Nucleotide sequence of phenylalanine transfer RNA from Schizosaccharomyces pombe: implications for transfer RNA recognition by yeast phenylalanyl-tRNA synthetase. The nucleotide sequence of Schizosaccharomyces pombe tRNAPhe was determined to be pG-U-C-G-C-A-A-U-G**-G*-U-G-psi-A-G-D-D-G-G-G-A-G-C-A-psi-G*-A-C-A-G-A-Cm-U-Gm-A-A-Y-A-psi-m5C-U-G-U-U-G-m7G-U*-C-A-U-C-G-G-T-psi-C-G-A-U-C-C-C-G-G-U-U-U-G-U-G-A-C-A-C-C-AOH. This sequence differs from that of S. cerevisiae tRNAPhe in 27 nucleotides. Saccharomyces cerevisiae phenylalanyl-tRNA synthetase aminoacylates both the homologous tRNAPhe and S. pombe t-NAPhe; the reactions have similar Km and Vmax values. However, the nucleotide sequence in the D stem is different in the two tRNAs. This region was proposed by Roe, B., et al. [(1973) Biochemistry 12, 4146--4154] to be the major recognition site for yeast phenylalanyl-tRNA synthetase, but the present results cast doubt on the validity of this hypothesis.


Chemical and physical properties of mammalian mitochondrial aminoacyl-transfer RNAs. I. Molecular weights of mitochondrial leucyl- and methionyl-transfer RNAs. The sedimentation and electrophoretic properties of Syrian hamster cytosolix and mitochondrial methionyl- and leucyl- +RNAs have been compared under denaturing conditions. Mitochondrial leucyl-tRNA could be separated into three species by chromatography on RPC-5. Their apparent molecule weights as determined by polyacrylamide slab gel elecltrophoresis were 23 000 for one species and 24 000 for the other two compared to the five cytosolic leucyl-tRNA species whose apparent molecular weights ranged from 26 000 to 28 000. Mitochondrial leucyl-tRNAs sedimented more slowly than their cytosolic counterparts, again indicating a lower molecular weight. The apparent molecular weights of the mitochondrial methionyl-tRNAs were identical or only slightly lower than their cytosolic counterparts as determined by polyacrylamide slab gel electrophoresis but both mitochondrial methionyl-tRNA and formylmethionyl-tRNA sedimented slightly more slowly than cytolsolic methionyl-tRNA. It is suggested that mitochondrial tRNAs fall into the size range of other t RNAs and might be uniform in size.


Chemical and physical properties of mammalian mitochondrial aminoacyl-transfer RNAs. II. Analysis of 7-methylguanosine in mitochondrial and cytosolic aminoacyl-transfer RNAs. The 7-methylguanosine (m7G) content of two individual mitochondrial tRNAs, labelled in the aminoacyl moiety was assayed by the specific cleavage of the tRNA at this nucleotide followed by electrophoretic analysis to identify the 3'-terminal fragment of the tRNA. Neither Syriam hamster mitochondrial tRNALeu nor tRNAMet were found to contain m7G. In contrast, cytosolic tRNAMetS were cleaved indicating the presence of m7G, apparently 27--28 and 29 nucleotides from their 3' terminus. Cystolic tRNALeu was not cleaved. These results are discussed in relationship to the reported low content of methylated nucleosides in mitochondrial 4 S RNA.


Independent temporal expression of two N-substituted aminoacyl-tRNA hydrolases during the development of Artemia salina. Encysted embryos of the crustacean Artemia salina contain an enzymatic activity which hydrolyzes N-acetylphenylalanyl-tRNA to N-acetylphenylalanine and tRNA. The enzyme apparently does not hydrolyze other free or N-substituted aminoacyl-tRNAs. The levels of this enzyme do not significantly change during embryonic and early larval development. In contrast, an unspecific hydrolase active on several N-substituted aminoacyl-tRNAs is practically absent in the encysted embryos and during embryogenesis and appears abruptly during larval development. The independent temporal expression of these two hydrolases during Artemia salina differentiation makes this organism siuitable for the study of the physiological role of these enzymes.


Sensitivity of ribosomal bound N-acetylphenylalanyl-tRNA to hydrolysis by a spectific hydrolase. Binding of N-acetylphenylalanyl-tRNA, either enzymatically or non-enzymatically, to yeast 80-S ribosomes renders the substrate resistant to the hydrolytic action of a specific hydrolase present in yeast. In contrast, N-acetylphenylalanyl-tRNA bound to the 40-S ribosomal subunit is sensitive to enzymatic hydrolysis. The presence of the hydrolase in the aminoacyl-tRNA binding factor preparations greatly interferes with the formation of complexes between N-acetylphenylalanyl-tRNA and the small ribosomal subunit.


Other views about the hepatotrophic concept. In this paper two main questions are approached. The first relates to the aspects of the proliferative response which are influenced by alleged hepatotrophic substances and experiments will be recounted which were designed to test whether hepatocyte enlargement and division are separable. Both short-term and long-term data suggest the need to consider that these two reactions may be controlled by different factors. The second question is concerned with the indentification of hepatotrophic substances and the circumstances in which these are found to be effective. Experiments have been carried out which attempt to assess the extent to which normal liver cells are affected by specific hepatotrophic substances in vivo. The findings do not completely support the hypothesis that the integrity of the liver cell is dependent on a single identifiable hepatotrophic substance.


Signals for glucagon secretion.

Signals for glucagon secretion. The normal physiological role of glucagon is in controlling hepatic glucose output. Glucagon subserves the role of homeostasis by maintaining plasma glucose and of a stress hormone by producing hyperglycaemia. While control of glucagon release by circulating metabolites and also other hormones is clearly important, it seems likely that the nervous system exerts an over-riding influence. The parasympathetic nervous system maintains homeostasis and the sympathetic acts in stress. Glucagon levels are found to be high in cirrhosis and also after acute hepatic failure. It is likely that these changes in glucagon concentration are secondary to metabolic abnormalities. While some glucagon is cleared by the liver, a similar clearance is seen by many other tissues and it is not likely that the elevation of glucagon seen in liver failure is due solely to a gross deficiency of glucagon clearance. No liver abnormality is seen in the glucagonoma syndrome, where glucagon concentration are chronically high, or in patients who have had a total pancreatectomy, where plasma glucagon is undetectably low. It thus seems unlikely that liver mass is importantly controlled by glucagon.


Liver atrophy, hypertrophy and regenerative hyperplasia in the rat: the relevance of blood flow. Liver perfusion can be measured sequentially by monitoring the clearance of 85krypton injected into the portal circulation. Preliminary studies in dogs show that the method reflects gas clearance from a homogeneously perfused liver parenchyma and correlates well with measurements of total hepatic blood flow. The method has been adapted to measurement of liver blood flow in normal rats, partially hepatectomized rats and after portacaval transposition with and without partial hepatectomy. There is a marked rise of approximately 250% in the first four hours after partial hepatectomy in the rat. After portacaval trans-position, liver blood flow remains within the normal range and no great rise occurs after partial hepatectomy. In animals subjected to portacaval transposition, there is a reduction in relative liver weight (liver weight/body weight ratio) and when partial hepatectomy is performed three weeks after portacaval transposition, the relative liver weight is regained within three weeks, and does not differ from that of non-hepatectomized controls. DNA synthetic activity, studied during the 72 hours after partial hepatectomy performed three weeks after portacaval transposition, shows an uptake of tritiated thymidine into liver DNA of the same magnitude as and contemporaneous with that of controls. Liver atrophy after portal diversion is not a result of a decrease in absolute liver blood flow. Regenerative hyperplasia appears to be independent of a direct supply of portal blood and occurs in the absence of the post-hepatectomy rise in liver blood flow seen in normal rats.


Insulin as a cellular growth regulator.

Insulin as a cellular growth regulator. Previous studies from this laboratory have shown that insulin treatment greatly stimulates liver cell growth in chronically diabetic rats. The effect is striking, being preceded by massive glycogen deposition and water imbibition as well as enchanced RNA and protein synthesis. More recently we have directly confirmed the stimulatory effects of insulin on liver RNA and glycogen synthesis in intact hepatocytes isolated from normal and diabetic rats. The hepatocytes specifically bind insulin (KD = 3.5X10(-9) M) and the bound hormone is degraded systematically, indicating the possibility of receptor-mediated uptake of the hormone. Recent studies in other laboratories of the growth factors, non-suppresible insulin-like activity (NSILA) and nerve growth factor (NGF), as well as of relaxin, have disclosed structural relationships between these peptides and pro-insulin, indicating the existence of families of closely related anabolic effectors. A new hypothesis regarding the role of the insulin-receptor complex in initiating the metabolic and mitogenic effects of the hormone is briefly discussed.


Insulin-induced liver hyperplasia: evidence for a negative liver-size-correcting process. The fate of the increased liver DNA induced by insulin treatment of rats with chronic steptozotocin-induced diabetes was studied. The DNA content of the organ was restored to normal by an active process having a half-time of 32 days. The half-time of disappearance of thymidine-labelled DNA in the same livers was 81 days. The results indicate the existence of a mechnanism which acts to restore normal liver cellularity when an over-production of cells has occurred.


Hepatotrophic effects of pancreatic and gastrointestinal hormones in the rat in vivo and in vitro. The role of gastrointestinal and pancreatic hormones in regulating liver growth was evaluated by measuring their effect on DNA synthesis in the normal and regenerating liver of rats in vivo and in maintenance cultures of adult rat hepatocytes in vitro. After partial liver resection DNA synthesis reached peak levels after 24 hours while serum concentrations of immunoreactive insulin in portal and peripheral blood at this time were still suppressed. Increase of endogenous insulin levels by intravenous glucose infusion or portal infusion of insulin, glucagon or both together with glucose did not change DNA synthesis in normal or regenerating rat liver. After acute carbon tetrachloride poisoning of rats, survival rate and degree of liver necrosis was not changed by intraperitoneal infusion of glucagon and insulin with glucose. In vitro, insulin, glucagon and somatostatin synergistically stimulated the specific thymidine uptake in seven-day-old maintenance cultures of rat hepatocytes. The hormones did not cause cell multiplication but enhanced cell survival, probably by improving the uptake and utilization of nutrients. Gastrin G-17, secretin and cholecystokinin (contaminated with gastric inhibitory polypeptide) had no effect. It is concluded that the results do not support the contention that liver regeneration is regulated by the known pancreatic hormones. However, a trophic effect of pancreatic hormones on liver cells in vitro could be demonstrated. Gastrointestinal hormones had no such effect.


