[Revaluation of gentamicin in laboratory and clinical studies (author's transl)]. The MIC of gentamicin and other antibiotics against clinical isolates was determined, and the following sensitivity distribution was obtained. a) Against 54 strains of Staphylococcus aureus, GM had the lowest MIC, followed by TOB, DKB, BB-K8 in order. The distribution range of 0.1-6.25 mug/ml was noted with GM. The peak of MIC was 1.56 mug/ml. b) Against 54 strains of E. coli, the lowest MIC was obtained with GM, and 53 strains (98%) were in the range of 0.4-6.25 mug/ml. The peak of MIC was 3.12 mug/ml. GM was followed by TOB, CL, DKB in order of superiority. c) Against 27 strains of Klebsiella pneumoniae, GM and TOB had the lowest MIC, showing the peak of MIC of 0.8 mug/ml. No significance difference was noted between GM and TOB. GM and TOB were followed by DKB, CL, BB-K8 in order of superiority. d) Against 27 strains of Proteus, GM had the lowest MIC, followed by TOB, DKB and BB-K8 in order. But the peak was 6.25 mug/ml even in GM. The activity of antibiotics against Klebsiella pneumoniae was generally low. e) Against 54 strains of Pseudomonas, the peak of MIC of GM was 3.12 mug/ml and 49 strains (91%) were in the range of 1.56-12.5 mug/ml. Whereas TOB had the peak value of 0.8 mug/ml and 49 strains (91%) were in the range of 0.4-3.12 mug/ml. TOB was followed by DKB, GM, BB-K8 in order of superiority.


Clinical experience with gentamicin in complicated urinary tract infections (author's transl). Gentamicin 40 mg was intramuscularly admininistered two times daily to 15 patients with complicated urinary tract infections. The results are as follows 1. The clinical efficacy of gentamicin was excellent in 12 cases (80.0%), good in 2 cases (13.3%) and null in 1 case (6.7%). The effective rate was 93.3%. 2. Bacteria disappeared in 16 strains (84.2%), colonized in 3 strains (15.8%) out of 19 isolates. 3. BUN, GOT and GPT values were determined before and after GM administration, and no significant abnormal finding attributable to GM was observed in this clinical study.


[Double-blind studies of the effect of ampicillin-cloxacillin (Rectocillin) on acute otorhinolaryngological infections (author's transl)]. Patients with acute otitis media, tonsillitis and upper respiratory tract infections were divided into 2 groups and treated with ampicillin-cloxacillin (Rectocillin) 1 g/day or ampicillin (AB-PC) 1 g/day, respectively. The therapeutic effect and side effect of these two drugs were studied comparatively by double blind tests. The effective rate in the Rectocillin group was 85.1%, and that in the AB-PC group was 86.7%. There was no significant difference in the therapeutic effect between two drugs. Ten cases in the Rectocillin group and 4 cases in the AB-PC group complained of disorders supposedly due to administration of these drugs. Such side effects in the former group were all gastrointestinal disorders, but in the latter, 2 cases of eruption, one case of headache and one case of gastrointestinal disorder.


Eliminatory action of glycine on drug resistance of Escherichia coli K12 harboring an R factor. Glycine, known to inhibit the synthesis of a peptidoglycan component of the bacterial cell wall, was effective in eliminating drug resistance of Escherichia coli K12 JE2100 strain harboring theR100-1 factor although in lower frequencies than that of sodium dodecyl sulfate (SDS). The action of glycine was found to be less effective on the same R factor in JE177 strain, and not effective on the F factor in W6. Infection of R factors from R+ cells to R- cells was found to take place in the glycine broth as efficiently as in broth without glycine. This might result in lowering the apparent efficiency of the action of glycine on those plasmids. The segregation patterns of drug-susceptible clones obtained by the glycine treatment were different from those obtained after the SDS treatment. These results coupled with other evidences suggest that the mode of action of glycine on R+ cells maybe different from those of other curing agents and may involve mechanisms other than selection of R- or drug susceptible segregantsthat are present in R+ culture.


Characterization of background anti-trinitrophenyl plaque-forming cells observed in several strains of mice. Normal mice have a large number of background anti-trinitrophenyl (TNP) antibody-forming cells (AFC) in their spleens (about 40-50 anti-TNP PFC/10(6) cells). We investigated this among several mouse strains, i.e., C57BL/6, C3H/He, Balb/c, ddd, and ICR mice, and found that all strains had a similar number of anti-TNP PFC (plaque-forming cells). Developmental aspects of background anti-TNP PFC in the ontogenic process were also investigated. The number of anti-TNP PFC increased logari thmically during the first few days of age, reached a peak on the 13th day and attained a constant value within 30 days. Neonatal thymectomy did not decrease the number of background anti-TNP PFC but such treatment decreased the anti-TNP PFC response to TNP-HRBC (horse red blood cells) immunization. Germ-free ICR mice had a number of background anti -TNP PFC similar to that of conventional ICR mice. Avidity of background anti-TNP PFC was compared among mice of several ages and it was shown that there were no differences among them. These results suggest that the occurrence of these background anti-TNP PFC is not elicited by the immune response but by the natural maturation of precursors of ACF without antigenic stimulation.


Immunosuppressive effect of bacterial lipopolysaccharide on antibody response. Injection of endotoxins (bacterial lipopolysaccharide: LPS) several days prior to immunization causes the suppression of antibody response. The supressive effects of several kinds of LPS preparations on the plaque-forming cell (PFC) antibody response in the spleen of mice were examined after immunization with sheep red blood cells (SRBC). Glycolipids obtained from heptoseless mutants(Reform) of salmonella or its lipid A preparation coupled artificially with bovine serum albumin (BSA) are capable, like LPSobtained from a wild type (S form) strain, of inducing suppressionson of the PFC response, while alkaline-detoxified LPS can not. The refractory periods of the PFC response induced by LPS injection last only a few days. However, the use of cyclophosphamide (CY) together with LPS can extend the refractory periods of antigenic stimulation for several weeks. Injections of LPS andCY can also induce unresponsive states of OH agglutinin antibody response to antigenic stimulation with formalin-killed organisms of Escherichia coli or Salmonella enteritidis (presumably both thymus-independent antigens). These unresponsive states induced by LPS and CY are easily terminated by a transfer of syngeneic bone marrow cells but not by thymocyte transfer.


Infection rate of simple suturing.

Infection rate of simple suturing. Four hundred consecutive patients with superficial lacerations participated in a study of infection rate of lacerations sutured in an emergency department. Of these, 322 (85%) returned for suture removal. An infection rate of 5% was noted. Reported incidence of infection among the 68 (17%) non-returnees was 5.8%.


Poliomyelitis and the sources of useful knowledge. Dr. Richard Ross during his introduction observed that Dr. Bodian made three contributions to the study of poliomyelitis which laid the groundwork essential to the ultimate triumph over the disease by immunization. The first was the identification of three types of poliovirus. This was absolutely basic to the development of a vaccine. The second was the identification of the viremia which occurred before the paralysis began and thus, indicated how it would be possible for an immune response to be effective. The third important contribution was the demonstration that immunity could be developed in primates with very low antibody levels.


[The polemics on strabogenesis between A. v. Graefe and F. C. Donders (author's transl)]. In the literature of their time one can read of a divergence of views between A. v. Graefe and F. C. Donders concerning strabogenesis. The conception of A. v. Graefe was criticized by Donders as "a somewhat obscure explanation". On the other hand A. v. Graefe could not accept Donders' view that hypermetropia in itself can cause convergent strabismus. The polemics has its actuality - in somewhat changed from - even nowadays.


[The mode of action and technique of trabeculectomy. II. Technique of trabeculectomy (author's transl)]. The technique of trabeculectomy is presented as it has been done in 370 eyes at the University Eye Clinic in Graz. Possible mistake are pointed out. The knowledge of the mechanism of this operation enables us to prevent a hypotony and to create the best conditions for the incorporation of veins and lymphatic vessels in the surgic area.


[One year's experience with pilocarpin-ocusert in the therapy of glaucoma (author's transl)]. The authors report on their own treatment results with the drug carrier Ocusert (Federal Rep. of Germany: Chemie Grunenthal). Furthermore the effect on the IOP and the compatibility including the accomodative myopia is discussed. The effect on IOP was approximately equal to Pilocarpine 2% four times daily. The accommodation myopia was significanly less than using Pilocarpin drops. A short time after insertion the conjuntiva was irritated but the irritation faded within a short time.


[Heterotopic corneal transplantation in the treatment of conjuctival sac insufficience (author's transl)]. To reform the conjunctival sac in cases of symblepharon or when the globe is not present, various procedures and materials are used. The cornea showed itself to be suitable material for covering areas which are left naked after removing corneal adhesions. Heterotopic corneal transplantation leads to good results in the treatment of clinical and thermic burns and also in insufficience of the conjunctival sac in cases of anophthalmia. The procedure allows the simultaneous transplantation of several corneae. The operation can be repeated when necessary. The author has applied this procedure in eight cases with good results.


Impairment of granulocyte function in juvenile diabetes. Granulocyte function of 10 diabetic children has been investigated. At the time of testing the diabetes was in poor control. Five children were retested one week later after adjustment of diet and insulin dose. In contrast to some reports we did not find a phagocytic defect in the ingestion of particles, but the capacity of intracellular killing of Staphylococcus aureus was impaired. Chemotaxis was also reduced whereas the NBT-index and intracellular killing of Candida albicans were normal. Better control of the diabetes led to an improvement of bactericidal killing capacity.


[Template activity of chromatin and DNA-dependent RNA polymerase III during postnatal development (author's transl)]. The template-activity of chromatin isolated from liver nuclei of developing rats increases sharply at birth and decreases remarkable until the 10th day. Between the 10th and the 40th day a slow increase was shown in template activity of chromatin tested with purified E.-coli RNA-polymerase (EC 2.7.7.6). We correlated these findings with changes of RNA-polymerase III-activity in rat liver during development.


