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In the context of a training study, the functional relationship between discrimination and production was investigated. Four subjects were selected for study. For two subjects, Condition I consisted of production training followed by a discrimination probe and Condition II consisted of discrimination training followed by a production probe. For the other two subjects, the conditions were reversed. In production training, the subjects were trained to correctly articulate three consonant-vowel (CV) syllables in response to nonsense pictures. In discrimination training the subjects were trained to find nonsense pictures in response to three CV syllables. Probe measures were administered to determine if changes occurred in one modality after training the other modality. Results indicated that production training was effective in changing both articulation and discrimination; however, discrimination training was effective in changing only discrimination.

The attachment of the bacterial chromosome to the cytoplasmic membrane in Escherichia coli was studied. The initiator DNA was specifically labeled and the outer and cytoplasmic membranes were separated in a step sucrose gradient. The labeled DNA was localized mainly in the cytoplasmic membrane fraction. The DNA . cytoplasmic membrane complex was isolated from cells uniformly labeled with [Me-3H]thymidine, solubilized with deoxycholate and chromatographed on Sepharose 4B. A high percent of the labeled DNA was excluded in the void volume but a small fraction eluted associated with the second protein elution peak. The isolation of such a DNA . cytoplasmic membrane protein complex, suggests useful strategies for future studies about the molecular components of the initiation complex in E. coli.

The interaction between ethidium bromide and ribosomal RNA has been studied by means of absorption, fluorescence, circular and electric dichroism measurements in the near ultraviolet and visible regions at low ionic strength (1 . 10(-3) and 6 . 10(-3). The results have been interpreted on the basis of a model of interaction involving the intercalation of the phenanthridinium ring of the dye in the double-stranded regions of the RNA molecule, resulting in an increase of the dye-dye interactions as compared to DNA, and a stiffening of the intercalation regions.

When Escherichia coli 50-S ribosomal subunits are treated with increasing concentrations of urea partial deproteination occurs. Furthermore, we observed that the number of sulfhydryl groups which react with Ellman's reagent is a sigmoidal function of the urea concentration. These results are similar to those previously reported for the 30-S subunit (Acharya, A.S. and Moore, P.B. (1973) J. Mol. Biol. 76, 207-221). For both subunits we identify the proteins which dissociate (split proteins) or are recoverable in a ribonucleoprotein particle (core proteins) under the action of 6 M urea in a buffer of moderate ionic strength.

This report concerns the synthesis of poly(5-aminouridylic acid) and of 5-aminouridine-containing trinucleotides. Starting from 5-aminouridine the nucleoside 5'-phosphate was prepared enzymatically with carrot phosphotransferase whereas the nucleoside 5'-diphosphate was prepared chemically and polymerised with polynucleotide phosphorylase. The aminouridine-containing trinucleotides were prepared by known enzymatic procedures. Besides an increase of stability in the secondary structure poly(nh25U) forms a triple-stranded complex with poly(A) and stimulates the poly(Phe) synthesis like poly(U). In contrast to U-nh25U-U, the triplet containing the 3'-terminal aminouridine does not stimulate the binding of Phe-tRNA to 70-S ribosomes. This behavior is discussed with respect to the influence of a modification on the stacking geometry of a codon and the base pairing scheme between the 5'-nucleotide of the anticodon and the 3'-nucleotide of the condon.

Energy conservation and uncoupling in mitochondria are examined in the light of three important new findings: (a) Studies with the photoaffinity-labeling uncoupler 2-azido-4-nitrophenol have shown that mitochondria contain a specific uncoupler binding site (apparently a polypeptide of Mr = 30,000 +/- 10%). (b) This site fractionates into an enzyme complex (complex V), which is capable of oligomycin- and uncoupler-sensitive ATP-Pi exchange. It is absent from electron transfer complexes I, III, and IV, which represent segments of the respiratory chain containing coupling sites 1, 2, and 3, respectively. (c) Trinitrophenol is a membrane-impermeable uncoupler (uncouples submitochondrial particles, but not mitochondria) and a poor protonophore. There is an excellent correlation between the uncoupling potencies and the affinities of uncouplers for the mitochondrial uncoupler-binding site. There is no correlation between uncoupling potency and protonophoric activity of uncouplers when a membrane-permeable uncoupler is compared with a membrane-impermeable one.

A new chlorambucil ester of prednisolone (LEO 1031) has been evaluated in patients with advanced lymphocytic lymphosarcoma and chronic lymphocytic leukemia. All 11 patients had been previously treated with radiotherapy and/or combination chemotherapy. Three complete remissions and one partial remission were seen in 4/7 lymphocytic lymphosarcoma patients treated with LEO 1031. In the chronic lymphocytic leukemia group, 3/4 have had benefit. This new drug is considered worthy of further trial.

Barotrauma has been used to describe several specific complications related to mechanical ventilation. These include tension lung cyst, pneumothorax, pneumomediastinum, pneumoperitoneum, and subcutaneous emphysema. Pulmonary hyperinflation, another such complication, occurred in 6 patients, being fatal in 3. Two pathophysiologic mechanisms are discussed. The simpler, and well-recognized, ball-valve airway obstruction allows inspiration of air delivered by the mechanical ventilator but prevents expiration. A more complex circumstance exists when pulmonary contusion or infiltration produces differential lung compliances. This allows extreme hyperinflation of areas of normal lung during attempts to ventilate abnormal lung of low compliance. This mechanism is particularly evident when positive end-expiratory pressure (PEEP) is used in an attempt to open collapsed ventilatory units. Functional complications of lung hyperinflation include decreased alveolar ventilation and compression effects on adjacent structures. Interference with and shifts of regional lung perfusion may worsen gas exchange. Proper treatment includes airway clearance by bronchoscopy, the judicious use of bronchodilators, the discontinuance of PEEP, and adjustments of mechanical ventilators to prevent high airway pressures.

A study evaluating the durability of two recent techniques of tricuspid annuloplasty was conducted simultaneously in two institutions. One group working in Madrid, Spain, used Carpentier's ring in 32 patients. The other in Montreal, Canada, employed De Vega's semicircular annuloplasty in 17 cases. Competence of the tricuspid valve was obtained in nearly all cases at the time of surgery and persisted after a mean follow-up of 10.3 months (Madrid) and 11.5 months (Montreal) in 77 per cent of the cases. Light (1/3) residual tricuspid insufficiency was detected in 16.5 per cent; moderate (2/3) incompetence persisted in only 6.5 per cent. The majority of the patients with residual tricuspid insufficiency had unsuccessful or incomplete repair of left-sided heart lesions.

A simple technique of resuscitation of the canine cadaver heart is described. The method includes internal manual cardiac massage and positive-pressure ventilation of the lungs after isolation of the heart-lung preparation from the rest of the systemic circulation. This techniqle proved successful in 20 of 25 cases after periods of anoxic cardiac arrest ranging from 15 to 128 minutes (average 35 minutes). An evaluation of the state of the myocardium in the postresuscitation period was made by a number of hemodynamic, electrocardiographic, blood chemistry, and histopathological observations, with particular note being taken of those relating to left ventricular contractility and to hematoxylin-basic fuchsin-picric acid (HBFP) staining.

A major focus of efforts to monitor and control health care expenditures has centered on factors related to hospital length of stay. Age, in particular, is usually assumed to be an important correlate of hospital length of stay, especially when diagnosis and hospital variables are also taken into account. In an analysis of data representative of Medicaid cases in 23 large New York City hospitals during 1972, these effects turn out to be less clear-cut than generally assumed. Although the first-order coefficients of length of stay regressed on age and the rank order correlation of the means are statistically significant, such wide differences in length of stay within age groups remain as to reduce the substantive impact of the observed findings. This same pattern of wide variations within age groups persists even when diagnosis is controlled by use of up to 80 covariant groups. In over half the 80 diagnostic categories, no significant age effects was found. When the age analysis is repeated using 23 hospitals as the covariants, estimated age effects differed between institutions, and a similar pattern of large within-group variation was observed. These findings are interpreted as a caveat to health care researchers who might otherwise plan overly sophisticated utilization review systems.

A simple method of dystopic cardiac transplantation as a left-heart bypass was experimentally studied and details of the method are described. The hemodynamic investigation of this biological assisted circulation on the normal and failing heart, which was induced by subtotal occlusion of the asc. aorta, as well as its longtime support of the chronically damaged left myocardium showed the efficacy of this method. The advantages of this biological method in comparison to that of mechanical devices and orthotopic cardiac transplantation are discussed.

The conchal setback is a useful technique for correcting many prominent ear deformities. A disadvantage of the technique in some cases is meatal stenosis of the external auditory canal. By excising a portion of meatal cartilage, this problem is prevented. The technique is illustrated and post-operative result is shown.