Studies on plasma cytotoxicity and liver regeneration in fulminant hepatic failure. The possibility that the blood of patients with fulminant hepatic failure might contain substances which prevent or delay liver regeneration was investigated using a microcytotoxicity assay system based on the culture of isolated rabbit hepatocytes in vitro. Results showed significant cytotoxicity of the plasma as compared to controls, an effect which was reduced by charcoal haemoperfusion. The effect was also reduced in vitro by heating and dialysis. The bile acids chenodeoxycholic and lithocholic acid were cytotoxic when added to control human plasma. Evidence was also obtained from a completely different in vivo assay system that high blood levels of ammonia may inhibit hepatic regeneration.


Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver. An analysis of hepatocellular proliferation in regenerating rat liver reveals a dependence of kinetic parameters on the microvascular structure of the liver. Influx kinetics of hepatocytes into DNA synthesis as well as cell cycle phases vary in different parts of the liver lobule between the afferent and efferent vascular poles. Heterogeneity of the proliferative response and size limitations on cell cycle compartments appear to be intimately related to the actual functional state of the individual liver cell. Modifications of liver cell functions result in variations of the proliferative activity. Phenobarbital-induced hypertrophy of hepatocytes reveals a permissive action on G1- S influx. Selective destruction of the subpopulations, by allyl formate, leads to a new functional determination of the residual liver and to a change in proliferative compartments. Maximum modulation of cell cycle compartments is obtained by hydroxyurea-induced synchronization of hepatocytes after partial liver resection. During hydroxyurea treatment, the regenerating liver shows a pronounced cellular hypertrophy. After release from hydroxyurea block, cells embark on DNA synthesis simultaneously. The DNA synthesizing compartment comprises almost the entire liver cell population. Heptotrophic factors might play a part in regulating or modifying hepatocellular function and proliferative response after cell loss.


Hepatotrophic factors: implications for diabetes mellitus. In view of the importance of insulin in hepatic cell proliferation and regeneration, disturbances might be expected in these processes in diabetics. The relative importnace of insulin replacement given intraportally rather than subcutaneously is discussed. Results are presented showing that even when normoglycaemia is achieved with peripheral insulin infusion using the 'artificial pancreas' there are still abnormalities in intermediary metabolism. The incidence of cirrhosis in diabetes is reviewed and it is concluded that the evidence is poor for an increase in diabetics. Finally it is shown that in the normal diabetic rat changes are observed after partial hepatectomy consistent with an increase in redox potential within the regenerating liver. Insulin treatment improves redox status but does not completely reverse the changes shown.


Regulation of Na+ and Cl- transport and mucous gland secretion in airway epithelium. Ussing's short-circuit technique was applied to canine airway epithelium in vitrol and a net flux of Cl- towards the airway lumen was demonstrated, with a smaller net flux of Na+ in the opposite direction. Furosemide decreased and acetylcholine, terbutaline, and histamine increased net ion transport towards the airway lumen. Associated changes in water content in the airway lumen could affect mucociliary clearance, and therefore inhibition of ion transport may play a role in disease states. To study secretions from submucosal glands in vivo, two techniques were used to identify the duct openings in the exposed canine tracheal epithelium. (a) The exposed mucosal surface was coated with powdered tantalum; accumulated secretions produced elevations under which the duct openings were located. (b) A vital dye (0.1% Neutral red) was placed on the exposed mucosal surface; the dye stained the duct openings. With these techniques, the innervation of the submucosal glands and the autonomic regulation of their secretions were studied. Micropuncture techniques were used to sample the secretions from the glands and ducts.


Chemical aspects of tracheal glycoproteins. The chemical characteristics of tracheal mucus obtained directly from the epithelial surface of the trachea indicate that the mucus from each animal source consists of a group of sulphated sialic acid-containing glycoproteins. Fractionation of the native glycoprotein from the cat by gel chromatography in the presence of urea and dithiothreitol suggests a value of about 3 X 10(6) for the molecular weights. The chief monosaccharide constituents are N-acetylneuraminic acid, N-acetylglucosamine, N-acetylgalactosamine, fucose and galactose. In the goose tracheal mucin, mannose is present (serum proteins being absent). Doubly labelled cat mucus, obtained by giving Na235SO4 and [3H]glucose simultaneously into the lumen of the trachea, is massively released by parasympathetic agents, e.g. pilocarpine. The resulting mucus has a high content of 35S and is derived largely from submucosal gland cells. Subsequent exposure to an irritant, ammonia, releases a low sulphation fraction, highly labelled with 3H, arising from goblet cells. Evidence supports the view that the overall mucus is composed of mixed secretions, chemically distinct, from different cellular synthesizing sites. Differential nervous stimulation of the various sites may cause far-reaching changes in the chemical and physical properties of the mucus by selective action on the secretion of one or more of the contributing glycoproteins.


The glycoproteins of secretory cells in airway epithelium. Quantitative histochemical methods demonstrate a variety of glycoproteins within mucus-secreting cells of airway epithelium. A single cell may synthesize one or a combination of four major types--(i) neutral glycoprotein, (ii) and (iii) sialylated either sensitive or resistant to sialidase and (iv) sulphated. In human airway disease, or in experimental response to inhalation of an irritant, there is mucus cell hyperplasia and change in the proportion of cells synthesizing the various types. Experimental studies show how speedily these changes occur. In rats exposed to tobacco smoke changes are found within 20 h of the first exposure. Only in the extrapulmonary epithelium is there discharge of  the secretions, with an apparent fall in cell number. Modification of glycoprotein may occur with an unchanged or increased cell number, suggesting that it occurs in existing and newly appearing secretory cells. Modification of the contents of the granule occurs toward the cell apex. Modification of glycoprotein synthesis towards the normal is also the most sensitive and earliest sign of recovery.


Structure and function of mucus.

Structure and function of mucus. A glycoprotein building block is common to mammalian mucins. This structure is composed of several protein chains having the same sequence. The carbohydrate side chains, which constitute over three-quarters of the weight, coat only some two-thirds of the backbone chain. The bare protein chains are linked by disulphide bridges and can be digested away with trypsin. Either procedure rapidly solubilizes mucus and results in a structural unit of about 500 000 molecular weight. Mucus solubilizes spontaneously. The first size unit which reaches solution is about 15 X 10(6) molecular weight but continues to break down further. Mechanical agitation considerably speeds up this process. The gel-like character which is an essential feature of mucus--which cannot otherwise act as transport coupler--is thus a transient phenomenon. The problem of how such a structure can arise from the building blocks known to be available is discussed.


Nasal mucociliary clearance in man.

Nasal mucociliary clearance in man. Nasal mucociliary clearance was measured in healthy young human subjects and tracheal clearance in the experimental animal under a wide variety of conditions. There is a broad range of clearance rates whether at standard ambient conditions (23 degrees C, 50% relative humidity) or in the face of a number of environmental variables. The degree to which those differences are attributable to the effectiveness of ciliary beating or the character of airway secretions is not known. Studies of tracheobronchial secretions simultaneous with clearance measurement in the anaesthetized dog have not yet provided a definite answer. Variations in upper respiratory defence mechanisms may bear some relationship to the aetiology of small airway disease in the lungs.


Tracheobronchial clearance in health and disease: with special reference to interciliary fluid. Rats were exposed to influenza B virus for 2 hours. Mucociliary function in the isolated airway preparation of these animals was studied from the first day after exposure and at regular intervals for up to 190 days. Transmission electron microscopy (TEM) studies were done at times corresponding to the mucociliary function studies. TEM studies confirmed the results of the mucociliary function studies: pathological changes were first apparent three days after exposure and began in the distal bronchioles. The morphological studies further demonstrated that the infection progressed proximally to include the entire tracheobronchial tree by the 18th day. The alterations observed included an increase in the number of goblet cells, a decrease in the number of microvilli and a reduction in the amount of interciliary fluid. The last two changes were closely correlated with the severity of the infection. The abnormalities found in mucociliary function included hypersecretion of mucus, inactive and hypoactive zones, synchronization of cilia beating, and a sticking together of the cilia tips.


Site of synthesis, intracellular transport and secretion of glycoprotein in exocrine cells. The site of attachment of the first sugar, N-acetylgalactosamine, to the seryl and threonyl residues of the protein chain is unknown in exocrine cells. The subsequent sugars of the carbohydrate side chains, galactose and N-acetylglucosamine alternately, and the end-group sugars, galactose, N-acetylgalactosamine and fucose, are attached in the Golgi complex. Sulphate too is attached in that structure. In the stomach, sulphate is probably transferred in the most mature cisterna of the Golgi stacks, galactose and fucose in other cisternae, suggesting a gradient in transferase activities along the stack. The possibilities of regulating the amount and relative sugar composition of the glycoproteins are discussed. The secretory product is stored in granules. Their polygonal, large and swollen appearance and complex formation by loss of bordering membranes, as observed in many kinds of glycoprotein-secreting cells ('mucous cells') might be caused by ineffective fixation techniques. Direct vascular perfusion results in a picture no different from what is found in non-mucous cells. Whether secretion is merely exocytotic, as in non-mucous cells, or whether it is accompanied by a loss of membrane and even cytoplasm needs thorough investigation, with the effects of various fixation techniques being compared.


The isolation and partial characterization of the major bronchial glycoproteins. Partial characterization of glycoprotein obtained from mucous secretion of the bronchi and stomach has been attempted. The isolated glycoproteins and the glycoproteins from gastric aspirates showed similar carbohydrate and amino-acid composition. They consist of a protein core to which are attached carbohydrate side chains of galactose, N-acetylglucosamine and N-acetylgalactosamine in the ratio of 4 : 3 : 1. Superimposed on this structure were additional sugar residues, the blood group determinants. The carbohydrate side chains are linked by an alkali-labile O-glycosidic linkage to the threonine and serine residues of the protein core, with N-acetylgalactosamine forming the link.


