Detection of circulating immune complexes in patients with glomerulonephritis. A panel of three immune complex (IC) assays was used in this study to test sera from patients with glomerulonephritis (GN): the Raji cell radioimmune assay (IRCA), the radio-labeled C1q binding assay (IC1qBA), and the microcomplement consumption test (MCT). The sensitivity and specificity of each assay was evaluated in preliminary studies, and the greater sensitivity (5 to 10microgram of aggreagated human gamma-globulin (AHG) per ml of serum) and IgG specificity of the IRCA was apparent. Problems related to the preliminary heat inactivation of test sera, the interaction of C1q with substances other than IC, and the effects of suboptimal storage of test sera were experienced with the MCT and, to a lesser extent the IC1qBA. The individual reactivities of the different assays were exploited by using them in combination. Thus ICs were detected by one or more of the assays in 87% of patients with systemic lupus erythematosus (SLE), 65% of patients with GN associated with other systemic diseases, and 39% of patients with primary GN. ICs were detected more frequently in patients with acute GN than chronic GN, and in patients with low serum C3, C4, and properdin factor B (C3PA) levels.


[Perforating keratoplasty: preconditions, indications, complications, follow-up treatment (author's transl)]. The results of a penetrating keratoplasty depends not only on certain morphological-biochemical and immunological factors, but also on an adequate surgical technique. The indications for perforating corneal grafting have constantly extended during the past 20 years and are classified according to the chances of success and to the emergency of grafting; some unusual indications are mentioned. Complications are rarely observed, but may occur during or after the surgery. Postoperative care is discussed.


[Allograft rejection reactions after keratoplasty (author's transl)]. Immune reactions against corneal transplants cause most of the graft failures during the first 24 months after keratoplasty. This is partly due to inadequate diagnosis and therapy. After a short discussion of the experimental and clinical background, different kinds of characteristic immune reactions are demonstrated by case descriptions and photos. The importance of immune reactions is substantiated by an evaluation of 88 recently performed keratoplasties. Finally, detailed suggestions are made for prophylaxis and therapy of postkeratoplasty immune reactions.


[Perforating keratoplasty in the presence of considerable changes of the anterior segment of the eye (author's transl)]. A report is given on 44 patients with penetrating keratoplasty in severe damage of the anterior eye. The first group consisted of 31 patients with acute, deep inflammatory processes of the cornea, threatened by perforation or with perforation and severe iritis. The second group of 13 patients had had perforating injury with corneal scar, broad anterior synechiae and lens remnants. In group 1 55% had visual function between 0.3 and 1.0; 35.5% showed no improvement, 10% got worse. In group 2 only 5 patients had visual improvement from 0.3-1.0. In 3 patients there was a negative outcome. The indication for corneal graft in these groups and the right moment of operation are discussed. We tried to compare our own results with other statistics.


[Clinical observations on the continuing presence of gilded molybdenum-wire in eye tissues (author's transl)]. Gilded molybdenum-wire remains in the sclera and episclera without any reaction of the tissue. Adjacent eye muscles are not involved. In two cases the loops penetrated slowly the sclera and choroid but not the retina.


[The toxicity of bilirubin (author's transl)]. This report is a short review about the cytopathogenic effect of bilirubin on the different cells of the human organism. Own investigations deal with the excretion of enzymes in urine in relation to the bilirubin in serum. The second part concerns bilirubin and teeth. Unconjugated bilirubin is only toxic, when it is not coppled to albumin. Therapeutic efforts must consider this aspect.


[Connatal malaria (author's transl)].

[Connatal malaria (author's transl)]. A case of connatal malaria due to Plasmodium vivax in a newborn of turkish origin is presented. Most likely the infection was acquired by materno - fetal transfusion during labor. Pathophysiological aspects and mode of transmission of this rare disease are discussed.


[Idiopathic periostal hyperostosis with dysproteinemia (author's transl)]. The idiopathic periostal hyperostosis with dysproteinemia shows typical symptoms: acute onset with high fever and severe pain in the forearms and the praetibial area, periostal reaction along the ulnae and tibiae accompanied by hypalbuminemia and alpha2-globulin increase. The clinical entity has yet been described in only 2 cases. Our own case illustrates the longterm follow-up. The differential diagnosis especially of Caffey-Syndrom is discussed.


[On the problem of praetherapeutic sensitivity testing of human tumours based on incorporation studies of nucleic acid precursors in vitro (author's transl)]. Praetherapeutic sensitivity tests of human solid tumours based on incorporation studies of nucleic acid precursors have been described by various authors. This review intends to show that such tests may only be of rather limited value for the design of individual chemotherapeutic regimens. In many drugs, a correlation between biochemical and clinical effects has not yet been established. The reliability of praetherapeutic sensitivity tests is further impaired by general methodological difficulties of short-term cultures, individual pharmacology and toxicology of cytostatic agents as well as pharmacological and biochemical drug interactions in combination chemotherapy. Praetherapeutic testing with individual cytostatic drugs is discussed.


Pathologic localization of Tamm-Horsfall protein in interstitial deposits in renal disease. Interstitial periodic acid-Schiff positive deposits of amorphous or fibrillar material were observed in 32% of kidneys with a variety of tubulointerstitial diseases, including medullary cystic disease (60%), chronic pyelonephritis (20%), and hydronephrosis (33%). Immunofluorescent staining for Tamm-Horsfall protein showed interstitial localization of this protein which was identical in distribution, shape, size, and fine detail with the periodic acid-Schiff positive deposits. The deposits appeared to originate from disrupted tubules and were sometimes surrounded by inflammatory infiltrate. The intrarenal localization of Tamm-Horsfall protein outside of distal tubules in pathologic states indicates that this protein may have a role in the pathogenesis of renal disease.


Ultrastructural studies of canine interalveolar pores (of Kohn). Normal canine lungs were prepared for ultrastructural studies using two different routes for fixation: the airways route and the vascular route. Using the airways route, under conditions of controlled pressure, scanning and transmission electron microscopic studies of alveolar surfaces allowed identification of an average of 19 alveolar pores per exposed alveolar surface, each pore averaging approximately 3 micron. in diameter. The alveolar surface was honeycombed in appearance, with the walls of multiple capillaries bulging into the alveolar space. Using the other route, vascular perfusion of the lungs with the fixative and controlling pressures in both the vascular and airway compartments, scanning electron microscopic studies showed that most exposed alveoli exhibited a smooth or slightly wrinkled surface, essentially devoid of pores and averaging only three pores per alveolus. By transmission electron microscopy, alveolar surfaces were found to be covered with an extracellular material suggestive of lung surfactant; alveolar pores, averaging approximately 1 micron. in diameter, were filled with the same material. It is concluded that most alveolar pores of normal dogs are bridged by and filled with lung surfactant. These findings can be demonstrated most reliably by using vascular perfusion of the lungs for introducing the fixative.


[Ways to study the work capacity of pilots in flight]. On the basis of a careful study of the Soviet and foreign literature, informativeness of physiological, biochemical, psychometric, biomechanical methods used to measure pilot performance inflight is evaluated. It is suggested that such performance can be assessed via a systemic approach and with the aid of the following parameters: functional state as indicated by physiological and biochemical recordings; subjective evaluations of the state using the psychometric scale; quality of the flight task performed; precision of piloting; and structure of controlling movements. This complex of parameters can be used only after landing. Inflight evaluation of pilot performance still remains an unresolved problem. The greatest promise holds search for objective criteria of automatic evaluation of the quality of pilot performance, structure of controlling movements, and physiological parameters on an integral time scale.


Prediction for secondary structures of ten proteins from the 50S subunit of the Escherichia coli ribosome. Predictions of the secondary structures of the following 10 proteins from the large subunit of the E. coli ribosome were made using their known amino acid sequences: L6, L16, L19, L27, L28, L30, L31, L32, L33, and L34. The predictions were made according to 4 different methods and the results for each protein are presented as diagrams indicating the conformational states, helix, extended structure, turn, and random coil, of each residue. From these diagrams, regions of highly probable secondary structure for the proteins are calculated. Estimates are made of the maximum possible lengths of the proteins in order to correlate these with the results obtained from antibody binding sites in the 50S subunit as determined by electron microscopy.


Rationale for the use of cimetidine in pancreatic insufficiency. The failure of standard oral pancreatic enzyme replacement therapy to correct malabsorption in patients with advanced pancreatic insufficiency is likely due to acid-peptic inactivation of ingested enzymes. Theoretically, the use of cimetidine, an H2-receptor antagonist, in conjunction with oral enzymes, would permit greater transgastric passage of ingested enzymes with resulting improvement in intraluminal lipolysis. To test this hypothesis, we studied the effects of orally administered cimetidine in two groups of patients by utilizing a previously validated double-marker perfusion technique. Cimetidine, in varying doses, had no effect on postprandial exocrine pancreatic function in 16 duodenal ulcer patients without pancreatic disease. In six patients with pancreatic insufficiency, cimetidine produced a pronounced decrease in the output of gastric acid and secretory volume, resulting in reduction of postprandial acidity and intragastric volume. These actions of cimetidine should retard or prevent inactivation of ingested enzymes and also increase their intragastric concentration, with resulting enhancement of luminal duodenal enzyme activity. Supplemental cimetidine may thus be useful in the medical management of patients who fail to respond to routine pancreatic extract therapy alone.


Immunofluorescent study of histone H5 in chick erythroid cells from developing embryos and adults. Indirect immunofluorescence has been used to detect the presence of histone H5 in single cells during avian erythropoiesis. Evidence is presented which demonstrates that this method specifically detects histone H5. The results show that the increase in the amount of H5 which can be extracted from nuclei during erythropoiesis is accounted for both by an increase in the amount of H5 per cell and by an increase in the total number of cells containing histone H5. Of particular interest are the observations that histone H5 is arranged within the nucleus in several distinct, reproducible patterns and that different patterns predominate at different stages of erythroid cell development. In addition to suggesting new possibilities for the role of histone H5, these findings indicate that immunofluorescence may be used profitably to explore the supramolecular organization of chromatin.