Advances in automation for experimental pathology. The establishment of the National Center for Toxicological Research (NCTR), Jefferson, AR, to study long term effects of low doses of potentially toxic substances, including carcinogens, resulted in the initiation of chronic experiments requiring histophatologic studies of large numbers of animals. Processing the tissues and recording and analyzing the massive amount of pathologic data from these studies required innovative automated technics. The result was a unique computerized pathology data system of NCTR. The system encompasses the development of training programs for necropsy techincians, histology technicians, and pathology tissue screeners; the use of automated equipment for processing, embedding, sectioning, and staining tissue; the use of prelabeled cassettes, slides, and pathology forms; the use of mark-sensitive forms for the collection of gross and microscopic findings; the use of data collection terminals for animal identification, animal weights, and organ weights; the collection of gross and microscopic data on a Mod Comp III minicomputer; and the storage, analysis, and generation of pathology reports and tables over a data link from an IBM 370-158 computer. Some of the features of this system may be applicable in other toxicology laboratories and medical pathology departments.


Bacterial mastitis in guinea pigs.

Bacterial mastitis in guinea pigs. Necropsy of 37 guinea pigs revealed mastitis to be the primary cause of death in 70% of these animals. Epidemiologic study failed to establish correlation between age, parity, or litter size and the onset of mastitis. The disease did not appear to be contagious. Although mastitis frequently developed during lactation, survivability of offspring was unaffected. The agent most consistently isolated from affected mammary glands was Escherichia coli (17 of 37). Other isolates in decreasing order of occurrence were Klebsiella pneumaniae (6 of 37), Streptoccus zooepidemicus (2 of 37), and Proteus sp (1 of 37). The etiologic agent of 111 cases was undetermined.


Breeding and reproduction of fifteen wild rodents maintained as laboratory colonies. Data on reproduction and production were presented for laboratory colonies of Microtus pennsylvanicus tananaensis, M oeconomus macfarlani, M o operarius, M mirurus, M abbreviatus, Lemmus lemmus, L sibiricus trimucronatus, Dicrostonyx stevensoni, Clethrionomys rutilus, Peromyscus maniculatus borealis, P m bairdii, Baiomys taylori, Calomys ducilla, C callosus, Acomys cahirinus. Litter size varied from 2.0 in A cahirinus to 5.5 in C callosus. Infant (neonatal) and juvenile losses through the end of the first month ranged from 9% in C callosus to 45% in M o operarius. Young successfully weaned per female ranged from 3.4 in L sibericus to 15.2 in P m bairdii. The number of young weaned per female per month, which may be the most useful measure of production, ranged from 0.6 in A cahirinus to 2.6 in C ducilla. The most common 21-da interval between litters confirms postpartum estrus and mating, and a 21-da gestation in most cricetids.


Use of the golden hamster in toxicology. The choice of an appropriate species and strain of laboratory animal is one of the toxicologist's major concerns. The biochemical, anatomical, and other characteristics of the golden hamster which make it a valuable though limited tool in toxicologic research were reviewed. The effects of organochloride insecticides on rats, mice, and hamsters were compared. These substances can be classified into 3 groups based on the hamster's sensitivity to acute toxic effects. The hamster is so insensitive to DDT and its immediate metabolites, DDD and DDE, that an LD50 cannot be established, whereas the hamster's sensitivity to other  organochlorides varies when compared with mouse and rat sensitivity. The long-term effects of sub-lethal doses of organochloride insecticides on biochemical pathways were evaluated, particularly on liver function. The details of the induction of drug-metabolizing enzymes in the hamster and in the rat were also explored.


The hamster as a model for experimental pulmonary emphysema. The Syrian hamster was chosen as an animal model for experimental studies of papain aerosol-induced emphysema. The extent of the developed lesions correlated with concentration of papain and progressed with time following exposure. The same correlations of dose and time were similar to those found in man and were evaluated physiologically and histologically. The intratracheal administration of alpha1-antitrypsin prior to exposure to the single dose of papain aerosol prevented the development of lesions, whereas systemic administration of alpha1-antitrypsin did not.


Function of external respiration after experimental lung autotransplantation. The function of external respiration was studied by way of a dynamic observation of 15 animals whose course was uneventful following autotransplantation of the left lung. The longest follow-up period was 4 years. The following studies were conducted: spirography, bronchospirography, functional tests with the right (intact) lung excluded from respiration, bronchopneumotachygraphy, electromyography of the intercostal muscles, and analyses of blood gases and acid-base balance. During the early hours and days after left lung autotransplantation, hyperventilation and gas exchange decrease were observed in the operated lung, along with arterial and venous hypoxemia and signs of metabolic acidosis. With the right (intact) lung excluded and only the autograft breathing, a considerable reduction of oxygen saturation of the peripheral arterial blood was observed, which indicated the low compensatory capacity of the autotransplanted lung. Restoration and normalization of ventilation and gas exchange, blood gases, and acid-base balance were noted within 8 days after left lung autotransplantation. The compensatory capacity of the lung autograft, as shown by the test with the right (intact) lung excluded, was restored within the first 2 months after surgery. Following lung autotransplantation, in the absence of the Hering-Breuer reflex, the adaptative reactions of the external respiration apparatus are provided by the reflexes from the proprioreceptors of the breathing muscles of the thoracic wall and by humoral factors that acquire a leading role in the regulation of respiratory mechanisms. After removal of the right (intact) lung in the late postoperative period, the left lung autograft supports normal vital functions of the body (with the longest follow-up being 3 1/4 years). This convincingly proves that the organ's function and structure have been restored.


Resection of aortic arch aneurysm: a simplified technique. Aortic arch aneurysm has long been considered one of the most serious diseases in the circulatory system, and its resection is associated with great technical difficulties and hazardous consequences. Temporary shunts created with multiple graft anastomoses, deep hypothermia, progressive insertion of the graft, and cardiopulmonary bypass have been used to facilitate resection of the aneurysm at this vital segment of aorta. However, all of these techniques have certain disadvantages. To circumvent these disadvantages, we are proposing a simplified technique of external shunting combined with a permanent bypass graft. This method was used successfully in resection of a syphilitic aneurysm of the transverse aortic arch. The new technique is simple and easy to set up, and it greatly facilitates resection and graft replacement of the aneurysm. Because it does not require a pump oxygenator for bypass, it eliminates the postoperative blood coagulation problem. This technique is considered to be applicable in resection of aneurysms of the descending thoracic aorta as well.


Snaring of a Swan-Ganz catheter.

Snaring of a Swan-Ganz catheter. Insertion of a Swan-Ganz catheter for measurement of pulmonary artery and pulmonary capillary wedge pressures is common for operative management of patients with borderline left ventricular function, particularly patients undergoing cardiac surgery. The transatrial course of the catheter may allow it to lie against the lateral and anterior walls of the right atrium, where it can be caught in a suture used to control bleeding. This report documents such a complication of cardiac surgery: A Swan-Ganz line was caught by a right atrial suture. The tip of the Swan-Ganz catheter was in the distal right pulmonary artery, so that the usual means of removal with a loop-snare catheter was impossible. Instead, a Teflon sleeve, inserted percutaneously was used to stabilize the right atrium while gentle traction was used to break the catheter at its point of entrapment. In this manner, the proximal portion of the catheter was removed. The distal segment of the catheter then was removed with a biopsy forceps inserted percutaneously through the femoral vein.


Transfer factor: a potential agent for cancer therapy. This review has attempted to describe the characteristics of transfer factor which make it a very attractive potential agent for immunotherapy. Preliminary observations suggest that it may be capable of modifying resistance to a variety of diseases including cancer but considerable progress in basic knowledge regarding this agent is crucial to its successful application in clinical disease states. Fortunately, a sizable number of interested and dedicated investigators are exploring these difficult problems and their success may lead to new approaches in immunotherapy.


The biology of cadmium.

The biology of cadmium. Industrial exposure to large amounts of cadmium is known to be toxic to man; however, the low levels of cadmium in water, food, and air to which everyone is continually exposed have no obvious effects. During childhood and adolescence, ingestion and inhalation of cadmium are responsible for the average American accumulating about 30 mg of cadmium in his body, with the highest concentration being in the kidney. It has been suggested on the basis of two observations that elevated renal cadmium might be associated with essential hypertension: (1) Hypertensives have been reported to have higher renal cadmium concentrations than normotensives. (2) Long-term exposure to low levels of cadmium has reproducibly caused mild hypertension in animals. Finally, increased levels of cadmium have been found in lungs and other tissues of emphysematous subjects.


Phenylpropanoid constituents of essential oils. While the major constituents of essential oils are generally mono- and sesquiterpenes, in certain plant families or genera phenylpropanoid compounds are also found in the essential oil, sometimes as the main component. A survey is given of the distribution of these substances, as well as of their structural properties and biochemical origin. In particular, cinnamic acid not only occurs in some cases as a constituent of essential oils, but together with p-hydroxycinnamic acid is the most important metabolic intermediate in the pathways leading to the volatile phenylpropanoids found in these essential oils. These compounds are mostly phenolics, and often occur as their non-volatile glycosides. However, after enzymatic cleavage, which happens frequently during catabolic or postmortal processes, the resulting aglycones, which are not normally components of the essential oil, act as the carriers of flavors and fragrances. These compounds too are included in the survey.


Antimicrobial agents from higher plants. Additional alkaloids and antimicrobial agents from Thalictrum rugosum. Further study of mother-liquors from ethanolic extracts of Thalictrum rugosum resulted in the identification or partial characterization of 10 alkaloids, bringing the total to 17 characterized in our work on this plant. Five of the new alkaloids were active in vitro against microorganisms. Structures, based upon spectroscopic properties and chemical transformations, are proposed for a new bisbenzylisoquinoline alkaloid named thalrugosaminine, and a protopine alkaloid named protothalipine. A phenanthrene base (thaliglucinone), an aporphine (thalphenine), and three protoberberine bases (columbamine, thalifendine and deoxythalidastine) were identified; three very minor bases of unknown identify were partially characterized.


Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Relapsing polychondritis (RP) is not a totally rare rheumatic disease. We have seen 23 patients from 1960-1975, and there are now a total of 159 reported cases, which form the basis of this study. RP occurs equally in both sexes, and has a maximum frequency in the fourth decade. 2) Empirically defined diagnostic criteria are proposed, to include the most common clinical features: a) Bilateral auricular chondritis b) Nonerosive sero-negative inflammatory polyarthritis c) nasal chondritis d) Ocular inflammation e) Respiratory tract chondritis f) Audiovestibular damage The diagnosis is based primarly upon the unique clinical features, and is quite certain if three or more criteria are present together with histologic confirmation. 3) Fifty percent of patients present with either auricular chondritis or the arthropathy of RP; but with prolonged follow-up, a majority of patients develop four or more of the above mentioned criteria. 4) Approximately 30 percent of patients have a preceding or coexistent rheumatic or autoimmune disease, which can lead to initial diagnostic confusion. 5) Laboratory and radiographic investigations help mainly to rule out other diagnostic possibilities, with no characteristic abnormalities being present in a majority of patients. 6) On follow-up, three-fourths of our patients required chronic corticosteroid therapy with an average dose of 25 mg per day of prednisone. Corticosteroids decrease the frequency, duration, and severity of flares, but do not stop disease progression in severe cases. 7) The mortality rate has been 30 percent in our series and 22 percent in the other 136 reported cases. Of the 29 cases where the cause of death was known, 17 were from respiratory tract involvement and 9 from cardiac valvular or vasculitic involvement, emphasizing the need to search for critical involvement of either of these organ systems in each patient. 8) Detailed reports of selected cases are presented to illustrate the clinical diagnosis and differential diagnosis, and to demonstrate the need for careful prolonged follow-up. 9) Although the etiology remains unknown, there is a frequent association with, and clinical similarity to, other rheumatic diseases. 10) Careful clinicopathological study of our 23 patients leads us to postulate an underying systemic vascultis as an important pathologic mechanism in RP.


Hyperinsulinism in endotoxin shock dogs. Extreme hyperinsulinism was observed in endotoxin-shock dogs made hyperglycemic by glucose infusion. Qualitatively (at least in terms of gel filtration characteristics), the insulin secreted under these conditions was normal. Hyperinsulinism was not observed in endotoxin-shock dogs not given glucose. Thus hyperinsulinism does not explain the hypoglycemia so frequently observed in endotoxin-treated dogs. Hyperinsulinsm could not be impaired degradation of insulin as disappearance of labeled insulin as well as cold insulin was comparable in control and endotoxin-treated animals. An adrenergic mechanism (either beta receptor stimulation or postadrenergic hyperresponsiveness of the beta cells) probably does not explain the hyperinsulinism observed in endotoxin-shock dogs given glucose as beta blockade failed to inhibit the hyperinsulinsm. Hyperinsulinism was not observed in endotoxin-shock dogs given tolbuamide. A tenfold rise in plasma IRG was observed in endotoxin-treated dogs whether glucose was infused or not. The persistently low IRI levels in endotoxin-treated dogs not given glucose suggest that hyperresponsiveness of the beta cell to glucagon was not present in these animals. Extreme hyperinsulinsm in response to induced hyperglycemia in endotoxin-shock dogs is unexplained. Hyperresponsiveness of the beta cell to glucose during endotoxin shock seems likely.


[Relation of acetoin and valine in Enterobacteriaceae cultures on media with glucose and glycerin]. The ratio between acetoin and valine produced by the cultures of the family Enterobacteriaceae changes upon the addition of glucose and glycerol or their mixture to a defined medium. The experiments were carried out with 12 strains of Aerobacter aerogenes and 2 strains of Aerobacter cloacae and Serratia marcescens. The highest yield of acetoin was found on the medium with glucose (12.5--13.0 g/litre); the maximum accumulation of valine was registered on the medium with glucose and glycerol (1.8--4.8 g/litre). The presence of glycerol in the medium decreased the production of acetoin by 27--85 percent compared to that on the glucose-mineral medium.


[Function of surface membrane structures in Thiobacillus thiooxidans]. The function of the surface membrane structures was studied with cytochemical techniques on ultrathin sections of Thiobacillus thiooxidans. The transport of elementary sulphur inside the cell involves the surface membrane structures, while oxidation of the sulphur to sulphuric acid takes place on the outer surface of the cytoplasmic membrane. The surface membrane structures are supposed also to participate in the primary dissolution of elementary sulphur at the site of contact of the cells with the mineral.


[New data on the karyology of formation of L forms of Proteus vulgaris]. The growth and development of the Proteus vulgaris culture as well as the process of formation of its L-forms were studied following the Pitzurra method on slides covered with an agar layer. The latter were kept upon inoculation in a vertical position in a moist chamber at 37 degrees C. On fixed and stained after Giemza preparations, it was possible to follow the consecutive stages of the cytoplasmic "hernia" formation due to the local disruption of the bacillary cell wall. It was easy to disern the penetration of the nucleoid into this evagination. The growth of the formed cytoplast was followed by multiple reduplication of the nucleoid which ultimately grew out into a scalloped ribbon whose length served to estimate the ploidy of the developing speroplast. Gigantic individuals with massive nuclei were observed. The ploidy of such nuclei could reach 2000--4000 haploid units. The data of light microscopy were confirmed by electronograms of the ultrathin sections of the L-forms of Proteus vulgaris. Frame-by-frame microcinematography of the multiplying Proteus cells grown in the Fonbrun oil chamber and photographed with the aid of the Peshkoff loop-hole objectives has made it possible to register the division of the nuclear apparatus of bacillary forms. On penicillin-containing media, it was easy to observe the formation of the cytoplasmic "hernia", the penetration into it of the nuceloid, and its successive multiplication in the growing cytoplast to form a massive nucleal mass.


[Application of the method of capillary microscopy to determing the total population and biomass of microorganisms in seas and oceans]. The total number and biomass of microorganisms in samples of sea water were determined by direct counting in capillaries by Perfiliev and Gabe after preliminary concentration of water by filtering it through membrane filters. Reliability of the figures obtained upon concentration of diluted bacterial suspensions (10(3) to 10(5) cells/ml) was checked with dilutions of the cell suspension of Bacterium parvulum. The total number of the microorganisms was determined in 22 samples of sea water fixed with 4 to 5 per cent formalin, and deviations for each capillary were calculated.


AN 448 Sandoz (Mazindol) in the treatment of obesity. The clinical value of a new anorectic agent, AN 448 Sandoz (mazindol) has been assessed in a double-blind trial against placebo in 50 obese patients. Over the 12 weeks of the trial, mazindol was shown to be an effective adjunct to carbohydrate restriction in weight reduction.


Three score and ten.

Three score and ten. Excluding infant and child mortality, the average "natural" life span seems to be about 70 years. It has remained so for several thousand years. It shows little sign of change. Hard work and stress appear to increase rather than decrease longevity.


Mass single layer closure of abdominal wounds. A prospective study to evaluate the technique of mass single layer closure of abdominal wounds is presented. This consists of 616 cases operated upon in one hospital, and includes a large variety of procedures performed in a diverse group of patients, the majority of whom were elderly. Complete wound breakdown occurred in two patients (0.3%) and partial wound breakdown occurred in two patients (0.3%)--a total incidence of 0.6%.


[The efficacy of Piracetam on the mental functional capacity of chronic alcoholics (author's transl)]. Piracetam, 1-pyrrolidone acetamid, was tested in 40 chronic alcoholics with a more or less marked psycho-organic syndrome by means of psychological tests. It was a double-blind-cross-over study. Statistical analysis of the results showed that Piracetam improves the energo-functional capacity of the cortex i.e. the basal functions of the cortical cells such as activating capacity, vital dynamic, flexibility, intellectual reactivity and stress tolerance. Apart from the overall improvement we also observed an improvement of specific cerebral performances which is however unimportant in comparison with the greneralized effect.


Reversion of the gal3 mutation of Escherichia coli: partial deletion of the insertion sequence. The gal3 mutation of E. coli is an insertion of a DNA sequence, 1,100 base pairs in length, into the operator-promoter region of the galactose operon. This mutation reverts spontaneously to gal+ by excision of the insertion to produce stable, inducible revertants, or by tandem duplications of the gal operon to produce unstable, constitutive revertants. The nature of a third class of revertants, which are stable and constitutive, is the subject of the present study. The stable, constitutive class of revertants included approximately 30% of all gal+ revertants obtained from a gal3 (lambda) strain. Although the constitutive reversions could be transduced by lambda, the efficiency was found to be extremely poor and the rare transductants which did appear seemed to originate from abnormal transducing particles. It was concluded that these reversions were not normally packaged by lambda. In order to facilitate the packaging of these reversions, the chlD-pgl region was deleted from the parent gal3 (lambda) strain. Unexpectedly, the gal3 mutation in the majority of these deletions reverted to produce stable, constitutive reversions exclusively. The explanation proposed was that the chlL-pgl deletions had also removed part of the gal operator-promoter. These revertants were not considered to be true representatives of the stable, constitutive class. The specificity of deletion end-points at the insertion was found only in the gal3 (lambda) strain, and not in gal+, gal+(lambda), or gal3 strains. Moreover, the frequency of spontaneous chlD-pgl deletions increased 10- to 15-fold in presence of the gal3 insertions. A lambdagal phage bearing a true stable, constitutive reversion (galc200) was isolated from the revertant strain by subsequent deletion of the chlD-pgl segment (delta31). Electron micrographs of lambdagal+ and lambdac200 delta31(chlD pgl) DNA heteroduplexes were interpreted to indicate that the stable, constitutive reversion had arisen by a deletion of 3/4 of the gal3 insertion sequence. The main conclusions are: (i) the stable, constitutive reversions of gal3 can arise by partial deletions of the insertion sequence, apparently by elimination of the nucleotide sequence which causes polarity; (ii) the chlD-pgl deletions may exhibit preferential termination at the right extremity of the gal3 insertion in presence of prophage lambda; and (iii) the gal3 insertion appears to inhibit the production of lambdagal particles by providing a nucleotide sequence which is recognized and degraded by a specific endonuclease. It is suggested that inhibition of transducing particle formation by gal3 and the preferred termination of deletions at gal3 might represent related phenomena.


Alterations in mitochondrial DNA of yeast which accompany genetically and environmentally controlled changes in rho- mutability. Alterations in the physical characteristics of mitochondrial DNA accompanied increased spontaneous mutability to cytoplasmic respiratory-deficiency in yeast. Two systems were used to modify mutation rates, one physiological, the other genetic. Cells in log phase were shown to be more mutable than cells in stationary phase, and glucose-repressed cells were shown to be more mutable than unrepressed cells. A nuclear gene which acts as a mitochondrial mutator was found to increase spontaneous mutation rate by a factor of ten. An increase in endogenous formation of G+G-rich fragments of mt-DNA accompanied a physiological state conducive to higher mutability, and it is proposed that increased in vivo digestion of A+T-rich regions is involved in these alterations. Greater nuclease(s) activity accompanied the presence of the mutator gene, and it is proposed that this gene is concerned with the regulation of nuclease activity or with repair mechanisms.