Criteria for evaluating mucus functions and their disorders in chronic bronchitis. In chronic bronchitis, disorders of the physical and chemical properties of mucus may contribute to bronchial obstruction. The abnormalities are analysed in sputum collected by physiotherapy. Measurements of the rheological properties (apparent viscosity and strain recovery), content analysis of secretory immunoglobulin A (S-IgA) and of serum albumin, and determination of the transport velocity of sputum on the ciliated frog palate provide reliable indices of the functional capacity of bronchial mucosa. The effectiveness of mucociliary clearance and coughing is analysed in patients by measuring the rate of removal of radioactive particles deposited on proximal airways. Different types of pathological secretions may be observed. In subjects with occasional cough and sputum, the secretions are characterized by a high content of S-IgA and serum albumin, and a high viscosity and low elasticity, reflecting their high degree of cross-linking. In chronic bronchitics, the S-IgA content and viscoelastic properties of sputum decrease as the illness progresses. During infection, purulent sputum exhibits high viscosity and low strain recovery. Such modifications of the rheological properties of mucus may impair mucociliary clearance. The role of the elastic component is predominant. Sputum, characterized by very low strain recovery (SR less than 4 units) or conversely by very high strain recovery (SR greater than 15 units), is transported at a low rate by mucociliary clearance. A marked hyperviscosity (no greater than 200 poises (120 N s m-2)) also appears as a limiting factor of the mucociliary clearance.


Animal models in clinical disease.

Animal models in clinical disease. Hypersecretion of mucus is a feature of several clinical diseases and in some is associated with mucous gland hypertrophy and goblet cell increase. In a variety of species these changes have been produced by irritants, by infection, or by administration of drugs. While the end result may appear the same, differences emerge in the type and amount of glycoprotein secreted and in the amount retained within the cell. Organ culture can be used to ascertain functional activity. The use of animal models has not only established that these environmental changes cause hypertrophy but indicated some of the intracellular events associated with their development. When new types of granules appear within a cell, they appear first at the apex: a flow chart is offered of the way of which individual cells change and hence the population. The nature of glycoprotein elaborated by a secretory cell can change within hours. A Clara or serous cell can develop into a mucus-secreting or goblet cell. The pattern of reversibility is emerging.


Structure and function of mucus-secreting cells of cat and goose airway epithelium. In the cat and goose, studies have been undertaken to determine the ultrastructure of airway epithelia, the concentration and distribution of the secretory cells which produce respiratory tract mucus, and the histochemistry of mucins located within cells and on their luminal surfaces. By electron microscopy all the 11 cell types so far described can be found in the airways of the cat but not the goose. Both goblet cells and submucosal glands are abundant in the cat whereas the trachea of goose lacks the latter, having instead abundant goblet cells many of which form 'intraepithelial glands'. Histochemically, the goblet cells of the cat and goose are similar in that they contain mucins with a predominance of sulphate esters. A surface mucosubstance can be demonstrated which, histochemically, is similar to that described in dog and man. Interestingly, this surface layer may be sloughed in response to an inhaled irritant such as ammonia and thereby contribute to the respiratory tract mucus recovered experimentally. Incorporation into macromolecules of radioactively labelled mucin precursors is assessed by autoradiography of tissue sections, and preliminary results of experiments designed to test the response of mucus-secreting cells to airway irritation and the parasympathomimetic drug, pilocarpine, are also presented.


Studies on the control of mucin production. The process of synthesizing a mucin molecule is discussed, primarily from the standpoint of glycoconjugate biosynthesis. The control of the activation steps in the making of nucleotide sugars is detailed, stressing the molecular mechanisms operating. These include: supply of glycolytic intermediates; the pyridine nucleotide redox potential; the energy state as expressed in nucleotide potential; and feedback modifiers. Next, the glycosyl transferases are discussed, as are suggestions of control at the first committment step and the subjects of specificity of donor and acceptor molecules and the associational state of the glycosyl transferases. The secondpart of the paper describes a model system in vivo. The paired cat submandibular glands are exposed and, in one, blood supply and salivary duct are cannulated and the parasympathetic and sympathetic nerve exposed. This preparation uses the contralateral gland as control and enables certain questions to be asked: 1. Does the cell produce incomplete mucins when the biosynthetic rate is high? 2. Does the energy state of the cell 'keep up with' the high rates of synthesis? 3. What is the extent of post-synthetic modifications? 4. What cell types are involved in mucin elicited by different chemical or electrical stimuli? 5. What is the time involved in synthesis and storage?


[The idiopathic orthostatic hypotension -- Shy-Drager syndrome (author's transl)]. The idiopathic orthostatic hypotension can be characterized as a presenile degenerative process with a liability to attack especially multiple systems. In the course of the disease clinically the autonomic functional failure stands in the beginning. It also determines the serious illness in the later stages, which is associated with an additional variable neurologic syndrome. By means of an own clinically and pathologically examined case it is given a survey of the present knowledge about the disease process. Especially it is declared on the localization of the lesions. Phaemacological tests point to a main disturbance of the preganglionic respectively central part of the sympathetic system. The analysis of the neuropathologically examined cases shows as the most regular finding a neuronal loss in the nucleus intermediolateralis, which certainly is hold responsible for a great part of the functional failure. But it is to assume, that lesions in other structures cooperate in the genesis of the syndrome, which morphologically are not yet recorded.


[Cysticercosis of the brain (author's transl)]. Two cases of cysticercosis of the brain with multilocular parasite infestation are reported. Case 1 showed temporal lobe epilepsy with corresponding EEG and parkinsonism. Pathomorphologically there were parasites in the sylvian fossa and a bilateral necrosis of the pallidum. In case 2 there was a cranial nerve deficit (n.vestibulo-cochlearis) with pronounced vestibular ataxia. Parasite vesicles were surgically removed from the cerebello-pontine angle. Neurohistologically, chronic inflammatory changes were present in the immediate vicinity of the parasite. In both cases there was cysticercosis of the rhomboid fossa and base of the brain (leptomeningitis) with evidence of a process of the posterior cranial fossa. Psychic changes (hysteriform behavioral abnormalities, psychotic episodes and, increasingly, an organic psychosyndrome) were observed particularly in case 1. This case was followed for 11 years on the basis of documented and personal investigations. This report discusses the differential diagnosis and therapy of brain cysticercosis with reference to the two cases and the literature.


[Symptomatology, diagnosis, and treatment of nervous tissue affecting toxoplasmosis in adult (author's transl)]. The neurological manifestations of three adult cases with acquired toxoplasmosis appearing like a focal lesion, multiple sclerosis and with symptoms indicating a cerebellar lesion are reported. The discussion with respect to the literature shows the following results: 1. The diagnosis of mono- and oligosymptomatic toxoplasmosis with neurological symptoms is only approximate after the introduction of the indirect immunofluorescence test too. 2. The toxoplasmosis of the nervous system in the adult is not characterized by a special syndrome like the connatale form. In contrary, it often is mimicking many well known neurological or psychiatric syndromes. 3. There may be an exacerbation of a latent infection in cause of immunosuppressive therapy or radiation of malignancy or after transplantations. 4. Treatment with the combination of pyrimethamine and sulfonamids today is handled less in spite of the possible complications and of doubtful serological results, because an early diagnosis and onset of treatment is important for a good restitution.


"Chemical aminoacylation" of tRNA's.

"Chemical aminoacylation" of tRNA's. Incubation of abbreviated tRNA's (tRNA-C-COH's) with (chemically) preaminoacylated P1, P2-di(adenosine 5'-)diphosphates in the presence of purified RNA ligase effected transfer of an aminoacyladenylate moiety to the 3'-terminus of the abbreviated tRNA's in good yield. Aminoacylated (or misacylated) tRNA's may thus be prepared from fractionated or unfractionated tRNA-C-COH's; each of the five aminoacylated dinucleoside diphosphates tested was utilized as a substrate by RNA ligase. That the resulting "chemically aminoacylated" tRNA's were identical with those prepared by enzymatic aminoacylation was judged by comparison of 1) chromatographic properties on benzolated diethylaminoethyl-cellulose, 2) rates of chemical deacylation, and 3) affinities for elongation factor Tu, as well as 4) the ability of misacylated tRNA's so derived to be deacylated chemically and then reactivated enzymatically with their cognate amino acids.


Susceptibility patterns of Staphylococcus in a family practice population. Nasal swabs were obtained from 408 patients seen in a family practice office in an attempt to identify Staphylococcus aureus carriers. Isolated strains were tested for sensitivity to 11 antibiotics. Study participants were interviewed to obtain the following data: age, history of recent hospitalization and/or recent antibiotic use, number of household members, and occupation, if employed in a health-care facility. S aureus was isolated from 109 nasal swabs. This represents a 26.7 percent carrier rate. Only 25.7 percent of the isolates were sensitive to penicillin G and ampicillin. No statistically significant association was found between the patient variables and either the carrier rate or the sensitivity of the S aureus isolates to penicillin. The sensitivity testing demonstrated that 94.5 percent of the isolates were sensitive to tetracycline and erythromycin. Ninety-nine to 100 percent of the isolates were sensitive to all other antibiotics tested. The authors conclude that penicillin G should not be used in the treatment of S aureus infections. Erythromycin, due to demonstrated sensitivity and reasonable cost, is recommended for mild to moderate infections.


Synthesis of potential antineoplastic agents XXVI: 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]2-quinolizinone derivatives. A number of 3-alkyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]2-quinolizinones and 2-substituted 3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]quinolizines were prepared and submitted for antineoplastic and anticonvulsant screening.


Is a mandated comprehensive health education program a guarantee of successful health education? This study evaluated the health knowledge of a selected population of 12th grade students. A random selection of 30% of the total senior population from 7 public high schools was obtained. The Kilander-Leach Health Knowledge test was used. An analysis of variance was performed by sex and by health area. The FLSD multiple range test was utilized where significance was found among groups. The findings revealed that students' health knowledge was weak; moderate strength was indicated in the area of chronic disease; no significant differences were observed between males and females on the total test; there was significant differences in health knowledge on the total test among the schools.