Erythropoiesis in the duck embryo: accumulation of H5 histone during red blood cell maturation. We have studied the variation in histone composition of the red blood cell during embryonic development of the duck. The problem has been approached by fractionating the cells according to maturity and type in bovine serum albumin density gradients and analyzing electrophoretically histones which have been extracted from purified cell populations. Additional data have been obtained by pulse-labeling experiments and by immunofluorescence techniques. The results indicate that histone H5 may be absent from very immature primitive embryonic red blood cells and that it accumulates in the nucleus during maturation of the cell. A similar relative increase in H5 content is observed during maturation of the definitive erythroid series. Mature adult erythrocytes and mature erythrocytes of the definitive series contain comparable amounts of histone H5 which is present in lower amounts in the mature cells of the primitive cell line.


Consumer decision making and health maintenance organizations: a review. This article reviews studies relevant to the understanding of the consumer's decision-making processes with respect to health maintenance organization (HMOs). Research in this area is critical to the development of sound marketing programs for HMOs. A simple model is formulated and used to organize the review into four sections, each reflecting a different research approach. Critical comments on the state of current knowledge are made and suggested directions for further research are outlined.


Hospital admission before and after Medicare in Quebec. A 1 in 60 random sample of Quebec hospital admission records ("separations") for the years 1966 through 1974 was studied for evidence of change associated with the introduction in 1970 of universal health insurance. Non-surgical separation rates continued to decline in Montreal and remained steady in the rest of the province. In contrast, separations following surgical operation did not decline in Montreal and have increased substantially since 1970 in the rest of the province. Ten operative procedures accounting for 41 per cent of all surgical admissions were selected for separate study: of these, cholecystectomy, hysterectomy and hernia repairs conformed most closely to the new pattern. Directly or indirectly, Medicare may have contributed to these changes but more study is required to confirm or explain this.


Laboratory aids in the diagnosis of pancreatitis. The diagnosis of both acute and chronic pancreatitis continues to be a challenge despite the development of new techniques and the refinement of old methods. The problem is best approached by the application of a combination of tests which can provide a reasonable degree of sensitivity and specificity applicable to the different forms of pancreatitis. In acute pancreatitis an elevation of serum amylase and amylase/creatinine clearance ratio is diagnostically useful. In chronic pancreatitis, several tests are needed to enhance the diagnostic yield, and such tests can include the secretin-pancreozymin test, ERCP, fecal fat measurement, Lundh test meal, and the administration of the synthetic peptide BZ-Ty-PABA.


Chronic diarrhea. A practical approach.

Chronic diarrhea. A practical approach. Many patients who present with chronic diarrhea are not found to have an important organic disease. Most will have "functional" diarrhea. The history, the physical examination and the initial laboratory tests should lead to a provisional diagnosis, with respect to the organic or functional origin, and the location of disease in the small or the large bowel. Specific tests are then done to define particular organic causes of which malabsorption, inflammatory bowel diseases, carcinoma of the large bowel, parasitic infections, and metabolic disorders are most common. Patients with suspected functional diarrhea should be investigated at least by stool analysis, proctosigmoidoscopy, and barium enema. Functional diarrhea is common and these patients are no less susceptible to severe disease than is the rest of the population.


The management of facial paralysis due to extracranial injuries. Improvements in surgical capabilities in the management of malignancies about the ear and parotid gland, increasing vehicular and interpersonal trauma, and greater concern with cosmetic factors by the public at large, have led to increasing need for the surgeon's ability to manage injuries to the facial nerve. Several important anatomic, physiologic and technical factors bear upon a logical approach to repair of such facial nerve injuries. Careful attention to these concepts had led to satisfactory return of facial function in most cases managed by the author.


Fallibility of the intravenous glucose tolerance test as a measure of endogenous glucose turnover. We have used hepatectomized, nephrectomized dogs receiving a constant infusion of unlabeled glucose as well as conscious, unrestrained guinea pigs in order to investigate the calculation of basal glucose kinetics from intravenous glucose tolerance tests (IVGTT). In the dogs, we were not able to determine the known rate of appearance (Ra) or disappearance (Rd) of glucose within 50% of the actual value by means of IVGTT. In the guinea pigs, we found that Ra calculated from IVGTT was 250% higher than Ra determined by means of the validated technique of the primed-constant infusion of 6-3H-glucose in tracer quantities. When live Escherichia coli were infused into the guinea pigs, the isotope-tracer technique revealed a 100% increase in Ra yet Ra appeared to be decreased by 80% when calculated by means of IVGTT. We concluded that basal glucose kinetics cannot be determined reliably from IVGTT, and that in certain pathologic conditions the direction of change in Ra and Rd from the basal state may be incorrectly predicted.


Diabetic regulation and its relationship to microangiopathy. This review addresses the question of the effectiveness of rigid regulation of the blood glucose in delaying or preventing the vascular complications of diabetes mellitus. Morphometric, pathologic, biochemical, and clinical evidence on both sides of this question are presented. It is concluded that because of present inadequate methods of completely returning glucose homeostasis to normal in diabetics, the question remains moot.


[Isolation of Salmonellae from streams in and about Ankara (author's transl)]. S.typhimurium, S.paratyphi B, S.typhi were isolated from 132 samples, collected from sewage of eight different regions, by using selenit F, Wilson Blair and Mac Conkey media. Isolations were done in September, October, November and December. The isolations were 53% positive in these months. It was seen that S.typhimurium was dominant in Ankara and Widal reaction has to be concidered.


Group B streptococcal infection in neonates. A study of 866 vaginal swabs from non-pregnant women showed that 167 (19.3%) contained Group B beta-haemolytic streptococci, with a predominance of Types 3 (31.4%) and Ib (25.2%). The incidence of severe neonatal infections due to Group B streptococci during a 3 1/2 year period at The Prince of Wales Hospital was examined, and a study was made of the distribution of serotypes and associated clinical features (including prematurity and abnormal deliveries) in 16 neonates with septicaemia and/or meningitis admitted to the Royal Alexandra Hospital for Children, and the Paediatric Department of The Prince of Wales Hospital. From this study it was concluded that prophylactic antibiotic therapy should be administered to neonates with evidence of Group B streptococcal colonization of the throat, umbilicus, or gut, when there is also evidence of prematurity, prolonged interval between membrane rupture and delivery, or other associated obstetric complications.


Neonatal osteomyelitis and meningitis caused by group B streptococci. A case of neonatal osteomyelitis and meningitis caused by group B streptococci is reported; the organism isolated was found to be similar or the same as an organism cultured form the maternal vagina. The clinical course and management is also described.


[The effect of glucose on induced synthesis of exocellular protease of Serratia marcescens]. The sensitivity of induced synthesis of exocellular protease to catabolyte repression was studied in Serratia marcescens growing on media containing inductors, viz. leucine and albumin. A lower sensitivity of the leucine-induced synthesis of the enzyme to glucose as compared to that induced by albumin seems to be caused by the penetration of leucine into the cell prior to the appearance in the medium of organic acids, possible inhibitors of its transport, whereas on the medium containing albumin, leucine appears only after hydrolysis of the protein by the "basal" enzyme.


[Yeast peroxisomes, their development and operation]. Yeast peroxisomes (microbodies) were studied, particularly with yeast methylotrophs, using light-optical microscopy, viz. intravitam phase- and anoptral-contrast microscopy, with cytochemical as well as fixed and stained objects. The data obtained were compared with cytochemical as well as fixed and stained objects. The data obtained were compared with other evidence that we had gained on methylotrophs studied by electron microscopy and with the results obtained by investigating the peroxisomes of yeast cultures grown on nutrient containing other carbon sources. The activity of exocatalase and endocatalase, the enzymes characteristic of peroxisomes, was assayed at different growth phases of yeast methylotrophs and was found to be correlated with the cycle of development of peroxisomes. The content of biotin and inositol and its dynamics were studied in the methylotroph cells. Possible origin of peroxisomes is discussed as well as their development and the mechanism of degradation. A close contact and functional relationship have been established between peroxisomes and mitochondria.


Aspiration cytology in the diagnosis of autoimmune thyroiditis. We have found aspiration cytology to be a useful and reliable procedure in the diagnosis of autoimmune thyroiditis. This disorder affected more than half of 50 patients who presented with bilateral non-toxic goitre.


What's new in electrosurgical instrumentation? A 1976 report of the use of radiofrequency current to devitalize carcinomas in man stimulated this review of the historical background, the presently used techniques, and the problems associated with electrosurgery. Difficulties in electrosurgical techniques requiring further research are identified--i.e., the high heating and variable performance of dry dispersive electrodes, the hazards of tissue stimulation, high-frequency interference, and the potential impact of government regulation.


Infection in the intensive care unit.

Infection in the intensive care unit. An epidemic of infection associated with Serratia marcescens and other Gram-negative organisms resistant to aminoglycosides and other chemotherapeutic agents occurred in the intensive care unit of St Vincent's Hospital, Melbourne, and spread to other areas of the hospital. This paper describes the problems of sepsis in the critically ill patient, outlines the occurrence of organisms in the patients concerned in this epidemic, and discusses the policies adopted to control the incidence of life-threatening infection caused by bacteria resistant to all other agents.


[The effect of piracetam on global and regional cerebral blood flow in acute cerebral ischemia of man (author's transl)]. Regional cerebral blood flow (rCBF) was investigated in 18 patients with acute cerebral ischemia by the intraarterial 133Xenon clearance method using a 10-detector-equipment. Intravenous administration of 6-10 g Piracetam caused an overall increase of the fast component of rCBF after 30 minutes corresponding to blood flow in the grey matter, of 10.0 ml/100 g/min (18.9%). The slow component of rCBF corresponding to the cerebral blood flow in the white matter remained unchanged. The regional CBF was influenced to a varying degree, the areas marked by an insufficient blood supply showing a mean increase by 17.5% and the areas marked by normal basic values showing a mean increase by 6.3%. This difference in alteration is statistically significant (p is less than 0.005) comparing the differences as %. The increase of cerebral blood flow in grey matter is interpreted as a secondary effect after activation of central nervous system metabolism by Piracetam.


The historical development of modern virus research in Germany, especially in the Kaiser-Wilhelm-/Max-Planck-Society, 1936--1954. This is lecture on the historical development of modern virus research in Germany to introduce a symposium dedicated to Prof. Werner Schäfer, Tübingen, on the occasion of his 65th birthday. The author was set the task of relating from his memories the beginning of modern virus research in Germany. This research has, since 1936, essentially taken place in the Kaiser-Wilhelm/Max-Planck-Society and in 1954 led to the founding of the Max-Planck-Institute for Virus Research in Tübingen, an institute which to the present day owes its scientific reputation in considerable part to the activity of Werner Schäfer. Since the author personally experienced and participated in the Institute's development from 1936-1954, his remarks are predominantly influenced by personal recollections, which have been sharpended by a renewed study of old records in the 'Library and Archive of the History of the Max-Planck-Gesellschaft', Berlin-Dahlem.


