. Studies with inhibitors disclosed that puromycin blocked the synthesis of both albumin species, while dactinomycin affected only mouse albumin synthesis. It appears, therefore, that in the experimental situation used, the function of exogenous liver mRNA is 2-fold: (i) it programs the synthesis of alien albumin in uterine epithelial cells, and (ii) it stimulates the synthesis of mRNA in epithelial cells. The mRNA thus produced primes the synthesis of mouse albumin.


Reconstitution of tobacco mosaic virus rods occurs bidirectionally from an internal initiation region: demonstration by electron microscopic serology. RNA of a common strain of tobacco mosaic virus was sequentially reconstituted first with protein of the same strain and then with protein of a tomato strain. The reconstituted particles were treated with specific antibodies against the two strain particles and were examined electron microscopically to locate the regions of rods encapsidated with the respective proteins. The results demonstrated that reconstitution starts at an internal region of the RNA about 830 nucleotides from an end that recent studies indicate to be the 3' terminus. Evidence was obtained to show that reconstitution proceeds toward the 5' terminus of the RNA until it is fully encapsidated. Encapsidation of the 3' distal portion of the RNA apparently occurs later and in a direction opposite to that of the encapsidation of the 5' distal portion.


Use of a distant reporter group as evidence for a conformational change in a sensory receptor. A highly sensitive method for demonstrating ligand-induced conformational changes in protein molecules  in solution is described. The method utilizes an environmentally sensitive reporter group that is known to be distant from the active site. In the present application a conformational change is demonstrated in the galactose receptor of Salmonella typhimurium, involved in bacterial sensing and transport, by means of an extrinsic fluorophore, 5-iodoacetamidofluorescein, attached at a single methionine residue, and the intrinsic tryptophan fluorophore. Binding of the ligand galactose perturbs the microenvironment of both the fluorescein and tryptophan, as shown by both spectral and potassium iodide quenching changes. The distance between the two dyes is established by fluorescence energy transfer methods to be 41 +/- 10A. Since only one molecule of galactose binds per molecule of receptor and since the galactose molecule is only about 5 A in length, changes at one of these sites reflect the result of an indirect effect. Hence, there must be a ligand-induced conformational change that is propagated a minimum of 30 A through the receptor molecule.


Enzymatic initiation of DNA synthesis by yeast DNA polymerases. Partially purified yeast RNA polymerases (RNA nucleotidyltransferases) initiate DNA synthesis by yeast DNA polymerase (DNA nucleotidyltransferase) I and to a lesser extent yeast DNA polymerase II in the replication of single-stranded DNA. The enzymatic initiation of DNA synthesis on phage fd DNA template occurs with dNTPs alone and is further stimulated by the presence of rNTPs in DNA polymerase I reactions. The presence of rNTPs has no effect on the RNA polymerase initiation of the DNA polymerase II reaction. RNA polymerases I and III are more efficient in initiation of DNA synthesis than RNA polymerase II. Analyses of the products of fd DNA replication show noncovalent linkage between the newly synthesized DNA and the template DNA, and covalent linkage between the newly synthesized RNA and DNA.


Dynamic structure of whole cells probed by nuclear Overhauser enhanced nitrogen-15 nuclear magnetic resonance spectroscopy. The proton-decoupled 15N Fourier transform nuclear magnetic resonance (NMR) spectra of 15N-enriched Escherichia coli, Bacillus licheniformis, baker's yeast, and Friend leukemic cells were obtained. The 15N NMR spectra of whole cells displayed 15N resonances originating from (i) protein backbones with lysine, arginine, and histidine side chains, (ii) ribonucleic acids, (iii) peptidoglycan, and (iv) phospholipids. Several additional amino and amide resonances were observed but not identified. In bacteria and yeast, the cell wall was found to be the site of a relatively mobile group of molecules, whose resonances dominate the proton-decoupled 15N NMR spectra of whole cells. 15N NMR chemical shifts and nuclear Overhauser effects have provided information on the in vivo structure of cell wall peptidoglycan. In Staphylococcus aureus the pentaglycine cross-bridge of cell wall peptidoglycan was found to have a random coil conformation. In B. licheniformis considerable segmental motional freedom was detected in teichuronic acid and peptidoglycan polysaccharide chains in the wall of the intact cell.