Cardiovascular disease education in Texas health education classes -- a needs assessment. This study ascertained to what extent cardiovascular diseases and associated risk factors are taught in public secondary health education classes in Texas, the disparity between what is taught and what is desired in terms of time allotment and educational materials, to what extent health education teachers are academically prepared to teach cardiovascular diseases and associated risk factors, and to what extent teachers utilize self-instructional materials. A questionnaire was mailed to a random sample of health education teachers in Texas. There was a return of 45.4%. The findings indicated that more time is devoted to teaching the cardiovascular system than disease and risk factors; there is a disparity between what is taught and what is desired; the teachers rated their preparation as average; and the use of self-instructional materials by high school students as average to excellent.


A comparison of perceived and actual sexual behaviors of college students. This study investigated the relationships between reported sexual behaviors of college students and their perceptions of sexual behaviors of peers. Seventy-four subjects completed the survey instrument. Chi-square comparisons determined the relationship between reported sexual behaviors and perceived sexual activities. Males were more accurate than females in perceiving sexual activities of males but not of females. Females were unable to perceive accurately male or female behaviors.


[Human nutrition under hyperbarism].

[Human nutrition under hyperbarism]. In a 15-day experiment six test subjects were exposed to a hyperbaric environment. Their actual food and water consumption was measured. The consumption of a diet with a caloric value of 3300--3500 kcal did not alter the body weight of exercising test subjects. During decompression the food consumption decreased. Certain food products caused dyspepsia. The total amount of consumed water was not more than 2500 ml/day.


The reduction in the intensity of meaning attached to sex words. This investigation utilized 192 college students to determine if the intensity of meaning attached to sex words could be reduced, if change in this meaning intensity was affected by the passage of time, if the intensity of meaning was related to the students' anxiety level, and if students felt more comfortable in using sex words after treatment than they did before treatment. Pretest instruments determined the intensity of meaning and anxiety level. A verbal satiation method was used with the experimental groups. Three posttest time delay measurements were taken in both experimental and control groups. It was concluded that technical health words and common health words produce communication blockages.


An instrument for the recording of student health complaints. This study described the development and uses of an instrument for the systematic collection of student health complaints in school. A booklet was prepared listing all student's names for one rural elementary school. A code to indicate date, class period, complaint, and outcome was utilized for collecting data. After a 2.5 month trial period, data were analyzed. The findings revealed 418 visits to the school health room -- range of visits by classroom was 3 to 71 -- most visits were for stomach ache or physical injury -- one classroom accounted for 16% of all visits -- fourth and sixth grades had a significantly larger number of visits than grades three, five, and seven.


[Nature of the heterogeneity of 30S ribosomal subparticles in vitro. I. Effect of large centrifugal fields during 30S subparticle isolation on their capacity for codon-dependent tRNA binding]. Measurements of association constants (Ka) of specific [14C]Phe-tRNAPhe with a 30S..poly(U) complex revealed that values of these constants vary from 0.5.10(7) up to 1.5.10(8) M--1 when different 30S subunit preparations were used at the same medium conditions (20 mM Mg2+, 200 mM NH4, 0 degrees C). Analysis of these data showed that the higher the rotor speeds were used during separation of 70S ribosomes into subunits, the less Ka values were measured. In special experiments on sedimentation of pure 30S subunits at different rotor speeds it was found that the decrease of Ka values was caused due to the additional reversible dissocation of ribosomal proteins from 30S subunits at high (the order of 100 000.g) centrifugal fields. As a possible mechanism of such dissociation we suggest the influence of high hydrostatic pressure on the association constants of S-proteins with 30S subunits. Data presented in this paper demonstrate that at least one of the reasons for the physical and functional heterogeneity of 30S subunits in vitro derives from the application of high centrifugal fields during isolation of ribosomal subunits.


Cardiac rehabilitation: a patient education program. Hospitalized cardiac patients were given an education program that covered, in five 45-minute discussion sessions, anatomy and physiology, dietary management, appropriate activity programs, the adjustment process, risk factors, and signs and symptoms of complications of therapy. A sample of 36 patients was given pre- and posttests and followed at six weeks and three months postdischarge. Significant (p less than .05) increases in knowledge were found among study subjects which resulted in improved conditions for the subjects.


Conceptual systems of undergraduate nursing students as compared with university students at large and practicing nurses. Phase I of a longitudinal study compared characteristics of abstractness-concreteness of junior-level baccalaureate nursing students at the University of Colorado with characteristics of practicing nurses and other college students. Three measurement instruments were used: Harvey's Conceptual Systems Test, the Role Survey, and the Self-Esteem Questionnaire. Nursing students were found to be more abstract than practicing nurses; no difference was found on abstractness-concreteness between nursing and the other students. More nursing students than practicing nurses or other students were found to have a need for structure and order. And, nursing students showed higher overall expanded role orientation than practicing nurses. Phases II and III of the study will examine nursing students' changes in abstractness-concreteness during the second and third years of study.


Increasing nurses' person-centeredness.

Increasing nurses' person-centeredness. In a two-phased study, two samples of registered nurses listened to audiotaped disclosure statements from simulated patients and responded to each statement "in as helpful a manner as possible." Their responses were judged for degree of "person-centeredness." Nurses in sample one (N=24) received no intervention between the two phases of the study; nurses in sample two (N=20), after completing phase I, listened to a brief message designed to enhance the helpfulness of their responses. No differences were found for the phase I person-centeredness scores; the nurses who received the intervention showed significant improvement in their degree of person-centeredness as compared to those who did not receive the intervention. Implications of these results are discussed.


Sex-role stereotyping in assessments of mental health made by psychiatric-mental health nurses. To determine the amount of sex-role stereotyping in judgments of mental health made by psychiatric-mental health nurses, 150 of these nurses, divided into three equal groups, were asked to rate ideal states of mental health in males, females, and adults, respectively. An 83 percent return rate was obtained. Results showed: 1) there was less sex-role stereotyping than in a similar study reported in 1970 with other mental health professionals; 2) judgments of mental health closely resembled assessments of social desirability; 3) healthy females were rated closer to that which was considered desirable and closer to the healthy adult pole than males or adults; 4) healthy females possessed the valued male traits without losing the female-valued characteristics; and 5) nurses who had longer experience as therapists, who were older, and who were still practicing viewed men and women as more alike rather than placing higher expectations on women.


Methodologic dilemmas in tapping the concept of patient needs. Patients' awareness of their own physical and emotional needs during hospitalization and nurses' perception of those needs were tested by a questionnaire constructed for the purpose. The test took place in five units of a large university medical center and included 30 patients and their 20 nurses. A comparison group included ten patients and eight nurses. Despite apparent reliability after pretesting, the questionnaire proved unreliable after use with the study group. This difference may have resulted from differences in responses between the pretest and study groups or from interviewer variability. Or contrary to pretest findings, the real contents of physical and emotional needs may not have been tapped.


The BOEL test as a screening device for otitis media in infants. Two hundred and forty-five infants with a mean age of nine months were given screening tests in private pediatric offices by two nurses. Low scores on the BOEL test, a measure of selective attention developed at the Karolinska Institute in Sweden, were found to be significantly associated with the presence of otitis media. Of the 12 items on the BOEL, only the four relating to auditory orienting behavior were discriminative. As a screening device for otitis media, these four items had a validity of 87 percent correct predictions, with 11 percent false positives but only two percent false negatives. BOEL scores also had positive correlations with three of four areas tested by the Denver Developmental Screening Test, but these relationships were modest in magnitude, suggesting that the BOEL and the DDST measure different aspects of the infant's behavior.


Values and value changes of graduate nursing students: their relationship to faculty values and to selected educational factors. Values of 75 graduate nursing students in one university school of nursing were compared at times of entry into the program and at the completion of one academic year of study. Gordon's Survey of Interpersonal Values and Survey of Personal Values and a questionnaire were used to collect data. The students' perceived impact of certain educational factors was explored for possible relationship of these factors to changes that occurred. Values of the graduate nursing faculty and their perception of the importance of the same factors were obtained and compared with those of the students. Students showed signficant increases in values of support, recognition, and independence and significant decreases in benevolence, conformity, and practical mindedness. These changes bore similarity to those reported in previous studies of undergraduate nursing students and medical students. Differences between the students and faculty on two values, practical mindedness and independence, had disappeared by the end of one year; difference on one value, recognition, had appeared; and difference on one value, achievement, remained the same. The influence of specific educational factors was not clear. Faculty judged almost all factors as having a greater impact on students than students judged their impact to have been. Students' preestimate of probable influence of the same factors was significantly higher than their postestimate. Some uniform processes of socialization occurred even though students and faculty were not always in agreement about the importance of educational activities and outcomes.


Using nursing research findings to meet the needs of grieving spouses. This article describes the utilization of nursing research findings in a coronary care setting. A standardized nursing care plan, based on Hampe's eight research-identified needs of grieving spouses, was developed by staff nurses in an intensive care unit. The 13 spouses of acutely ill coronary patients who had received specific nursing interventions reported more of their needs were met by nurses than did 13 spouses on whom base-line data were collected prior to the adoption of systematic nursing interventions.


Impact of a management-oriented course on knowledge and leadership skills exhibited by baccalaureate nursing students. This study evaluated the impact of a one-month management concept course on 80 senior baccalaureate nursing students. Findings revealed that leadership values held by nursing students did not affect their leadership behaviors. Nursing students who took the course demonstrated significantly more leadership behaviors and knowledge of leadership concepts than students who did not take the course. Reasons for the findings are discussed.


Cognitive and affective consequences of formative evaluation in graduate nursing students. To test the effect of formative evaluations on cognitive learning and affective behaviors, 57 graduate nursing students were placed in experimental (E) and control (C) groups. Two hypotheses were stated: that E students learn and demonstrate affective behaviors significantly more than C group students. The 25 E group subjects were taught by means of formative evaluations. The 32 C group subjects were taught by lecture-discussion. The content taught dealt with conditions of learning and instruction in nursing. Pre- and posttests measured cognitive learning. Demographic data and affective measures were obtained only at the posttest. Results showed: The E group learned and demonstrated affective behaviors significantly more than the C group. Both groups learned significantly. Subjects preferred the formative evaluation technique significantly more than the LD. Significant positive correlation was found between amount of learning and affective behaviors. Implications were made for education of patients, students, and stall.