Coronary arteriography: current technique and standards of equipment. Coronary arteriography has become one of the most important diagnostic procedures. It is considered indispensable prerequisite in all cases of coronary, valvular, and primary myocardial disease for definition of diagnosis as well as planning of cardiac surgical interventions. Indications seem well established today. Complications have been reviewed in detail and are well known for the different procedures being practiced today. Each examiner should have command of the Sones as well as the Judkins technique. High standards of experience and skill are demanded. Equally important is high performance technical equipment. Current status of generators, power supply, X-ray tubes, image-intensifiers and camera technique is reviewed. Cine-angiocardiography on 35 mm film with simultaneous video-tape recording can be considered standard today. Layout of the equipment should include either cradle-mount for patient rotation or better U-stands for rotation of tube-image intensifier system around the resting patient. Oblique and angulated views in multiple directions are mandatory. Bi-plane equipment seems desirable both for ventriculography as well as coronary arteriography. Future developments can be expected mainly in the field of television technology with improved camera tubes, high resolution systems, and possibly digital processing of video signals.


A multiple-electrode hearing prosthesis for cochlea implantation in deaf patients. A multiple-electrode hearing prosthesis for cochlea implantation in deaf patients has been developed at the University of Melbourne. It has been designed as a multiple-electrode implant to provide the best chance of enabling patients to understand speech. It has been shown that an electrode array can be threaded along the coills of the inner ear close to residual auditory nerves. Experimental studies have indicated that the long-term implantation of the array will not lead to significant degeneration of auditory nerve fibres. Loss of platinum from the stimulating electrodes can be minimized with a biphasic constant current pulse, where the first phase is negative with respect to ground. The receiver-stimulator component has also been designed to provide 10-15 channels of stimulation. Furthermore, the phase and amplitude of the stimuli to individual electrodes can be varied to enable the localization of the electrical fields to discrete groups of nerve fibres, and the correct method of frequency and intensity coding to be determined. Finally, the device should be used in the first instance for a specially selected group of adults who are post-lingually deaf.


An improved technique for the rapid continuous measurement of whole blood glucose, suitable for clinical application in an artificial endocrine pancreas. An improved bedside technique for the continuous monitoring of glycemia is described. A linear relationship results between whole blood glucose concentration and plasma glucose levels, and allows the calibration of the system in terms of plasma glucose levels. In operation venous blood is withdrawn at a steady rate using a double-lumen catheter and directed to a continuous-flow laboratory analyzer, where glucose analysis is carried out using a modified glucose oxidase-peroxidase methodology. The improvements in this technique include: i) a reduction in the delay of the analyzer to 90 s, making it suitable for application in a system for blood glucose regulation, ii) a minimal blood requirement of 3 ml/h, permitting long-term monitoring, iii) elimination of the need for systemic anticoagulation, iv) an excellent correlation (r = 0.993) between the measured whole blood glucose and the actual plasma glucose concentration, v) an average baseline drift of +0.5 mg%/h, vi) a sensitivity loss of less than 0.1%/h, and vii) a reasonable operating cost. This technique was implemented as part of a clinical apparatus known as an artificial endocrine pancreas which has been reliably applied in clinical and animal studies.


Defective excision and postreplication repair of UV-damaged DNA in a recL mutant strain of E. coli K-12. The mutation recL152 leads to a reduction of excision repair as measured by an increase in the time required to close uvrA uvrB dependent incision breaks, and by a reduction of host cell reactivation ability. Postreplication repair is also delayed when measured in a uvrB5 recL152 double mutant. Such a determination could not be made using the recL152 single mutant because the excision defect led to an accumulation of breaks in the unlabeled high molecular weight DNA to which the labeled DNA synthesized after irradiation must attach in order to achieve normal high molecular weight. Further, the recL gene product seems to be required to rejoin breaks in parental strand DNA which are generated during postreplication repair, since such gaps accumulate in a recL152 uvrB5 double mutant but not in a recL+ uvrB5 single mutant. We have noticed a striking phenotypic similarity between recL152 and polA1 and suggest that recL152 is required for full in vivo activity of DNA polymerase I.


The dependence of postreplication repair on uvrB in a recF mutant of Escherichia coli K-12. Mutants carrying recF143 or recF144 show wild type levels of host cell reactivation of UV-irradiated lambdavir and wild type rates of excision gap closure in repairing UV damage to their own DNA. The same mutants showed reduced rates of postreplication repair strand joining. When uvrA- recF- or uvrB- recF- strains are tested, postreplication repair strand joining is incomplete or does not occur at fluences above 1 J/m2. We suggest that there may be a UvrAB and a RecF pathway of postreplication repair or that the repair functions controlled or determined by uvrA uvrB and by recF may be similar. An intermediate in postreplication repair may accumulate in the uvr- recF- strain.


Repressor and int synthesis of bacteriophage lambda in the E. coli host mutant ER437. Analysis of lambda phage infection of the host mutant ER437 by SDS polyacrylamide gel electrophoresis and autoradiography has revealed altered expression of repressor and integration function (Int). We show that in this host Int as well as repressor synthesis is not dependent upon the lambdacIII gene product in the usual manner, nor is their synthesis turned off in the normal way.


Growth inhibition of Escherichia coli K-12 by L-valine: a consequence of a regulatory pattern. We studied the production of the ilvG gene product, the valine resistant acetolactate synthase isoenzyme II, in an ilvO+ G+ ilvB ilvHI derivative of Escherichia coli K-12. This strain contains mutations in the structural genes for the valine sensitive acetolactate synthase isoenzymes I and III. We find that the ilvG gene is not expressed in this strain when gworn with either isoleucine and valine or with isoleucine, leucine and valine, or when limited for either isoleucine or valine. Since we previously found that the ilvG gene is expressed in an ilvO603 containing strain (Favre et al., 1976), we presume that the mechanism by which E. coli K-12 regulates the ilv gene cluster is responsible for the lack of ilvG expression in the ilvO+ strain. The valine sensitivity of E. Coli K-12 is a consequence of this regulatory pattern.


Replication of the ampicillin resistance plasmid RSF1030 in extracts of Escherichia coli: separation of the replication cycle into early and late stages. The replication cycle of the small resistance plasmid RSF1030 can be divided into two stages with different enzyme requirements: (1) Synthesis of early replicative intermediates containing 7 S DNA catalyzed by DNA polymerase I in the absence of functional dnaZ protein, and (2) replication of early intermediates requiring DNA polymerase III holenzyme (including the dnaZ protein). Early intermediate DNA synthesized in a dnaZ extract can be converted to fully replicated plasmid molecules upon addition to a replication enzyme fraction prepared by ammonium sulfate fractionation of polA I extracts. The first-stage reaction is sensitive to rifampicin, novobiocin, and oxolinic acid, but insensitive to arabinosylcytosine triphosphate (aCTP). Addition of aCTP interferes with the second-stage reaction resulting in the accumulation of late replicative intermediates.


Induction of lambda prophage and of mutations to streptomycin resistance in separate small fractions of a lysogenic derivative of Escherichia coli B/r by very low doses of ultraviolet light. The number of induced mutations to streptomycin resistance is compared at doses of ultraviolet (UV) light between 0.2 and 6.4 J/m2 in a Uvr- (excision-deficient) derivative of E. coli B/r, strain WU, and in its lambda lysogen, strain WU(lambda). At UV doses up to about 1 J/m2, which converts about 5% of the lysogenic population into enfective centers, no difference is observed in the number of mutations to streptomycin resistance produced by the two strains. It is concluded that the capacity to produce UV-induced mutations is not coupled with lysis due to the induction of lambda prophage at low doses of UV radiation. At UV doses above 1 J/m2, the number of mutatants detected in the lysogenic strain decreases appreciably compared to the number detected in the nonlysogen, and is only about 10% as high at UV doses of 3 J/m2 and higher, doses which cause maximal induction of prophage. The results are compatible with the operation of a common "all-or-none" induction signal resulting in expression of UV-inducible functions at high UV doses, but not at low doses.


Regulation of yeast mitochondrial DNA synthesis. I. Analysis of a mutant conditionally deficient in mitochondrial DNA metabolism. A single nuclear gene mutation has been isolated from strain 123.1C of Saccharomyces cerevisiae which is conditionally deficient in mitochondrial DNA metabolism. Growth of the haploid in media containing dextrose, a repressing carbon source, at 36 degrees C causes the rapid cessation of mitochondrial DNA synthesis as analyzed by radioactive 3H-adenine incorporation into mitochondrial DNA. These cells continue to grow and divide giving rise to neutral petites which are devoid of mitochondrial DNA as measured by radioactive incorporation of 3H-adenine at the permissive temperature. Growth of the haploid cells in media containing glycerol, a non-repressing carbon source, at 36 degrees C does not prevent mitochondrial DNA synthesis, however, the population of cells becomes partially petite. When such petites are analyzed, they are found to be suppressive and to contain mitochondrial DNA as measured in the manner described above. The action of this mutated gene appears to involve the sunthetic aspects of mitochondrial DNA metabolism, as haploid cells prelabeled in dextrose media with 3H-adenine show no loss or degradation of mitochondrial DNA at the restrictive temperature of 36 degrees C.


Genetic studies with a phosphoglucose isomerase mutant of Saccharomyces cerevisiae. A mutation pgi1 in the yeast Saccharomyces cerevisiae conferring deficiency of the glycolytic enzyme glucose 6-phosphate isomerase is characterised genetically. The mutation segregates 2+:2- in tetrads from diploids heterozygous for the mutant phenotype. The mutation is semi-dominant and is located on the right arm of chromosome II in the order: tsm134--lys2--pgi1--tyr1 approximately 15 map units from tyr1. The mutation pgi1 defines the structural gene of glucose 6-phosphate isomerase and can be suqpressed intragenically giving revertants that have an unstable enzyme. In one temperature-sensitive revertant no enzyme activity in excess of the mutant level could be detected although fructose 6-phosphate was converted to glucose 6-phosphate in vivo. The suppressor locus in this revertant is dominant and is unlinked to the pgi1 locus.