Interaction of filamin with f-actin in solution. Filamin is a major high-molecular-weight protein in smooth muscle which was recently identified and isolated [Wang, K., Ash, J. F. & Singer, S. J. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 4483-4486]. In the present studies, we shown that highly purified chicken gizzard filamin and muscle F-actin react in solution to form aggregates containing both proteins. Occasionally, these aggregates coagulate and contract into a dense gel in the absence of MgATP or CaATP. Immunofluorescence and electron microscopic studies suggest that the F-actin filaments are collected into fiber bundles and a crosslinked fiber meshwork by the binding of filamin molecules. These studies suggest that the function of filamin intact cells may be to regulate the ultrastructural state of F-actin filaments in a variety of dynamic cellular processes.


Cell-free synthesis of fish preproinsulin, and processing by heterologous mammalian microsomal membranes. Poly(A)-containing mRNA isolated from the islets of Langerhans obtained from two species of fish, angler fish (Lophius americanus) and sea raven (Hemitripterus americanus), stimulated protein synthesis 16-fold in a wheat germ cell-free system. Characterization of the translation products by polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed a major polypeptide weighing 11,500 daltons that was specifically precipitated by an antibody against angler fish insulin. Partial sequence analysis of the amino terminal revealed that this polypeptide is preproinsulin, in which the amino terminus of proinsulin is preceded by either 23 (angler fish) or 25 (sea raven) amino acid residues. Translation of fish islet mRNA in a wheat germ cell-free system in the presence of dog pancreas microsomal membranes led to the correct cleavage of the nascent preproinsulin, resulting in the synthesis of authentic fish proinsulin, as verified by partial sequence analysis. Moreover, the synthesized fish proinsulin was segregated, presumably into the luminal space of the dog pancreas microsomal vesicles, because it was found to be resistant to proteolysis by added trypsin and chymotrypsin. Our data thus suggest that the mechanisms and information for the transfer of secretory proteins across the microsomal membrane are highly conserved during evolution.


Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs. N-Acetylmuramyl-L-alanyl-D-isoglutamine and four other synthetic adjuvants that are structural analogs of part of the mycobacterial peptidoglycan monomer are shown to enhance the nonspecific immunity of mice infected by Klebsiella pneumoniae. These compounds are active by various routes, including oral administration; they are also effective when administered after challenge. Of the seventeen other analogs tested, none is able to increase significantly resistance to infection, although seven of these molecules are adjuvant-active in saline. Previous results have shown that in contrast to lipopolysaccharides, these synthetic adjuvants are devoid of immunogenicity, mitogenicity, and toxicity in normal or adrenalectomized mice.


Pancreatic immunoreactive somatostatin release. The location of the somatostatin-containing D-cells of the pancreatic islets between the A- and B-cells suggests that their function might be to inhibit insulin and/or glucagon secretion by these neighboring cells. To determine if insulin and/or glucagon, in concentrations that might be present in the extracellular space surrounding the D-cells, stimulate immunoreactive somatostatin (IRS) release, we perfused  10 microng of glucagon or 10 milliunits of insulin per ml in 11 isolated dog pancreases, for 40 min in seven experiments and for 100 min in four experiments. In eight of the nine experiments in which glucagon was perfused, a prompt and significant rise in mean IRS release, ranging from 71 to 128% above the control level, was observed. In the eight experiments in which insulin was perfused. IRS did not increase during the first 40 min; in the two 100-min insulin experiments, it did rise during the final 50 min, however. To determine the effect of an A- and B-cell secretogogue on IRS release, we perfused 20 mM arginine for 60 min in six experiments. In all, IRS rose within 3 min and reached a level 71-465% above the control, remaining significantly elevated throughout the perfusion, while glucagon and insulin rose to peak levels at 2 min and then declined somewhat despite continuing arginine perfusion. The results indicate that perfusion of the normal dog pancreas with high doses of glucagon or arginine is accompanied by a prompt increase in IRS release and are compatible with a local feedback circuit involving A- and D-cells. Insulin appears not to augment IRS release, at least not promptly, but IRS stimulated by local endogenous glucagon could inhibit the B-cell response to locally secreted glucagon and thereby influence the composition of the insulin/glucagon secretion mixture.


