Pineal factors in the control of testicular function. The mammalian pineal gland has become firmly established as a neuroendocrine structure possessing the ability to influence the functions of the sex glands. There is substantial evidence in the literature that pineal factors also affect the activities of other endocrine systems. The pineal gland is thus conceivably far-reaching in its regulatory actions on physiological function, involving actions on the adrenal cortex, the thyroid, and parathyroid glands as well as the gonads of both sexes. The pineal gland of the hamster and the rat responds to environmental influences, particularly changes in length of the daily photoperiod, and in turn exerts regulatory effects on the activity of the testis. This relation is much more sensitive in the hamster where lack of adequate illumination stimulates pineal antigonadal activity to produce inhibition of both testicular gametogenesis and androgenesis. Involvement of the pineal in these responses to darkness or blinding has been clearly demonstrated by the negating effects of its removal. The physiological role of the pineal in regulating seasonal changes in testicular activity and reproductive capacity of the hamster has now been formulated (Reiter, 1973a, 1973b). The laboratory rat, a continuous breeder, is far less sensitive to lack of photic input. Surgical and environmental manipulations involving altered pineal activity invariably lead to less dramatic changes in various parameters of male reproductive function. The evidence would seem to indicate that pineal function in the rat is primarily related to the regulation of testicular endocrine function. Consequently, its physiological role may be associated with seasonal changes in libido in relation to environmental influences, by virtue of the action of pineal factors on androgen status. Spermatogenesis, on the other hand, was unaffected for periods as long as 1 year after the blinding of rats at the time of puberty (Kinson and Liu, 1974). There is evidence that the pineal gland has a part to play in the timing of puberty in the rat and in circadian variations in testosterone levels in the adult animal. Two groups of compounds have been identified as pineal agents and possibly pineal hormones. While the indoles have been more widely investigated as pineal antigonadal factors, the involvement of polypeptides in pineal actions was indicated a decade ago and these compounds are now receiving vigorous attention. Pineal factors influence testicular function by interaction with the neuroendocrine system to affect pituitary gonadotropin secretion. The higher neural centers appear to be responsive to indoles and via the releasing factors give rise to changes in pituitary content and circulating levels of FSH and LH. Prolactin also has been shown to respond to change in ambient lighting and to pinealectomy. Partially purified polypeptide fractions are now claimed to be considerably more potent antigonadotropically than melatonin, the indole most favored as a pineal hormone...


SC-29333: a potent inhibitor of canin gastric secretion. The gastric antisecretory effects of SC-29333, a novel prostglandin E1 analogs, were compared to the reference standard PGE1 methyl ester (PGE1ME) in gsstric fistula and Heidenhain pouch dogs. Secretion was stimulated submaximally by continuous intravenous infusion of either histamine or pentagastrin. Meal-stimulated gastric secretory studies were also conducted. SC-29333 effectively inhibited volume, acid output, and papsin secretion, in a dose-dependent manner. Intravenously (i.v.), SC-29333 was found to be approximately 30 times more potent than PGE1ME. The ranges of active i.v. bolus doses for SC-29333 and PGE1ME were 0.3-3.0 and 10-30 mug/kg, respectively. Unlike PGE1ME, SC-29333 was orally effective at doses of 10-30 mug/kg and was considerably better tolerated and longer acting than PGE1ME at active antisecretory doses. It is concluded, therefore, that SC-29333 is a potent, long-acting, orally effective inhibitor of gastric secretion in the dog.


Immunological aspects of sarcoidósis.

Immunological aspects of sarcoidósis. The results are reported of an immunological study conducted on 37 cases of active sarcoidosis, in which some in vivo and in vitro tests related to the cell-mediated immunitary response were effected. The results are discussed, with relation to the clinical use of the immunological tests adopted, and their immunopathogenetic significance. In particular, the occurrence of false-positive and false-negative results in the in vitro Kveim antigen test (LMT) using the antigen preparations currently available, limit its use in clinical practice.