The effect of dose and time on the induction of genetic alterations in Saccharomyces cerevisiae by aminoacridines in the presence and absence of visible light irradiation in comparison with the dose-effect-curves of mutagens with other type of action. Aminoacridines induce frameshift mutations and are photodynamically active, depending on whether visible light is absent or present. Therefore, a test system which allows to compare quantitatively the genetic effects of aminoacridines irradiated or unirradiated by visible light ought to be susceptible to the different DNA alterations which can be induced by these substances. For this reason in most experiments mitotic gene conversion and only in some selected experiments reverse mutation was chosen as the indicator of genetic activity. In contrast to mutation systems mitotic gene conversion has never shown a response specific to only some types of mutagens. The three aminoacridine derivatives used-acridine orange (AO), proflavine (PF), and acridine yellow (AY)-were successful in the induction of convertants at two different loci. No locus-specificity could be observed. The time-dependent induction of convertants proceeds quickly but soon reaches-especially after treatment without light-a saturation point. The dose/effect-curve after treatment in the dark has a slope increasing with increasing concentration. Irradiation with visible light results in a dose/effect-curve consisting of three parts. Af first the increase of convertants is nearly linear extending one (AY) to three (AO) orders of magnitude. After a saturation effect begins at the point at which an effectiveness of the acridines in the dark is apparent. At high concentrations an induction of convertants can again be observed which is nearly the same as that after treatment in the dark. To determine whether the dose/effect-curves obtained for gene conversion refer to similar curves for gene mutations after treatment with AO at the same locus not only gene conversions but also reverse mutations were scored for. AO-treatment in the dark is ineffective in inducing reverse mutations. Irradiation with visible light results in a dose/effect-curve beeing parallel only in its first part to the dose/effect-curve obtained for gene conversion, while in its second part a mutation frequency decline can be observed. Comparing the dose/effect-curves of AO resulting from the induction of gene conversion and gene mutation, and taking into account that no mutants can be induced by AO-treatment in the dark, the increase in convertants at high acridine-concentrations can be explained as an addition of light-dependent and light-independent effects. That means, in mutation systems at low concentrations of aminoacridines irradiation with visible light should cause transitions, transversions and microlesions, at intermediate concentrations frameshift lesions should begin to appear, and at very high concentrations nearly exclusively frameshift lesions should occur. The dose/effect-curves of aminoacridines compared with those of other mutagens are very complex. The dose/effect-curves of the mutagens of other type of action tested are linear in a double logarithmic scale, and parallel for induced gene conversion and induced gene mutation...


Detection of ribonucleic acids which are larger than 30S precursor ribosomal RNA in RNase III deficient E. coli cells. 1. New high molecular weight RNA species have been found in an RNase III deficient mutant of E. coli. These RNA's were very minor but stable components of the cells, and their molecular weights, which range from 3-5.5 million daltons, are higher than that of 30S precursor ribosomal RNA. In these respects these RNAs are similar to the 2.5 M RNA reported previously (Yuki and Wittmann, 1974). 2. A method to analyse minor RNA components is described. A linear relationship between logarithms of molecular weights and logarithms of distance moved in 1.5-7.5% polyacrylamide concentration gradient gels is also described in this report. 3. DNA species whose molecular weights ranged from 1.8 to 5.5 million daltons and also a species of 8 million daltons are described. two techniques commonly used to identify RNA, viz. DNase treatment and labeling with radioactive uridine, are discussed in connection with these DNAs. 4. The determination of the molecular weight of 30S precursor ribosomal RNA is discussed and it is suggested that this RNA is heterogenous, consisting of two species of molecular weight 1.8 million daltons and 2.0 million daltons, respectively.


Mutants of the Clo DF13 plasmid in Escherichia coli with a decreased bacteriocinogenic activity. Three Clo DF13 mutant plasmids (designated as clp03, clp05 and clp21) that show a decreased cloacin activity were isolated. The decreased cloacin activity was not due to a reduced number of Clo DF13 copies per cell. The cloacins produced by the clp03 and the clp21 mutant plasmids have a strongly decreased killing activity in vivo in comparison with the wild type cloacin and the cloacin of the clp05 mutant plasmid. Furthermore no lacunae could be observed from clp03 or clp21 harbouring strains, while strains harbouring the clp05 plasmid showed a 50-100 times decreased frequency of lacunae. In addition the clp05 mutant showed a decreased rate of RNA synthesis in clp05 harbouring Escherichia coli minicells. No complementation between the three mutant plasmids was observed. We suggest that the clp03 and clp21 mutations are located in the gene coding for the cloacin. Since the cloacin produced by the clp05 mutant plasmid has retained all the known wild type cloacin activities, the reduced inhibition zone in the stab test is probably caused by a mutation affecting the expression of the cloacin gene. The nature of this mutation is discussed.


Plasmids controlling synthesis of hemolysin in Escherichia coli. II. Polynucleotide sequence relationship among hemolytic plasmids. Plasmids of three different sizes, designated as plasmid A (mw: 65 X 10(6), plasmid B (mw: 41 X 10(6) and plasmid C (mw: 32 X 10(6) respectively, have been isolated from various hemolytic wild-type strains of E. coli. DNA-DNA hybridization was performed to determine their relationship. The wild-type strain, PM167a, harbours plasmids of all three sizes. Hybridization studies indicate that all three plasmids share extented sequence homologies but that plasmid A is not composed of plasmids B and C. Hybridization between plasmids of the donor strain and those of appropriate transconjugants demonstrates that in some cases plasmids with identical size are not longer completely homologous in their nucleotide sequences. This indicates that despite their defined sizes these plasmids are not stable genetic entities, but rather they undergo frequently recombination and dissociation during conjugation. In one particular transconjugant strain, K12-PM152/1, a plasmid D was found which is a stable recombined molecule of plasmids B and C of the original strain. Plasmids of size B found as the only extrachromosomal elements in a hemolytic wild-type strain (P224) and two transconjugant strains (e.g. K12-CM20 and K12-PM167/1) share extended nucleotide sequence homologies but are not identical. Little sequence homology was observed between two different hemolytic plasmids and the F and the Col Ib plasmids suggesting that the former do not belong to either the F-like or the I-like group of plasmids. Another hemolytic plasmid is F-like based on its sequence homologies with the F factor.


Consequences of losing ribonuclease III on the Escherichia coli cell. An isogenic pair of Escherichia coli strains, one carrying an rnc+ and the other an rnc- allele (a mutation which reduces the level of ribonuclease III), was compared. The rnc- strain fails to grow at very elevated temperatures (for E. coli) while the rnc+ strain does grow exponentially. Assaying the residual RNase III like activity in extracts of the rnc- strain at different pHs and at different temperatures suggested that this residual RNase III like activity is not due to RNase III. This raised the possibility that the rnc- strain is devoid of any RNase III activity in the cell. Comparing the decay of newly synthesized RNA and functional decay of beta-galactosidase mRNA in such strains revealed that in both strains these parameters proceed in similar rates, which suggests that RNase III is not involved in the metabolism of mRNA. During carbon starvation preexisting total RNA, as well as 23S and 16S rRNA, decay faster in the rnc- strain, thus eliminating the possibility that RNase III is the endoribonuclease which initiates the decay of rRNA during starvation (Kaplan and Apirion, 1975a).


Site c27 in phage P22 and control of the pathway to lysogeny. Phage P22 mutation c27 defines a site required for establishment , but not maintenance of repressor synthesis. This study confirms that P22 c27 is able to synthesize repressor if active repressor is present. An interaction involving gene products of c1 and c3 and the site c27 retards expression of the lytic genes of P22. Mutations in gene c1 eliminate the retardation of lytic gene expression, but c27 does not alleviate the retardation. These results are used to construct a model that postulates that binding of c1 and c3 products to DNA at or near c27 is sufficient to cause retardation of lytic gene expression. The functioning of c27 is contrasted to that of the analogous cy mutants of lambda. The effect of the c27 mutation upon alleviation of "cl repression" was studied in a partial revertant of Salmonella typhimurium Pox-1 in which c1 repression is exaggerated. The higher frequency of lysogenization seen in the mutant host is related to enhanced cl repression.


Identification of components of the streptomycin-binding center of E. coli MRE 600 ribosomes by photo-affinity labelling. The [H3]-labelled photo-activated analog of streptomycin (photo-Sm) is obtained as a result of the streptomycin reaction with 2-nitro, 4-azidobenzoylhydrazide and subsequent reduction with NaBH34. The analog retains the functional activity of the initial antibiotic as judged by two criteria: (1) it binds only to the 30S subparticle of ribosomes and (2) it inhibits the factor-free ("non-enzymatic") PCMB-stimulated polyU-dependent system of translation (Gavrilova and Spirin, 1971). After irradiation of the reaction mixture containing photo-Sm and either the 30S or 50S subparticles of ribosomes under similar conditions, the analog covalently binds chiefly to the 30S subparticle. Irradiation of the photo-Sm mixture with whole 70S ribosomes  leads to a uniform distribution of a covalently bound label among the subparticles. A comparison of the effects obtained allows the conclusion that the analog is located on the interface of the ribosomal subparticles. In the 30S subparticle the photo-Sm attacks mainly the protein component (more than 95% of all the covalently bound label). The proteins labelled by photo-reaction are identified as S7 (main), S14 (additional) and S16/S17 (minor).


Mutational properties of supP amber-ochre supersuppressors in Saccharomyces cerevisiae. Mutational properties of the supP amber-ochre supersuppressor locus in Saccharomyces cerevisiae are described. They are consistent with the proposition that the supP locus encodes a protein.


The maintenance affinities of KLF-1 proximal F merogenotes in Escherichia coli. In conjugation with donor strains carrying proximal F merogenotes of KLF-1 type about 100-fold lower frequency of Leu+ or Lac+ recombinants was found. The determination of the level of beta-galactosidase synthesis during the initial period of mating indicated that the transfer process of plasmid DNA was not impaired. Among the recombinants selected a large fraction have not expressed the plasmic fertility functions. This phenomenon was found to be replicon specific and was observed only with proximal F merogenotes but not with classical F'lac and F'ORF-1 elements or R1-19 plasmid. The expression of KLF-1 plasmid functions in the cell seems to be affected by a chromosomal gene of the proximal F merogenote closely linked to leu marker.