Marijuana: dose-response effects on pulse rate, subjective estimates of potency, pleasantness, and recognition memory. 34 experienced marijuana users were divided into four equated groups of eight subjects each based on recognition memory test performance. One week later each group was retested following administration of marijuana containing 0, 5, 10 or 15 mg delta9-tetrahydrocannabinol. A dose-related effect of marijuana on pulse rate and subjective measures of potency and pleasantness occurred. Ratings of potency and changes in pulse rate were highly correlated, but this relationship did not hold within a given dosage group as determined by partial correlations. No effect of marijuana on the distribution of hit and false alarm rates or confidence ratings during the recognition memory test was noted.


Serratia marcescens in a general hospital. Fourteen patients with infections caused by Serratia marcescens were seen over an eight-month period in a large general hospital. Predisposing factors suggested an 'opportunistic' pattern similar to that previously described in the United States. S. marcescens is an important pathogen which may be increasing in significance in the United Kingdom. Multiple resistance of the organism to antibiotics other than gentamicin makes the finding of apparent sensitivity to co-trimoxazole of potential therapeutic value.


Occlusive arterial disease in uraemic and haemodialysis patients and renal transplant recipients. A study of the incidence of arterial disease and of the prevalence of risk factors implicated in the pathogenesis of arteriosclerosis. The prevalence of clinical and sub-clinical occlusive arterial disease and of risk factors implicated in the pathogenesis of arteriosclerosis was assessed in 21 patients with chronic renal failure, 27 on maintenance haemodialysis and 51 renal allograft recipients. Clinical occlusive arterial disease was present in 27 patients, and sub-clinical arterial disease in 34. Myocardial infarction, cerebral thrombosis and lower limb arterial thrombosis had occurred only in the transplant recipients; these patients had, however, been followed for a longer period of time than the other two groups. In the allograft recipients, the cumulative incidence of any occlusive arterial disease was 416 per 1000, and that of coronary heart disease was 267 per 1000 at six years. Hypertension was present in 76 per cent of patients prior to renal replacement therapy. Following institution of definitive therapy, hypertension was of shorter duration and less common in haemodialysis patients than in renal transplant recipients. Uraemic and haemodialysis patients with occlusive arterial disease had required antihypertensive medication for significantly longer than those free of arterial disease. Transplant recipients with hypertension had a greater mean serum creatinine, were receiving a larger maintenance dosage of corticosteroids and less frequently had undergone prior bilateral nephrectomy than those transplant patients without hypertension. Serum lipid levels were elevated in 62 per cent of patients. In the uraemic and haemodialysis patients hypertriglyceridaemia was the predominant abnormality while in the transplant recipients combined hypertriglyceridaemia/hypercholesterolaemia was more frequent. Despite regular aluminium hydroxide therapy 81 per cent of uraemic and haemodialysis patients had a calcium X phosphate product higher than normal. Arterial and/or soft tissue calcification as demonstrable in 20-38 per cent of patients within each group, but could not be related to the calcium X phosphate product of radiographic evidence of hyperparathyroidism. Glucose intolerance was present in 71 per cent of the uraemic and haemodialysis patients and 33 per cent of the transplant recipients. Hyperuricaemia, cigarette smoking, obesity and a sedentary existence were also prevalent. The majority of patients had several risk factors implicated in the pathogenesis of arteriosclerosis. Occlusive arterial disease is a major problem in patients with end stage renal disease, being no less common after transplantation than with long-term maintenance dialysis. The aetiology is multifactorial.