Evening telephone call management by nurse practitioners and physicians. History-taking, disposition, and telephone communication skills of pediatric nurse practitioners, pediatric house officers, and practicing pediatricians were assessed and compared. To evaluate the management of five common acute pediatric problems, a "programmed mother" made 148 unidentified calls to these health professionals during evening hours. The calls were tape recorded, and scored for history-taking, disposition, and interviewing skills. The scoring system, developed by a panel of 11 experts, assessed the relevance and completeness of each history obtained. Nurse practitioners averaged 79.6 percent of the total possible score, as compared to 52.6 percent for pediatricians  (p less than .001). When disposition was similarly analyzed, the nurse practitioners scored significantly higher than pediatricians. Analyzing only those items of history-taking and disposition deemed most critical by the panel, nurse practitioners included 91 percent and pediatricians only 55 percent (p less than .001). Parameters of interviewing skill were scored by the interviewer and each author with agreement of 80 percent or above; nurse practitioners obtained significantly higher scores than pediatricians (p less than .001). Calls handled by nurses averaged 7.4 minutes, those by pediatricians 3.2 minutes (p less than .001). Nurse practitioners, it was concluded, can safely and effectively share responsibility with physicians for night and weekend telephone call coverage for a pediatric practice with adequate physician back up.


Death and dying: selected attitudes of Minnesota's registered nurses. A study of attitudes toward dying patients of 1,061 Minnesota nurses who practiced in the metropolitan area (210 nurses) and outside the metropolitan area (851 nurses) revealed that they supported home care for dying children. They reported they would be willing to care for the dying adult or child in the home, but would feel more comfortable if they had added specialized preparation.


ODWIN expansion program: a study in success. Of 182 students who successfully completed an eight-week program for high school graduates with marginal credentials and who were admitted to schools of nursing, 125 (69 percent) subsequently received degrees or certificates. This success rate compares favorably with national and regional norms. This study documents the marginality of the students' credentials and evaluates their success rates. Of 11 academic variables correlated with successful completion of nursing programs, the two subjective evaluations of each student by the academic personnel teaching the eight-week program were the only variables to reach significance (p = .01).


Self-actualization and the baccalaureate nursing student's response to stress. A sample of 144 senior nursing students from four baccalaureate schools in the New York metropolitan area was used to study the relationship between self-actualization and the baccalaureate nursing student's response to stress. Levels of self-actualization and state and trait anxiety were measured at a time defined as low in stress; state and trait anxiety were measured again at two high-stress times. Instruments used for the study were Shostrom's Personal Orientation Inventory and the Spielberger et al. State-Trait Anxiety Inventory. The three hypotheses were supported by significant results (p less than .05), confirming the prediction that level of self-actualization is a factor in the differential perception of evaluative events as stressful. Findings are considered applicable to the revision of recruitment and selection procedures and to incorporating in baccalaureate nursing curriculums measures more likely to produce graduates who can sustain the personal values prerequisite to a professional level of nursing practice.


The nurse practitioner: role, physician utilization, patient acceptance. A comprehensive study of nurse practitioners was undertaken by the University of Virginia Schools of Medicine and Nursing in the summer of 1974 to evaluate nurse practitioner training programs of the University of Virginia and to determine the effectiveness and responsibilities of nurse practitioners in various practice settings. Data on nurse practitioners in a number of locations in Virginia and in the Philadelphia metropolitan area were collected and analyzed to determine the way in which the nurse practitioners' time was allocated among various duties and to evaluate nurse practitioner performance by physicians and patients. Nurse practitioners performed a wide variety of clinical and nonclinical tasks. Most physicians were satisfied with the practitioner's performance, although there was some inconsistency between physicians and nurse practitioners regarding actual duties performed. A high percentage of physicians stated they would hire a nurse practitioner to replace one who left their employ. Physicians' reasons for hiring a nurse practitioner, as well as their previous contact with such personnel, were examined. Regarding patient attitudes toward nurse practitioners, data indicated that patients were satisfied with nurse practitioners and felt comfortable being treated by them.


Comparison of manifest needs of nurses and physicians in primary care practice. Nurses, among other professionals, have been tested extensively using the Edwards Personal Preference Schedule. High scoring needs found in previous studies were order, deference, and endurance. In this study, questions focused on whether these needs remained prominent in a group of nurses, whether there were shifts in the need patterns over time, and how the nurses' needs compared with the needs of physicians. In this study 127 graduate nurses enrolled in a medical nurse practitioner program and 31 physician colleagues completed the EPPS. The rank order of needs among nurses was strikingly different from those collected in previous samples. Need for heterosexuality, dominance, intraception, change, and achievement consistently appeared highest since 1973, whereas need for deference, order, and endurance scored consistently among the lowest six needs. The rank-order correlation between nurses and physicians in this sample, all of whom were working in primary care settings, was high (r = .9). Only one of the 15 needs, intraception, differed significantly between the nurse and the physician groups, the nurses scoring higher. The shift in needs of the nurses and the high similarity of needs of the nurse and physician groups suggest an emerging assertiveness on the part of the nurses and a trend toward similarity of need patterns with physicians practicing in primary care.


Effect of negative pressure on tracheobronchial trauma. To test the effect of different negative pressures on tracheobronchial trauma in the presence of simulated mucus, measured amounts of simulated mucus were injected into the trachea of two anesthetized mongrel dogs. Suctioning was performed using a different negative pressure for each animal. To identify the effects of negative pressure alone, endotracheal tube size, suction catheter type, suction duration, and suction procedure were identical for both dogs and were selected on the basis of current practices at the hospital with which the investigator was affiliated. Arterial pressure and electrocardiogram were monitored throughout each experiment. The trachea was excised and examined for pathologic changes. Tracheobronchial trauma occurred with suctioning at negative pressures of 100 mm Hg and 200 mm Hg; damage was greater, however, at 200 mg Hg. Results were consistent with postulates made by other investigators in that the extent of tracheobronchial trauma was directly related to the magnitude of negative pressure applied. Comparison of this study with studies which omitted mucus simulation suggests that the amount of damage is not related to the amount of mucus in the trachea. In addition, aspiration efficiency proved to be the same regardless of the negative pressure used. Suctioning at 200 mg Hg recovered approximately the same amount of mucus as suctioning at 100 mm Hg.


Histidine transfer RNA levels in Friend leukemia cells: stimulation by histidine deprivation. Friend leukemia cells incubated with sublethal concentrations of histidinol for 5 to 6 days show up to twofold increases in their relative concentrations of histidine transfer RNA and no change in the relative concentrations of leucine transfer RNA. A similar effect is seen when cells are grown to stationary phase in the presence of 0.2 times the amount of histidine in Eagle's minimum essential medium. These observations support the theory that the concentrations of specific transfer RNA's are regulated by a mechanism that is sensitive to the extent of their aminoacylation.


Cefuroxime, a beta-lactamase-resistant cephalosporin with a broad spectrum of gram-positive and -negative activity. The in vitro activity of cefuroxime, a cephalosporin antibiotic, was investigated against 604 isolates and compared with the activity of other beta-lactam compounds. Cefuroxime had activity comparable to that of other cephalosporins, including cefamandole and cefoxitin, against streptococcal and staphylococcal species; most streptococci were inhibited by 0.1 mug or less per ml, and staphylococci were inhibited by 1.6 mug or less per ml. Enterococci were relatively resistant. Cefuroxime inhibited beta-lactamase-producing Neisseria gonorrhoeae and Haemophilus influenzae. Cefuroxime had excellent activity against members of the Enterobacteriaceae; 83% of beta-lactamase-producing Escherichea coli, 100% of Salmonella, 100% of Klebsiella, 90% of Proteus mirabilis, 95% of Citrobacter, 56% of Enterobacter, and 58% of Shigella were inhibited by 12.5 mug/ml. Cefuroxime had activity comparable to that of cefamandole and cefoxitin; it inhibited isolates of E. coli and Klebsiella resistant to cefamandole and inhibited Enterobacter and Citrobacter resistant to cefoxitin. Many isolates of Serratia, some indole-positive strains of Proteus, and Bacteroides fragilis were resistant to cefuroxime. Resistance of cefuroxime to hydrolysis by beta-lactamases played a major role in its activity against both gram-positive and gram-negative organisms.


Antibacterial activity of apalcillin (PC-904) against gram-negative bacilli, especially ampicillin-, carbenicillin-, and gentamicin-resistant clinical isolates. Apalcillin (PC-904) is active against carbenicillin- and ampicillin-resistant strains of gram-negative bacilli. Among Pseudomonas aeruginosa strains highly resistant to carbenicillin (>/=3,200 mug/ml), half of them were susceptible to PC-904 at a concentration of 50 to 1,600 mug/ml. The minimal inhibitory concentration of PC-904 against P. aeruginosa strains resistant to carbenicillin (400 to 1,600 mug/ml) ranged from 3.1 to 25 mug/ml. Ampicillin- and carbenicillin-resistant Enterobacteriaceae strains were similarly susceptible to PC-904. However, drug resistance to PC-904 was already apparent among some strains of P. aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris, and P. morganii, recently isolated in Japan; i.e., 4, 35, 32, 4, 6, and 14% of strains isolated were resistant. PC-904 was more active, on the other hand, than ampicillin and carbenicillin against antibiotic-susceptible Enterobacteriaceae and also showed high activity against most species of Pseudomonadaceae, especially P. cepacia and P. aeruginosa. The minimum inhibitory concentrations of PC-904 were greatly affected by inoculum size when the organisms tested were strains producing large amounts of beta-lactamase.