Ocular manifestations of systemic diseases. This is a review of papers on ocular manifestations of systemic diseases published, in essence, during the period from October 1, 1974 to September 30, 1975, with emphasis on papers that may contain knowledge of interest to optometrists.


Alcohol and marijuana effects on ocular tracking. Experienced alcohol and marijuana users were instructed to track with their eyes a small spot that moved horizontally back and forth in pendular (sinusoidal) motion across a 7.5-degree field. The frequency of spot oscillation was gradually increased from 0.5 to 3.0 Hz in 40 sec. Eye movement recordings showed the frequency at which smooth tracking and, soon thereafter, saccadic tracking broke down. These smooth and saccadic cutoff frequencies were reduced after administration of alcohol, but not after marijuana or placebo. For low alcohol doses, smooth tracking was impaired and saccadic tracking was unaffected, much like an effect previously reported for barbiturates. Alcohol seems to affect smooth tracking by increasing the central processing time required to generate the appropriate eye movement. It affects saccadic tracking by slightly decreasing saccadic velocity and to a greater extent by increasing latency time, part of which may be devoted to central processing. The site of action of alcohol appears to be central to both the paramedian pontine reticular formation and the flocculus of the cerebellum.


General Grant: his physicians and his cancer. In early June 1884, seven years after leaving office as President of the United States, General Ulysses S. Grant was found to have carcinoma of the right tonsillar pillar. The General's physicians kept a detailed record of the course of their patient's disease. Speaking was quite painful for the patient, and his words and thoughts have been preserved on the scraps of paper on which he communicated to family, physicians, and friends. The diagnosis, symptomatic treatment, and inexorably progressive course of General Grant's mouth cancer taking place in an atmosphere of personal financial ruin are discussed in detail.


A two-year crossover therapeutic trial with halofenate and clofibrate. Twelve patients with Type IV hyperlipoproteinemia were treated with clofibrate and halofenate in a double blind, crossover trial for two years. Drug intake was monitored by determination of the level of the drugs in serum. Halofenate and clofibrate were equally effective in lowering plasma triglycerides and cholesterol levels. Patients who were secretors of ABO blood group antigens in saliva had a greater hypocholesterolemic response to both drugs than those who were nonsecretors. Clofibrate treatment resulted in a significant rise of low density lipoprotein cholesterol. Both drugs lowered serum bilirubin levels and this effect had a significant positive correlation with that on uric acid levels. Halofenate had a greater hypouricemic effect than clofibrate and may be a useful drug for treatment of patients with Type IV hyperlipoproteinemia who have concomitant hyperuricemia.


The management of carcinoma of the larynx in a prominent patient, or did Morell Mackenzie really cause World War I?. The influence of fate on history is a fascinating subject. This paper reviews the death of the Crown Prince of Prussia from carcinoma of the larynx. This was a critical turning point in history. The roles of the European physicians involved in his care are reviewed. It was not until after the death of Queen Victoria that the true character of these physicians was revealed.


A double blind study of the effects of zinc sulfate on taste and smell dysfunction. A randomized, double blind crossover study of the effects of zinc sulfate and placebo was carried out in 106 patients with taste and smell dysfunction secondary to a variety of etiological factors. In the patient group prior to treatment, mean serum zinc concentration and leukocyte alkaline phosphatase activity were significantly lower than normal. Results indicate that zinc sulfate was effectively equivalent to placebo in the treatment of these disorders. Although these results demonstrate abnormalities of zinc metabolism in some patients with taste and smell dysfunction they fail to provide evidence for a single, therapeutic approach to the many disorders which are associated with abnormalities of taste and smell. However, the methods and procedures developed in this study demonstrate that taste and smell dysfunction can be studied in a quantitative, systematic manner.


The Penlon Oxford ventilator. A new ventilator for adult or paediatric use. A pneumatically powered lung ventilator for anaesthesia and intensive care of both adult and paediatric patients is described. The design criteria were selected to produce a small machine with high power, simple to control, sterilise and service. Laboratory and clinical results are presented andprocedure for clinical use of the controls suggested.