This analysis of asthma mortality has emphasized the roles played in its pathogenesis by different modes of therapy as reported in the literature. In addition attention was directed towards yet another potentially lethal therapeutic modality, IPPB, the efficacy and potential benefits of which are critically questioned. IPPB treatments were related to every fatal episode of asthma which made up the entire asthma mortality experience during a 12 month period at Morrisania Hospital. The adverse consequences of IPPB therapy were reviewed and it was further suggested that its use in acute asthma attacks was related to lethal episodes of hypoxia and pneumothorax. The patient must, in order to trigger an IPPB apparatus, create a pre-determined negative pressure to initiate inflation. The machine may, therefore, be ineffective in a patient with severe obstruction and greatly increased airway resistance either because of the inability to trigger it or with adequate triggering the subsequent delivery of an inadequate tidal volume at the pressure limitation set. Thus, severe hypercapnia and hypoxia may result especially if oxygen enriched gas mixtures are not used. This may occur even with the delivery of an adequate tidal volume since its distribution within the lungs is poor resulting in a worsening of ventilation-perfusion relationships as evidenced by an increase in the measured physiologic dead space. This experience and review of the literature suggests that IPPB treatment in asthma, especially during an acute attack, should always be administered with small doses of nebulized bronchodilators and oxygen with careful monitoring of arterial blood gases. This will allow for the detection of the adverse effects of this mode of therapy which may exceed the hoped for benefits, the most important being bronchodilatation and subsequent mobilization of secretions with continued treatment.

Sub-lethal levels of the folate analogue, pyrimethamine, caused pronounced cell elongation in Saccharomyces cerevisiae strain B41 when grown in glycerol medium. The orientation of bud development was also altered. Electron microscopy of thin sections showed an increase in cell wall thickness, but apart from this and the overall cell shape, the ultrastructure of the cells was normal. The structural abnormalities are attributed to alterations in the plasmalemma caused by protein synthesis inhibition in the mitochondria.

Deoxyribonucleic acid-ribonucleic acid (DNA-RNA) hybridization technique was used to investigate nucleic acid homologies among acid Candida albicans, Syringospora albicans and the Leucosporidium species (L. nivalis, L. capsuligenum, L. frigidum, L. gelidum, L. antarcticum). The nucleic acid homology between C. albicans, S. albicans and the Leucosporidium species was very low (ranging from about 7-11% for C. albicans and 8-12-5% for S. albicans), indicating the unrelatedness of C. albicans to the basidiomycetous yeast genus Leucosporidium.

A history of the interplay between the physical and life sciences is presented. Many of the discoveries that resulted from research conducted by life and physical scientists are described. The type of training required for effective interdisciplinary work is briefly discussed.

The historical development of techniques and instrumentation for electroresuscitation is traced from its inception in 1774 to the twentieth century; an overview of recent developments in electroresuscitation terminates with the introduction of modern defibrillators and cardiac pacemakers.

This paper traces the history of the use of electricity to treat pain, beginning with the first century A.D. practice of using the torpedo fish to treat gout, continuing through the eighteenth-century use of electrostimulation as an analgesic, up to 1900 when electroanalgesia fell into disrepute. The author recognizes the early empiric nature of electrotherapy as it was catalogued by the Reverend John Wesley, and the beginnings of speculation on the mechanism of pain relief by Berlioz, Sarlandière, and others.

On December 28, 1895, W.C. Röntgen submitted to the Wurzburg Physical Medical Society his paper, "On a New Kind of Rays," for publication. By the time he presented it orally on January 23, 1896, worldwide interest had been generated by newspaper publicity, which first appeared on January 7. Scientific societies through their meetings and official journals played an important part in stimulating interest and fostering research on X-rays. This paper notes specific contributions of some of these medical societies, particularly the American Philosophical Society, the New York Electrical Society, the New York Academy of Sciences, the National Academy of Sciences, and the American Electro-Therapeutic Association. By the end of 1896, 50 scientific books and more than 1000 scientific papers on X-rays had been published.

A double blind comparison is reported of a new tetracyclic antidepressant, maprotiline, with amitriptyline and placebo in psychiatric outpatients. Amitriptyline was significantly more effective than placebo in its global effect on depression. Maprotiline emerged as neither inferior to amitriptyline nor superior to placebo. Methodological difficulties prevented an adequate assessment of the anxiolytic activity of maprotiline.

During the period 1880-1900, the first studies were conducted to aid in understanding the effects of electricity on the human body. Commercial electrical systems were being developed, with the first central station for incandescent lighting placed in operation in 1882. The proliferation of these new stations and their distribution systems inevitably led to accidental electrocutions. The early investigators of electrical death were primarily physicians who were troubled by the incomplete electrical knowledge of that time as they evaluated the different effects of direct and alternating currents and high and low currents. Most of the studies used animals, while postmortem examinations of electrocuted criminals provided some information, though of little practical value, concerning high-current shocks. Various theories concerning suspended animation and concerning the action of electricity on the nervous system were proposed and discarded. In 1899, Prevost and Battelli in Europe, and Cunningham working independently in the United States, showed that ventricular fibrillation was the usual mode of death for low-voltage shocks. The possibility of electrical defibrillation of the heart was clearly described by Prevost and Battelli in 1899.

Using a double-blind crossover technique in patients suffering from maladies associated with gastrointestinal spasm, sustained-release 40 mg dicyclomine hydrochloride tablets (Merbentyl Dospan) have been compared with 20 mg plain dicyclomine hydrochloride tablets (Merbentyl). It has been concluded that these two dicyclomine formulations are equivalent in terms of efficacy and low incidence of side effects.

Theoretical considerations in immunotherapy, such as the timing of challenge, which could rank second to reduction of tumour volume in producing lasting regressions, are outlined and illustrate the need for tests to monitor immune status. Estimation of immunosuppression, in order to define cancer therapy schedules providing least interference with what might be useful host response to tumour, is described in terms of a reliable radioimmunoassay method assessing lymphocyte replicating ability (LRA). The extent of the effect of radiation or radiomimetic drugs in vitro can be shown upon LRA in response to phytohaemagglutinin or to irradiated cells. In clinical research LRA assessment makes a satisfactory test of the general immune state of patients undergoing cancer treatments, given that matched control subjects are available throughout the period of observation to allow repeated assessment of the relative response. An assured relative response seems feasible if all examinations are related to a common standard, the stored reference lymphocyte. Conversely a relative response can be measured against stored target cells.

With Trivastal, a double blind study including placebo control was carried out with 66 patients at the age between 55 and 67. These persons were patients of several practioners and were treated because of different phenomena of the neurovascular psychosyndrome. They received 1 dragee daily at the beginning of the treatment, then additional dragees up to the amount of 3, 4 and 5 (or 6 according to the case) over a period of 14 weeks. The control of efficiency consisted in 13 psychometrical measurements: Measurement of reaction time, flicker fusion test, "fluency"-tests according to Guilford, self rating scale for the measurement of general psycho-physical condition, several tests for the control of memory functions, projective tests to determine emotional factors and a semi-standardized interview for the control of subjective symptoms of the neurovascular psychosyndrome. Data were evaluated by variance analysis and covariance analysis. Trivastal improved the cerebral metabolism, so that the treatment resulted in an improvement of vigilance and of psychomotor functions, in a better adaptation to demands of everyday affairs and in a higher efficiency of different memory functions. Finally, the patients returned to a normal level of psychic behaviour and managed their social integration more easily.

With a modification of the Astrup - fibrin - plate method about 300 patients were investigated. In chronic infections of the skin and mucous membranes a spontaneous peripheral proteolysis was found. There is a connection between infections, proteolysis and chronic continuance.

In 32 cases of acromegaly growth hormone analyses in serum were carried out by means of intra venous dosing of glucose (hyperglycemia suppression test). Both in individual cases and collectively the growth hormone concentrations fluctuate considerably. 19 patients had average concentrations of 10 to 30, 5 of 30 to 70, 4 of more than 100 and 3 patients of 5 to 10 ng/ml. The level of the pathological growth hormone concentrations doesn't correlate with the presumable duration of the affection, the glucose tolerance and the extension of the acromegalic alterations. 5 patients showed an euthyroid recidiv goiter, 4 patients a hypothyroid goiter, 2 of these patients at the same time showed a secondary hypoadrenalism and 3 patients an autonomous thyroid adenoma. The eosinophilic hypophysis tumors were mostly intrasellar. 4 patients out of 5 with suprasellar tumor distension showed an optic chiasm syndrome.

Streptococcus pyogenes, group A, type 50, in contrast to other group A streptococci, causes spontaneous disease in mice thereby providing a suitable experimental model for the study of human streptococcosis. Type 50 possesses various peculiar morphological and immunobiological characteristics and under certain conditions forms and extremely thick non-antigenic capsule which seems to interfere with the binding of antibody. This interference is most likely responsible for the difficulties in detecting type 50 streptococci in the tissues of infected mice by immunofluorescent staining. Whereas the surface components (hyaluronic acid, M-antigen) of the type 50 Streptococcus exhibit several uncommon features, the more deeply located cell wall antigens, like peptidoglycan and C-carbohydrate, do not differ in either their chemical constituents or their serological reactions from the comparable components of other group A streptococci.