Genetic and biochemical studies of phosphomannose isomerase deficient mutants of Saccharomyces cerevisiae. Three mannose-negative mutants of Saccharomyces cerevisiae have been isolated. These mutants showed growth inhibition when mannose was added to a growth medium containing glycerol or fructose. Crosses between wild type mutants showed segregation of 2+/2-. Crosses between the mutants themselves showed that they were closely linked. Two mutants (XM3 and D2) showed characteristics of allelic structural alteration of phosphomannoseisomerase. Mutant D4 had a deficiency of phosphomannoseisomerase activity, but with a normal thermostability. Revertants from D4 had a normal thermostability.


Factors affecting petite induction and the recovery of respiratory competence in yeast cells exposed to ethidium bromide. When growing cultures of S. cerevisiae are treated with high concentrations of ethidium bromide (greater than 50 mug/ml), three phases of petite induction may be observed: I. the majority of cells are rapidly converted to petite, II. subsequently a large proportion of cells recover the ability to form respiratory competent clones, and III. slow, irreversible conversion of all cells to petite. The extent of recovery of respiratory competence observed is dependent on the strain of S. cerevisiae employed and the temperature and the carbon source used in the growth medium. The effects of 100 mug/ml ethidium bromide are also produced by 10 mug/ml ethidium bromide in the presence of the detergent, sodium dodecyl sulphate, and recovery is also observed when cells are treated with 10 mug/ml ethidium bromide under starvation conditions. Genetic analysis of strain differences indicates that a number of nuclear genes influence petite induction by ethidium bromide. In one strain, S288C, petite induction by 100 mug/ml ethidium bromide is extremely slow under certain conditions. Mitochondria isolated from from S288C lack the ethidium bromide stimulated nuclease activity found in D243-4A, a strain which shows triphasic kinetics of petite formation. This enzyme may, therefore, be responsible for the initial phase of rapid petite formation.


Molecular and genetic events accompanying petite induction and recovery of respiratory competence induced by ethidium bromide. The treatment of yeast cells with high levels of ethidium bromide causes a rapid induction of respiratory deficient mutants followed by a period of recovery to respiratory competence in 60 to 70% of the cells. Prolonged exposure then results in a final irreversible phase of petite formation. Sucrose gradient sedimentation analysis of 3H-adenine labelled mtDNA indicates that limited fragmentation (to about 16-18S) occurs during the initial phase of petite induction followed by a reassembly of the fragments during the period corresponding to the recovery of respiratory competence. The reassembly is associated with an ethidium bromide insensitive incorporation of 3H-adenine into mtDNA at a level consistent with repair synthesis. Genetic analyses, based on the transmission of five markers carried on the mtDNA of "repaired rho+" clones, suggests that reassembly occurs with a high degree of fidelity, though in two of a total of twenty five clones differences in marker transmission frequency were observed which could possibly reflect an altered gene order. In addition, a description is given of the marked changes in the suppressive nature of the treated cells and the temporary reduction in the capacity for marker transmission seen to accompany the transitory fragmentation of the mtDNA. The final phase of petite induction is an energy dependent degradation of the mtDNA to produce a rho degrees culture.


Some physiological alteration associated with pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae. A mutant strain (2-20) isolated by growth on medium containing oligomycin and cycloheximide was also found to be cross resistant to antimyicn, cerulenin, chloramphenicol, tetracycline, triethyltin and triphenylmethylphosphonium bromide, but collaterally sensitive to dequalinium chloride, gentamycin, neomycin, paromomycin and thiolutin. Growth of 2-20, compared to the parental strain and 2 complete revertants, under a variety of environmental conditions revealed that strain 2-20 had an enhanced sensitivity to increased osmolality, elevated pH, and high temperature; in addition, strain 2-20 was unable to polymerize aminoimidazole ribotide at 37 degrees C as shown by the failure to develop a red colony in the presence of ade 2. Four complex solid media (glucose--KCI, galactose, ethanol, ethanol--KCI, Table 1) unable to sustain the growth of strain 2-20 were arbitrarily chosen to monitor cellular growth under different physiological conditions. Tetrad analysis indicated that the complex phenotype (cross resistance, collateral sensitivity, inablity to polymerize aminoimidazole ribotide, absence of growth under adverse physiological conditions) was inherited by an allele of a locus previously shown to result in a permeability barrier of the plasma membrane to chloramphenicol. 582 of 640 subclones used to isolate revertants of 2-20, under four different physiological conditions, were observed to produce a complete revertant of the complex phenotype. It is proposed that the pleiotropic phenotype could result from an alteration of the plasma membrane and mitochondrial inner membrane by a single nuclear gene mutation.


Cytoplasmic inheritance in Saccharomyces cerevisiae: comparison of zygotic mitochondrial inheritance patterns. Mitochondrial movements in Saccharomyces cerevisiae (Sc) zygotes were monitored with phase-contrast microscopy and compared to known mitochondrial inheritance systems. The mitochondria of Sc were convincingly identified by integrated use of phase-contrast, cytochemical and electron microscopic observations. Mitochondria in Sc appear to move by saltatory jumps, which appear to be oriented towards movement of mitochondria into developing buds. Tracking of mitochondria of different genotypes was made possible by positive identification of each mitochondrial population before zygosis, and by the low degree of mixing (less than 10%) of mitochondrial populations before first bud septation. A grande by grande cross demonstrated equal numbers of mitochondria from each haploid moving into the first zygotic bud. A grande by neutral petite cross gave a 2:1 ratio of grande to petite mitochondria. However, a grande by suppressive petite cross gave equal numbers of grande and petite mitochondria. Using drug resistance systems, a comparison was made of highly biased (97%) and moderately biased (71%) chloramphenicol resistant inheritance patterns. In both cases, the ratios of drug resistant to sensitive mitochondria were 1:1. When numbers of mitochondria moving into an individual bud were compared to the phenotypic content of the clone of that bud, no model could be constructed which could predict the latter from the former. The data indicate (with the exception of the neutral petite by grande cross) that the numbers of each mitochondrial type "inserted" into the first zygotic bud are equal, regardless of the degree of asymmetry of inheritance of mitochondrial markers.


Macromolecule synthesis in a mutant of Saccharomyces cerevisiae inhibited by S-adenosyimethionine. Saccharomyces cerevisiae strain 83384-B3 carries the sai-1 mutation which confers sensitivity to S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). It was shown that the mutant is impermeable to precursors of ribonucleic acid (RNA) and protein during inhibition by SAM (0.2 mM). Inhibition of uptake of adenine and uracil was nearly complete 3 h after growth in the presence of SAM and the uptake of leucine was at least 10-fold lower. The incorporation of 3H-adenine into ribosomal RNA, transfer RNA and heterodisperse RNA, believed to be messenger, was reduced 10-fold when measured after 1 h inhibition. The inhibition of growth was completely reversed by methionine (2.0 mM) in cells previously exposed to SAM for 90 min. The polysome content in cells inhibited by SAM was 25% less than the control after 4 h inhibition. Ribosome synthesis increased only about 40% in the presence of SAM and about 5-fold in the control over an 8 h period. All classes of RNA were synthesized during inhibition.


Characterization of the antibiotic resistance plasmid ERL1 from Streptococcus pyogenes. The streptococcal plasmid ERL1 determining inducible resistance to erythromycin, lincomycin, and staphylomycin S was isolated by dye-buoyant density centrifugation and shown to have a molecular weight of about 17.5 Mdal, as revealed by sedimentation through neutral sucrose gradients. In SM60 cells entering the stationary phase its covalently closed circular form was present to the extent of 5 copies per chromosomal genome equivalent, ERL1 was subject to the DNA restriction and modification mechanism discovered in strain 56188. It did not appear to exercise restriction of phage DNA but mediated a partial release of the restricted growth of A25.


Analysis of the proteins synthesized in ultraviolet light-irradiated Escherichia coli following infection with the bacteriophages lambdadrifd 18 and lambdadfus-3. The presence of EF-Tu, RNA polymerase subunit alpha, and EF-G on the lambdadfus-3 genome and EF-Tu, ribosomal proteins L7/L12, and RNA polymerase subunit beta on the lambdadrifd 18 genome has been confirmed using a two-dimensional gel electrophoresis technique sensitive to changes in isoelectric point and molecular weight. In this system two EF-Tu gene products could not be resolved. Following infection of ultraviolet light-irradiated Escherichia coli with either lambdadfus-3 or lambdadrifd18, the EF-Tu gene, tufA, near 65 minutes on the genetic map is expressed as 3-4 copies per EF-G molecule. The EF-Tu gene, tufB, near 79 minutes on the genetic map, is expressed at about one-third of this rate. alpha is expressed as 1 copy per EF-G molecule, beta as 0.14 per EF-G molecule and L7/L12 as 2.5 per EF-G. These figures compare well with the relative amounts found in exponentially-growing cells, in which the ratio of EF-Tu to EF-G is approximately 5. Almost 90% of the total number of proteins (calculated on a molecular weight basis) which theoretically can be encoded on the lambdadrifd18 have been identified on the two-dimensional gel.


Mutagenesis of plasmid DNA with hydroxylamine: isolation of mutants of multi-copy plasmids. An investigation of in vitro mutagenesis of plasmid DNA with hydroxylamine is described. The treated plasmid DNA was used to transform Escherichia coli K12. Mutants of the plasmid NTP3, which codes for resistance to ampicillin and sulphonamides, were isolated and characterised. They were classified according to the reduction in level of their beta-lactamase activity. Hydroxylamine-induced mutants of NTP14 were also isolated. This plasmid codes for ampicillin resistance, synthesis of colicin E1, and the EcoRI restriction and modification enzymes. One class of mutants is lethal to the host strain at temperatures above 33 degrees C, but carrier strains grow well at 28 degrees C. There is evidence that these mutants code for a temperature-sensitive EcoRI modification activity: the lethal effect probably results from the cleavage of the host-cell DNA by the restriction enzyme at non-permissive temperatures. The possible genetic uses of the mutant plasmids for the production of hybrid plasmids in the bacterial cell are discussed.


Transformation in E. coli K12: relation of linkage to distance between markers. E. coli K12 transformants, selected as leu+ or pyrA+ transformants, were analysed for inheritance of some closely linked unselected markers. Based on the observation that the number of recombinants which require, besides an integration event, one or more crossing-over events was negligible, a simple mapping function was deduced. The function L= e-kd, which directly relates observed linkage of an unselected marker and the relative distance of that unselected marker to the selected marker, gave a consistent interpretation of the experimental results.