Mapping of the two mitochondrial antimycin A resistance loci in Saccharomyces cerevisiae. Retention or loss of the two new mitochondrial antimycin A resistance loci AI and AII has been analyzed in a large number of stable cytoplasmic petite mutants. Using these deletion mutants it was possible to localize the two antimycin A resistance loci in the OI--OII region of mitochondrial DNA. The genetic loci are mapped in the following order: OII--AI--AII--cobl--OI. The mapping relationship of mutants resistant to antimycin A or funiculosin to various cob mutants is described.


Effects of chloramphenicol and caffeine on postreplication repair in uvr A- umuC- und uvrA- recF- strains of Escherichia coli K-12. Postreplication repair and its inhibition by chloramphenicol and caffeine, as seen in alkaline sucrose gradients, were compared between a uv non-mutable strain uvrA- umuC- and normally mutable strains uvrA- recF- and uvrA- umu+rec+ of Escherichia coli K-12. The uvrA- umuC- strain performed postreplication repair as efficiently as the parental strain, while the repair in uvrA- recF- strain was dependent on UV dose. Both chloramphenicol and caffeine inhibited postreplication repair to an equal extent of about 25%, and 10%, respectively, in all three uvrA- strains of umuC36, recF- and umu+rec+. These observations suggest that postreplication repair is largely not responsible for UV mutagenesis.


Isolation and characterization of mutants of Escherichia coli deficient in induction of mutations by ultraviolet light. Mutants of E. coli defective in susceptibility to UV-induction of mutations were isolated by direct screening for their UV nonmutable phenotype (Umu-). Screening of about 30,000 mutagenized clones of a uvr-B derivative of AB1157 yielded six Umu- strains. The mutants can be classified into three groups by the location of the mutations, umuA, umuB and umuC. Mutations umuA and umuB are, respectively, mapped close to lexA and recA genes and mutations at both loci partially reduce UV mutagenesis. The locus of umuC is between hemA and purB and the mutations at this new locus result in a moderate increase of UV sensitivity. The mutation diminishes UV mutagenesis and UV reactivation of phage lambda without affecting the inducibility of phophage lambda nor the inhibition of cell division following UV irradiation. Related properties of an isogenic strain of a recF- mutant are compared with those of umuC-.


Analysis of heme biosynthesis in catalase and cytochrome deficient yeast mutants. Mutants of Saccharomyces cerevisiae, described as catalase and cytochromes deficient (Pachecka et al., 1974), have been analyzed for heme biosynthesis ability. Some enzymatic activities involved in protoheme synthesis were measured in acellular extracts, whereas whole cells were analyzed for cytochrome spectra and for possible accumulation of porphyrin synthesis intermediates. A good correlation was found between these in vitro and in vivo studies. Results show that two mutants were impaired in 5-aminolevulinate synthesis, two mutants were devoid of uroporphyrinogen I synthetase activity and one mutant presented defects in coproporphyrinogen III oxidase activity.


Purification and some properties of presumptive tof gene product of Coli phage 434. The presumptive tof gene product of Coli phage 434 has been purified from cells carrying lambdaimm434cIdv plasmid known to contain only some of the "early" genes of phage 434 and lambda. It was detected and tentatively identified as tof protein primarily by its ability to specifically bind to phage 434 DNA. The protein has a molecular weight of about 11,000 and requires Mg2+ for specific DNA binding, unlike 434 cI-repressor.


Suppression of a defective alanyl-tRNA synthetase in Escherichia coli: a compensatory mutation to high alanine affinity. Among temperature resistant revertants of a temperature sensitive E. Coli alanyl-tRNA synthetase mutant a strain was found which contains an alanyl-tRNA synthetase with an additional mutation in the structural gene of the enzyme. This mutant enzyme has a 9 or 38 fold decreased Km value for alanine compared to that of the thermolabile parental enzyme or to wild-type enzyme, respectively. The alaS gene maps just counterclockwise from recA on the E. coli map (94% cotransduction frequency). It appears that the enzyme's increased affinity for alanine is the mechanism of suppressing the temperature sensitive character of the cell. In addition, some cold-sensitive temperature resistant revertants were found, where the cold-sensitive character mapped near strA. Presumably they are due to changes in ribosomal proteins as characterized by Ruffler et al. (1974).


Unusual stability and translation kinetics of an Escherichia coli lac messenger RNA synthetized during amino-acids deprivation. Escherichia coli, cultured on minimal medium and deprived of its required amino-acids, was induced for lac genes transcription. After inducer removal and restoration of growth, beta-galactosidase synthesis was measured. Two different kinetics of enzyme synthesis were observed depending on the starvation conditions employed during the induction period: 1. beta-galactosidase synthesis was immediately obtained and a plateau was reached, in 20 min after restoration of growth, when cells had been induced during deprivation of amino-acids and carbon source. 2. beta-galactosidase displayed an unusually long rate of synthesis, and plateau was not reached before two doubling times, when cells had been induced during the deprivation of the sole amino-acids. The latter result points out a problem of messenger stability during those long translation kinetics and led us to study the behaviour of strains carrying lac genetic determinants on different replicative structures; chromosomic and plasmidic. In those two situations, induction of lac messenger RNA was obtained and ratify our previous observations. However, their translation kinetics suggest a DNA linkage of this induced messenger.


A procedure for isolation of spontaneous mutants with temperature sensitive of RNA and/or protein. A procedure for the isolation of spontaneous temperature sensitive mutants of Escherichia coli has been developed. They are selected as survivors at high temperature against the combined killing effects exerted by a temperature inducible lambda prophage and either streptomycin plus ampillicin or ampicillin plus cycloserine. The mutants so obtained are blocked in vivo in the synthesis of RNA or protein or both at restrictive temperature.


Properties of ribosomes from erythromycin resistant mutants of Escherichia coli. We have studied the in vitro properties of ribosomes from several mutants resistant to erythromycin. Mutations in three different genes may confer resistance to erythromycin. Two of them are structural genes for proteins L4 and L22 of the large subunit. The third mutation (in eryC gene) seems to affect mainly the small subunit. The mechanism of action of the antibiotic may involve both subunits.


Extranuclear recombination in Aspergillus nidulans: closely-linked multiple chloramphenicol- and oligomycin-resistance loci. A nuclear, chloramphenicol-sensitive mutant cas-1 has been isolated which is cross sensitive to a number of drugs, including oligomycin and cycloheximide. Approximately one-third of the chloramphenicol-resistant mutants isolated from mutagenized conidia of this strain were found to be extranuclear, and exhibited a variety of phenotypes. One of these mutants, designated (camB51), was slow growing on drug-free medium and recombined at low frequency with the previously described mutant (camA112) (Gunatilleke et al., 1975). The majority of extranuclear oligomycin-resistant mutants isolated from cas-1 were indistinguishable from (oliA1) (Rowlands and Turner, 1973). Two mutants, (oliB322) and (oliB332), with similar but not identical phenotypes to (oli A1), recombined with the latter at low frequency but not with each other, thus representing a new class of extranuclear mutants.


An effect of F-like plasmids on the maintenance of Flac in a dnaC mutant of Salmonella typhimurium. Flac maintenance was aberrant at permissive temperature in a temperature-sensitive dnaC mutant of Salmonella typhimurium when the normally resident pLT2 plasmid was present. Flac was, however, efficiently transferred into the dnaC pLT2+ strain and the resulting Flac derivative was almost as efficient in transferring Flac as was dnaC+ pLT2+ Flac strains indicating that aberrant Flac maintenance was not associated with appreciable inhibition of transfer replication. A range of F-like plasmids behaved like pLT2 in causing aberrant Flac maintenance when present in the dnaC pLT2- strain. Flac was, however, stably maintained in the dnaC strain in the absence of other plasmids. Although the F-like plasmids destabilized Flac, each was stably maintained when introduced into strain 11G dnaC pLT2+ and pLT2 was also apparently stable under these conditions. The destabilizing effect of pLT2 and other fi+ plasmids was not consequent upon their inhibiting the formation of a repressible F transfer component needed for Flac replication in the dnaC strain. Incompatibility between Flac and the other plasmids induced by the dnaC lesion also appeared unlikely to be a cause of the aberrant Flac maintenance. The possibility is discussed that the initiation of Flac replication differs from that of pLT2 and the F-like plasmids with F competing less effectively than the others for the DnaC gene product.


Genetics and biochemistry of cryptopleurine resistance in the yeast Saccharomyces cerevisiae. Protein synthesis by ribosomes from several cryptopleurine-resistant yeast mutants is also resistant to emetine and tubulosine. These mutants can be classified into two different types: Class I mutants which display high levels of resistance to emetine and tubulosine and Class II mutants that are only weakly resistant to tubulosine and are slightly more sensitive to emetine than those of Class I. Apparently all mutants have similar levels of resistance to cryptopleurine. The distinct phenotypes of Class I and Class II strains are expressed through their 40S ribosomal subunit. Genetic analysis has shown that the mutations to cryptopleuring resistance are allelic and that in a particular case (strain CRY6) the pleiotropic phenotype is a result of the expression of the cry1 locus. It is suggested that Class I and Class II mutants arise from two independent mutational events within The cry1 allel. In heterozygous (+/cry1) diploids both the sensitive and the resistant genes are expressed as shown by studies of the action of cryptopleurine on polyphenylalanine-synthesizing systems derived from each parental sensitive and resistant haploid strain and heterozygous diploid strains. The apparent dominance of sensitivity over resistance which may be observed in vivo in heterozygous (+/cry1) diploids has been explained in terms of the mode of action of the inhibitors.


The structure of the cysCDHIJ region in unstable cysteine or methionine requiring mutants of Salmonella typhimurium. A genetic method was devised to test the hypothesis that in some cysteine or methionine requiring (cym) mutants of Salmonella typhimurium suppression of auxotrophy is due to an insertion at the site of the cym mutation. It was found that suppressed strains have an insertion of about 9kb in the cysCDHIJ region and that in unstable suppressed strains it is the instability of this insertion which results in the segregation of cym auxotrophs.