Distribution of total and fecal coliform organisms from septic effluent in selected coastal plain soils. Distribution of total and fecal coliform bacteria in three Atlantic coastal plain soils in Virginia were monitored in situ over a 3-year period. The soils studied were Varina, Goldsboro, and Beltsville sandy loams. These and similar soils are found extensively along the populous Atlantic seaboard of the United States. They are considered only marginally suitable for septic tank installation because the restricting soil layers result in the subsequent development of seasonal perched water tables. To determine both horizontal and vertical movement of indicator organisms, samples were collected from piezometers placed at selected distances and depths from the drainfields in the direction of the ground water flow. Large reductions in total and fecal coliform bacteria were noted in the perched ground waters above the restricting layers as distance from the drainfield increased. These restricting soil layers appear to be effective barriers to the vertical movement of indicator organisms. The reduction in the density of the coliform bacteria above the restricting soil layers can probably be attributed to dilution, filtration, and dieoff as the bacteria move through the natural soil systems.


Scintigraphic patterns of gallium-67 uptake in the breast. A review of 542 67Ga scans was undertaken to determine the incidence of 67Ga uptake in the "normal" breast, to establish factors modifying the uptke of 67Ga, and to define patterns of "normal" vs. pathologic accumulation. Nonpathologic uptake of 67Ga was demonstrated in 29 patients (12% of female patients) and was most often associated with conditions stimulating prolactin production or related to estrogenic hormone administration. This type of uptake was symmetrical but of varying pattern depending on the underlying stimulus. Pathologic uptake of 67Ga was demonstrated in 3 cases and always resulted in asymmetrical appearance of the breasts.


Cerebrospinal fluid serology--is its routine use justifiable? Although neurospyhilis has become a rare disease, requests for cerebrospinal fluid (CSF) syphilis serology tests at the Colorado Department of Health have increased in recent years. Because of the low rate of positive results, questionnaires were sent to the physicians who requested these tests to determine the criteria for their use. Neurosyphilis was neither suspected nor an important consideration to rule out in 63 percent of the 337 patients sampled. Of the patients whose ages were specified, more than half were under age 40. No concomitant reports of blood serology were available for 63 percent of the study patients, and only 13 percent of the available blood serology reports indicated reactivity. One of the two patients with positive test results was appropriately treated, but the other patient for whom the test was ordered 'routinely' to rule out neurosyphilis was lost to followup. One-half of the tests were requested by neurologists, neurosurgeons, and orthopedists. The survey findings indicated that most of the CSF serologic tests for syphilis were done without appropriate preliminary testing for patients who had no evidence of syphilis by physicians who perform lumbar punctures as a consequence of their specialties. The authors recommend that use of the test be reviewed in light of the changing epidemiology of the disease. They further suggest that directors of laboratories performing CSF serologic tests are in a unique position to initiate an educational exchange and a consequent change in physicians' behavior.


The use of intra-arterial lidocaine to control pain due to aortofemoral arteriography. Intra-arterial lidocaine has been utilized to decrease pain by administration prior to contrast material injections during aortofemoral arteriography in over 600 patients. Because this observation was uncontrolled, a double-blind study was performed in 15 patients comparing the effectiveness of intra-arterial lidocaine and saline in  the control of pain from contrast material injections (methylglucamine iothalamate) in pelvic and peripheral arteriography. Two per cent lidocaine was compared with 1% lidocaine in the same manner in an additional 10 patients. Peripheral vein blood samples were obtained in 4 patients to measure the plasma concentration of lidocaine. Intra-arterial lidocaine is safe and effective in reducing pain from intra-arterial contrast agent injections.