Methicillin-resistant Staphylococcus aureus susceptibility testing by an automated system, Autobac I. The Autobac I system was used to evaluate the antibiotic susceptibility pattern of methicillin-resistant Staphylococcus aureus isolates. The results of the Autobac I were compared with the results of the disk diffusion method. The disk diffusion susceptibility pattern showed resistance to methicillin/oxacillin, penicillin, erythromycin, clindamycin, and kanamycin. All isolates were susceptible to cephalothin, chloramphenicol, tetracycline, and gentamicin. There was at least 96% agreement using the Autobac I system with all antibiotics except methicillin and clindamycin. Seventy percent of 57 isolates were recorded as susceptible to methicillin, whereas 9% had an intermediate susceptibility. With clindamycin, 14% were recorded as susceptible and 7% were recorded as intermediate. Upon prolonged incubation of the Autobac I cuvette, the agreement between the two methods was 44% for methicillin and 93% for clindamycin. Changes in the environmental conditions, such as use of 5% sodium chloride broth and a 32 degrees C incubation temperature, did not increase the detection of methicillin-resistant isolates by the Autobac I system.


Mechanism of penicillin-erythromycin synergy on antibiotic-resistant Staphylococcus aureus. Clinically isolated strains of Staphylococcus aureus that are inducibly resistant to both erythromycin and penicillin were susceptible to a combination of the two antibiotics. The synergistic effect of the combination results from an inhibition of penicillinase induction by erythromycin, sparing penicillin and allowing this drug to inhibit growth. When resistance to erythromycin is constitutive rather than inducible, the combination is no longer synergistic.


Chemical modification as a probe of conformational changes in transfer ribonucleic acid on aminoacylation. Treatment of Escherichia coli CA265 phenylalanyl-tRNA with 3M-NaHSO3, pH6.0, at 25 degrees C resulted in modification of four bases and in the deacylation of the charged tRNAphe. The similarity of the rates of base modification and of the deacylation of the phenylalanyl-tRNA permitted the isolation of partially modified phenylalanyl-tRNAphe and partially modified deacylated tRNAphe. The sites and extents of base modification in these fractions were determined and found to be the same as those in uncharged tRNAphe modified under identical conditions. These findings are discussed in relation to previous evidence for and against a conformational change in tRNA on its aminoacylation. The methods described should prove adaptable to study of other aminoacyl-tRNA species.


Binding of reticulocyte elongation factor 1 to ribosomes and nucleic acids. The present study has examined the requirements for the binding of rabbit reticulocyte elongation factor 1 (EF-1) to ribosomes under different assay conditions. When a centrifugation procedure was used to separate the ribosome EF-1 complex, the binding of EF-1 to ribosomes required GTP and Phe-tRNA, but not poly(U). The results suggested that undr these conditions a ternary complex, EF-1 . GTP . aminoacyl-tRNA, is necessary for the formation of a ribosome . EF-1 complex. However, when gel filtration was used to isolate the ribosome . EF-1 complex, only template and tRNA were required. These studie emphasize the fact that the procedure used to isolate the ribosome . EF-1 complex determines the requirements for stable complex formation. EF-1 can also interact with nucleic acids such as 28 S and 18 S rRNA, messenger RNA and DNA. In contrast to the binding to ribosomes, EF-1 binding to nucleic acids requires only Mg2+.


The role of guanine nucleotides in protein biosynthesis. It is not possible to select one competing substrate molecule over another one when the selection system is at equilibrium. Therefore, it is convenient to view all substrate selections as transport phenomena. The requirement for a displacement from equilibrium to effect a substrate selection can be met in different ways. One particularly convenient way is to drive a nonselected substrate, such as GTP in protein synthesis, far from equilibrium. This allows the flux of selected substrate to be relatively slow, but effectively irreversible. Accordingly, the conventional view that GTP hydrolysis drives protein synthesis is amended. It is suggested that the regeneration GTP from GDP is the driving force for protein synthesis. Several different selection mechanisms are described in the context fof systems driven by displacements from equilibrium of the nonselected substrate. These are then evaluated in light of recent experimental results. The data argue against the relevance of proofreading mechanisms for aminoacyl-tRNA selection by the messenger RNA-programmed ribosome. Similarly, recent data suggesting that the translation of messenger RNA is not dependent on the presence of elongation factors and guanine nucleotides are reevaluated.


Outcomes of 575 British opiate addicts entering treatment between 1968 and 1975. Five hundred and seventy-five opiate addicts (455 male, 120 female) who were treated at two clinics in London between 1968 and 1975 had their current situation reviewed in October 1975. Fifty-two per cent were still in treatment (258 at the clinics, 42 elsewhere), 28 per cent were not in treatment and not known to be using opiates, 11 per cent had died, 6 per cent were in custody and 3 per cent had left the country. Sixty-one per cent of the patients in treatment had remained so continuously. Twenty-eight per cent had also had in-patient hospital treatment. Some patients were very unstable and those treated as in-patients in hospital two or more times for drug abuse had an average of nine hospitalizations. Forty-six per cent of patients in clinic treatment said they were working regularly at the end of the study (23 per cent at entry). Some 7-8 per cent of patients left treatment each year and the death rate remained between 2 and 3 per cent each year. The prescribing of heroin for addicts was gradually superseded by the prescribing of injectable methadone. The authors concluded that a methadone maintenance programme probably had some value in the treatment of opiate dependence.


Drug abuse in Poland.

Drug abuse in Poland. The abuse of drugs in Poland, a lesser problem than that of alcoholism, has only recently become a subject of interest. Although at present it is not of crucial importance in the pathology of social life, it may still have serious effects on the individual and society. This paper discusses the results of several surveys carried out by different researchers in Poland to assess different aspects of the drug abuse phenomenon. Drug abuse patterns in Poland, as in other countries, change rapidly. Therefore, yesterday's situation may not be considered as valid today. The first part of this article presents some of the characteristics that were observed since 1968, when the phenomenon appeared, up to 1976. The second part describes the provisions of the Polish criminal law to fight drug abuse, and envisages some measures to better control this phenomenon in the future.


Influence of photoperiodism on cannabinoid content of Cannabis sativa L. Cannabis sativa plants submitted to 10 and 12 hours of natural light showed different content in cannabinoids. An increase of exposure to natural light of only 2 hours a day, at least, doubled the average amoung of THC, but decreased that of cannabichromene.


How vascular smooth muscle works.

How vascular smooth muscle works. Electrical recordings made from vascular smooth muscle during the last 15 years make it clear that the role of electrical activity in controlling contraction is often important but varies greatly both between different vessels and for different responses of a given vessel. Only a few mammalian vessels have widely conducted electrical activity, but others can develop this activity, with consequent rhythmical contraction, when made anoxic and stimulated. Action potentials play a part in smooth non-rhythmical responses of arteries to nerves and hormones, while passive conduction of depolarization round the vessel wall is responsible for ring contractions of arteries after local injury. Ca and K cause vasodilatation largely by hyperpolarizing the smooth muscle cells. Electrical activity plays no part in some responses. In particular noradrenaline can contract arteries by directly promoting entry of extracellular Ca, and also by releasing Ca stores by non-electrical means. These processes are particularly important in the inner muscle of arteries, which is not directly innervated.


Stimulation of enzymatic phe-tRNA binding to mammalian ribosomes by thallium ions at concentrations blocking other ribosomal functions. Thallium acetate (TIOAc) effectively stimulates poly(U)-directed Phe-tRNA binding to mouse ascitic tumour ribosomes under conditions when other ribosomal functions are completely blocked. The TI+ optimum is about 200 mM. The reaction is stimulated by EF-1, but not significantly by GTP. EF-1-dependent ribosomal GTPase is inhibited by T1+. The isolated Phe-tRNA . ribosome complex is relatively stable. The bound Phe-tRNA does not react with puromycin in the presence of 175 mM KCl. The complex formed in the presence of 90-100 mM TlOAc can, after isolation, be directly utilized for polyphenylalanine synthesis. The complex formed at 200 mM TlOAc is less active, apparently because of damage to the 60-S subunits. TlOAc at low concentrations (8 mM) stimulates K+ -containing poly(U)-translating systems, probably by stabilizing the translation complex.


[Medical aspects of cerebral death determination of the time of death (author's transl)]. As a result of the development of intensive-care medicine and organ transplantation, an increasing number of neurologists and other physicians are being confronted with problems of cerebral death and relevant diagnostics. Subsequent to a survey of the, after all, rather uniform pathogenesis, and of the anatomic findings, the clinical syndrome is described in detail with the object of helping to avoid a diagnostic misinterpretation of individual neurologic findings. The diagnostic aids or methods which can be applied at present, are judged with regard to the problems involved and their diagnostic value (experiences with the computer-tomogram have been omitted, since too few observations have been made to date). The paper concludes with a few pointers as to how these guidelines can be utilized when dealing with the concrete everyday situation of diagnosing cerebral death.


[On the use of computer tomography (CT) in clinical psychiatry (author's transl)]. 220 hospitalized psychiatric patients were examined by computerized tomography (CT) mostly to exclude organic brain dammage. A third of the material proved to be within the normal range, when also slight cortical and subcortical atrophies are considered to be abnormal. Pronounced cerebral atrophy was found in 26.8% of the cases, 5% revealed other significant lesions. CT is a very promissing help in distinguishing vascular from purely degenerative processes. Chronic alcoholism showed an amount of 67% cortical atrophies of all degrees. Endogenic psychoses on the other side failed to demonstrate characteristic results. Many of possible unspecific pathogenetic factors seem to play an important role in this and other disease processes. CT as an almost non-invasive method may be repeated in dubious cases.


[The idiopathic paroxysmal myoglobinuric myopathy (Meyer-Betz) (author's transl)]. The idiopathic paroxysmal myoglobinuric myopathy (IPMM) as a genuine disease can be differentiated from other myoglobinurias by clinical criterias. Concerning the course of the disease two different types of IPMM are to be seen, sporadic cases are observed as well as familiar, autosomal recessive inherited ones. Regarding the pathogeny of IPMM several metabolic disorders are discussed: Provocation of the disease by physical exertion and glucose deficiency point to a disturbance of carbohydrate metabolism. Disorders of lipid metabolism are reported, too. So we tried to analyse the results of a case study in relation to the presently discussed - still hypothetical - pathogenetic ideas. Our laboratory, histological and electromyographic findings suggest a primary myopathy, which might be based on a peripheral glucose utilisation disorder (ATP-deficiency). Under the condition of exertion this disorder leads to a decompensation of the muscular functional and structural metabolism manifested by an excessive efflux of myoglobin and enzymes.