Genetic analysis of mutations in the transfer genes of pDU202 tra::Tn10 plasmids, caused by the excision of Tn10. Transfer-deficient derivatives of pDU202 (a Tcs deletion mutant of R100-1) caused by the insertion of Tn10 into the R factor's transfer genes have been described previously. Tetracyline-sensitive mutants of four of these were selected. In the majority of cases the Tcs mutation was caused by a deletion of the Tcr genes which was often accompanied either by a deletion of some of the flanking transfer genes or by a secondary mutation which was probably an inversion. A number of preferred end points for the deletions and inversions occur in the transfer operon of pDU202. Analysis of the mutants by complementation tests with Flac tra elements confirmed that the order of genes in the promoter distal part of the tra region of pDU202 is traKBCFHGSD and traI.


Mapping of the drug resistance genes carried by the r-determinant of the R100.1 plasmid. We have cloned the EcoRI fragments of pLC1, a circular DNA element found in an Escherichia coli dnaAts strain integratively suppressed by R100.1 (Chandler et al., 1977a), using the plasmid vector pCR1. All the resistance genes known to be present on the r-determinant of R100.1 were found to be present on pLC1. The isolation of pCR1 derivatives carrying various EcoRI fragments of either pLC1 or R100.1 has allowed a more precise mapping of the position of the resistance genes on the R100.1 molecule.


The use of gene conversion to study synaptinemal complex structure and molecular details of chromatid pairing in meiosis. Gene conversion can be used to study: the topography and pairing relationships of the four chromatids of a bivalent at the time of crossing over and hybrid DNA formation, the lengths of intimately paired segments and the frequency of intimate pairing at particular sites. Conversion ratios of different types, corresponding-site interference, co-conversion, and the range and distribution of conversion frequencies are discussed in relation to DNA and chromatid pairing, and synaptinemal complex organisation. Conversion data from Ascobolus immersus and other fungi are compared with electron microscope data from various organisms and with models of the synaptinemal complex.


The genetic characterization of lexB32, lexB33 and lexB35 mutations of Escherichia coli: location and complementation pattern for UV resistance. Mutants of LexB have been isolated by their resistance to lysogenic induction by thymine starvation, their resistance to thymine starvation and on the basis of their UV sensitivity. Here, three mutations identified originally in strains lacking mutagenic response to UV-irradiation, unmB (Kato and Shinoura, 1977), have been further characterized, mapped by P1-mediated transduction with srl into the recA-tif-zab-lexB cluster at the lexB position and analysed for complementation with various lexB and recA mutations. From the results it was concluded that unmB mutations are identical to lexB mutations; consequently these mutations have been termed lexB32, lexB33 and lexB35. The mutations lexB33 and lexB35 do not complement any of the other lexB mutations and define therefore a new complementation type. The lexB32 mutation, which like the lexB34 mutation, results in moderate UV sensitivity has a complementation pattern similar to that of lexB34. However, unlike lexB34 the lexB32 behaves like a leaky mutation. The results are discussed in relation to the recA gene product and its control.


Genetic mapping of the lexC-113 mutation. A mutation, previously designated lex-113 and suspected to be situated in the lexA locus, has been positioned by transductional studies to a unique site on the chromosome of E. coli B separate from the lexA102 and uvrA155 mutations. The order of genes in this chromosomal region was demonstrated to be malB-lexA-uvrA-lex-113. The allele designation lexC-113 is suggested for this mutation in a new gene functional in the regulation of inducible lex+ - and rec+-dependent SOS activities.


DNA synthesis and degradation in UV-irradiated toluene treated cells of E. coli K12: the role of polynucleotide ligase. Toluene treated cells have been used to study the processes of DNA synthesis and DNA degradation in ultra-violet irradiated Escherichia coli K12. Synthesis and degradation are both shown to occur extensively if polynucleotide ligase is inhibited, and to occur to a much lesser extent if ligase activity is optimal. Extensive UV-induced DNA synthesis in toluene-treated cells requires ATP for the initial incision step, and DNA polymerase I. Extensive degradation also depends on the early ATP-dependent incision step, and the subsequent degradation shows a partial requirement for ATP. Curtailment of degradation by ligase requires DNA polymerase activity, but is not dependent upon DNA polymerase I. Apparently this process can be carried out with equal facility by either DNA polymerase II or polymerase III. These observations suggest that extensive DNA polymerase I-dependent repair synthesis and extensive DNA degradation are facets of two divergent pathways of excision repair, both of which depend upon the early uvrABC determined ATP-dependent incision step.


Transposition and insertion of intact, deleted and enlarged ampicillin transposon Tn3 from mini-R1 (Rsc) plasmids into transfer factors. The miniR1-(Rsc)-plasmids which derive from the copy mutant R1drd-19B2 (pKN102) are non-conjugative extrachromosomal elements which can not be co-transferred by various transfer factors to recipient strains under standard mating conditions. The attempts to mobilize Rsc11 by F'lac lead to transconjugants carrying F'lac::Tn3 with Tn3 mainly inserted into the lac operon. In addition it can be shown that Rsc11 can become inserted as a complete unit into the transfer factor giving rise to rather unstable recombinant intermediates. Dissociation of these intermediates may lead to alterations of the original plasmids. The Tn3 part of Rsc13 can be enlarged or deleted by in vitro manipulations. In vitro insertion of EcoRI-fragments into an EcoRI+ site of Tn3 leads to new transposable units which can be transposed to the RTF part of R1. This new genetic entity can be stably integrated into the chromosome of E. coli by integrative suppression of a dnaAts-mutation. Deletions at one end or the central region of Tn3 abolish the capability of transposition. However, the Rsc-plasmids containing the deleted Tn3 can still be inserted into the transfer factor as complete units. The resulting recombinants are unstable leading after dissociation in some cases to new plasmids with altered properties.


Purification and properties of a lambda operator-binding protein which is expected to be autorepressor (tof protein) from E. coli carrying lambdadv plasmid. In order to study the mode of action of the tof gene product, which is an "autorepressor" of the bacteriophage lambda and plasmid lambdadv, we have purified a DNA-binding protein which is specifically produced in bacteria carrying lambdadv. This protein possesses characteristics expected for the product of the tof gene, since it is produced under conditions where cI-repressor is not made, and since it binds to oL and oR operators on the lambda phage genome. The molecular weight of the native protein is 16,000-17,000 daltons, and the monomeric molecular weight as measured by gel electrophoresis in the presence of sodium dodecyl sulfate is about 10,000 daltons. Denaturation and renaturation experiments demonstrated that the native protein is a dimer of 10,000-dalton monomers. The lambdaDNA-specific binding protein is not produced in cells carrying i21dv or ø80dv.


Amber mutations in Escherichia coli essential genes: isolation of mutants affected in the ribosomes. A method to obtain amber mutations in ribosomal protein genes is described. tit relies on the P1-mediated localized mutagenesis (Hong and Ames, 1971) and on the fact that the recipient strain contains (a) an efficient but genetically unstable suppressor, (b) a particular thermoinducible lambda prophage which kills suppressor hosts at 42 degrees C. Exposure of these bacteria to the high temperature yields frequent suppressor-free derivatives while none will be found if the strain carries an amber mutation in an essential gene. Eleven mutants have been isolated by this method, of which at least six appear to carry amber mutations. All of them map close to, and to the right of spcA, in a region which codes mostly for ribosomal proteins. Three mutants were studied biochemically; all three show defective ribosomal assembly in vivo upon loss of suppression.


Synthesis of the Escherichia coli K12 isoenzymes of ornithine transcarbamylase, performed in vitro. The in vitro synthesis of enzymatically-active ornithine transcarbamylase (OTCase) directed by each of the E. coli K-12 OTCase genes (argF and argI) is described. The E. coli OTCase isoenzyme subunits are not identical, whether synthesized in vivo or in vitro, the argF-coded product being about 5% smaller. The OTCase protomers are enzymatically inactive but associate in vitro to an enzymatically active multimer. The rates of subunit association of argF and argI isoenzymes are considerably different. Utilizing the facile assay protocol presented, the regulation of in vitro OTCase synthesis by the specific holorepressor of the arginine regulon is demonstrated. Calculations based upon data presented indicate that there are about 65 molecules of argR gene product per bacterium, a substantially lower estimate than previously reported.


Complementation analysis of Klebsiella pneumoniae mutants defective in nitrogen fixation. A series of mutants defective in nitrogen fixation (nif) were isolated in Klebsiella pneumoniae strain M5a1. The nif mutations were either located on plasmid pRD1 or on the K. pneumoniae chromosome. A total of 37 plasmid mutants and 28 chromosomal mutants were employed in complementation tests using the acetylene reduction technique. Most mutants could be assigned to one of seven nif cistrons: nifA, nifB, nifD, nifE, nifF, nifH, and nifK. Complementation analysis of two nif deletion mutants confirmed transductional evidence that these strains carry nifB-A-F deletions. One deletion mutant had, in contrast to previous transductional analysis, a functional nifK cistron and presumably is deleted for nifB-A-F-E. Examination of the biochemical phenotype of several mutants suggests that the nifA product has a regulatory function, and nifK, nifD and nifH are most probably the structural genes for nitrogenase.


Linkage map of the nitrogen fixation (nif) genes in Klebsiella pneumoniae. The nif cistrons indentified by complementation analysis in the preceding paper (Dixon et al., 1977) were mapped with respect to hisD and to each other other by P1 cotransduction and three-factor reciprocal crosses. The order obrained was hisD nifB nifA (nifL) nifF nifE nifK nifD nifH. Analysis of hisD2-nif cotransduction data by the Wu equation (Wu, 1966) suggested that the nif genes are divided into two clusters: a his-proximal cluster comprising nifBA(L)F and a his-distal group of nifEKDH.


Exchange of ribosomal proteins among the ribosomes of Escherichia coli. The exchange of ribosomal proteins among ribosomes of E. coli has been measured, using a density label technique. As expected most of the proteins do not exchange appreciably. However a substantial fraction of each of proteins S1, S2, S21, L7/L12, L9, L10, L11, L26 and L33 is found to exchange, but exchange of S1, S2, L7/L12, L10, L11 and L26 is found to occur in vitro after lysis of the cells, and therefore it is not possible to say whether or not these proteins also exchange in vivo. tin contrast S21, l9 and L33 do not exchange after lysis of the cells and we therefore conclude that these proteins exchange in vivo. The maximum level of exchange of S21, L9 and L33 is attained so rapidly that we were unable to show whether or not it was dependent on protein synthesis.