A haploid strain of Asp. nidulans with a chromosome segment in duplicate (one in normal position on chromosome I, one translocated to chromosome II) shows mitotic recombination, mostly by conversion, in adE in a frequency slightly higher than in the equivalent diploid. A method has been devised, using this duplication, for the selection of rec and uvs mutations. Six rec mutations have been found which decrease recombination frequency in the haploid. One mutation selected as UV sensitive showed a hundred fold increase in recombination frequency in the haploid (pop mutation) and probably the same in diploids. The increased frequency is both in gene conversion and in crossing over, and the exchanges appear in clusters of two or more. pop is allelic to uvsB (Jansen, 1970) which had been found to affect mitotic but not meiotic recombination. It is suggested that mutations of this type interfere with the control mechanism which determines that high recombination is confirmed to the meiotic nuclei and avoided in somatic nuclei.

Streptomycin or spectinomycin treatment of an E. coli strain, carrying the strR and spcR alleles on the chromosome and the wild-type (sensitive) alleles on the episome, selects for inactivation of the relevant sensitive allele. After Mu induced mutagenesis, in the absence of selection against extended deletions upon the episome, a large proportion of stro mutants are also spco, and vice versa. However, when markers flanking the strA and spcA gene cluster are simultaneously selected, effectively eliminating long deletions, the majority of stro mutants continue to express the spcs allele, and vice versa. Insofar as inactivation after Mu treatment is due to prophage insertion within or proximal to the genes in question, this result indicates that the genes strA and spcA are not parts of a single operon. In virtue of the high frequency of extended deletions observed in the absence of suitable counter-selection, we must place a word of caution upon the use of phage Mu-1 as a means of isolating polar mutations and defining transcriptional units.

An unlinked regulatory mutation hisT1504, causes an approximate 11-fold derepression of the histidine (his) operon and a linked constitutive mutation hisO1242 causes an approximate 15-fold derepression. In this study we demonstrate that hisT1504 provokes a significant increase in the UV-induced reversion frequency of his ochre and frameshift mutations. Analysis of revertants derived from frameshift mutants show that this increment in derepressed strains compared to the repressed strains is due to better growth of suppressed revertants by weak frameshift suppressors. The frequency of revertants suppressed by strong frameshift suppressors appears to be the same in repressed and derepressed strains. In contrast, intragenic revertants appear at two-fold decreased frequency in derepressed strains carrying either of the histidine constitutive mutations, hisT1504 or hisO1242. A possible competition is indicated between frequently transcribing RNA polymerase and error-promoting recombinational repair within the histidine operon.

The messenger RNAs for the outer membrane proteins in E. coli are more stable than the bulk of the messenger RNA s (Hirashima et al., 1973). Polysomes, enriched in those containing stable mRNAs have been isolated following rifampicin treatment and have been shown to contain quantitatively the same complement of ribosomal protein as normal polysomes. There is one exception: ribosomal protein S1 is present in larger amounts in the polysomes containing stable messengers. However, there are grounds for believing this finding to be an artifact. It is concluded that the differences between outer membrane protein synthesis and bulk protein synthesis are not due to a difference in the ribosomes.

The RNA polymerase inhibitor, lomofungin has been used to determine the half life of specific synthetic capacities (invertase and alpha-glucosidase) as well as that for gross protein synthesis. In both cases the studies conclude that cognate messenger RNAs decay with a half life of approximately 20 minutes. This antibiotic has been used to determine the half life of allophanate hydrolase specific synthetic capacity. We find that it decays with a half life of about three minutes; a value that agrees with the decay rates of allophanate hydrolase synthetic capacity following removal of inducer. These observations argue that mRNA may be metabolized by two separate routes in Saccharomyces.

When E. coli F+ cells carrying the dna-167 or dnaC2 mutation, which causes the temperature-sensitive initiation of DNA replication, are exposed to a non-permissive temperature to stop the replication of chromosome and F factor, and then transferred back to a permissive temperature with the addition of chloramphenicol, one round of the chromosomal replication occurs, but further replication is inhibited. Under these conditions, F DNA replicates coincidentally with the initiation of the chromosomal replication in both strains. When rifampicin is added to the cells upon lowering of the temperature, the chromosome can not replicate in the F+ dna-167 strain, but can do so in the F+ dnaC2 strain. F DNA can replicate in both of the mutant strains under these conditions.

Temperature-sensitive mutants defective in the initiation of DNA replication are exposed to a non-permissive temperature to complete already initiated replication, and are transferred back to a permissive temperature. DNA synthesis can resume in the presence of rifampicin or rifampicin plus chloramphenicol in strain PC2 (dnaC2), but not in strain N167 (dna-167). In the presence of chloramphenicol alone, however, DNA synthesis can resume in both strains (Hirage and Saito, 1973, 1974). The double mutants carrying the dna-167 and dnaC2 mutations show the rifampicin-sensitive resumption of DNA replication as the dna-167 mutant. The rifampicin-sensitive character (designated as Rrr-) is closely linked with the temperature sensitivity of the dna-167 mutant in P1 transduction. The gene order is dna-167-tna-phoS-uncA-ilv. The Rrr- character does not correlate with the inactivation of the altered product of the mutated dna-167 gene at various temperatures in the double mutant carrying dna-167 and dnaC2. Although dnaC2 strains show the Rrr+ phenotype, the dnaC2 strains received the ilv-dnaA region of the Ts+ revertants obtained from a dna-167 strain show the Rrr- phenotype. These results suggest that the dna-167 mutant has two mutations which are closely linked to each other, controlling the Rrr- phenotype and the temperature sensitivity, respectively.

Double lysogens for prophages lambda cI+ and lambda cI ind-ts-857 are induced only by the combined effects of ultraviolet (UV) irradiation and high temperature, not by either treatment alone (Sussman and Jacob, 1962). We have followed the kinetics of inactivation of the cI+ repressor brought about by irradiation in asynchronously and synchronously growing cultures of B/r (lambda cI ind- ts-857). Assays of the yield of phage released as a result of temporary thermal inactivation of the UV-resistant ind- ts-857 repressor at intervals after the irradiation accurately reflect the time course of UV-induced inactivation of the cI+ repressor. The results show that UV-induced derepression takes place in all cells of the population approximately 20 min after the irradiation whether the cells were growing asynchronously or synchronously. Hence UV induction of prophage lambda is not triggered at a particular stage in the cell cycle.

Two chloramphenicol resistance mutations out of 123 tested in Aspergillus nidulans are inherited extranuclearly as judged by transmissibility in heterokaryons, lack of segregation at meiosis, and independent segregation from all of the eight nuclear linkage groups. They do not recombine with each other. However, experiments in collaboration with G. Turner and R.T. Rowlands show that they do recombine with cytoplasmic mutations to oligomycin resistance (Rowlands and Turner, 1973) and cold-sensitivity (Waldron and Roberts, 1973). These cytoplasmic chloramphenicol resistance mutations are stable and do not affect growth or morphology on antibiotic-free media. Nuclear mutations to chloramphenicol resistance map at a minimum of three loci. At one of these loci, most, but not all, mutations lead pleiotropically to cycloheximide hypersensitivity, and most of these, but not all, also confer pleiotropic hypersensitivity to salicylhydroxamic acid.

We describe a method for the direct selection of E. coli mutants restricting efficiency of suppression and misreading levels using a T4-coded nonsense suppressor. One mutant isolated has the phenotype expected for a restrictive mutant and may be ribosomal. Other possibilities are discussed.

Mutation of the gene m3 of phage P22 causes permanent depression of macromolecular synthesis in the infected host and thus inhibits phage development as indicated by burst size and lysozyme production. The permanent depression of macromolecular synthesis is most probably due to blockage of the transport process. The m3 allele is dominant over m+. m3 allows some transcription of phage genes (however, the difference between early and late function is not clear). The inhibitory effect of m3 on DNA synthesis may be indirect.

The RNA synthesis in non-viscous lysates containing the intact folded chromosome and cytoplasm fractions prepared from Escherichia coli has been examined in vitro. The RNA synthesis not only by chain extension but also by new chain initiation occurs in this system. While the RNA synthesis by chain extension takes place on the chromosome fraction alone (Pettijohn et al., 1970), an addition of the cytoplasm fraction is necessary for the synthesis by new chain initiations (de novo synthesis). Analyses of the in vitro synthesized RNA by hybridization-competition and by sucrose gradient centrifugation show that 16S and 23S ribosomal RNAs account for about 40% of the total RNA products. The cytoplasm fraction is required for the de novo synthesis of ribosomal RNA at high relative rate. Guanosine tetraphosphate (ppGpp) does not specifically inhibit ribosomal RNA synthesis in this system.