Punch, on anaesthesia.

Punch, on anaesthesia. References in Punch to ether and chloroform during the first two years after the first successful public demonstration of anaesthesia are quoted and considered.


[Treatment of Ewing's tumor (author's transl)]. Eight cases of Ewing's tumor are reported. Four cases (50%) were localized forms at diagnosis and the remaining presented metastasis. The localized forms were treated with a combination of irradiation at dose of 4,500-5,000 rads and chemotherapy with vincristine and cyclophosphamide during two years. Three of these patients (75%) are alive and free of disease for more than two years. In the metastatic forms the treatment used was radiotherapy and diverse chemotherapy combinations with palliative intention. Bibliography related with this subject is reviewed and new chemotherapeutic combinations are discussed, the superiority of any treatment being not yet established.


["Cellular synchronization" method in treatment of infantile tumors]. Results obtained by the "cellular synchronization" method in 19 patients are reported; there were five Ewing's sarcomas, three nephroblastomas, nine neuroblastomas and two Burkitt lymphomas. Ages ranged between four months and six years. Most of them had metastatic diseases, resistent to previous therapies. The protocol consisted on vincristine as "synchronizator agent" days 1 and 2, and cyclophosphamide as "effector agent", days 3, 4, 5 and 6 of each pulse. The clinical and hematologic tolerance was generally good. Results were: 12 complete remissions, two partial remissions and three failures.


Anaesthesia for orthotopic allogenic liver transplantation in pigs. Anaesthesia with a mixture of halothane, nitrous oxide and oxygen was used for allogenic liver transplantation in 24 pigs. All animals had haemodynamic disturbances due to the technique of the operation: metabolic acidosis, disturbances of bioelectric activity of the heart and electrolyte level changes. The methods of management of these disturbances are discussed. Favourable results were obtained when transfusing heparinized stored blood in place of initially used ACD blood which increased the intensity of metabolic acidosis. Details of the technique and method of anaesthesia and monitoring of animals during operation are discussed.


Peptichemio in children with neoplastic disease. 32 children with different types of tumors have bben treated with peptichemio. The efficacy was excellent in rhabdomyosarcoma and embrional sarcoma; encouraging in neuroblastoma, Wilms tumor and histiocytosis X. Side and toxic effects were minimal. In conclusion we can say that peptichemio is effective in oncologic diseases, but a larger number of patients is required in order to have a better knowledge about the antitumor activity of this drug.


Evaluation of P a-A CO2, P A-a O2 and VD/VT measurements during controlled respiration in children. Preliminary communication. The indices of P a-A CO2, P A-a O2 and VD/VT were evaluated in a group of children treated with controlled ventilation (IPPV) for: pneumonia, congenital heart disease, respiratory distress syndrome or central nervous system diseases. The P A-a O2 index is regarded as the most useful one, since it enables the possibility to select a F IO2 value for obtaining an optimal P aO2. For calculation of VD/VT according to Bohr's formula during connection of the child to respirator P ECO2 was determined planimetrically from the capnographic curve. P a-A CO2 was recognized as a less useful index and difficult to interpret.


Early haemorrhage from brachiocephalic trunk as a complication of tracheostomy. A 27-year-old patient suffered injuries to the facial bones and brain contusion in a traffic accident. On the third day after the accident the patient was admitted to an intensive care unit in view of increasing respiratory failure. Tracheostomy was performed for prolonged controlled respiration. On the 6th day after tracheostomy the patient died from a sudden massive hemorrhage from the tracheostomy site. Autopsy findings showed that the direct cause of death was injury to the brachiocephalic trunk communicating with a focus of tissue necrosis in the tracheal wall. The authors stress the early development of this complication and the necessity of the earliest possible commencement of intensive care in cases of injuries to the facial bones.