Identification of a mutation within the structural gene for the a subunit of DNA-dependent RNA polymerase of E. coli. An E. coli mutant rpoA109 unable to support the growth of phage P2 produces DNA-dependent RNA polymerase with an altered alpha subunit. Histidine is substituted for leucine in one tryptic peptide from the mutant alpha subunit. The existence of only one rpoA gene within the E. coli chromosome is indicated.


Occurrence of a regulatory deficiency in purine biosynthesis among pur A mutants of Salmonella typhimurium. A defect in the repression of the de novo purine biosynthetic enzymes was detected among purA mutants of Salmonella typhimurium. We suggest that the defect is caused by an altered purine regulation gene (purR) which affects the response level of at least five of the de novo enzymes to repression by excess adenine. Thus the unlinked genes controlling these enzymes constitute a regulation controlled wholly or in part by a purR gene product. The regulation of the guanine operon is regulated by some other mechanism independent of purR.


Haemoprotein formation in yeast. II. Isolation of catalase regulatory mutants. A procedure was described for the isolation of mutants affected in the regulation of catalase activity. Two such mutants, cgr 1 and cgr 2 were obtained. Both of them show catalase activity that is resistant to repression by glucose, but is sensitive to anoxia to the same extent as the wild type.


A bacterial RNA polymerase mutant that renders lambda growth independent of the N and cro functions at 42 degrees C. We describe a bacterial RNA polymerase mutation, rif 501, which confers rifampicin resistance and thermosensitivity to E. coli K 12. The purified RNA polymerase enzyme from rif 501 bacteria shows increased heatsensitivity in vitro at 51 degrees C. However, in vivo, at 42 degrees C the non-permissive temperature, mutant bacteria continue to grow and to synthesize RNA for 90 min. On a lawn of the mutant bacteria, at 40-41 degrees C, phage lambda forms clear plaques (LycA phenotype); this is probably due to an enhancement of cro function; we surmise that at 42 degrees C the transcription originating from the pR (but not from the pL) promoter on the lamdba genome becomes N-independent and less sensitive to the absence of the cro product. We discuss the possibility that both the N and cro proteins of phage lambda interact directly with the bacterial RNA polymerase. These observations indicate that the loss of viability of the rif 501 mutant at the restrictive temperature is not a consequence of an immediate inactivation of RNA polymerase; rather we feel it is due to a modification of the activity of RNA polymerase, leading to a disruption of the cellular regulation.


Glyceraldehyde 3-p dehydrogenase, glycerate 3-P kinase and enolase mutants of Escherichia coli: genetic studies. The genetic loci for two enzymes of glycolysis have been established by transductional crosses. The eno locus, likely to be the structural gene for enolase maps in the 52-minute region of the Escherichia coli chromosome. A structural determinant for glycerate 3-P kinase (pgk) is located near serA. The map order is speB-pgk-serA-lysA-argA-eno-cysC. In the 35-minute region maps a locus affecting the structure of glyceraldehyde 3-P dehydrogenase.


Deletion mapping of mitochondrial transfer RNA genes in Saccharomyces cerevisiae by means of cytoplasmic petite mutants. Mitochondrial transfer RNA genes have been ordered relative to the position of five mitochondrial drug resistance markers, namely, chloramphenicol (C),1 erythromycin (E), oligomycin I and II (OI, OII), and paromomycin (P). Forty-six petite yeast clones that were genetically characterized with respect to these markers were used for a study of these relationships. Different regions of the mitochondrial genome are deleted in these individual mutants, resulting in variable loss of genetic markers. Mitochondrial DNA was isolated from each mutant strain and hybridized with eleven individual mitochondrial transfer RNAs. The following results were obtained: i) Of the seven petite clones that retained C, E, and P resistance markers (but not O1 or O11), four carried all eleven transfer RNA genes examined; the other three clones lost several transfer RNA genes, probably by secondary internal deletion; ii) Prolyl and valyl transfer RNA genes were located close to the P marker, whereas the histidyl transfer RNA gene was close to the C marker; iii) Except for a glutamyl transfer RNA gene that was loosely associated with the O1 region, no other transfer RNA genes were found in petite clones retaining only the O1 and/or the OII markers; and iv) Two distinct mitochondrial genes were found for glutamyl transfer RNA, they were not homologous in DNA sequence and were located at two separate loci. The data indicate that the petite mitochondrial genome is the result of a primary deletion followed by successive additional deletions. Thus an unequivocal gene arrangement cannot be readily established by deletion mapping with petite mutants alone. Nevertheless, we have derived a tentative circular map of the yeast mitochondrial genome from the data; the map indicates that all but one of the transfer RNA genes are found between the C and P markers without forming a tight cluster. The following arrangement is suggested: -P-pro-val-ile-(phe, ala, tyr, asp)-glu2- (lys-leu)-his-C-E-O1-glu1-OII-P-.


Defective prophages of bacteriophage Mu. A method is described for the isolation of thermoinducible defective Mu lysogens. Four of these defective lysogens were studied more extensively. By marker-rescue experiments it was shown that the strain harbouring the smallest defective prophage contains the immunity gene cts and the genes A and B; the strain with the largest defective prophage still contains all the known essential genes of Mu, A to S (see Fig. 1). After induction at 43 degrees C all the defective lysogens are killed, whereas no lysis occurs. Although in all the thermoinducible defective lysogens the A and B gene products could be demonstrated by complementation, these gene products are not responsible for the killing of the host, suggesting the presence of another unknown early gene product of Mu. The level of complementation of a mutation in gene A is reduced by the presence in the cell of another defective Mu prophage containing the "G" beta part of Mu. This effect on A gene complementation is markedly enhanced when the defective prophage, containing the "G" beta part, is located on an episome instead of on the chromosome. Complementation of late genes by a defective prophage located on the chromosome, is extremely low or undetectable. A stimulation of complementation by a factor of 10 to 40 was found when the same defective prophage was situated on a F' factor. A possible explanation for this "episome" effect will be discussed.


Thiolutin resistant mutants of Escherichia coli are they RNA chain initiation mutants? Four mutants of Escherichia coli KL16 resistant to the antibiotic Thiolutin have been isolated. This drug was earlier reported to be an inhibitor of RNA chain elongation. The first mutant, TLrI, is resistant only in rich or partially rich media: it can, however, grow in minimal medium containing the drug with a very long doubling time. The other mutants TLrII, TLrIIIa and TLrIIIb are resistant in rich as well as minimal media. beta-galactosidase could not be induced in TLrI and TLrII in the presence of thiolutin whereas the enzyme is constitutively synthesised in TLrIIIa and TLrIIIb irrespective of the drug. The mutants do not support the development of phage T4 in presence of the drug, if the drug is added along with the phage, but "escape" the inhibition if phage development is allowed to proceed for some time before the addition of the drug. The time of this escape is characteristic of the mutant. Even in a sensitive strain, T7 growth escapes inhibition very soon after infection, around the time the phage-specific RNA polymerase is synthesized. In the parent strain the kinetics of inhibition of beta-galactosidase induction resembles more the inhibition caused by rifampicin than by streptolydigin. It is proposed that thiolutin could be an inhibitor of RNA chain initiation and resistance might be due to mutation in the subunit(s)/factor(s) involved in initiation.


Stabilization and size of araC protein.

Stabilization and size of araC protein. AraC protein from Escherichia coli has been further stabilized and characterized. pH is a critical variable in conferring stability. araC protein has a sedimentation coefficient of 4.0 +/- 0.2s on standardized 5%-20% glycerol gradients. Its isoelectric point is at a pH of 7.1.


Studies on allosteric phenomena in glycogen phosphorylase b. This article attempts to trace, from a personal point of view, the history of discoveries of allosteric phenomena in phosphorylase b and the later development of systematic attempts to fit the data into comprehensive theoretical models. Work from our own laboratory is emphasized, but we try to integrate this into the results from other investigators and show their contributions to our ideas and experiments. Finally, some recent unpublished data is presented together with some conclusions and predictions from a new hypothesis. The discoveries by Carl and Gerty Cori of the activation of phosphorylase by AMP, the inhibition of glucose and the enzymatic interconversion of two forms fo the enzyme with different control properties helped lay the foundations of our present understanding of allosteric mechanisms. The later discovery of the oligomeric nature of phosphorylase and its relationship to AMP binding served as a basis for many years of research into the structure-function relationships of phosphorylase and other enzymes. Data showing that AMP lowers the entropy of activation is discussed with respect to the role of the nucleotide and its binding close to the active site. The discovery of the control of phosphorylase b by common metabolites and the impetus this gave to the intensive kinetic studies of the last ten years, wherein fitting to theoretical models has been a common feature, is reviewed.


A form of elongation factor G insensitive to N-ethyl-maleimide. Treatment of elongation factor G (EF-G) with the thiol reagent N-ethylmaleimide only partially inhibits (10 to 70%) the activity of the factor in (a) guanosine nucleotide-EF-G-ribosome complex formation, (b) uncoupled ribosome-dependent GTP hydrolysis, and (c) polypeptide synthesis. Moreover, a similar treatment of the factor with N-[3H]ethylmaleimide does not lead to 3H-label being associated with a GDP-EF-G-ribosome-fusidic acid complex. Thus, the results indicate the presence in EF-G preparations of a form of the factor that does not react with N-ethylmaleimide.


A study of possible mechanisms of the RNA-polymerase involement in mutagenesis in phage T4. Spontaneous and induced mutation frequencies of phage T4 have been measured in Escherichia coli strains containing altered RNA-polymerase. In the strain E. coli rif-r stl-r, with double RNA-polymerase mutation, spontaneous reversion rates were increased in different mutants of phage T4. The study of base analogues mutagenesis in rUV mutants of phage T4 has shown that the introduction of RNA-polymerase mutations did not increase reversion rates in a mutant of frame-shift type but enhanced the rate of mutagenesis in phage mutants with lesions of transition type.


Reaction of nitrosamines in the Udenfriend system: principal products and biological activity. Reaction of diethylnitrosamine in the non-enzymatic, ascorbic acid-dependent, hydroxylating system of Udenfriend yielded N-nitroso-2-(ethylamino)-ethanol as the major product extracted into methylene chloride. The major product derived from nitrosopiperidine in the same system was N-nitroso-4-piperidone. These products, however, were mutagenic to Salmonella typhimurium TA 1535 only when activated by a rat liver microsomal preparation.