Two classes of Salmonella typhimurium mutants resistant to inhibitory methionine analogues and defective in methionine transport have been examined. A mutant of the first class, resistant to alpha-methylmethionine, was shown by conjugation analysis to possess a single mutation in the metP gene which specifies a methionine transport system. Mutants of the second class, resistant to alpha-methylmethionine and methionine sulphoximine, possess two mutations. One is in the metP gene, which accounts for resistance to alpha-methylmethionine, and the other is in a gene designated glnP which results in reduced L-glutamine transport. Both of these mutations are required for resistance to methionine sulphoximine. A transduction analysis of three metP mutations was performed, based on the fact that they prevent growth of methionine-requiring strains on D-methionine. Two of the mutants are closely linked and therefore probably in the same gene, whereas the third mutant might be in a different gene.

21 amber-ochre supersuppressor alleles have been isolated in a strain of Saccharomyces cerevisiae. Their dominance-recessiveness, temperature sensitivity, allelism, intergenic and intragenic complementation properties and their effect on cell viability and colony growth rate have been characterized. They are compared with the yeast amber-ochre supersuppressors described by Inge-Vechtomov and Andrianova (1970a, b) and Hawthorne and Leupold (1974). The possible molecular basis of their suppressor activity is discussed in relation to their genetic properties.

De-repression of the plasmid R100 in Escherichia coli is essentially a transient phenomenon resulting in the transfer of several R factors to different recipient cells from a single donor cell.

Mutants of P22 which have been located in the c2 repressor gene were examined. The most rightward "c2 mutation" was found to define a site that is necessary only for the establishment and not for the maintenance of repressor synthesis. We conclude that this site c27 is an analog of cy mutants in phage lambda which define a promotor for repression establishment (pre). The K5 mutation of P22 maps between c27 and all other c2 mutants. Examination of its biological behavior and direct measurement of repressor activity show that K5 does not affect c2 repression. A model to explain these findings implies that c27 and K5 affect transcripts of opposite directions. P22 c1 mutants do not allow c2 repressor synthesis and we conclude that the activity of c1 product (and presumably c3 product) at the site defined by c27 is necessary for repressor synthesis. The combined activity of c1 and c3 product at c27 is postulated to promote repressor synthesis and block transcription of vegatative phage genes to the right of K5. After repressor synthesis has been established, another site analogous to lambda prm is sufficient for repressor synthesis and c27 is no longer required. These observations and conclusions point to a very close analogy between repressor synthesis and control in phages P22 and lambda.

The properties of minicell producing mutants of Escherichia coli deficient in gentic recombination were examined. Experiments were designed to test recombinant formation in conjugal crosses, survival following UV-irradiation in cells, and the state of DNA metabolism in minicells. The REC- phenotypes are unaffected by min+/- genotypes in whole cells. In contrast to minicells produced by rec+ parental cells, minicells from a recB21 strain have limited capacity to degrade linear, Hfr transfereed DNA. The lack of a functional recA gene product, presumably involved in inhibiting the recBC nuclease action(s), permits unrestricted Hfr DNA breakdown in minicells produced by a recA1 strain. This results in an increase in TCA soluble products and in the formation of small DNA molecules that sediment near the top of an alkaline sucrose gradient. Unlike the linear DNA, circular duplex DNA from plasmids R 64-11 or lambdadv, segregated into the minicells, is resistant to breakdown. By using in vitro criteria, and [32P]-labelled linear DNA from bacteriophage T7 for substrate, we found that the ATP-dependent exonuclease of the recBC complex (exo V) is present in rec+ and recA- minicells, and is lacking in the recB21 mutant. In fact, the absence of a functional exo V in recBC- minicells results in isolation of larger than average Hfr DNA from minicells. We suggest that recombination (REC) enzymes segregate into the polar minicells at the time of minicell biogenesis. This system should be useful for studies on DNA metabolism and functions of the recBC and recA gene products.

The effect of suppression on enzyme synthesis was examined in 43 amber mutations of the gene for beta-galactosidase in Escherichia coli. The ordering of mutations in the gene revealed two clear gradients in the number of molecules of suppressed beta-galactosidase formed by suppression. One gradient extended over the operator-proximal third of the gene and the other over the operator-distal third. The central third of the gene gave no consistent pattern of suppression. Assays of thiogalactoside transacetylase showed that the polarity produced by chain-terminating mutations was abolished by suppression. These experiments suggest that the polar effects of chain-terminating mutations on distal genes are the secondary results of translational defects in the mutant gene. The polarity gradients may result from a supposed secondary structure to the messenger RNA of the lactose operon.

Minicells derived from E. coli x796(F+) are refractory to infection by phage M 13. However, after infection of the minicell-producing strain with M 13, phage DNA is found to segregate efficiently into newly formed minicells. The M 13 specific DNA present in minicells isolated several hours after infection consists of single stranded viral DNA and double stranded replicative forms in nearly equal amounts. M 13 DNA containing minicells are capable of carrying out at least one complete round of single stranded DNA synthesis as shown by the flow of label from replicative forms to free single strands.

When hamster cells are infected with the bacterial plasmid colicinogenic factor E1 (ColE1), as much as 5-8% of the input plasmid radioactivity is found in the recipient cell, mainly in the nuclear fraction. Density shift experiments with bromodeoxyuridine labeled ColE1 DNA indicate that part of the input DNA may be replicated in the nucleus. ColE1 specific RNA but no colicin E1, can be detected during the first two generations after the uptake of ColE1 DNA. However, extrachromosomal ColE1 DNA is unstable in the mammalian cells and is degraded to acid soluble fragments after a few generations.

Mutants with a feedback resistant N-acetylglutamate synthase have been isolated from a proA/B, argD, argR strain by screening for proline excretion on minimal medium with arginine. The feedback resistant character of three mutants was transduced into an argA (N-acetylglutamate synthase negative) strain. It was cotransducible with argA at a frequency of greater than 99%. N-acetylglutamate synthase extracted from the three mutants was approximately one hundred times less sensitive to L-arginine than the enzyme from the feedback sensitive parent strain.

113 pyrimidine auxotrophs, unable to synthesise UMP have been selected in Aspergillus nidulans. These mutants can be classified by complementation into eight groups, and genetic analysis has shown that five loci are involved. One complex locus consists of the mutually complementing pyrA, pyrB and pyrC groups, as well as the cis-dominant pyrN group, members of which do not complement with members of the A, B or C groups. pyrA mutants have been shown to lack CPSase-ur, pyrB and pyrC mutants have been shown to lack ACTase, and pyrN to lack both these enzymes. This locus appears to code for products which form an enzyme aggregate. The four simple loci, as well as the complex loci have been located genetically, and distinguished from one another on the basis of accumulation of pyrimidine precursors in vivo. The synthesis of ACTase has been shown to subject to end-product repression.

Hybridization of messenger ribonucleic acid (mRNA) isolated from Escherichia Coli K-12 to deoxyribonucleic acid (DNA) from lambdaCI857st68h80dilv was used to detect isoleucine-valine (ilv) specific mRNA. A number of strains partially constitutive for the isoleucine-valine enzymes had levels of ilv mRNA 2 to 3-fold higher than the parent strain. Starvation for any of the branched-chain amino acids resulted in a 20 to 23-fold increase in ilv mRNA as compared to repressed levels. These differences were not due to altered growth rates or to changes in the stability of ilv mRNA. These data indicate that regulation of the isoleucine-valine enzymes by multivalent repression occurs mainly at the level of transcription. Kinetics of elongation of ilv mRNA after repression are consistent with the assumption that the mechanism of multivalent repression involves the prevention of further initiations by RNA polymerase.

By screening 42 Salmonella strains with P3, a temperate bacteriophage with an unusually wide host range, five new DNA restriction and modification systems (R-M systems) were identified in five different serotypes in Kauffmann-White group C. One of these systems, SP, in a Pl-sensitive strain of S. potsdam, was analyzed genetically by Pl transduction methods in which SP was transferred into S. typhimurium and C. coli/S. typhimurium hybrids. It was found that the genes of the SP system were allelic and functionally homologous to the genes of the SB system of S. typhimurium.