[Neuroradiologic and clinical correlations in asymmetric lateral ventricles and posterior cornua in pneumo-encephalograms (author's transl)]. Retrospective study of 452 out of 4155 pneumoencephalograms continuously investigated by two independent observers over 20 years. Follow-up and statistics of frequency and sex-differences of asymmetries of lateral ventricles and posterior cornua. Criteria of selection: history and clinical findings in favor of a general cerebral cause and against circumscribed changes due to local damage. Technique standardized and equal bilateral filling in pneumoencaphalography. Results of the numerous findings: 1. Posterior cornua were symmetrical in 370 patients 81.9% (256 male, 114 female, 18.1%). Definite asymmetry of posterior horns in 72 males and 10 males. 2. These asymmetries showed variations from unilateral to bilateral, but clearly different sizes of posterior horns. 3. Unilateral posterior horn "anlagen" seen in 64 (14.1%) of all patients. Males predominated 8:1, left more common than right 3.5:1. 4. Bilateral "anlagen", with one posterior horn predominating, in 18 patients (3.9%). Once more males more common 8:1. Larger "anlagen" on left: 8:1. 5. Accompanying further asymmetries of lateral ventricles with equal bilateral posterior horns were of similar size in 73.7%. In 21.1% the lateral ventricle was larger on the right, in 5.1% on the left. The left side was more common 4.15:1. 6. Large ventricles were of equal size in 45.1 of patients with asymmetry of the posterior horns, 45.1% on left, 9.7% on right the ventricle was larger. Once more the left side predominated 4.6:1. 7. Trying to correlate clinical-neurologic, neurophthalmic, neurophysiologic and tachistocopic findings with pneumoencephalograms with or without asymmetry showed no regular relation with handedness, ocular dominance, limitations of visual fields or--neglect or shapes of ventricles. In all subgroups frequency and sex-distribution corresponded to the norm. 8. Numerical frequency of coupling of right-handedness and right predominant eye with left increased size of ventricle was within the statistically expected and was, therefore, not interpreted as a sign of functional dominance of the left cerebral hemisphere, as done by others. 9. When eliciting from the occiput visually evoked potentials 8 patients showed important findings, in spite of their small number. In 3 patients with symmetrical "anlagen" of the posterior horns, latency and amplitude of potentials were the same; in 5 patients, with asymmetry of posterior horns the side of the larger horn showed significant reduction of amplitude without exception. The investigations show, quantitative statistical findings of frequency and sex-distribution and their negative correlation with examined clinical parameters apart, the anatomic-morphologic variation of asymmetry of posterior horns corresponds to a correlate which can also be shown with a neurophysiologic technique.


[Influence of a central cholinergic mode of action on the regulation of the intact and disturbed cerebral blood flow (author's transl)]. Cerebral chemical vasomotor reactivity and autoregulation were tested in normal baboons before and after intravertebral, intravenous and (or) intracarotid infusion of atropine and neostigmine. Furthermore, disordered cholinergic neurotransmission and dysautoregulation after acute experimental cerebral infarction have also been investigated. Intravertebral injection of atropine suppressed the increase of CBF by inhalation of 5% CO2 and enhanced the decrease of CBF induced by hyperventilation, but did not appreciably affect autoregulatory response. On the other hand, cerebral autoregulatory vasoconstriction during increases of CPP was significantly reduced following both intravertebral and intracarotid neostigmine infusion. Cerebral vasodilatory reactivity to CO2 inhalation was significantly enhanced only following intravertebral neostigmine and cerebral vasoconstrictive response to hyperventilation was not influenced by neostigmine. Following experimental cerebral infarction regional dysautoregulation was found in infarcted gray matter and correlated significantly with increased AChE levels in the same zones of cortex and basal ganglia. Intravenous infusion of scopolamine restored autoregulation to the ischemic zones. The results thus obtained support the view that central cholinergic cerebrovascular influences exist and are vasodilatory in nature. Furthermore, in acute experimental cerebral infarction disordered cholinergic neurotransmission seems to play a role in vasoconstrictive dysautoregulation.


Oxygen therapy and delivery in obstructive pulmonary disease. The guidelines for O2 therapy in acute decompensation of COPD and even the indications for short-term use of O2 during periods of increased requirements in stable COPD are fairly clear-cut. With regard to continuous O2 therapy in hypoxemic patients with stable COPD, most would agree that in patients with cor pulmonale treatment with low concentrations of O2 for periods of more than 12 hours per day will result in improved pulmonary hemodynamics, mental function, polycythemia, and perhaps exercise tolerance. In similar patients without cor pulmonale the potential benefit of continuous O2 is unknown. Many other serious questions remain. The optimum duration of chronic O2 therapy must be clarified. More data are needed to determine the effect of continuous O2 therapy on mortality rate at both sea level and high altitude. It is not known whether O2 therapy has any prophylactic value in those patients with COPD who have not developed severe pulmonary hypertension. The potential value of O2 therapy in exercise rehabilitation programs needs further study. Finally, lightweight, longer-lasting, and less-expensive O2 delivery systems must be sought.


Outbreak of a multiply resistant Acinetobacter in a surgical intensive care unit: epidemiology and control. During January, 1976 seven patients in an SICU became colonized or infected with Acinetobacter calcoaceticus (variation, anitratum) at an attack rate of 12.5 per cent. The organism showed a marked reduction in antimicrobial sensitivity from previous experience. Comparison with 34 uninfected control patients indicated that intubation and continuous ventilatory assistance were significantly associated with acquiring the organism (p = 0.0154). Acinetobacter was cultured from nurses' hands, AMBU adaptors, respirator apparatus, respirometers, and unlabeled bottles of saline used for tracheal irrigation. Control measures were designed to interrupt transmission. The investigation identified the nursing techniques and reservoirs that allowed this outbreak to occur, and we emphasize the need for close surveillance of patient care procedures in an intensive care unit.


A systems approach to the nursing process. This paper makes the point that for psychiatric patients the nursing process based on a systems approach may be more useful than that based on problem-solving or activities of daily living. Some of the key concepts used in this approach are (1) listing component parts of a system, (2) defining the inside and outside of systems, the outside being described as environment, (3) changing the boundaries or the interface of various systems, as appropriate, (4) observing the impact of the environment and especially of the nurse herself as a part of the system or the environment, (5) tracing input, output and throughput, and (6) drawing distinctions between open and closed systems and accounting for a steady state in the system.


A strategy for patient teaching.

A strategy for patient teaching. A theoretical model is described whose particular emphasis is directed towards operationalizing the statements: 'effective teaching bridges the gap between information and practice or 'teaching is more than telling'. It concentrates on nurse behaviours (facilitation) designed to actively engage the patient in learning whereby he accepts his diagnosis or situation, projects the effects of prescribed therapy on his future life, and commits his intentions to practice. It utilizes principles of learning derived from the perceptual (phenomenological) approach and indicates the nurses' responsibilities. The model identifies four critical elements in the engagement process--the patient's values, his perception of the disease threat, his perceived utility of prescription, and facilitating behaviours of the nurse. The strategy is adapted from a combination of the Health Belief Model and the Personal Choice Model.


Participation in decision-making in the health services. There is widespread discussion at the present time of 'participation'--allowing members of an organization to exert an influence on the process of decision-making. The National Health Service is not isolated from this debate and already a number of experiments have been carried out at various levels of the service to allow a wider range of opinion to influence decisions than hitherto. This paper reports on a study the author carried out into one such exercise, designed to assist a Health Board reach decisions about the longterm pattern of health care in its area. Nurses, paramedical staff and local authority staff, as well as doctors, were appointed to a series of programme planning committees to advise the Health Board on issues of longterm policy. After 2 years of operation, a study was carried out into the operation of the committees and the lessons drawn from the experience should be relevant to actual and potential members of any consultative or decision-making body.


The need for a comprehensive counselling service for nursing students. The responses to 'given situations' in a questionnaire administered to 50 nursing students indicate that they are conscious of high stress factors in nursing. Role conflict is created when they are given instructions in the wards contrary to what they are taught in the schools of nursing. Some of the responses also indicated that learners may be developing attitudes which are contrary to what they are taught in the schools of nursing. Some of the response also indicated that learners may be developing attitudes which are contrary to good nursing practice as a protection from external pressure. The majority of the respondents had opportunities for discussion of their problems, but 28% were unsure about available facilities. The author argues that the counselling needs of nursing students must be met by provision of a comprehensive counselling service.


Nurse--teacher behaviours in the clinical field: apparent effect on nursing students' learning. One primary source of feedback on the effectiveness of their teaching, which instructors may easily overlook, comprises of students' reactions. The purpose of this study is to identify students' perceptions of teacher behaviours, which either facilitate or hinder students' learning in the clinical field, and to determine if there is a difference in the perceptions of 1st and 2nd year students. This study is exploratory and descriptive in nature. Firstly, some research studies regarding effective clinical teaching in nursing are reviewed, followed by a discussion of the research design. The tool used for collecting data is a modified form of the critical incident technique. A description of illustrative incidents is requested within five divisions: professional competency, relationship, personal attributes, teaching methods, and evaluation of  practice. A system for analysis and coding of data is then discussed. Finally, the finding of this study is presented. It would seem ot the investigator that students in 1st year are particularly sensitive to how the teacher makes them feel, whereas students in the 2nd year would seem to be more concerned with the teacher's competency in teaching. The teacher behaviours reported as helpful or hindering to students' learning, as identified by the students, are outlined.