Genetic effects of formaldehyde in yeast. II. Influence of ploidly and of mutations affecting radiosensitivity on its lethal effect. Haploid and diploid cells of Saccharomyces cerevisiae have the same sensitivity to formaldehyde, exponentially growing cells being more sensitive than stationary phase cells for both degrees of ploidy. Strains defective (rad 1-3) or with a reduced capacity (p-, cytoplasmic respiratory deficient mutants) in excision repair of ultraviolet-induced pyrimidine dimers show a greater sensitivity to formaldehyde than the corresponding wild type. A mutant defective in radiation-induced gene conversion (rec5) shows the same sensitivity as the wild-type strain. It appears that the excision-repair system plays an important role, especially in stationary phase cells, in repairing a fraction of formaldehyde-induced lesions.


Yeast mutants resistant to basic fuchsin: a genetic approach to the integration of nuclear and mitochondrial information. In yeast, basic fuchsin both inhibits mitochondrial functions and is a potent mutagen for the mitochondrial genome. A genetic analysis of two mutants resistant to the dye indicate that: (1) resistance is specified by a nuclear gene; (2) the onset of resistance in sensitive cells is controlled by the mitochondrial genome; and (3) sensitive mitochondrial structures can be carried over for many cell generations in the presence of a resistant nuclear genotype.


Induced mutagenesis in bacteriophage T4 growing in strains of E. coli with altered RNA-polymerase. Enhanced reversion frequencies of T4 r mutants in E. coli strains with altered RNA polymerase have been obtained. The results reported have confirmed previous data on the effect of RNA-polymerase on the process of mutagenesis [2]. No such effect has been found in the course of studies of the recombination process.


Suppression of dimethylnitrosamine mutagenicity by nitrososarcosine and other nitrosamines. Nitrososarcosine, not mutagenic itself in the host-mediated assay using Salmonella typhimurium G46 as indicator organism, lowered the mutant frequency produced by dimethylnitrosamine (DMN). Mutant frequency was significantly depressed when 1.0 g/kg nitrososarcosine was administered by gavage 0.5--2.0 h prior to intramuscular injection of 500 mg/kg DMN. Doses of nitrososarcosine as low as 37.2 mg/kg administered 45 min prior to dimethylnitrosamine treatment produced statistically significant reduction of mutant frequency. Dimethylnitrosamine, diethylnitrosamine and dibutylnitrosamine (500 mg/kg) also partially suppressed the mutant frequency produced by 500 mg/kg DMN when administered 45 min prior to dmn. diethylnitrosamine and dibutylnitrosamine were not found to be mutagenic in this test system.


Proposed mechanisms of propranolol's antihypertensive effect in essential hypertension. We studied the antihypertensive effect of propranolol alone and in combination with diuretics in 13 patients with high, 18 with normal and nine with low-renin essential hypertension whose blood-pressure response to diuretics was previously established. Propranolol (160 mg daily) significantly lowered mean arterial pressure in high-renin (129 +/- 2.6 to 114 +/- 2.1 mm Hg) and normal-renin (131 +/- 2.7 to 119 +/- 3.5 mm Hg) patients but not in low-renin patients. A positive correlation (r = 0.36, P less than 0.05) between fall in pressure and fall in plasma renin activity occurred at this dose when the whole group was considered. An antihypertensive effect occurred in both high-renin and low-renin hypertension during large-dose (320 to 960 mg daily) propranolol therapy. This effect was independent of changes in plasma renin activity. The antihypertensive effects of propranolol and diuretics were additive in normal-renin and high-renin hypertension. These data suggest that propranolol's pressure-lowering activity is due to both renin-dependent and renin-independent effects.


Randomized clinical trials. Perspectives on some recent ideas. In spite of the controversy over the role of randomized clinical trials in medical research, the rationale underlying such trials remains persuasive as compared to recent suggestions for alternative non-randomized studies such as those relying on the use of historical controls and adjustment technics. Others have suggested that recent statistical innovations for improving clinical trials, including adaptive allocation of treatment to patients and sequential stopping procedures, are underutilized. These innovations, though theoretically interesting, are not easily adapted to large-scale, complex medical trials in which there may be multiple end points and delayed response times. Ethical considerations suggest that randomized trials are more suitable than uncontrolled experimentation in protecting the interests of patients. Randomized clinical trials remain the most reliable method for evaluating the efficacy of therapies.


Leukemic reticuloendotheliosis. A failure of monocyte production. In five cases of leukemic reticuloendotheliosis studied, profound monocytopenia was demonstrable. In 48 normal subjects, monocyte counts ranged from 215 to 921 per cubic millimeter, whereas in the five patients with leukemic reticuloendotheliosis, the counts ranged from 0 to 17 per cubic millimeter. The properties of the "hairy" cell are consistent with those of an incompletely developed monocyte. The susceptibility to infection, characteristics of these patients, may result from a lack of normal monocytes in blood and tissues.


Abundance and membrane association of elongation factor Tu in E. coli. Elongation factor Tu is present in a fourfold excess over the amount seemingly involved in protein synthesis. It is identical to a major protein which we have found associated with the plasma membrane. The possibility of a specific role in that location is considered.


Short term screening tests for carcinogens. There are now short term tests with a high predictive value for mammalian carcinogens. Many of them are based on the ability to detect damage to DNA in bacteria or mammalian cells after metabolic activation by microsomal enzymes. Their introduction will enable provisional safety assessments to be made for the many thousands of industrial and environmental chemicals for which long-term animal testing cannot at present be considered.


Study on the mechanism of interference between Friend leukemia and Sindbis viruses in tissue culture. Some mechanisms of interference developing in BALB/c mouse embryo fibroblast culture (MEC) infected with Friend leukemia virus (FLV) and 48 hours later superinfected with Sindbis virus (SV) was studied. In FLV-infected cells the amount of SV antigen formed was 2-3 times lower than in SV monoinfection, as indicated by immunofluorescence and cytofluorimetry. Electron microscopic examination showed that in mixed infection the number of newly formed SV particles decreased markedly (by 90%) despite the presence of compact aggregates of viral nucleocapsids in the cytoplasm. When the cells were initially infected with arbovirus and then superinfected with FLV, formation of virus antigen and virions of both viruses was not disturbed. Pre-treatment of cell monolayer with dactinomycin (0.2 mug/ml) blocked interferon production in MEC culture and inhibited interference between FLV and SV. It is assumed that interference between FLV and SV is associated with known mechanisms of interferon action as well as with disturbance of the stage of SV particles assembly and their release from the cell. Due to incomplete cycle of SV reproduction interrupted at the stage of ribonucleoprotein formation, productive type of its interaction with MEC cells is disturbed.


Sexual impotence: a double-blind study of LHRH nasal spray versus placebo. A double-blind study comparing application of 1.0 mg LHRH nasal spray per day against a placebo was performed in a group of 20 sexually impotent patients in whom no clinical endocrinological pathology was evident. After a 2-week placebo-spray period, LHRH was given for 4 weeks. A 2-week placebo-spray period followed. A better therapeutic effect was seen in the LHRH as opposed to the placebo group (p = 0.024) 4-6 weeks after cessation of LHRH medication. After 4 weeks of LHRH medication there were no changes in basal LH/FSH levels or in the LH response after administration of 25 mug LHRH. The FSH response was, however, significantly lower.


The common pathophysiology of monaminergic psychoses: a new hypothesis. Several recent data indicate the blood-brain transport of amino acids as a critical factor in the synthesis of monoamines. The complex, peripheral and central regulation of TP transport plays an essential role sine TP-hydroxylase is not a saturated enzyme. The hydroxylated derivatives 5-HTP and dopa are probably transported into the brain by similar mechanisms as their precursors TP and tyrosine, respectively. The maic-depressive patients show an increased uptake of administered L-5-HTP in the depressive phase, whereas L-dopa uptake is enhanced in the manic phase. Heuristically, we propose a biochemical model of manic-depressive psychosis in which an increased TP uptake causes alternation in the balance of monoaminergic system activity. Depression is possibly characterized by a hyperserotonergic and a relative hypocatecholaminergic activity. In contrast, mania is possibly determined by a hypercatecholaminergic (NA and DA) and a relative hyposerotonergic activity. The data offered by the physiology of monoamines, the semeiology and the biological alterations of the manic-depressive psychosis, as well as the monoaminergic and the electrolyte theory of manic-depressive psychosis. A diminution of the transport of TP with consequent increase of that of tyrosine represents a possible biochemical model of schizophrenia which may be well explained by a hyposerotonergic-hyperdopaminergic activity, with or without noradrenergic insufficiency. This model is compatible with our knowledge on the monoamine physiology, the biological alterations of schizophrenia, the therapeutical results as well as with the classical clinical notions (typology, intermediate syndromes and crossed heritance).


The impact of health policy on access to medical care. This article presents national data on a social-indicator-type measure of access to medical care, prior to and after the introduction of Medicare and Medicaid in the United States. The analyses confirm that the access of the poor, especially those with a regular source of medical care did improve, relative to the non-poor, between 1963 and 1970. Access for middle-class and low-income persons with no usual doctor and the high-income with a regular family physician declined considerably over this period, however. One explanation of these findings proffered is that after Medicare and Medicaid were introduced, providers may have begun to ration the number of visits by the "well-to-do" to accommodate the influx of low-income patients with newly acquired purchasing power and a backlog of unmet need. Many poor with no previously established source of care continued to experience barriers to entry. Much more sophisticated analyses are required to test this and other propositions suggested here, however.


[Reinterventions for immediate obliterations in aorto-iliac and femoro-popliteal reconstructions]. The reasons for immediate failure in aorto-iliac and femoropopliteal surgery are examined in the light of personal experience. Technical errors are the most common cause of such failure. Ways in which the flow can be re-established during a second operation are also explained and the need for urgency is stressed.


The hypothalamus as a regulator of reproductive function. In this review of the role of the hypothalamus as a regulator of reproductive function we have presented a short history of the important anatomical and physiological findings, the structure and properties of gonadotrophin releasing hormone and its function and mode of action in the reproductive process. The latest clinical studies have been presented and we have discussed the therapeutic and diagnostic applications of GnRH. Although the progress in the last few years has been relatively enormous, research on the physiological and clinical implications of these discoveries has probably only now reached its peak and it was thus felt that the time was ripe to write this summary.