Antibodies to guinea pig lymphokines. III. Reactions with radiolabeled lymphocyte activation products. An antiserum raised against a purified fraction of guinea pig lymphokines exhibits marked in vivo properties; it suppresses delayed hypersensitivity reactions and binds migration inhibition factor (MIF) from supernatants of activated lymphocyte cultures in vitro. This serum was analyzed for specificity using a radioactive double labeling technique which distinguishes products synthesized either de novo or in increased amounts by stimulated lymphocytes. Combined supernatants of stimulated (concanavalin A or PPD) and unstimulated cultures labeled with either tritiated or [14C]leucine, respectively, were fractionated on Sephadex G-75. Pooled fractions were precipitated using the antibody sandwich technique, and solubilized precipitates were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Using this procedure the anti-lymphokine serum recognized primarily three newly sythesized lymphocyte activation products with molecular weights of approximately 60 000, 45 000 and 30 000 daltons. By contrast, these molecules could not be detected in radiolabeled lymph node cells which had been solubilized with NP-40 detergnt. The isoelectric point of all three molecules was found to be 5.2 +/- 0.3. The previously determined characteristics (mol.wt. 45 000, pI 5.2) of MIF and the property of the anti-lymphokine serum to absorb MIF activity suggest an identity between MIF and one of the molecules. In view of the previously described in vivo effects of the anti-lymphokine serum it is concluded that at least one of these three molecules plays an important role in the early events of delayed-type hypersensitive reactions in vivo.


Restoration of immune responsiveness in early thymectomized xenopus by implantation of histocompatible adult thymus. Larvae of the South African clawed toad, Xenopus laevis, were thymectomized at Nieuwkoop and Faber stages 45-46 (4-5 days after fertilization). The 1-1.5-year-old thymusless toads thus obtained were implanted with histocompatible thymus from 1-year-old toads, and 4 weeks later were given skin allografts or rabbit red blood cells (RRBC) to determine their immune response. In contrast with the perfectly tolerant thymusless controls, the thymus-implanted toads rejected skin allografts after longer survival times (25-66 days) than the nonthymectomized controls (18 - 19 days). Accelerated rejection (15 - 27 days) of the second-set skin allografts was evident in the thymus-implanted individuals. Similarly, the capacity of antibody production against RRBC was restored to the thymus-implanted toads to roughly the normal extent. Implantation of thymus also restored the histological features of the spleen in thymectomized toads. The experiments clearly demonstrate that in Xenopus the thymus plays an essential role for immunity at the early stages of its histogenesis. The restorative capacity of the adult thymus is also stressed.


Production of osteoclast-activating factor by normal human peripheral blood rosetting and nonrosetting lymphocytes. This study has tested the ability of human mononuclear cells and the subpopulations of lymphocytes that rosette (E-RFC) or do not rosette (non-E-RFC) with sheep red blood cells to synthesize DNA and to produce a mediator with bone resorbing activity (osteoclast-activating factor, OAF) in response to stimulation with phytohemagglutinin (PHA). Mononuclear cells were stimulated by PHA both to synthesize DNA and to produce a factor that caused bone resorption. E-RFC enriched for T lymphocytes and depleted of macrophages synthesized considerable DNA in response to stimulation with PHA, but were unable to produce significant bone resorbing activity in tissue culture unless macrophages were re-added to the E-RFC. In contrast, mononuclear cells depleted of E-RFC (non-E-RFC enriched for B cells) did not synthesize DNA in response to stimulation with PHA, but did produce a mediator that caused significant bone resorption in tissue culture. In most of the experiments, unstimulated non-E-RFC produced as much OAF as the PHA-stimulated non-E-RFC. These results suggest that both activated T lymphocytes (E-RFC) and B lymphocytes (non-E-RFC) can produce OAF.


Affinity and specificity of penicillin-antibody interaction determined by an enzyme (E. coli beta-galactosidase) immunoassay. An enzyme immunoassay (EIA) for a penicillin derivative is described with a sensitivity at least at the nanogram level. The label, E. coli beta-galactosidase is a macromolecule of 540 000 daltons: the size of the enzyme and the ease of linking penicilloyl residues to it make it an interesting model to study the effect of the degree of haptenic substitution (DS) in the tracer on the parameters of EIA. Our results show that the affinity of the binding reaction between antibody and tracer is proportional to the DS but the sensitivity of inhibition is not affected, at least not between 1 and 10 penicilloyl residues per GZ molecule. The theoretical consequences and practical applications of multivalent tracers in EIA are discussed.