The use of non-ionic detergents in sanitary cleansing: a report of a preliminary trial. A preliminary trial was carried out to establish the most suitable hygienic wipe for sanitary cleansing in incontinence and to study and compare the difference between cleansing with soap and non-ionic detergents in incontinent patients. Four non-ionic detergents were tested against National Health toilet soap in 290 incontinent episodes. Other observations were made on the skin condition following cleansing, the ease of cleansing, odour control, detergency, and allergenicity. The results showed that a scrim wipe was the best for this purpose and also indicated that the non-ionic detergent Cetomacrogol 1000 B.P.C. to be preferential to all other creams and soap in the time taken for cleansing. The skin condition, odour control and detergent ability were all superior with this cream. It was revealed by the trial that in cleansing faecal incontinence with non-ionic detergent, an initial wipe, followed by about 7.0 grams of detergent on a moistened wipe to achieve emulsification and than followed by another dry wipe, is all that is required. The condition of the skin was recorded as excellent and the figures indicated a possible saving of 20% in nursing time.


Prospects and problems in health services research. Health services research has an important--and unique--role in affecting the climate of policy formulation and in defining future options. This very uniqueness, however, places the endeavor in a vulnerable position between the usual rigors of scientific investigation and the desire for simplicity and comprehensibility on the part of administrators and legislators. A constituency must be found to nurture the continuance of this modest but invaluable research activity.


Group practice recommendations of the Committee on the Costs of Medical Care: a new look at an old issue. The model of comprehensive group practice advanced by the CCMC in 1932 has been an elusive reformist vision. Changes in the techniques and techology of medical practive will require new professional agendas as well a new political constituencies. Analysis of the process of these changes must balance avocacy of any uptopian forms of practice.


Effects of hospital cost containment on the development and use of medical technology. The early hope for more effective, safer, and less expensive care through the "medical technological revolution" is critically examined. Inflated costs--and imperfect expectations--have led to broad proposals for hospital cost containment which may constrain development and use of new technology. But concerns for care and cost will be better served by selective shifts in the type of technology employed and incentives for its use.


Delay and noncompliance in cancer detection: a behavioral perspective for health planners. Professionals and public alike believe in the benefits of early cancer detection. Yet screening programs have encountered serious problems in engaging their clients to seek prompt medical follow-up. If benefits of early detection are to be achieved, and fear and mistrust overcome, a more reliable connection between screening and treatment must be forged.


Toward the measurement of primary care.

Toward the measurement of primary care. The renaissance of rhetoric about primary care--"continuous, coordinated, comprehensive, family-centered"--has paralleled the growth of entrants into formal training programs. The extent to which primary care is actually practiced this way has not been examined, nor have the routes to preparing for it. A preliminary set of measurements is suggested.


Blunt abdominal trauma.

Blunt abdominal trauma. Blunt abdominal trauma is a possible sequel of many accidents and can result in death from hemorrhage or sepsis if it is not detected early and managed aggressively. A thorough history of the causative accident, a systematic abdominal examination, selected laboratory studies, and x-ray films are helpful in establishing the diagnosis. Peritoneal lavage is, however, the most reliable assessment tool (besides an exploratory laparotomy) for confirming significant viscus injury and intra-abdominal hemorrhage. Nurses who are assisting in the evaluation of trauma victims should be thoroughly familiar with the mechanics responsible for blunt abdominal injury, the initial steps for stabilizing the victim, and the usual tests and procedures that aid in diagnosis.


Emergency nursing care of the burned patient. The emergency nursing care of patients with major burns presents one of nursing's greatest challenges. Priority is given to lifesaving measures. After a quick overall assessment, a careful estimate of fluid and electrolyte loss is made. An issue in burn care is whether colloids should be given in the immediate postburn period. Large amounts of fluid are always given, and balanced salt solutions are being used increasingly without colloid. The patient's response to fluid therapy can be monitored by central venous pressure readings, vital signs, and hourly measurements of urinary output. Psychologic and physiologic stress intensify the problems and should be kept to a minimum. Only after other aspects of care have been attended is attention directed to care of the burn wound.


Autotransfusion--a technique for the trauma patient. The use of autotransfusion--the retrieval and reinfusion of shed blood--has been demonstrated to be a beneficial therapeutic modality for the trauma patient. The use of autotransfusion is indicated for major blood losses of the patient who experiences blunt or penetrating trauma and has an external or a cavitational bleeding source. Advantages and disadvantages are numerous. It does appear that because of the low incidence of complications and the many advantages, autotransfusion will become a widespread resuscitative technique for use with the trauma patient. The procedure also has clinical application for those other than trauma patients. The nursing implications suggested by this new modality are many, including legal considerations, safety factors, protocol adoption, and new nursing roles. Perhaps the most positive benefit to nursing is the opportunity for clinical nursing staff (ER and OR) to become involved in nursing research that they can apply directly to their clinical setting.


Incidence and characteristics of antibiotic-tolerant strains of Staphylococcus aureus. Thirty clinical isolates of Staphylococcus aureus were tested for tolerance to oxacillin, cephalothin, and gentamicin by using killing curves and broth dilution susceptibility tests. Tolerance was defined as the presence of>/=100 colony-forming units per ml remaining after 24 h of incubation of the killing curve suspensions. Nineteen of 30 isolates were tolerant to oxacillin and cephalothin, but none was tolerant to gentamicin. Among the tolerant isolates, there was a wide spectrum of tolerance, with from 0.2 to 43% of the colony-forming units in the starting inoculum remaining after 18 to 24 h of incubation. Tolerance was unrelated to phage type or to any of several other characteristics studied.


[Microbiological basis of antibiotic therapy (author's transl)]. The multitude of antibiotics is divided into groups according to their chemical origin and therapeutical demands. The knowledge of antimicrobial activity and side effects is essential for an effective antibiotic therapy. Clinical cases are exposed to demonstrate the main rules of antibiotic medication: a) Bacteria with solid or with varying susceptibility ratio; b) susceptibility testing.


Chromosomal map location of the methicillin resistance determinant in Staphylococcus aureus. Three-factor genetic crosses performed by transformation have shown that the methicillin resistance determinant of Staphylococcus aureus strain DU4916 (the mec-4916 marker) is linked to a novobiocin resistance (Novr) marker (nov-142) and mutational sites affecting pyrimidine (pyr-141), purine (pur-102), and histidine (hisG15) biosynthesis in S. aureus strain 8325. The linkage group thus defined is pyr-141-hisG15-nov-142-pur-102-mec-4916. Phage 80alpha previously propagated on a novobiocin-resistant, methicillin-sensitive (Mecs) 8325 strain was used to infect 21 novobiocin-sensitive, methicillin-resistant clinical isolates (including strain DU4916). Among the novobiocin-resistant transductants so obtained from each recipient, between 1 and 5% were methicillin sensitive (reflecting cotransduction of Novr and Mecs). These results are consistent with the genetic determinant of methicillin resistance having a single chromosomal locus in most, if not all, strains of S. aureus.


The function of the histidine tRNA isoaccepting species in hemoglobin synthesis. Rabbit reticulocytes contain two RNA isoaccepting species for histidine as resolved by various chromatographic methods, while rabbit liver contains only one. These isoacceptors cannot be distinguished on the basis of coding properties, consistent with the "Wobble Hypothesis" (Smith, D.W.E., Meltzer, V.N., and McNamara, A.L. (1974) Biochim. Biophys. Acta 349, 366-375). Their function in hemoglobin synthesis in reticulocyte lysates has been investigated. Each of the tRNA isoacceptors of reticulocytes and the tRNA species of liver can incorporate histidine into positions in hemoglobin encoded by both of the histidine code words, CAC and CAU, and it is likely that each can incorporate histidine into all of the histidine-containing positions of hemoglobin. Even in experiments in which the two histidine tRNA species of reticulocytes are placed together in a lysate and are therefore in competition with each other, each incorporates histidine into all of the histidine-containing positions. There is no evidence that any residues are incorporated preferentially by either of the tRNA species. The two species are attached to reticulocyte ribosomes in the same proportion as they occur in the reticulocyte, also suggesting that neither of them is used preferentially in hemoglobin synthesis. The first of the two reticulocyte histidine isoacceptors and the histidine tRNA of rabbit liver contain Q base.


Protein synthesis in rabbit reticulocytes XXI. Purification and properties of a protein factor (Co-EIF-1) which stimulates Met-tRNAf binding to EIF-1. The peptide chain initiation factor, Co-EIF-1 has been purified to homogeneity. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the homogeneous preparation gives a single protein band corresponding to a molecular weight of approximately 20,000. In the crude preparation, Co-EIF-1 exists in two molecular forms: Co-EIF-1H (Mr = 200,000) and Co-EIF-1L (Mr = 20,000). Both forms are equally active in all the reactions studied. Upon heating, the heavy form (Co-EIF-1H) is completely converted into the light form (Co-EIF-1L). Radioactively labeled [14C]Co-EIF-1 was prepared by reductive alkylation using [14C]formaldehyde and borohydride. [14C]Methyl-Co-EIF-1 binds specifically to EIF-1; EIF-1.[14C]Co-EIF-1 complex was analyzed by gel (Sephadex G-100) filtration. EIF-1.Co-EIF-1 complex is distinctly more stable towards heat than EIF-1 alone and the quarternary complex, Met-tRNAf.EIF-1.Co-EIF-1.GTP is more resistant to aurintricarboxylic acid than the ternary complex, Met-tRNAf.EIF-1.GTP. Both the quarternary complex, Met-tRNAf.EIF-1.Co-EIF-1.GTP, and the ternary complex, Met-tRNAf.EIF-1.GTP, are equally sensitive to Mg2+ in the presence of EIF-2 (TDF). In the presence of Co-EIF-1, the initial rate of Met-tRNAf binding to 40 S ribosomes was significantly increased.


mRNA-induced dissociation of initiation factor 2. The GTP-dependent initiator methionyl-tRNA (Met-tRNAi) binding protein, eukaryotic initiation factor 2 (eIF2), binds mRNA, as well as Met-tRNAi with high affinity and both RNA species appear to bind to the 48,000-dalton subunit of eIF2. Binding of mRNA by eIF2 produces an alteration in its molecular  configuration resulting in dissociation of component subunits as assayed by isoelectric focusing. In contrast, GTP, GDP, or Met-tRNAi produce no subunit dissociation. Phosphorylation of the 37,000-dalton eIF2 subunit by the heme-controlled translational repressor does not alter the ability of mRNA to produce subunit dissociation of eIF2. A role for mRNA binding by eIF2 in initiation of protein synthesis or in recycling of eIF2, or both, is postulated.