The presence of mitochondrial sex factor, omega, was demonstrated in haploid strains of yeast Saccharomyces cerevisiae which came from our laboratory. Transmission and recombination of the mitochondrial genes (CR/CS, ER/ES and OR/OS), conferring the resistance/sensitivity to chloramphenicol, erythromycin and oligomycin, respectively, were non-polar in homosexual crosses and highly polar in heterosexual crosses. Different results were obtained in crosses involving an erythromycin resistant mutant G706E11 (CSEROS) which was found to contain cellular DNA of diploid level. This strain was omega- and showed no alleles from G706E11 (CS, ER and OS) were transmitted to the zygote progeny in preference to the CR, ES and OR alleles. When crossed to omega+ haploid strains, there was a highly polar recombination, but no transmission was seen for the E and O alleles. Polar transmission of markers from omega+ haploid parental strain, characteristic of heterosexual crosses, was noticed only for the C allele. The crosses of G706E11 to omega+ haploids featured an increase in the recombination frequency. The values of % suppressiveness of sigma- petite mutants were relatively low when determined by crossing to G706E11 or to sigma+ diploid strain M2-8C rather than by crossing to sigma+ haploid strains, indicating that there is a positive correlation between the polar transmission of drug resistance markers and the suppressiveness degrees. Genetic mechanism of the anomalous behaviors if mitochondrial genes in crosses involving G706E11 was discussed and interpreted as due to an unbalanced supply of mitochondrial genomes from parental strains.

After matings between T6 sensitive (Tsxs) Hfr and T6 resistant (Tsxr) F- cells, the Tsxs zygotes have been observed by electron microscopy: They adsorb a small number of T6 particles if compared to what is observed several generations later. Moreover, the T6 receptors synthesized by these zygotes are not located randomly but in a central region of the cell surface.

Integrative suppression of a dnaA mutation in Salmonella typhimurium may result from the integration of F'lac or F'his into the chromosome in the left hand side of the chromosomal map. The suppressed revertants resulting from this integration do not contain DNA of the F' elements in the covalently closed circular (CCC)1 form but still contain the CCC DNA of the cryptic LT2 plasmid. Two suppressed revertants isolated from dnaA/F- strains were found in which the suppression of dnaA character was accompanied by the loss of CCC DNA from the cell lysates. From one of these revertants a segregant was isolated in which the return to the dnaA phenotype was accompanied by the reappearance of CCC DNA in the cell lysate. It is suggested that the cryptic plasmid may integrate into the chromosome of S. typhimurium and this integration may result in suppression of the dnaA mutation. Additional evidence suggesting that the cryptic plasmid controls its own initiation of replication independently of the function of the chromosomal dnaA gene is supplied by the results of the determination of incorporation of labelled thymidine into CCC DNA of the dnaA1 strain at the nonpermissive temperature.

Calcium-treated cells of E. coli K-12 C600 were transfected with lambda-heteroduplex DNA carrying the marker cIts857 in one strand and wildtype in the other. In single burst analyses of the phage progeny, 72-79% of the bursts were "pure" bursts containing either exclusively wildtype phage or exclusively mutant phage, indicating that conversion of the cIts857/+ mismatch to a homoduplex structure prior to replication occurred with this frequency. The r-strand1 appears to be "preferred", since pure bursts of progeny with the r-strand genotype were almost twice as frequent as those with the l-strand genotype. Examination of the conversion frequency of a number of rec and uvr E. coli mutants showed that the mutants uvr D and UVR E are deficient in mismatch repair. Conversion is reduced in the former by a factor of 2 and in the latter by a factor of 3.

When synchronous populations of Escherichia coli B/r (lambda) were exposed to low doses of ultraviolet light, the yield of infective centres varied with cell age. The yield was highest if the lysogenic bacteria were irradiated at a time which coincides approximately with the termination of rounds of DNA replication and it was lowest when dividing cells were irradiated. No such variation was detected following either irradiation of excision-defective lysogenic cells or thermal induction of lambdacI857 prophage in irradiated bacteria. It is suggested that the variation reflects a relationship between prophage induction and inhibition of cell division. This hypothesis is supported by data showing that irradiation promoted induction and curtailed division in E. coli K12 dnaA mutants which were dividing in the absence of DNA replication.

A diploid yeast strain, D81, was constructed heterozygous for seven recessive markers linked on the left arm of chromosome VII to study the localization of induced mitotic crossing over. The mutagens used were carofur also called nifurprazinum (1-(5-nitro-2-furyl)-2-(6-amino-3-pyridazyl)-ethylene hydrochloride), diepoxybutane, ethylmethanesulfonate, nitrous acid and 1-nitrosoimidazolidinone-2. All agents induced high frequencies of mitotic crossing over at doses exerting only a low degree of killing. The distribution of recombinational events was compared for five intervals. The distribution pattern of spontaneous mitotic crossing over was different from all the patterns obtained after mutagenic treatments. Nitrous acid and diepoxybutane induced the same pattern, which was different from the patterns induced by carofur, EMS and 1-nitrosoimidazolidinone-2. The patterns induced by the latter three mutagens were again different amongst each other. Repeat experiments showed that the patterns induced by a given mutagen were reproducible. Tetrad analysis with a representative sample of segregants induced by diepoxybutane and carofur showed that the treatments actually induced mitotic crossing-over. The pattern of meiotic recombinational events was different from those of spontaneous and mutagen induced mitotic recombination. Inducibility of mitotic crossing-over was low at the proximal and distal ends of the chromosome arm and highest in the middle. Each interval showed a different response to those mutagens that differed in their patterns of induced mitotic crossing over. The observed mutagen specific effects are considered as an indication of mutagen specificity. No plausible explanation for mutagen specificity could be given. However, the data presented reveal the same situation as found in induction of chromosome breaks, as reported by other authors. Apparently, mutagen specificity is quite a general phenomenon even for genetic effects in larger intervals of a chromosome.

The regulatory gene (argR) for the arginine biosynthetic pathway has been located at 106 min on the chromosome of S. typhimurium. In addition, the location of the gene specifying cytosine deaminase (cod) has been more precisely determined.

Thermosensitive mutants of E. coli defective in DNA replication were tested for their capacity to support multiplication of phiA and phiX174. At the restrictive temperature, the viral growth was markedly affected in dnaH, dnaZ, or ligts7 mutants. Even when these strains were transfected with RF1 molecules, the virus yield was still very low. The dnaI function was, however, dispensable for replication of phiA and phiX174. In addition, these viruses could multiply in dnaP or polAts mutants at the high temperature.

Relationship of citrate synthase (EC 4.1.3.7) to the biosynthesis of glutamic acid was investigated by characterizing a new glutamic acid auxotroph FL100-D1 (glu 3) of Saccharomyces cerevisiae. Nutritional requirement of the mutant was satisfied by L-glutamic acid, L-glutamic acid peptide as well as several analogs of glutamic acid, but not by proline, ornithine, arginine, lysine or aspartic acid. The mutant was unable to utilize nonfermentable carbon sources, glycerol, acetate or lactate. Mutant glu3 unlike aconitaseless glutamic acid auxotroph glu 1, failed to accumulate 14C-citric acid in vivo from 1-14C-sodium acetate or U-14C-glutamic acid. Both spectrophotometric and radioactive assay procedures demonstrated a lack of significant citrate synthase activity in the dialysed extract of the mutant compared to the wild type strain. Mutant glu 3 complemented with glu 1 and glu 2 individually in vivo and exhibited a significant aconitase (EC 4.2.1.3) activity in vitro.

The DNA dependent synthesis of proteins was studied with a system composed of DNA, washed ribosomes, centrifuged (150,000 X g) bacterial extract from Escherichia coli and purified initiation factors IF-1 and IF-2. Synthesis of active enzymes encoded by the tryptophan (trp)-operon of E. coli was found to depend strongly on the addition of IF-3, with the same IF-3 dependency for all 5 gene-products of this operon, irrespective of the presence of the promotor proximal gene trpE. Synthesis of T7 RNA polymerase with T7 DNA as a template, however, was completely independent of the addition of IF-3. The same difference in IF-3 requirement was found when we compared the overall protein synthesis directed by these templates. This difference could be related to the effect of IF-3 on the formation of initiation complexes with the in vitro prepared mRNA: initiation complexes are readily formed with T7 mRNA also in the absence of IF-3, whereas the formation of these complexes with phi80trp mRNA almost completely depends on the presence of this factor.

A large number of spontaneous, cytoplasmic petite mutants from six grande strains of Saccharomyces cerevisiae were crossed to a pair of isogenic tester strains. Suppressivity values were obtained by randomly sampling the diploid progeny from these crosses, and this basis, crosses were broadly categorized as having high, intermediate, or low suppressivity. For each cross, individual zygotes were obtained also. All successive first-generation buds were isolated from the zygotes, and analyzed for the presence of petite genotypes. We found that, though early buds may be mixed, all zygotes eventually produce a succession of buds which have the same genotype--either all petite or all grande. Many more zygotes from crosses in all categories of suppressivity purified to petite than expected from the population values for suppressivity. Reconstruction experiments indicate that most petite mutants may actually generate over 90% petite progeny in a petite X grande cross.

Cytoplasmically inherited chloramphenicol- and erythromycin-resistant mutants were obtained in three unrelated and two isogenic haploid strains of yeast. The bias favoring the transmission of these resistance alleles in crosses to the isogenic strains was compared on two levels: on the population level by means of observing random diploid progeny from mass matings, and on the zygote level by zygotic pedigree analyses. The genetic basis of this bias was determined by tetrad analysis. Our results suggest that 1. an intracellular selection mechanism operates within zygotes to determine the degree of bias; 2. the selection mechanism operates differently with respect to the two loci, C and E, under consideration; and 3. the selection mechanism is controlled by a set of nuclear genes. Other models which have been suggested to explain bias are critically examined in light of our results.