Effect of carrier-specific tolerance on the generation of helper cell function. The effect of carrier-specific tolerance on the development of helper cell function was studied in irradiated rats reconstituted with normal or carrier-tolerant bone marrow. Bone marrow (BM) from normal rats or rats tolerant to sheep IgG (SGG) was transferred to lethally irradiated syngeneic recipients, which were challenged 3 to 5 weeks later when immunocompetence to T-dependent antigens was shown to have recovered. When recipients were challenged with the 2,4,6-trinitrophenyl (TNP) hapten coupled to SGG in adjuvant, groups which received SGG-tolerant BM were 70-80% unresponsive in terms of anti-TNP plaque-forming cells compared to recipients of normal BM. This effect was carrier (SGG)-specific and was reversed when normal thymocytes were transferred with tolerant BM. Moreover, neither tolerant BM nor tolerant thymocytes were able to suppress the responsiveness of normal BM at a 1:1 ratio. These cell-mixing experiments imply that the reduction in helper cell function is due neither to suppressor cells nor antigen carryover in the tolerant BM. It is suggested that a BM precursor of the helper T cell may be rendered tolerant and therefore already possesses antigen specificity prior to thymic migration.


Improved corneal storage for penetrating keratoplasties in humans. A group of 92 patients, who had penetrating keratoplasties with donor corneas that were stored for up to 7 days in M-K media, had 90% clear grafts 2 months postoperatively and about 80% at 6 months. A comparison of the postoperative corneal thickness measurements was made of the patients receiving donor corneas stored by cryopreservation for prolonged times in moist chambers for less than 24 hours, or in M-K media for several days. There was no statistical difference between the 3 storage methods during the 10 week follow-up nor was there any difference between 72 hours and 96 hours of storage in M-K media.


[The treatment of psoriasis].

[The treatment of psoriasis]. The therapeutic possibilities for psoriasis are multiple; they are based on experience and on empiricism and are harmless for the patient, or on the known pharmacodynamic action which limit their use. It should be remembered that psoriasis is not incurable, since it can be treated. But the definitive curative treatment will be discovered only when the cause of the disease is discovered.


[Interstitial deletion of the long arm of chromosome 7 in a female child with leprechaunism]. A case of interstitial deletion of the long arm of chromosome 7 with probable loss of segment 7q2 is reported in a infant with leprechaunism. This association suggests the possibility of a heterozygous deletion of the normal allele at the leprechaun locus.


The influence of conditions of growth on the endogenous metabolism of Saccharomyces cerevisiae: effect on protein, carbohydrate, sterol and fatty acid content and on viability. The nature of the endogenous reserves of Saccharomyces cerevisiae was examined with respect to conditions of growth, specifically extremes of oxygen tension and carbon source. Cells were grown in batch culture at 30 C under aerobic conditions on a galactose or glucose carbon source and under anaerobic conditions on glucose. The greatest effect of growth conditions on the chemical composition of the cells was on their fatty acid and sterol content. Cells grown under both aerobic and anaerobic conditions mobilised concurrently protein, glycogen, trehalose and fatty acids during a period of 72 hours' starvation under aerobic conditions. The viability of both types of the aerobically grown cells declined to 75% during this period and was not influenced by the initial fatty acid and sterol content of the cells. Cells grown anaerobically showed a more rapid decline in viability which was only 17% after 72 hours' starvation. This loss of viability was not due to a lack of available endogenous reserves but was probably due to an impaired membrane function caused by a deficiency of sterols and unsaturated fatty acids.