Resistance to 2-deoxyglucose in yeast: a direct selection of mutants lacking glucose-phosphorylating enzymes. When strains of Saccharomyces cerevisiae carrying a single glucose-phosphorylating enzyme such as hexokinase Pl or hexokinase P2 or glucokinase, are subjected to the selection pressure against the toxic sugar 2-deoxyglucose, the majority of survivors are mutants lacking the respective enzymes. All the 2-deoxyglucose-resistant segregants recovered from backcrosses of these mutants to a wild type strain are glucose-negative and all the sensitive ones are glucose-positive. The hexokinase mutations are located in the same complementation groups as defined by the structural genes of hexokinase P1 and hexokinase P2. No interallelic complementation has been observed either in hexokinase P1 or in hexokinase P2 amongst a total of 4 X 64, and 5 X 60 different combinations of independent mutants at the hxk1 and hxk2 loci respectively. There appears to be neither a common genetic regulator controlling two or more of these glucose-phosphorylating enzymes nor a sugar carrier that can be dispensed with.


Interaction of E. coli RNA polymerase with promotors of coliphage T5: the rates of complex formation and decay and their correlation with in vitro and in vivo transcriptional activity. The genome of virulent coliphage T5 contains about 30 sites which form stable complexes with E. coli RNA polymerase. Some of these sites bind RNA polymerase with high rates, others form extremely stable complexes as compared with promotors of other E. coli systems. The transcriptional activity of these promotors in vivo and in vitro reflects the rate of complex formation with RNA polymerase rather than the stability of the enzyme/promotor complex. The fastest, i.e. the most active promotors are found in the "early" region of gene expression followed by promotors of the "preearly" class. The few binding sites for the E. coli holoenzyme within the "late" region react more slowly with the enzyme.


The role of misrepair processes in the isolation of new types of streptomycin-resistant mutants in Escherichia coli. Treatment of Escherichia coli cells with ethylmethanesulfonate followed by a prolonged delay for phenotypic expression allows to select new types of streptomycin-resistant mutants, which are double mutants with one change resulting from base mispairing and the second one from misrepair. The error-prone recA-dependent pathway is involved in this misrepair, as evidenced by the fact that recA strains do not provide double mutants.


Synthesis and turnover of ribosomal proteins in the absence of 60S subunit assembly in Saccharomyces cerevisiae. We have measured the synthesis and stability of ribosomal proteins in a temperature sensitive strain of yeast which at the restrictive temperature is specifically blocked in the processing of 27S ribosomal precursor RNA. We find that in the absence of 60S ribosomal subunit assembly, the synthesis of all the ribosomal proteins studied continued. However, the proteins of the 60S subunit fail to accumulate and are rapidly degraded.


Overproducing araC protein with lambda-arabinose transducing phage. Escherichia coli infected with bacteriophage lambda-arabinose transducing phage were tested as sources of araC protein. Infection of cells with such phage produces an intracellular concentration of araC protein up to 100 times that present in wild-type E. coli, apparently resulting from fusion of the araC gene to bacteriophage lambda promoters. Lysates from these phage-infected cells may be fractionated to yield another 100-fold enrichment in araC activity so that the total enrichment is 10,000-fold. A nonsense mutation in araC provided proof of the identification on gel electrophoresis of a band in the purified material. Biologically active araC protein is a dimer with 28,000 M.W. subunits. The araC gene in these phage replaces the int-xis genes but is oriented in the opposite direction. Nonetheless, it appears to be transcribed in this position by the phage promoter pr via transcription the long way around. Furthermore, because araC gene is in this position, we were able to isolate phage on which the araC gene was under phage late gene control by deletion of the late gene transcription stop signals in the b2 region.


In vitro construction of plasmids which result in overproduction of the protein product of the araC gene of Escherichia coli. Derivatives of the Escherichia coli drug resistance plasmid pMB-9 were constructed which contain the promoter from the lactose operon of E. coli fused to the araC gene of E. coli. E. coli possessing these plasmids contain about 50 times as much of the araC gene product as do cells with a wild-type araC gene and promotor.


The regulation of RNA synthesis in yeast II: Amino acids shift-up experiments. A study has been made of the effects of a casamino acids shift-up on a prototrophic strain of yeast growing under conditions of ammonium repression. The shift-up produced an increase in growth rate some 120 min after the addition of amino acids to the medium. This growth rate increase was slightly preceded by an increase in the rate of accumulation of DNA. In contrast, the rate of accumulation of protein increased immediately and that of RNA 15-20 min after the shift. RNA was initially accumulated at a rate greater than that required to sustain the new steady state. This was shown to be due to an increase in the rate of synthesis of the rRNA species derived from the 35S precursor. The rate of synthesis of 5S rRNA and of tRNA increased much later and to a lesser extent than that of the 35S derived species. The implications of these results for general theories of regulation of RNA synthesis are discussed.


Improved electrophoretic and immunochemical techniques for the identification and characterization of mutant proteins, applied to ribosomal protein S8 in Escherichia coli mutants. The ribosomal proteins of 11 mutants which are sensitive to starvation at elevated temperature and of 36 transductants derived from them were studied with several electrophoretic, immunochemical and proteinchemical methods. The following results were obtained: (1) Ribosomal protein S8 is altered in three of these mutants. (2) The amino acid exchange in proteins S8 of mutant N4128 is Glu leads to Lys in position 59 of the protein chain. (3) Temperature sensitivity and inability to recover from starvation at elevated temperatures are caused by the same mutational event which is, however, unrelated to the alteration in protein S8. Several electrophoretic and immunological procedures were applied during the characterization of these mutants. A modified immunoelectrophoresis on cellulose acetate gels was developed, and proved to be the most applicable procedure for the detection of mutationally altered ribosomal proteins. This procedure may gain general importance for detecting mutational alterations in other proteins.


UV-sensitivity and repair of UV-damages in Salmonella of wild type. The UV-sensitivity of wild type Salmonella strains has been compared to that of wild type E. cole and its UV-sensitive mutants. Many wild type Salmonella strains are 4-5 times more sensitive than wild type E. coli and their inactivation curves is similar to that for E. coli with a mutation in the polA gene. Alkaline sucrose gradient centrifugation has shown a deficiency of these strains in normal excision repair of UV-damaged DNA. This deficiency is not a Salmonella genus feature because one strain as resistant as wild type E. coli was found. This resistant strain showed normal excision repair in alkaline sucrose gradient centrifugation experiments. The possible influence of plasmids and mutations in repair genes on the ability of Salmonella to repair UV-damages DNA is discussed.


Molecular properties of yeast glucokinase. Glucokinase from baker's yeast has been purified to homogeneity. The molecular weight of the subunit is 51,000. The native enzyme sediments with S20,w values in the range of 19 to nearly 4S. The presence of glucose and phosphate favors the heavier species while ATP causes depolymerization. Titration experiments with the Ellman reagent support this view. The enzyme subunit has four sulfhydryl residues of which one is more reactive than the other three. However, it does not seem to be directly responsible for the catalytic activity. The amino acid composition of the enzyme is similar to those of the hexokinases P1 and P2 but for aspartic acid and histidine.


The polymerization reaction of muscle actin. Recent advances in the studies of the aggregation of G-actin monomers, containing one molecule of ATP, to long filaments of F-actin, with a concomitant hydrolysis of the nucleotide to ADP, are reviewed. With the aid of omega-ATP, the association and dissociation rate constant of the nucleotide could be determined. The binding of the nucleotide is enhanced by the binding of one Ca++ ion, probably at a different site. The delta G value of the Mg++ or Ca++ induced polymerization has been determined to --39 to--59 kJ/mole, the critical protein concentration for the ATP-G-actin to ADP-F-actin conversion is very strongly influenced by the concentration of bivalent cations. The rate constants of the protein monomers, and the rate and equilibrium constants for the propagation step show the process to be extremely cooperative. Actin shows the interesting phenomenon of translocational head-to-tail polymerization, which may be regulated by ATP. The contact sites between the monomers in F-actin have been labeled by chemical modification. Two tryosine residues, 53 and 69, are probably close to one of the two sites. The ATP binding sites has been labeled by an ATP analog, and there is evidence that it is close to the contact site.


An evaluation of Tween 80 effects on the survival and DNA repair in Escherichia coli following UV or gamma irradiation. The notion that Tween 80 may be a DNA-repair inhibitor was tested with Escherichia coli. The results indicate that cell growth, colony-forming ability, and the rate and extent of removal of thymine-containing dimers from DNA are unchanged in the presence of Tween 80. We conclude that this detergent does not increase or diminish the effect of UV or gamma irradiation to bacteria.


Localization of gamma-rays induced chromatid breaks using a three consecutive staining technique. Three staining techniques (Giemsa, Q-banding and R-banding) are used consecutively to localize the breakage points in chromosomes of human lymphocytes, irradiated during G2-phase with gamma-rays, at doses ranging from 50 to 200 rad. The large majority, about 85% of the breaks, occurs at the interbands, between R- and Q-bands. The discrepancy of this result, with regard to previously reported ones, is attributed to the strong bias of analysis when only one staining technique is used.


Mode of mutagenic action of 4-benzoylamido- and 4-acetamido-4-carboxamido-n(N-nitroso)-butylcyanamide. The mode of mutagenic action of 4-benzoylamido- and 4-acetamido- 4-carboxamido-n(N-nitroso)-butylcyanamide (BCNBC, ACNBC) was studied using Escherichia coli K12 strains. The strains carrying defects in DNA-repair mechanism, AB2463 (recA) and P3478 (polA) were more sensitive than their parent strains to both compounds, while AB1886 (uvrA) showed the same sensitivity as the parental strain. About 90% of tryptophan revertants from BE1043 (trpambphoamb) by both compounds were due to mutation in suppressor genes. Suppressor analysis by using BE1047 (trpambphooch) revealed that the most frequently occurring reversion was due to a mutation in suppressor gene, supE. This implies that these two alkylnitrosocyanamides predominantly induce GC leads to AT transition.