In a mutant strain defective in polynucleotide phosphorylase, under conditions where the enzyme becomes limiting, it is possible to demonstrate that chemical as well as functional half lives of mRNA become longer if the strain is also missing ribonuclease II. These results allow to unify in a simple model a variety of observations about turnover of RNA in a variety of bacteria.

The nomenclature proposed by Otaka et al. (1968) for the 30S ribosomal protein components of Escherichia coli as separated by carboxymethyl(CM)-cellulose column chromatography was adopted in several papers in which the genetic loci for many 30S ribosomal proteins on the E. coli chromosome were determined. In order to compare these data with those obtained in other laboratories, the 30S ribosomal proteins fractionated by CM-cellulose chromatography were correlated with thestandard nomenclature proposed by Wittmann et al. (1971).

50-S ribosomal subunits from the extreme halophilic bacterium, Halobacterium cutirubrum, contain an alanine-rich acidic "A" protein which resembles the L7--L12 multimer (Kaltschmidt and Wittmann, 1970) found in the 50-S ribosomal subunit of Escherichia coli cells. The protein contains 24 mole % alanine and is devoid of histidine, tryptophan and cysteine. Unlike E. coli which has two forms of the "A" protein distinguished solely by the acetylation state of the serine amino terminus. H. cutirubrum 50-S subunits contain only one unsubstituted form of the "A" protein in vivo. However, during purification of ribosomes from cells grown between 25 and 37 degrees C the latter "A" protein undergoes rapid, specific, in vitro enzymatic alteration at its carboxy-terminal end. When the halophile is grown in the temperature range of 40 to 42 degrees C the cleaving enzyme is not active and only one form of the "A" protein is found on the ribosomes.

Replicating DNA molecules of a deletion mutant of the conjugative R-plasmid R 6 K are cleaved at a single site by the EcoRI restriction endonuclease. Electron microscope examination and measurements of the EcoRI treated replicative intermediate molecules indicate that replication can be initiated at two sites on the plasmid DNA molecule. The two sites are located at about 23 and 39% of total length, respectively, from the EcoRI cleavage site. About 5% of the replicating molecules use both replication initiation sites simultaneously.

The pattern of divergent transcription of the argEC BH cluster of genes previously demonstrated by the hybridization of RNA to the separated strand of a phi 80 darg transducing phage, is confirmed with the DNA of a set of different lambdadarg phages. The accurate determination of argE and argCBH m-RNA levels in different steady states of expression of the arg regulon supports the following conclusions: 1. The ratio between maximal (derepressed) and minimal (repressed) rates of expression is lower when it is expressed in terms of % hybridizable RNA than in terms of expression is lower when it is expressed in terms of % hybridizable RNA than in terms of enzyme specific activities. The discrepancy is about 3 fold. Thus in conditions of repression, the cell produces relatively more unused m-RNA than in derepression. Different interpretations of this phenomenon appear possible: a) the messenger RNA molecules synthesized in repressed cells could be degraded more rapidly or translated less efficiently than in derepressed cells. b) an untranslated segment of the RNA could account for a larger part of the RNA detected in repression than in derepression. These interpretations are not mutually exclusive. 2. The discrepancy observed between the amplitudes of variation of argE and argC BH expression, expressed in terms of enzyme specific activities, is, in fact, determined at the level of DNA transcription. This provides direct evidence for the occurrence of differential transcription effectiveness in a regulon exhibiting a correlative but not strictly coordinated pattern of enzyme synthesis. This also supports our earlier suggestion regarding the possible complexity of the internal operator region situated between argE and C.

Proteins S4 and S12 were isolated from ribosomes of three mutants of Escherichia coli in which dependence on streptomycin caused by alteration in protein S12 is suppressed by an altered protein S4. Proteinchemical studies on the mutant proteins gave the following results: Proteins S12 from all three mutants differ from S12 of the wild type by the replacement of proline to leucine in peptide T15. In all mutant S4 proteins a replacement og glutamine to leucine at amino acid position 53 was found. In addition to this replacement at position 53 a glutamic acid residue at position 199 near the C-terminus was deleted in one of the three mutants. However, this deletion is not necessary for the ability of the mutant S4 protein to suppress dependence on streptomycin. The results support the hypothesis that ram mutants and "revertants" from streptomycin dependence to independence belong to the same class although they were isolated by different selection procedures.

A 5 Megadalton segment of DNA carrying a gene for kanamycin resistance from R447 b (a plasmid of group N of molecular weight 33 Megadaltons) has been inserted into Plac (a plasmid of the A--C complex of molecular weight 101 Megadaltons) to produce the recombinant plasmid Plac-R447 b (Coetzee, 1974). The recombinant plasmid is a typical member of the A--C complex except that entry of an N group plasmid into a Plac-R447 b+ recipient frequently leads to the loss of 5 Megadaltons of DNA (including the kanamycin resistance determinant) from the resident plasmid. In those transcipients from which kanamycin resistance is not eliminated, both plasmids are stably inherited.

The phenomenon of glucose catabolite repression was studied in Escherichia coli mutants unable to transport this carbohydrate. The pts I,H mutant P34 was much less sensitive to permanent and transient repressive effect of glucose on beta-galactosidase synthesis than parental type. The 1103 mutant with lack of enzyme 1 of the phosphoenolpyruvate-dependent phosphotransferase system (ptsI) behaves as well as P34 mutant after addition of glucose to casamino acids mineral medium. But in minimal medium with succinate as the sole source of carbon cells of the 1103 mutant (in accordance with the data of Perlman and Pastan, 1969) show hightened sensibility to transient glucose repression. The effect of hypersensibility disappears when the lacI mutation rendering the beta-galactosidase synthesis to costitutivity is introduced in 1103 mutant. It is shown that the hightened sensibility of beta-galactosidase synthesis to glucose transient repression in 1103 mutant is not an effect of the pts mutation and most probably is due to "inducer exclusion" of the lac operon. It is also shown that if one introduces the P34 mutation in strain devoided of one of the enzymes II for glucose (gptA) (and due to this resistant to glucose catabolite repression) then the level of resistance in double mutant does not increase in spite of considerable supression of 14C glucose accumulation. It is discussed the role of separate components of Escherichia coli K12 glucose transport system in realization of the phenomenon of catabolite repression.

The introduction explains that the purpose of the Monograph is not to present a systematic history of child development in this country, which has been done by others, but rather to enrich portions of the record with individual accounts and reactions to personal experiences. It then proceeds to a discussion of the value, and pitfalls, of oral history for those who probe the past. The body of the Monograph necessarily is confined to certain areas and to a limited number of people who were interviewed, since hundreds of pages of transcripts representing some 80 people have been amassed. With a view to the widest possible coverage of materials in the tapes, three major topics are developed: (1) the reactions of people who have worked in child development to some of the major figures and influences in the field during the careers, (2) the relationship of the study of child development to pediatrics and child psychiatry through the years as viewed by various scientists in a position to hold opinions worth hearing, (3) the relevance of the child development movement to better child care practices in the United States. In this last section, questions of whether it is desirable to gear research to matters of social relevance and whether it is possible-or advisable-given the present state of knowledge for scientists to provide answers in planning for children are considered from vastly differing viewpoints. Also the related problem of the protection of research from misrepresentation by those who want a headline or have biases to buttress is briefly touched on in this section. The conclusion presents various viewpoints as to the appropriateness of the word "movement" as a description of what has taken place in child development. In that connection the Society for Research in Child Development is discussed, as are also the difficulties, encountered by the field in general and by the institutes in particular, which impeded the whole effort.

A review is presented of the many conceptual contributions of Charlotte Auerbach to the development of the field of chemical mutagenesis during the past thirty years. The following aspects are discussed: (1) differences between the genetic effects of chemicals and X-rays; (2) mosaicism, delayed mutation and replicating instabilities; (3) mutation as a cellular process; (4) specificity; (5) dose-effect curves, and (6) correlation between different kinds of damage.

This study demonstrates the feasibility of a randomized controlled investigation of terminating the phenylalanine-restricted diet in four-year-old children with phenylketonuria. The parents of 14 of 16 children gave informed consent, knowing their children would be randomly assigned to either a diet-continuation or a diet-termination group. Compared with the continuation group, the mean serum phenylalanine of the termination group was 15.1 mg per dl higher (P less than 0.005) one year, and 9.2 mg per dl higher (P less than 0.025) two years after diet termination. Mean weight gain between four and six years of age was 3.4 kg greater in the terminated than in the continued group (P less than 0.01). There were no significant differences in mean head circumferences, height or performances on psychologic tests. At age six, mean I.Q. in the terminated group was 99.8, in those continuing the diet 103.6. Children in both groups showed some subtest scatter in memory and concentration. Thus, no harmful effects of diet termination were noted, but a longer period of observation in a larger number of subjects is needed.