Metabolism of nitrophenols by bacteria isolated from parathion-amended flooded soil. Two bacterial isolates from parathion-amended flooded soil, Pseudomonas sp. and Bacillus sp., were examined for their ability to decompose nitrophenols. Uniformly labelled 14C-p-nitrophenol was metabolized by both bacteria, 14CO2 and nitrite being end products. A substantial portion (23% for Pseudomonas sp. and 80% for Bacillus sp.) of radioactivity applied as p-nitrophenol was accounted for as 14CO2 at the end of a 72-h period; 8 to 16% remained in the water phase after solvent extraction. Pseudomonas sp. produced nitrite also from 2,4-dinitrophenol, but only after a lag, and not from o- and m-nitrophenols. Interestingly, m-nitrophenol, known for its resistance to biodegradation because of meta substitution, was decomposed by Bacillus sp., resulting in the formation of nitrite and phenol; o-nitrophenol and 2,4-dinitrophenol resisted degradation by this bacterium.


[Systematic study of pharyngeal and nasal bacteria in children affected by relapsing diseases of respiratory organs (author's transl)]. The research was conducted on 191 nasal and pharyngeal swabs from children aged between two and ten years, affected by relapsing diseases of their respiratory organs. The aim has been that of isolating those bacteria whose action cause the most frequent respiratory diseases. They are: Haemophilus influenzae, Staphylococcus C+, Klebsiella pneumoniae, Pseudomonas and other Gram-negative bacteria. The isolated bacteria were submitted to sensitivity tests and to the normally used antibiotics. From this research follow the necessity to know which bacteria play the pathogenous role from patient's serological alterations.


[Micologic diagnosis fo the respiratory infections (author's transl)]. The Author briefly sums up the morphological featues of the pathogenic fungi which may be present in sputum and bronchoaspirates. Furthermore the opportunity of a histological test for every types of pathological material is pointed out.


[Comparative analysis between qualitative and quantitative features of orofaringeal and tracheo-bronchial bacterial flora in normal subject (author's transl)]. In 28 subjects surely without tracheo-bronchial phlogosis it had been observed that the trachea and the bronchi are mostly sterile, only rarely there is a normal bacterial flora. In the mouth and in the pharynx there is instead, almost always, normal bacterial flora and only exceptionally potentially pathogenous strains at a concentration inferior to 10(7).


Clinical use of the LH-RH in assessing gonadotropic reserve in children with idiopathic precocious puberty, premature thelarche and premature adrenarche. Serum LH and FSH were assayed in 31 girls with normal pre puberty, precocious puberty, premature thelarche, and premature adrenarche, aged 2 to 9 years. The effect of synthetic luteinizing hormone-releasing hormone (LH-RH) on serum gonadotropins was evaluated in eleven of them. In all girls with precocious puberty, serum LH was increased up to high levels. The mean releasable LH in two girls with idiopathic precocious puberty was significantly greater than in normal prepubertal or pubertal children. Basal FSH in children with precocious puberty was within the limits of normal prepuberal children, and FSH secretion in response to LH-RH was not significantly greater than in the group of normal prepubertal and pubertal girls. In children with premature thelarche and premature adrenarche, basal levels of LH and FSH, as well as gonadotropin response to LH-RH were in the prepubertal range. These preliminary results show that the LH-RH test might be of clinical value in differenitating abnormal puberal development.


[The possibility of an etiopathogenetic role of the fungi isolated from the respiratory tract (author's transl)]. The large number of fungous strains isolated from specimens coming from the respiratory tract is a possible source of diagnostic failures. For an accurate diagnosis it is necessary to screen between fungi in a saprophitic and in a parasitic position. This is very difficult both for fungi, which are largely spread in the environment, like Aspergillus sp., and for fungi, which are commonly found on the mucous membranes, like Candida or Torulopsis sp. The actual pathogenetic activity of a fungous strain may be established on a mycological approach by means of an accurate taxonomic definition: only few species have pathogenetic possibilities: f.i. A. fumigatus, C. albicans. For a clinical-immunological approach are very useful the presence of debilitating diseases and the defectiveness of immunological tests, especially those of delayed hypersentivitity.