Subtraction radiography: techniques and limitations. Subtraction radiography permits the use of 7-10 times less contrast material than is required without subtraction techniques. The first-order, second-order, and composite mask techniques are described and evaluated. While the second-order technique gives more complete cancellation of common structures, the more commonly used first-order technique was found to be adequate for most clinical uses. The smallest change in contrast which can be detected using subtraction radiography is limited by inherent background film noise in the original radiographs and not by statistical fluctuations in the x-ray quanta.


Analysis of the dense lesion at computed tomography with dual kVp scans. By scanning the brain first at 100 and then at 140 kVp one can distinguish, in vivo, between blood and calcium or iodine solutions. The higher atomic number of calcium or iodine causes their CT values to decrease significantly while blood shows no significant change. This principle was applied to eight patients with hemorrhages, calcified lesions, or iodine-contrast augmented lesions. Hemorrhages showed no significant change with change in kVp, while the lesions containing calcium or iodine showed a highly significant change. This is a useful maneuver for determining the nature of a high-value lesion.


The results of conservative management of neurogenic vesical dysfunction in children. Ninety-three cases of neurogenic vesical dysfunction were treated between 1957 and 1974, including 68 children with spina bifida, 10 with occult neurogenic bladders, 7 with sacral agenesis, 2 with spinal dysraphism, and 6 with miscellaneous disorders. No attempt at classification into types of neurogenic bladder was made. Three children in the series died, two from renal causes and one from neurosurgical complications. Treatment consisted of antireflux surgery, methods to lower bladder outlet resistance, operations to relieve obstruction or stasis, or urinary diversion as a last resort. Ureteral reimplantation was performed in 25 children. Reflux was cured in 29 of the 34 ureters reimplanted. Bilateral ureteral reimplantation is recommended because of the subsequent development of vesicoureteral reflux on the opposite side in more than half of the cases of unilateral ureteral reimplantation. Bladder outlet resistance must be lowered in most cases at the time of ureteral reimplantation. This was accomplished in these cases and the group of children as a whole by means of Y-V plasty of the bladder neck, transurethral bladder neck resection, urethral dilation, or pharmacological therapy with phenoxybenzamine (an alpha-symphathetic blocking agent). Urinary calculi were removed in six children in order to preserve renal function. Fifteen children underwent urinary diversion becuase of upper tract deterioration, and in eight children this was performed primarily for urinary incontinence. With conservative treatment, it was possible to preserve renal function as determined by intravenous urography in nearly two-thirds of the cases. Urinary incontinence was difficult to manage in most cases. Manipulations of the bladder neck were only occasionally helpful. Results with the Caldwell stimulator were disappointing. Pharmacological therapy was moderately successful. Phenoxybenzamine was the most useful drug. Imipramine was occasionally of benefit. It is concluded that the upper urinary tracts may be preserved in many cases by means of conservative therapy. Urinary diversion has been avoided in most cases because of its disappointing results. We believe that the trend will be towards increasingly conservative therapy of these children for some years to come.


Pleuropulmonary suppurations.

Pleuropulmonary suppurations. The neonatal pleural empyema, especially in its most serious form, following staphylococcal pneumonia, presents a surgical problem demanding immediate emergency treatment. In 1957, we proposed that after diagnosis the empyema should immediately by drained by intercostal suction although in those times drainage was only an attempt after numerous aspirations. Children treated for pleural suppuration in the past were subjected to follow-up studies over a period of 14 to 15 years. Two comparative groups of "early-drained" and "late-drained" empyema cases showed that after immediate drainage there was definite improvement. Careful study of all the data of our 273 cases (up to 1970) shows that immediate continuous suction drainage with specific antibiotic and general supportive treatment have been very successful.


Epidemiology of cancer of the penis.

Epidemiology of cancer of the penis. World-wide incidences of penile cancer are reviewed and epidemiologic factors including ciecumcision, hygiene, phimosis, smegma, irritation, infection, veneral disease, viruses, environment, race, immune response, trauma, and age are discussed. The lowest rates appear in groups practicing infant circumcision and in areas where standards of sexual hygiene are high.