Sulfinpyrazone in the prevention of cardiac death after myocardial infarction. The Anturane Reinfarction Trial. The Anturane Reinfarction Trial is a randomized, double-blind, multicenter clinical trial comparing sulfinpyrazone (200 mg four times a day) and placebo in the prevention of cardiac mortality among patients with a recent documented myocardial infarction. Results represent data accumulated on 1475 cligible patients entered 25 to 35 days after myocardial infarction and followed for an average of 8.4 months. The data reflect excellent randomization, compliance with therapy and tolerance of the drug. All 69 deaths were a cardiovascular nature (68 cardiac and one cerebrovascular). For cardiac deaths, the annual death rate was 9.5 per cent in the placebo group and 4.9 per cent in the sulfinpyrazone group, representing an observed reduction of 48.5 per cent (P = 0.018). The annual sudden-cardiac-death rate was 6.3 per cent for the placebo and 2.7 per cent for the sulfinpyrazone group, representing a 57.2 per cent reduction in sudden-cardiac-death rate (P = 0.015). Sulfinpyrazone appears to be effective in reducing cardiac deaths during the first year after myocardial infarction.


Bronchodilator effects of terbutaline and aminophylline alone and in combination in asthmatic patients. In 17 patients with moderate to severe asthma, we compared acute bronchodilator effects of the following drugs or drug combinations using a double-blind crossover design: terbutaline, 5; aminophyline 400; terbutaline, 5, plus aminophyline, 400; terbutaline, 2.5; aminophylline, 200; terbutaline, 2.5, plus aminophyline, 200 mg; and placebo. The higher doses of terbutaline and aminophylline alone produced comparable bronchodilation and similarly frequent adverse side effects; low doses of each drug also had comparable effects. The high-dose combination produced significantly (P less than 0.05) greater bronchodilatation than either drug alone. The low dose combination had bronchodilator effects comparable to those produced by the higher dose of either drug alone. These findings suggest therapeutic advantages in combining high doses of theophylline and an oral beta adrenergic agonist (terbutaline) in asthma not well controlled on high doses of either drug alone and in combining these drugs in lower doses in patients experiencing intolerable side effects from a high dose of either drug.


Pragmatic realities in uremia therapy.

Pragmatic realities in uremia therapy. The present status and future prospects of uremia therapy in the United States are reviewed. Approximately 3500 renal transplants were done in 1976 as compared to 3700 in 1975. Functional two-year survival of grafts has not changed recently (40 to 45 per cent for cadaver donors; 70 to 75 per cent for siblings), but patient survival with cadaver grafts continues to improve (now 65 per cent at two years). Patients on hemodialysis in facilities are increasing rapidly. Only 13 per cent are on home dialysis, as compared with nearly 40 per cent five years ago. Home patients do at least as well as those in centers (80 per cent two-year survival) and cost 40 per cent less. Physician bias probably explains the trend to center dialysis, but pending legislation may provide new incentives for home treatment. Prospects for technical advances are good, but a greater federal investment in research and development is needed. Dollars saved on the center dialysis could be used for this purpose.


Predicting treatment costs and life expectancy for end-stage renal disease. To estimate the cumulative 10-year direct medical costs and life expectancy associated with different methods of treatment for end-stage renal disease, we assessed predictively three treatment transition options. It is predicted that if 1000 patients shift from facility to home dialysis for each of 10 years, life expectancy of the cohort will not be reduced, but there will be a reduction of $241 million in total costs. The same number shifting from facility dialysis to cadaveric transplantation are predicted to have a $279 to $330 million reduction in total costs but a reduction of 7 to 17 per cent in life expectancy. Shifting from home dialysis to transplantation is predicted to reduce total costs by +103 to $142 million, and life expectancy by 10 to 20 per cent. As new program policies for treatment of end-stage renal disease are developed, their effect on both costs and life expectancy needs to be considered.


Efficacy of single-dose and conventional amoxicillin therapy in urinary-tract infection localized by the antibody-coated bacteria technic. Urine specimens from 61 women with symptoms of cystitis who are infected with amoxicillin-sensitive organisms were examined by the antibody-coated bacteria assay. Patients with negative assays were randomized to receive either a single 3-g oral dose of amoxicillin or 10 days of amoxicillin, 250 mg, given by mouth four times per day (conventional therapy). Patients with positive assays received conventional therapy. All 43 patients without antibody-coated bacteria in the urine, 22 given single-dose therapy and 21 treated conventionally, were cured of their infection. Of 18 patients with antibody-coated bacteria, nine relapsed within one week of completion of conventional therapy. The results of the antibody-coated bacteria assay appear to predict the therapeutic response: both single-dose and conventional amoxicillin therapy are completely successful in patients with negative assays; in contrast, conventional therapy is ineffective in 50 per cent of patients with positive assays.


Morphologic and functional evidence for release of mast-cell products in bullous pemphigoid. We studied nine patients with bullous pemphigoid, a generalized cutaneous eruption- for evidence of mast-cell involvement during development of lesions. As in other reports, six of nine patients demonstrated a serum antibody directed against the epidermal basement-membrane zone. Direct immunofluorescence studies of lesions revealed depostion of immunoglobulin and complement proteins at the basement-membrane zone in six of nine and nine of nine patients, respectively. Participation of mast cells was suggested by a sequence of pathologic alterations in which there was progressive mast-cell degranulation and late eosinophil infiltration. In addition, a factor chemotactic for human eosinophils with the size and charge characteristics of the eosinophil chemotactic factor of anaphylaxis was identified in blullous fluid. The data indicate that, in addition to activation of the complement system, involvement of mast cells is an early and continuing event in the development of the cutanenous lesions of bullous pemphigoid.


Paracoccidioides brasiliensis: cell wall structure and virulence. A review. Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis or South American blastomycosis. Many aspects of the disease and its agent are unknown. One of the most important factors regarding the infection and the host-parasite relationships seems to be the fungal cell wall whose biochemical aspects are reviewed here. Biochemical studies, done mainly by Kanetsuna et al., (21,22), have demonstrated that the yeastlike (Y) and the mycelial (M) forms have chitin as a common polysaccharide, with alpha-1, 3-glucan in the Y form and beta-1, 3-glucan in the M form. These polysaccharides are fibrillar and determine to some degree the fungal shape. Moreover, an amorphous galactomannan is found in the cell wall of the M form. This compound is responsible for the antigenic properties of the cell wall (1). Recent studies (30-33) suggest that the cell wall does not possess a stable chemical structure but a rather changing one, as a function of the environment in which the fungus is grown. At the same time, the cell wall composition seems to correlate with the degree of virulence of the particular strain. From these observations it may be deduced that the constituent polysaccharides of P. brasiliensis cell wall, play an important role in the active protection of the fungus against the defensive mechanisms of the host.


Chromatin.

Chromatin. The approximate shape of the chromatin subunit called the nucleosome is now known, but its internal architecture is not well understood. Recent studies reveal details of the organisation of DNA within the nucleosome, and show that the arginine-rich histones are essential to DNA folding. Nucleosomes or structures related to them seem to be present at points of DNA replication and transcription; interactions within and between nucleosomes are likely to play a critical part in these processes.


Evidence for the existence of LH-RH binding protein. LH-RH in rat hypothalamic extract (HE) emerges in 2 peaks after gel filtration on Sephadex G-25 with pyridine acetate buffer (PAB), pH 5.8, 1 peak in the unretarded protein fraction and the other near the salt region. A synthetic LH-RH marker was found only in the peak near the salt region by elution with acid. Using a dialysis technique, a protein fraction, from which LH-RH and other small molecular weight material were dissociated by gel filtration on Sephadex G-25 with acid, showed affinity for synthetic LH-RH. Synthetic LH-RH in the hypothalamic protein solution was retained in the dialysis bags more effectively than other types of protein solutions. This binding protein is of relatively small molecular size according to gel filtration behavior on Sephadex G-75. Since the dialysis experiment showed extremely poor recovery of total LH-RH, we determined the rate of loss of LH-RH under several conditions. The rate of disappearance was significantly less in solutions containing protein derived from cerebellum and hypothalamus, compared to bovine serum albumin (BSA) solution or salt solution. The ability of the hypothalamic protein to retard the rate of disappearance of LH-RH is further evidence for a special affinity between LH-RH and the protein factor. It is concluded that the protein LH-RH complex is dissociated by lowering the pH and that the dissociated protein and synthetic LH-RH can be re-associated to form a protein-hormone (PrH) complex at neutral pH.


Deanol, lithium and placebo in the treatment of tardive dyskinesia. A double-blind crossover study. A double-blind crossover study on the effects of deanol and lithium carbonate was conducted on a sample of 29 chronic schizophrenic patients with tardive dyskinesia. In addition to his usual treatment with different neuroleptics, each patient received during an 8-week period either deanol, lithium carbonate or placebo. A 4-week wash-out period was inserted between each of the 8-week periods of experimental treatment of the tardive dyskinesia. The administration of either deanol, lithium carbonate or placebo added to the neuroleptic treatment did not produce a statistically significant improvement of tardive dyskinesia in our patient population as a whole. Favorable and unfavorable responses are discussed.


[The mode of action of neurohormones on the central nervous system (author's transl)]. We tried to understand how hypophysiotropic polypeptides could be carried into some areas of the central nervous system. Granulations of neurosecretion in the ependymal cells and the presence of releasing hormones in the cerebrospinal fluid (CSF) suggest that CSF may transport these substances between the hypothalamus and other areas in the brain. Direct connections between the hypothalamus and other parts of the brain through secreting neurons are not necessary, the CSF transmitting to the cerebral hemispheres the hypothalamic polypeptides by the ventricles at the infundibulum.


Treatment of Bell palsy with prednisone: a prospective, randomized study. Two hundred thirty-nine patients with Bell palsy were randomly distributed into prednisone-treated and control groups. Patients were followed until complete recovery or for 1 year. In the steroid-treated and control groups, respectively, incomplete recovery of facial strength occurred in 12 percent and 20 percent; motor synkinesis in 9 percent and 15 percent; autonomic synkinesis in 1 percent and 10 percent; and electromyographic evidence of severe denervation in 9 percent and 17 percent. The differences reached statistical significance only for autonomic synkinesis. In the total series recovery of facial strength was incomplete in 16 percent. Residual weakness was mild in 14 percent and moderate in 2 percent. No patient remained with severe weakness. Age, hyperacusis, and severity of the initial palsy were associated with an increased risk of poor outcome.