[Ribosomal vaccine obtained from Salmonella typhimurium and tested against the challenge of an orally administered virulent microorganism]. Ribosomal preparation obtained from Salmonella typhimurium, used as a vaccine, was able to induce protection of 100% on mice challenged with 5.5 X 10(9) CFU of S. typhimirium administered by oral route. Effective dose at 50% was of 0.1085 mug, expressed as ribonucleic acid (RNA). This vaccine induced an important humoral response as soon as in nine days. The ribosomal preparation used in this work was maintained at 4 degrees C at least for eighty two days. This fact shows an adequate stability of this biological product.


[Immunofluorescence technique applied at serological diagnosis of the respiratory tract infections from gram-negatives bacteria (author's transl)]. The immunofluorescence indirect technique was evaluated for detecting specificities, Ig classes, and levels of serum and sputum antibodies against bacteria isolated from sputa in patients with broncho-pulmonary infections. Results obtained with the FA method were compared with those obtained with a passive haemagglutination test. The former method gave much more reliable results than the latter. By using FA indirect method it was possible to assess pathogenicity of baceterial strains isolated from sputum and to establish their ethiological significance in many clinical cases whose sputum cultures were impossible or difficult to evaluate, as for instance in a patient with a chronic bronchitis exacerabtion caused by a strain of Aeromonas hydrophila. Further investigation are suggested in order to improve technically the FA method and to find the easiest and most reliable way out to evaluated the effectual relationship between bacteria in sputum and immunoglobulin response in sputum or in serum of patient with respiratory tract infections due to bacteria.


Mating reaction in yeast protoplasts.

Mating reaction in yeast protoplasts. Protoplasts prepared from complementary haploid strains of Saccharomyces cervisiae were studied with regard to their ability of conjugating. Neither fresh protoplasts nor the growing protoplasts possessing fibrillar walls exhibited sex specific agglutination or fusion. However, they were capable of inducing sexual activation in normal cells of opposite mating type. After completing the regeneration of cell walls the protoplasts could conjugate either with each other or with cells of opposite sex. The frequency of conjugations was low, about 1%, and was largely dependent on the degree of completition of the wall during regeneration. From the results the following conclusions may be drawn: 1. The initiation of mating is dependent on the integrity of the cell wall. 2. The sex specific morphogenetic changes do not occur in wall-less protoplasts but may happen after the protoplasts have regenerated their cell walls. 3. The lysis of cell walls does not occur until the walls come into close contact. 4. The fusion of plasma membranes in sex-activated protoplasts cannot be induced by arteficial agglutination.


[Clinical problems about microbiological findings in pneumology (author's transl)]. Identification for clinical purposes of the etiological germs in individual cases of bronchopulmonary not tuberculous infections is usually very hard. Sometimes, particularly in acute cases, microbiological counts in sputum as in tracheobronchial secretions and exudates may be useful. In some chronic cases an amount of particular bacteria in tracheal (transcutaneous) secretion larger than in sputum is to consider an etiological sign.


[An antigenic extract analyzed by bidimensional immunoelectrophoresis (author's transl)]. An antigenic extract from broth culture of Aspergillus fumigatus has been analyzed by bidimensional immunoelectrophoresis of Clark and Freeman against rabbit antiserum. The analysis has show the extract to be constituted by seven different antigens.


Correlation among turnover of nucleic acids, ribonuclease activity and sporulation ability of Saccharomyces cerevisiae. The turnover of nucleic acids and changes in ribonuclease activity during sporulation of Saccharomyces cerevisiae were studied. In the sporulating strains, 37-58% of vegatatively synthesized RNA were degraded during the sporulation process. The degree of degradation of vegetative RNA was proportional to the sporulation ability. In the non-sporulating strains, the degradation of vegetative RNA was less than 28% in the sporulation medium. Accompanied by the degradation of vegetative RNA, a ribonuclease activity increased several times during sporulation. We have found a close relation among the sporulation rate, the degree of the degradation of vegetative RNA and the increase in ribonuclease activity in the sporulation medium, using cells of which sporulation ability was repressed by changing the age or carbon source in various degrees.