Psychological implications in temporomandibular pain and dysfunction. 1. Although psychological factors are an important etiological component in producing and perpetuating TMJ disorders a comprehensive view of the problem can be best understood through the concept of multifactorial etiology. 2. Psychological factors operative in TMJ disorders cannot be understood within any single frame of reference. It is appropriate to examine emotional, behavioral, and interpersonal relationships in parallel, not as dichotomous concepts. 3. The symptom complex defined in this review as "TMJ disorders" is the musculoskeletal component of a larger group of microtraumatic signs and symptoms, all of which are manifestations of a generalized injury-producing activity termed dysfunction. 4. More explicit diagnoses need to be identified if definitional problems involving TMJ disorders are to be overcome. 5. Classical psychoanalytic conceptualization of the etiology of TMJ disorders has not been systematically examined, but has been widely accepted and found clinically useful by some therapists. 6. Clinical impressions notwithstanding, there is little evidence to indicate that TMJ disorders are correlated with one specific personality trait. Perhaps more definitive assessments will reveal uniform personality characteristics in subclasses of TMJ patients. 7. Emotional factors (e.g., anxiety, fear, frustration, and anger) play a significant role in the etiology of TMJ disorders, in that they elicit muscular tension and oral habits. Although it would appear unlikely that emotionally induced muscle activity is a "necessary" factor, it is probable that it will be found a "sufficient" cause for TMJ disorders. 8. Learning principles, should not be considered as an alternative etiological position but should be viewed as a framework upon which any psychological theory of etiology must be based. 9. The presence of chronic pain in TMJ patients may be of as much clinical significance in the prognosis as the physical findings associated with the disorder itself. 10. The potential placebo effect resulting from any treatment, coupled with other nonspecific effects of the doctor's attitudes, remains a powerful tool that can be utilized in treating TMJ disorders. A vital ingredient in the placebo effect is the quality of the doctor-patient relationship. 11. Patient evaluation should not only include a) a search for the immediate organic stimulus or biomechanical disturbance, but also b) an assessment of situational or chronic anxiety and other emotional factors and c) an observation of interpersonal styles of behavior commonly associated with the chronically sick patient. 12. Unilateral etiological views of TMJ disorders and rigid treatment approaches need modification. Treatment involving simultaneous dental and psychological approaches appears to have more promise.


Neurophysiologic studies of temporomandibular joint dysfunction. An attempt has been made to relate clinical thinking to available experimental evidence of the physiological background to temporomandibular joint dysfunction. There is little or no evidence that the condition results from displacement of the mandibular condyles. The contention that muscle hyperactivity is a primary cause receives some experimental support, but there is no clear evidence that malocclusion of the teeth leads, through reflex mechanisms, to maintained hyperactivity. Instead there is an increasing weight of evidence that hyperactivity of jaw closing muscles may originate in the central nervous system. It is concluded that such centrally induced activity may be sufficient to cause muscle damage, which leads to disturbed function, local pain and tenderness and to pain referred to adjacent structures.


Epidemiological surveys of dysfunction of the masticatory system. Findings in epidemiologic studies referred to in this review appear to warrant the following conclusions: 1. Symptoms of dysfunction of the masticatory system are very common in unselected materials - much more common than hitherto assumed. This implies that dentists in the future must interest themselves more than hitherto for diagnosis and treatment of functional disturbances of the masticatory system in general practice. 2. There are no differences in frequency of dysfunction between men and women in the general population. Why women dominate in patient materials has not been convincingly explained in the literature. 3. Symptoms of mandibular dysfunction have been found in perons in all age groups. The slight differences as to age distribution reported, indicate more frequent symptoms in old individuals than in young ones. 4. No predominant etiologic factor of dysfunction of the masticatory system has been found in the population studies. Various factors are obviously involved in the etiology of functional disorders. A certain correlation between the degree of dysfunction and the general state of health and the number of residual teeth has, however, been demonstrated. Besides occlusal disturbances and psyhic factors the general health therefore should be observed as an important variable in mandilular dysfunction. 5. In order to faciliate future comparisons between different materials and interpretation of results it is necessary to use the same dignostic criteria and to collect data by reference to suitalbe induces permitting assessment of the prevalence of different symptoms with their severity. 6. With the aid of a generally accepted dysfunction index it should be possible further to elucidate the still many obscure aspects of the etiology and further course of dysfunctional diseases of the masticatory system in clinical materials and population studies. 7. More epidemiologic research of different populations is necessary to increase our knowledge in this field.


Use of meditative state for hypnotic induction in the practice of endodontics. Thirty-five patients who were referred for endodontic therapy were used in a study involving the use of a meditative state for hypnotic induction. Induction was by the use of relaxation, and the silent repetition of a simple word while the patient's eyes were closed. Deepening of hypnosis was by suggestion of whole-body numbness or "glove" anesthesia, orally directed. Supplemental local anesthesia was used in some cases. The method proved to be rapid, easily learned, and well accepted. It was effective for varying degrees of analgesia as well as sedation, anti-anxiety, saliva control, and bleeding control. It also improved the patient's image of dentistry in general and endodontics specifically.


[Immunosuppressive agents and infection (author's transl)]. Immunosuppressive agents often cause severe infection sometimes due to organisms rarely encountered in other circumstances. Virus and parasitic infections, together with tuberculosis and salmonella may be particularly frequent during treatments which depress. T lymphocytes. Gram positive bacterial infections are mainly caused by substances inducing cell B immune deficeincy. In the light of this data, verified both by animal experiments and clinical experience, it is important to determine the target cell of the main immunodepressive agents used in clinical medicine. Azathioprine and antilymphocyte serum act mainly on T lymphocytes whereas alkylating agent are at least as active on B lymphocytes as on T lymphocytes. The mode of action of corticosteroids is particularly obscure. T cells appear, on the whole, to be resistant to corticosteroids, whereas monocytes and macrophages are very sensitive.


[Pathophysiology of infectious diseases in immunosuppressive therapy (author's transl)]. The frequency and the nature of infections due to immunosuppressive therapy is well established now, but the pathophysiology of these infections is not very well known. Immunosuppressive effect itself, other secondary effects, and frequently the preexisting disease, decrease host resistance to infection. With some examples, it is attempted to link the nature of infectious diseases observed in the immunosuppressive therapy, to the effect of these drugs on host resistance to infections. The decrease of antiinfectious cellular immunity is one of the more important factors which may explain the frequency and severity of infectious diseases in these conditions.


[Indications and choice of antibacterial treatment in patients receiving immunosuppressive agents and antimitotic drugs (author's transl)]. Bacterial infections are the most common cause of death in patients with malignant blood diseases. After recalling the main bacteria responsible and the factors which predispose patients to infection, the authors consider various forms of treatment, including antibiotic therapy, transfusions of white blood cells, gammaglobulins, etc., and prophlyactic measures, such as antibiotics by mouth, isolation in a sterile ward, etc., which have been proposed for some years. During renal grafts, infective complications are also very frequenct. Their prevention is essential for on this, to a large extent, depends the success of the transplantation.


[A simple method for evaluation of the lecithin/sphingomyelin ratio in amniotic fluid. Variation in normal and abnormal pregnancies (138 cases) (author's transl)]. The determination of the lecithin/sphingomyelin ratio in amniotic fluid is a useful index for assessing fetal pulmonary maturity. The authors propose a simple and specific method : the amniotic lipids are extracted and thin layer chromatography is carried out in an acetic acid containing medium. The L/S ratio was studied and discussed in 138 normal and pathological cases.


[New opportunist infection due to a Bacillus. A case of bacteremia with Bacillus licheniformis]. The authors report a case of bacteriemia with Bacillus licheniformis in a pregnant woman with coagulation disorders (acute fibrinolysis). Eight blood cultures were positive. Recovery rapidly occurred. The origin of this affection is discussed : a venous mode of entry is possible, either by the use of contaminated infusion fluid, or following several catheterizations.


[Fungal and parasitic infections during immunosupressive treatment (author's transl)]. Deep visceral fungus infections, induced by occasional pathogens, have caused a new class of diseases, and occupy a more and more important place among the complications due to immunosuppressive agents. The experience of the Mycology Unit of the Pasteur Institute, where recent techniques of mycological and immunological diagnosis of these fungus infections are used, is reported here. 24 patients submitted to corticosteroids and other immunosuppressive treatments, including 6 renal transplants and one liver transplant, developed deep visceral infection with septicemia due to Candida, in a series of 106 cases of deep candidiasis due to massive antibiotic treatment diagnosed over the last few years. The mycological, immunological and therapeutic data obtained after treatment with amphotericin B and 5-fluorocytosine are reported here. 8 cases of meningeal, pulmonary and bony and cutaneous cryptococcosis, occurring after corticotherapy (6 cases), radiotherapy (1 case) and renal transplantation (one case), are presented together with the favourable results (6 cures out of 8) obtained with amphotericin B and 5-fluorocytosine, eight alone or in association. The authors also report 2 cases of aspergillosis, one in the lung, occurring in a case of renal transplantation who was given, at an early stage, amphotericin B and 5-fluorocytosine, thanks to rapid laboratory diagnosis, and another case in a heart transplant with pulmonary and cerebral localisations from which the patient died. The literature on these fungus infections, together with the mucormycoses, nocardioses and other fungus and antinomycosal complications are reported, together with parasitic infections the severity of which is emphasized in renal transplants, in particular P. carinii pneumonia, toxoplasmosis, strongyloidiasis and other parasitic diseases.


Characterization of two H2S-producing, multiple drug-resistant isolates of Escherichia coli from clinical urine specimens. Two H2S producing, multiple drug-resistant variants of Escherichia coli were isolated from clinical urine specimens. Both isolates transferred, eleven resistance determinants to recipient strains of E. coli K 12 and nine r-determinants to Klebsiella pneumoniae recipients; in no instance was transfer of the 'curing'-refractory H2S marker demonstrable.


Responses of disturbed adolescent on the Kahn Test of Symbol Arrangement. Responses to the Kahn Test of Symbol Arrangement (KTSA)by 22 adolescents in residential treatment center and 22 adolescents living at home were examined for differential reactions in 6 scoring classifications. The disturbed group did not differ in the relationships of objects in their arrangements, in objects liked and disliked, or in numbers of objects grouped by category. Reasons given for their arrangements by several members of the disturbed group held pathological implications, and significant differences were found between the two groups in the directional consistency in their arrangements. The kinds of objects sorted into good, bad, and hate by both boys and girls in the disturbed group differed significantly from the norms. It was concluded that level of symbolization, consistency in arranging, and the kinds of objects sorted into the categories should be useful in the assessment and treatment of adolescent problems.