[Immunopathology of the hepatic damage caused by alcohol. Recent acquisitions]. Recent findings in the pathogenesis of alcoholic liver disease suggest that immunological factors play a leading part in addition to the damaging action of alcohol. Immunological phenomena affected by Mallory's bodies take on considerable importance with respect to humoral immunity. As regards cell immunity, the leucocyte migration inhibition test shows that the lymphocytes of liver-diseased alcoholics can produce the migration inhibiting factor. Deposit of collagen in the liver appears to be induced by lymphocytes sensitized by Mallory's bodies. Recent experimental studies based on the use of collagen synthesis inhibitors (colchicine and penicillamine) may have therapeutic implications.


[Proposal for the introduction of a new substance into hospital practice: dipropyl acetate sodium in the prevention and treatment of alcoholic delirium]. Reference is made to two years' work with the sodium salt of N-dipropylacetic acid in the prevention and treatment of alcoholic delirium tremens in 1500 subjects. The drug impeded the onset of the syndrome, or reduced its duration and gravity in cases where it was already present. It appeared suitable for the specific correction of the CNS functional changes responsible for delirium tremens.


Management of compression injuries of the hand. Management of compression injuries of the hand. Primary treatment of extreme conversatism is recommended. Repair by local tissues is superior in every way as regards function, sensation and appearance of the hand. Where local tissues cannot be used free skin grafting and distant flaps should be considered.


The XX male: two case reports.

The XX male: two case reports. Two cases of phenotypic males with XX karyotype are described, illustrating the spectrum of physical and hormonal features found in this unusual condition.


Isolation of Mycoplasma hominis from blood cultures in patients with postpartum fever. Eight women with postpartum fever are presented in whom Mycoplasma hominis was isolated from cultures of their blood. Clinical disease consisted of a mild although often prolonged febrile illness, and all but one recovered without appropriate antimicrobial therapy. Five patients demonstrated elevated convalescent titers of mycoplasmacidal antibodies. The isolates of M. hominis were recovered from routine blood cultures in the diagnostic bacteriology laboratory using blind subcultures to blood agar plates. These cases lend support to the concept that endometritis with M. hominis is a cause of postpartum fever and suggest that these organisms may be recovered with increased frequency if minor changes in standard bacteriologic technique are introduced.


[Achievements in the study of the development and ultrastructure of spermatozoa (on the 300th anniversary of the discovery of spermatozoa)]. A review of principal advances in studying spermiogenesis and fine structure of spermatozoa is given on the occasion of the 3rd centennary of the discovery of spermatozoa by Loevenhuk. The most important achievements are the discovery of acrosome and its role in fertilization, the discovery of centriole and its role in the formation of flagellum, the discovery of axial complex and the role of its components in the flagellum movement. A study of spermatogenesis has revealed the syncytial nature of spermatogenic epithelium, synaptinemal complexes and their role in chromosome conjugation. The role of nuclear membrane in chromosome conjugation was established, the ultrastructural and biochemical transformation of chromatin was investigated, as well as that of microtubules in spermatogenesis. Some other discoveries were made which are of great importance for diagnosis of sterility.


RNA transport in the embryonic cell.

RNA transport in the embryonic cell. The modern data on RNA transport in the cells of early embryos are reviewed. A special attention is paid to the specificity of posttranscriptional mRNA transformation and the control of its transport from the nucleus to the cytoplasm. These processes in the embryonic cell differ from those in the adult one: in the embryos the rate of transport of mRNA molecules in the cytoplasm increases with the development (with the onset of gastrulation); the process of polyadenylation in some mRNA molecules takes place in the cytoplasm rather than in the nucleus; besides, the high molecular weight mRNA fractions are localized in the cytoplasm (in the adult cells they are found only in the nucleus). A study of the mechanisms of control of mRNA transport from the nucleus in the cytoplasm has shown that the now existing concepts on the participation of nucleolus, as well as of translation mechanisms in the control of mRNA transport appear to be true only for the differentiated cells and cannot be used to account for the control of mRNA transport in the embryos. For the embryonic cells the hypothesis on the selection of populations of mRNA molecules at the level of transport for their entry into the cytoplasm holds true. The patterns of RNA transport during the cell division are also considered, with respect to the phenomenon of migration of some RNA populations synthesized prior to the onset of division in the nuclei of daughter cells.


A tarsal resection procedure for senile entropion with lid retraction. 1. A method of tarso-conjunctival resection for correction of spastic entropion associated with lid retraction has been presented which prevents a) the presence of suture knots against the cornea, b) localized trichiasis, and c) tissue reaction to absorbable sutures. 2. These advantages are achieved through the use of several figure-of-8 silk sutures which are tied on the skin surface. 3. By keeping the apex of the excised triangle of tarsus 2 mm below the lid margin trichiasis may be avoided. 4. Twelve operations have been followed for 1 to 6 years. The retraction and entropion were markedly improved in eleven lids. One under-correction resulted. There were no other complications.


The biologic and physical criteria for suture selection in cataract surgery. This paper has disucssed histochemical, physical, and clinical considerations involved in proper suture selection for cataract surgery. Guidelines are proposed so that the surgeon can employ a standard method for evaluating each suture's performance. Accordingly, the surgeon can select the proper proper suture to satisfy his needs regardless of his operative technique.


The diagnosis and conservative treatment of myofascial pain dysfunction syndrome. The findings in 194 cases of myofascial pain dysfunction syndrome are summarized and the differential diagnosis of the condition is discussed. Conservative methods of treatment were used in all cases, and follow-up revealed complete or almost complete recovery in 75 per cent of the patients; this percentage was increased still further when relaxation and coping skills training were used. Those patients who had been involved in accidents with direct or indirect trauma to one or both joints showed a significantly higher proportion of nonresponse to therapy.


[Artificial ventilation of preterm and term infants (author's transl)]. One of the first aims of the neonatal care unit of the Paediatric Department of the University of Innsbruck (Austria) consists in taking care of dangerously ill children of Tyrol including the neighbouring federal states and the alpine part of Italy (South Tyrol). From SUMMER 1974 to the end of October 1976 1342 preterm and term infants were treated. 142 of these children died (mortality rate 10.5%). In 94 patients, i. e. 6.9% mechanical ventilation was necessary. 39 of these children, i. e. 41.5% survived. Two indications of artifical ventilation were predominant: Hyaline membrane syndrome in 59 children (survival rate 49%) and apnoe in 22 children (survival rate 27%). Electroencephalography was performed in 39 children during the neonatal period. 34 of these children were severely ill (gestational age of 24 to 37 weeks), 5 children were born at term nevertheless moribund. 18 of the 23 dead children of this group showed severe alterations in electroencephalography. The cause of death of 10 of these children was cerebral bleeding as verified by autopsy. 8 of the 16 surviving children showed a regular psychomotoric development, 5 children of this group had a normal electroencephalogram.


[Ventilatory response to lung inflation after induced bronchospasm in healthy conscious subjects (author's transl)]. In 10 healthy conscious subjects we have studied the effect of a sustained bronchospasm induced by aerosol of carbachol on the pattern of breathing and the ventilatory response to lung inflation which reflects the Breuer Hering reflex. Bronchospasm was assessed by measuring airway resistance and functional residual capacity by plethysmography. After bronchospasm the ventilatory response to inflation was unchanged and the role played by afferents related to such a reflex in controlling pattern of breathing was preserved. Moreover the ration between the threshold volume of the reflex and tidal volume (VT) remained constant. These data suggest that this ration could represent a central set point for VT control. Variable changes in the ventilatory pattern were also observed and are discussed in relation to the previous data.


[Comparative study of 7 cephalosporins on "Staphylococcus aureus" by the method of population analysis (author's transl)]. Miscellaneous Staphylococcus aureus populations were tested with seven commercialized cephalosporins. The strains were divided in five groups according to the following criteria: penicillinase production or not: sensitivity to methicillin and cephalosporins; RB type resistance to methicillin; RH and RO type resistance to every beta-lactamine (according to Chabbert and Baudens). For each cephalosporin studied, the population cell analysis performed with these different groups showed the constant heterogeneous arrangement of the individual MIC. However, whatever the staphylococcus group, cephaloridine remains the antibiotic that inhibits the largest number of cells at lower concentration than other cephalosporins. In vitro results were compared with pharmacokinetic data of the different cephalosporins.


[Present frequency of the different Serratia species isolated in Grenoble University Hospital Center (author's transl)]. Our study concerns 111 Serratia isolated during a period of seven months in a Grenoble hospital. The different species of Serratia are present with a high predominance of S. marcescens. Distribution, particular biochemical characteristics are discussed, and results of sensitivity to antibiotics, as well for antibiotics used against Gram negative bacteria as for the three quinolines against urinary bacteria. The place of Serratia in the hospital infections is discussed in the last part of this study.


[Bronchial mucociliary clearance in chronic bronchitics (author's transl)]. Bronchial mucociliary clearance is analysed in 13 clinically stable patients with chronic bronchitis in comparison with 7 normal non smokers by measuring the rate of removal of inhaled monodispersed particles of resin (diameter: 8.1 +/- 3.5 micrometer) tagged with 99mTc. Particles delivered with a high insufflation rate are uniformly deposited on proximal airways. The pattern of distribution is comparable in all the subjects studied. In normal non smokers, the percentage of bronchial radioactivity cleared 1 h after the inhalation was 34 +/- 11.2 percent. The patients may be divided into 2 groups: Group 1 (n = 6) is characterized by a  mucociliary clearance similar to the normals while group 2 (n = 7) shows a low mucociliary transport rate (decrease of bronchial radioactivity after 4 h less than 10 percent).


[Enzymatic hydrolysis of fat in the presence of Lamblia duodenalis (in vitro)]. The influence of Lamblia on the hydrolysis of fat by lipase was studied in vitro. The hydrolysis rate of fat in the presence of live Lamblia and without them was determined colorimetrically by the quantity of the formed glycerine. In addition, the kinetics of this reaction was studied by the method of compensating potentiometry by neutralization of fat acids with alkali. The intact organisms were found to cause an inhibition of fermentative hydrolysis of fat. The importance of this fact from the point of view of interaction in the host-parasite system is discussed.


[Determination of the erythrocytoplasma lithium ratio. Analytical considerations and clinical applications (author's transl)]. During eleven months the authors studied the erythrocytoplasma lithium ration in 46 patients on chronic lithium maintenance. They observed that the individual variations of this ratio are of the same magnitude in "cycloid psychosis" and in chronic schizophrenia. But, furthermore these variations are significantly more important than in neurosis. They report that this ratio increases significantly in manic depressive illness during the active manic or depressive phases, and they compare their results to those of the literature.