[Sports in neurological rehabilitation (author's transl)]. Little has been written about the effects of sports activities on neurological diseases such as cerebral palsy, hemiplegia, brain trauma and paraplegia, and the available reports are mainly related to cardiopulmonary parameters. Compared to the securing of physiological data, it is more difficult to operationally define, or quantify questions concerning the motivation and social background--in a broader sense, sociological background--of the patient. Both data, however, are indispensable to rehabilitation. The experiences gained with a group of children with spina bifida attending a school for the physically handicapped, are used to describe the sequela of the central nervous system defect with which the physical education instructor has to cope, and stresses how important mutual information amongst the team members is for successful rehabilitation. The criteria for sports activities with spina bifida children are: (a) to promote their independence, (b) to give them socialisation stimuli, (c) to enhance their physical performance. It is hoped with this programme that a further personality maturation and stabilisation be achieved.


[Portal blood flow in minipig and its change by nicotinic acid (author's transl)]. The chronic double catheterisation of portal vein permits estimation of portal flow by dye dilution for example, the withdrawal of blood from the mesenteric vein and proximal portal vein, the injection of drugs into the portal circulation and measurement of portal pressure simultaneously. Beside the well known diminution of portal flow by vasopressin, which is extreme in anaesthetised minipig, there could be shown a remarkable diminution by high intravenous doses of nicotinic acid too without significant changes of systemic blood pressure and heart rat. Nicotinic acid causes also a diminution of pH in portal and venous blood.


[Allorosettes after renal transplantation in inbred strains of rats (author's transl)]. 33 renal transplantations in the isohistogeneic rat strains DA/Han and BDE/Han were performed. The transplanted animals were killed at different days after transplantation and the following dates investigated: 1. number of rosette forming spleen cells with donor erythrocytes, calculated for 10,000 spleen cells and to the total number of extracted spleen cells, 2. haemagglutinin titers with donor erythrocytes. 3. titers of serum IgG, 4. Total number of spleen cells, weight of spleens, weight and volumes of kidney transplants and the number of peripheral blood lymphocytes and granulocytes. The results deomonstrate that the method of immunocytoadherence as described by BIOZZI and ZAALBERG in xenogeneic transplantation systems can also be used in allogenic systems. The course of the immune response was biphasic. Quantitation of allorosette forming cells can be considered as a paramter of allograft rejection. The current literature as to the T- or B-cell specificity of rosetting cells is discussed.


[Plain-x-ray diagnosis of midfacial lesions (author's transl)]. The basic radiologic features of disorders of the orbit and the paranasal sinuses are described and with characteristic cases illustrated. A critical evaluation of the radiologic signs and a brief summary of the normal roentgen anatomy are included. Emphasis is placed to less well known symptoms and differential diagnosis.


Effect of somatostatin on gastrointestinal secretions and peptic ulcer production in cats. In conscious cats with chronic gastric and pancreatic fisulas, the effect of somatostatin (GH-RIH) on gastric and pancreatic secretion and peptic ulcer formation was examined. GH-RIH infused intravenously in graded doses (range: 0.62 to 5.0 microng/kg-hr) inhibited dose-dependently gastric acid response to pentagastrin but failed to affect acid response to histamine. GH-RIH caused a marked inhibition of pepsin secretion induced by both pentagastrin and histamine and decreased pancreatic bicarbonate but not protein response to exogenous secretin or intraduodenal acid. It effectively prevented the formation of duodenal ulcers produced by prolonged administration of both pentagastrin or histamine.


Water hardness and cardiovascular disease. Elements in water and human tissues. The hypothesis that the hardness of drinking water has a causal role in the development of cardiovascular disease will be strengthened if it can be demonstrated that elements in drinking water find their way into human tissues in significant amounts. For biologically important metals, the evidence is reviewed for a relationship of tissue levels to levels in drinking water. Hard water can contribute significantly to daily magnesium intake. Residents of hard-water areas may have raised levels of magnesium in coronary arteries, bone, and myocardial tissue. Lead levels in bone and in blood have been shown to be elevated in individuals living in homes with lead plumbing and soft water. Cadmium intake from water is probably small compared to that from other sources, and there is no convincing evidence of alteration in human tissue levels via drinking water cadmium. Human zinc and copper tissue levels are of interest but have not been adequately studied in relation to drinking water levels.