The distribution of aminoglycosides in the cerebrospinal fluid (CSF) space was examined after intralumbar, intraventricular, and systemic administration during seven episodes of gram-negative bacillary meningitis. Six episodes were associated with culture proved ventriculitis. Parenteral therapy with gentamicin or tobramycin produced low concentrations of aminoglycoside (less than 1.0 mug/ml) in the lumbar, ventricular, and cisternal CSF. Administration of 5 to 10 mg of aminoglycoside into the lumbar intrathecal space resulted in 27-81 mug/ml in the lumbar CSF, but 0-2.1 mug/ml in the ventricular CSF. In contrast, aminoglycoside administered into the cerebral ventricles produced concentrations in the lumbar CSF of 11.5-27.5 mug/ml and ventricular CSF of 12.8-40 mug/ml. All six episodes treated via the ventricular route resulted in a bacteriologic cure. Intraventricular administration of aminoglycosides offers a reliable means of achieving high aminoglycoside concentrations throughout the subarachnoid space.

A randomized double-blind study was carried out in 26 patients with multiple myeloma to compare the therapeutic effect of sodium fluoride (50 mg twice daily) plus calcium carbonate (1 g four times daily) and placebo. All patients also received melphalan and prednisone for one week every six weeks. Bone biopsies for microradiography and histology, and videodensitometry as well as conventional roentgenograms, 99mTc-polyphosphate bone scans, and bone densitometry of the mid and distal radius, were done initially and one year after therapy. Microradiography and videodensitometry studies revealed significant increases in bone formation (P less than 0.01) and bone mass (P less than 0.005) in the fluoride-calcium group. Bone trabeculae appeared thickened on roentgenograms of six of 13 fluoride-calcium-treated patients (P less than 0.02). Technetium bone scans and bone densitometry determinations proved insensitive for detection of skeletal changes. Fluoride calcium should be considered a useful adjunct in the treatment for multiple myeloma.

With the object of studying the kinetics of imipramine and desipramine five healthy volunteers received single intramuscular, oral and intravenous doses and multiple oral doses of imipramine hydrochloride on different occasions. Two of the volunteers also received single intramuscular and oral doses of desipramine hydrochloride. Great interindividual differences were noted in the plasma concentrations of imipramine and the formed desipramine after single doses of imipramine hydrochloride. In all subjects more desipramine was formed after oral than after parenteral adminstration of imipramine. The bioavailability of an orally administered dose of imipramine ranged between 29.5 and 54.7%. The concentration of imipramine was generally lower in the blood cells than in the plasma, unlike the concentration of desipramine which was considerably higher in the blood cells. The half-lives of imipramine ranged from 4.0-17.6 hrs (M = 7.6 +/- 2.5) after single oral doses and between 9.2 and 20.2 hrs (M = 14.0 +/- 1.9) after multiple oral doses. The half-lives of the formed desipramine ranged between 13.5 and 61.5 hrs (M = 29.9 +/- 8.7) after multiple oral doses of imipramine hydrochloride. The observed mean steady-state plasma concentration after multiple oral doses of imipramine hydrochloride, 50 mg t.i.d. varied from 21.4-69.0 mug/1 (M = 38.2 +/- 8.7) for imipramine and from 33.7-136.0 mug/1 (M 72.3 +/- 19.5) for desipramine. The great difference in the ability to form desipramine after oral and parenteral administration of imipramine hydrochloride may have therapeutic consequences as imipramine and desipramine have differing pharmacological properties.

Porcine neurophysin-I iodinated with Na125I was injected intravenously into rats and rabbits, and the rate of disappearance of radioactivity from the peripheral system was measured. Radioactively-labeled neurophysin bound to polymethylmethacrylic particles was similarly infected into the animals. The half-time for the loss of radioactivity from samples of whole blood was 6.1--6.4 min as determined over the first 5 min after administration of the protein. There was no significant difference in the half-time calculated when the radioactivity present in the trichloroacetic acid-insoluble material present in the se-um was measured. 15 min after the injection of labeled protein there was a maximum and massive uptake of radioactivity in the kidney consistent with this tissue's being important in the degradation of neurophysin. Immunoperoxidase histochemical techniques were applied to formalin-fixed kidney slices and demonstrated the presence of neurophysin-like material localized in the cells of proximal tubules of the cortex and medulla. On binding neurophysin to acrylic particles there was approximately a 10-fold increase in the uptake of radioactivity in the lungs and a 33% reduction in activity in the kidneys, as measured at the 15-min time interval. Of the other tissues studied, excluding the thyroid gland and lungs, the uterus demonstrated the greatest uptake of radioactivity of fat tissue had the least accumulation of radioactive label.

370 patients exhibiting a brachial radiculalgia or a spinal cord disease due to cervicarthrosis were submitted to surgery according to Cloward's technique; freeing or grafting were performed in 682 levels. A study of this surgical management is made and compared with the other therapeutical modalities. A consensus of the results leads to offer this kind of mangement to the initial stage of the disease before the appearing of definitive sclerotic or atrophic lesions. The arthrosic lesions interesting numerous levels, the anatomic-clinical discrepancies concerning the injured level, the misknowledge of the exact physiopathogenesis of the nervous lesions, plead in favour of anterior cervical grafts interesting numerous levels.

The objective of this study was to determine the influence of estradiol-17beta and/or progesterone on gonadotropon secretion at the level of the pituitary. Female rats in which the hypothalamo-hypophyseal connections had been permanently interrupted after castration served as the experimental model in which the effect of estradiol and/or progesterone on LH-RH-induced gonadotropin release was examined. In out experimental animals, LH secretion was readily activated by LH-RH administration. LH release was greatly augmented by the prior administration of estradiol benzoate (1 mug/kg b.w./day). Progesterone (5 mg/day) in the absence of estradiol did not modify the 10-min responese to LH-RH but reduced the enhancement of LH secretion caused by estradiol pretreatment. Our findings suggest that estradiol potentiated the releasing effect of LH-RH at the level of the gonadotroph, whereas progesterone interfered with the potentiation effect. Plasma levels of FSH were not significantly elevated above the basal value by the administration of LH-RH alone, or in combination with estradiol and/or progesterone.

Actual preventive aspects on major neuropediatric handicaps -- particularly cerebral palsy and severe mental retardation -- are surveyed. Based on Swedish epidemiologic studies on the changing pattern through 1954--70 it has been possible to conclude that postnatal preventive measures are largely completed, and that perinatal brain damage syndromes have significantly decreased, while prenatal mechanisms now dominate and still constitute mainly unsolved problems. The study has convincingly revealed that modern neonatal intensive care does pay and has given favorable gains not only in surviving but in undamaged babies.

The results of a set of experiments conducted on a new non-steroid antirheumatic preparation--pyrasanone (Carudol)--are presented and its indications in the general management of the disease are noted. The pharmacokinetics and therapeutic efficacy of the new drug are described. Statistical analysis showed it to be more effective than hexahydropyrazine, diphenylbutazone, indomethacin and oxyphenbutazone. A basic therapeutic approach is suggested in accordance with the pharmacodynamic aspects of the drug and the results observed in a clinical trial on 719 subjects. Pyrasanone has low toxicity and is well tolerated. Due caution in the administration of antirheumatic drugs should nevertheless be maintained during its use.

Preliminary clinical results with an association of high doses of vincamine and chlordiazepoxide in subjects with recurrent depression are presented. It is felt that vincamine has a clinically appreciable psychoactive action.

20-40 Mg per day of gangliosides in association with the therapy already in use were given to patients suffering from acute cerebreal vascular lesions. The results reported in the present work refer to the time necessary for the return to normal functionality. It was observed that such parameter is practically half of that occuring in non-treated subjects. Therefore, the therapeutic usefulness of such glycolipids for the return to normal of the motor functionality and also of the coscience conditions of patients suffering from acute vascular CNS lesions is underlined.

The principal stages in the history of hypnosis are reviewed, from the forerunners of Mesmer to the founder of "animal magnetism" himself, to Braid, and the entire hypnological movement of the nineteenth century. The work of Freud and the then and later relationships between hypnosis and psychoanalysis are discussed. A personal interpretation is offered for the phenomenon of the ups and downs of the popularity of hypnosis and reasons given for why its application should never decline again. After a brief review of modern theories of hypnosis and hypnotic techniques, the importance of the subject, over and above its uses in medical treatment, is emphasized, for hypnosis can be used as an invaluable tool for investigating the extraordinary reconstructional and creative possibilities inherent in the outer reaches of the human psyche.