Rat insulin genes: construction of plasmids containing the coding sequences. Recombinant bacterial plasmids have been constructed that contain complementary DNA prepared from rat islets of Langerhans messenger RNA. Three plasmids contain cloned sequences representing the complete coding region of rat proinsulin I, part of the preproinsulin I prepeptide, and the untranslated 3' terminal region of the mRNA. A fourth plasmid contains sequences derived from the A chain region of rat preproinsulin II.


Intravenous naloxone administration in schizophrenia and affective illness. Fourteen schizophrenic patients and five patients with affective disorders were given naloxone (0.4 to 10 milligrams) or placebo intravenously in a double-blind fashion. Physicians' ratings of hallucinations, mannerisms and posturing, conceptual disorganization, psychosis, and mood did not change significantly. A single item, unusual thought content, improved significantly on the naloxone day compared to the placebo day. There was no improvement in mood in affectively ill patients rated either by themselves or by physicians. Naloxone did not markedly improve any patient studied, which suggests that the acute blockade of opiate receptors is not associated with global improvement in psychotic symptomatology.


Progressive hemifacial atrophy.

Progressive hemifacial atrophy. Twenty-three cases of progressive hemifacial atrophy with their modalities of treatment have been reviewed. The importance of and need for proper planning and a coordinated approach are stressed. Generally, the final result has been highly satisfactory to the patient.


Progress in the treatment of glaucoma in my lifetime. A period of great progress in the diagnosis and treatment of glaucoma began in the 1920's with the development of gonioscopy apparatus and the slitlamp, and the first application of epinephrine in the treatment of the disease. With the development of precise methods for examination, differentiation among the various forms of glaucoma became possible, knowledge and theories regarding the nature and mechanisms of the disease became available, and medical and surgical approaches to treatment were developed with varying degrees of success. Major events and concepts in the management of glaucoma during the last 50 years are reviewed, including literature reports and the personal experiences of the authors and his colleagues.


Spina bifida and so-called asplenia syndrome occurring separately in sibs. Attention is drawn to the possibility that neural-tube defects may sometimes be associted with the so-called asplenia syndrome (Ivemark syndrome). This hypothesis is based upon a family in which one child had spina bifida and hydrocephaly and another had cardiovascular and other fissural anomalies, similar to Ivemark syndrome. The family history, moreover, revealed several cases of anencephaly and/or spina bifida, both on the paternal and maternal sides.


Endogenous E. coli endophthalmitis.

Endogenous E. coli endophthalmitis. A case of Escherichia coli septicemia with associated metastatic en dophthalmitis and endocarditis is presented. The ocular signs and symptoms were the initial manifestations of sepsis. Irreversible damage to the eye occurred in less than 24 hours. The pattern of metastatic bacterial endophthalmitis has changed since the introduction of potent antimicrobial agents, with an increased incidence of Gram-negative bacillemia. E. coli endophthalmitis carries a poor prognosis. Early diagnosis and systemic treatment will prevent the life-threatening complications of sepsis.


Ultrastructural immunocytochemical localisation of lysozyme in human bronchial glands. An immunocytochemical unlabelled antibody method using rabbit antihuman lysozyme, antirabbit immunoglobulin, and soluble rabbit antihorseradish peroxidase/horseradish peroxidase complexes was used to study the fine structural distribution of lysozyme in human bronchial glands. None was identified in mucous cells but there was heavy staining of the serous cell granules. The serous cell granules were not stained uniformly, suggesting the presence of other secretory products but lysozyme secretion appears to be a major function of these cells. The pathological implications of this are discussed.