Thirty one patients were treated with either S-Adenosylmethionine or Imipramine in a double-blind clinical trial comparing S-Adenosylmethionine (25 mg i.m. three times daily) with Imipramine (25 mg i.m. three times daily) administered for a period of three weeks. Hamilton Rating scores showed no significant differences between treatments, but such slight differences as were observed favoured S-Adenosylmethionine.

In a 10 week experimental investigation the tissue reactions to implantation of standardised test pieces made of a polysilicone, Silastic, Tantalum, Titanium and a cobalt-chromium alloy, Vitallium, were studied in the white rat. After 2 weeks, polysilicone, Tantalum and Titanium caused slight reactions whilst a comparatively strong round cell infiltration was observed around the cobalt-chromium test pieces. After 10 weeks, no cellular infiltration was demonstrable around any of the implant materials. The now all appeared inert and were surrounded by a tough connective tissue.

The Copeland intraocular lens implant combined with the intracapsular cataract extraction technique is relatively easy to do when first starting intraocular lens surgery. It does not require switching over to the extracapsular technique or using suture material to secure the implant. It can be done with a Loupe by those who do not use a microscope. The lens is hinged securely in the plane of the pupil and is immobile even with extensive eye movement. The planned implantation should be cancelled if the eye is not soft with a shrunken vitreous body immediately after the lens is extracted. The talked about complications of uveitis and posterior lens membrane may be avoided by the use of steroids and No. 10-0 Ethylon or No. 9-0 silk sutures. After doing, over the past two years, 55 Copeland iris plane lenses combined with intracapsular cataract extraction, I find it to be a relatively simple procedure. It is certainly easier than using intraocular lenses that require either the remnants of lens cortex or capsule for implant fixation, or the tying of No. 10-0 Ethylon suture inside the anterior chamber.

In congenital microphthalmos and anophthalmos, the socket and lids are often underdeveloped. Progressive dilation of the socket often does not increase the horizontal lid aperture or permit the use of a larger prosthesis. The authors present two cases in which a modified Mustarde cheek flap, lined with a tarsal-conjunctival graft, was used to reconstruct and lengthen the lower lid. This procedure results in a larger horizontal lid aperture and permits a larger prosthesis to be contained in the socket.

Corneal scarring secondary to inactive phlyctenular keratoconjunctivitis (PKC) is a significant cause of decreased vision in Alaskan Natives. The results of primary penetrating keratoplasty for such cases at the Alaska Native Medical Center form the basis of this report. Eighteen cases met the criteria established for this study. Fourteen (79 percent) had clear grafts at least six months after surgery (average follow-up: 46 months). Of the twelve grafts performed using 10-0 nylon and the operating microscope, 11 (92 percent) were clear. Twelve of the 14 persons with clear grafts had improved vision of at least two lines on the Snellen chart. On the basis of this report, penetrating keratoplasty for corneal scarring due to PKC seems to have a favorable prognosis.

The making of a groove in cataract surgery and the preplacement of one or more sutures into the groove has been advocated by many surgeons. An instrument that facilitates the performance of the surgical groove is introduced. This instrument, a modification of a corneal trephine, provides a neat, smooth groove of adjustable depth.

Nine patients with severe keratoconus who were ready for penetrating keratoplasty underwent thermokeratoplasty with profound flattening of the cornea at the time of surgery. Keratometer readings returned to pretreatment levels in seven of the nine patients. Two patients have avoided penetrating keratoplasty due to improved contact lens fit following thermokeratoplasty despite the return of corneal steepness. Subsequent penetrating keratoplasty in five patients has been uneventful with all grafts remaining clear to date four to eight months postoperatively.

Protein antigens were prepared from rough strains of Salmonella typhimurium and S. dublin by phenol and veronal-buffer extraction. It was shown that the in vitro migration of peritoneal exudate cells from guinea pigs that were immunized with rough avirulent mutants could be inhibited effectively with these antigens. The cells obtained from S. typhimurium-immunized guinea pigs were also sensitive to S. dublin antigens and vice versa. A degree of sensitivity and inhibition could be demonstrated consistently in a group of immunized guinea pigs. However, the variation in samples, even from among individual animals that had survived challenge, was so great that it precludes the use of the macrophage migration technique as a routine standard assay procedure for immunity.

An experimental study was implemented to determine the effectiveness of isobutyl-2-cyanoacrylate (bucrylate) as an oral hemostat, its influence on sequential wound healing, and its potential as a carcinogen. Segregated groups of equal numbers of male and female Long-Evans Hooded Rats underwent deep (socket) and superficial (surface) aerosol placement of bucrylate to maxillary molar extraction sites. Bucrylate proved to be an effective oral hemostat, rapidly retarding postextraction hemorrhage. Deep placement of the adhesive resulted in retarding of healing and lingering macrohistiocytic aggregates in wounds. Superficial placement of the material resulted in very little long-term macrohistiocytic response, and would healing showed little retardation. A neoplastic potential was not demonstrated for bucrylate.

The buoyant density in CsCl of ribosomes from chloroplasts of the green alga Chlorella pyrenoidosa and two species of higher plants, Pisum sativum and Chenopodium album, has been studied. From the relative protein content it was calculated that 70S ribosomes from chloroplasts are much smaller than 80S cytoplasmic ribosomes (3.0-3.1 X 10(6) and 4.0 X 10(6) daltons) and slightly larger than 70S ribosomes from bacteria (E. coli 2.5 X 10(6) daltons). Chloroplast ribosomes from pea seedlings were analyzed by two-dimensional polyacrylamide gel electrophoresis. They appear to contain 71 proteins. This indicates that chloroplast ribosomes contain a larger number of proteins than do the ribosomes from E. coli and other species of Enterobacteriaceae. Further study will permit a probable evaluation of the validity of Mereschkowsky's hypothesis that the photosynthetic plastids of eukaryotic plant cells are the evolutionary descendants of endosymbiotic blue-green algae.

The intensity of Plasmodium berghei infections decreases as the age of the rat host increases. The nature of this 'age immunity' was investigated. No experimental support was found for innate resistance involving either serum non-antibody factors or changes in the erythrocytes that inhibit parasites in older rats. A cross reacting immune response active against P. berghei was not found. Evidence is presented which shows that rats less than 7 weeks old lack at least part of the functional immunological apparatus by which older rats produce a protective immune response. It is suggested that the defect might involve T lymphocytes.

In order to study the mode of action of a bovine anti-Escherichia coli lactoserum (BLS), we have used a new test measuring the adherence of pathogenic E. coli on epithelial cells isolated from the small intestine of rabbit. A mixed suspension of E. coli and of epithelial cells is incubated for 15 min and the number of bacteria adhering to the cells counted under the microscope. The BLS at a concentration of 3.5 mg/ml IgG is able to reduce this number by a factor of 3-5. After absorption of the BLS with formaldehyde-treated bacteria, this factor is smaller than 2. At a concentration of 5 mg/ml, D-mannose and alpha-methylmannoside are as efficient inhibitors of adherence as BLS; at the same concentration, L-mannose is ineffective. The cultures of E. coli strongly agglutinating guinea pig erythrocytes, adhere to a larger extent to the epithelial cells. The last two observations confirm the important role played by fimbriae for the adhesive properties of E. coli. The presence of fimbrial antibodies would partially explain the inhibiting effect of BLS on adherence.

Measurements were conducted of five species of Lamblia mounted and stained with ferreous hematoxylin. In order to obtain comparable results only mature trophozoites with medial bodies were measured. It was shown that the totality of biometrical indices of mature trophozoites is specific for each species studied; this demonstrates their distinct status and is contrary to Filice's view (1952). Of the studied species trophozoites of man (L. intestinalis), rabbit (L. duodenalis), vole (L. microti) and rat (L. simoni) have the same shape of the body but differ in absolute sizes. Trophozoites of the parasite of mice and rats, L. muris, differ from other species in a shorter body and in having spherical medial bodies. In this connection a question is raised concerning the according of a higher taxonomic status to this species.

Chenodeoxycholic acid labeled with 2H in the 11 and positions was prepared by catalytic reduction of delta 11-12 unsaturated derivatives of cholic acid. To validate the use of this stable isotope for the determination of bile acid kinetics by isotope dilution, it was administered to seven normal male volunteers simultaneously with [24-14C]chenodeoxycholic acid. Bile was collected at regular intervals over the following 5 days, and the chenodeoxycholic acid pool size and fractional turnover rate were determined from the specific activity decay curve for 14C and from the isotopic abundance curve for 2H. Estimates of the pool size by both isotopes showed a correlation of r = 0.95 and similar precision. Synthesis rate, the product of pool size and fractional turnover rate, also showed good agreement (r = 0.97), Because previous investigations have shown that bile acids tagged with hydrogen isotopes at the 11 and 12 positions are stable in man, the present data suggest that 11, 12-2H-labeled bile acids may be used in place of radioactive isotopes for valid isotopic measurement of bile acid kinetics in healthy infants and children.