[Intracellular organisation of bacteriophage tail-like bacteriocins of group A in Serratia marcescens (author's transl)]. The biosynthesis of a phage tail-like Bacteriocin by cells of the group A-bacteriocinogenic (bA+) Serratia marcescens strain no. 16 after induction with mitomycin C (MC) was examined electron-microscopically. This bacteriocin (total length 117 nm) consists of a hollow core and a contractile sheath. At 60 min following induction, rod-like bacteriocin-particles were identifiable in ultrathin sections. The particles were found to comprise three morphologically different forms of aggregation: 1. hexagonal inclusions, 2. contiguous, band-like particles, and 3. staples of superimposed layers of bacteriocin particles. At 120 min after induction bA+ cells revealed maximally 450 bacteriocin particles. Similarly, the phage tail particles could be demonstrated with the "in situ lysis technique" at 60 min following induction. Occasionally, phage heads were demonstrable, but in no instance were complete phage particles discenible. Dividing cells of the bA+ strain of S. marcescens maintained their rod-form following induction with MC until intracellular phage tail bacteriocin particles were seen. However, at 120 min after induction, the swollen, sphaeroplast-like cells lysed, an event that could be correlated with fine structural alterations of the cell wall.


[Using a new dilutor in serology (author's transl)]. The experiences acquired using a new dilutor in the serological field are dealt with here. The versatile dilutor is particularly adapted to the execution of two-fold dilutions. Among the many possible techniques, the relatives to ASLO, THPA and serum-agglutinins are thoroughly described.


Some physiological observations on the uptake of D-glucose and 2-deoxy-D-glucose by starving and exponentially-growing yeasts. Some methods for measuring the uptake of sugars by yeasts were investigated critically. A study was made of the effects of starvation of Pichia pinus, Candida utilis, Saccharomyces cerevisiae and Rhodosporidium toruloides on their uptake of D-glucose and 2-deoxy-D-glucose. Marked changes in the rates of uptake of these sugars occured during 10 h of starvation, including (a) an immediate increase of up to 75% above that for growing cells and (b) a continuous decline to as little as 4%. Each yeast behaved differently. The rates did not remain constant during the periods of starvation often used for studies on the transport of sugars into yeasts. For Pichia pinus, there were striking differences, associated with starvation, between the transport of 2-deoxy-D-glucose and D-glucose, despite evidence that the two sugars enter this yeast by means of the same carrier. Some physiological explanations for these findings are discussed.


Regulation of ornithine transcarbamylase in Rhodotorula glutinis. The regulation of ornithine transcarbamylase (OTC) of Rhodotorula glutinis has been studied, by growing the yeasts in different carbon and nitrogen sources and estimating the enzyme level in crude yeasts extracts. The results show a nutritional repression of OTC by arginine, when added to the culture media as carbon, nitrogen or carbon and nitrogen sources. On the other hand ornithine does not exert any effect in the same experimental conditions.


Characterization of purified nitrate reductase A and chlorate reductase C from Proteus mirabilis. Nitrate reductase A has been solubilized from purified cytoplasmic membranes by extraction with tert-amyl alcohol. The resulting aqueous solution contained monomeric reductase which polymerized slowly to dimers and tetramers with sedimentation coefficients of respectively 10.5, 16 and 23 Svedbergunits. The polymerization could be stopped to some extent by addition of a small amount of Triton X-100. These distinct entities of nitrate reductase A were separable on electro-focusing, DEAE-column chromatography and polyacrylamide gel electrophoresis, and have been proved to consist of similar subunits with molecular weights of 104000, 63000, and 56000 daltons. The molecular weights of monomeric nitrate reductase A was found to be about 240000 daltons. Chlorate reductase C has been solubilized by a similar procedure, resulting in only monomeric enzyme. Chlorate reductase C exhibited a sedimentation coefficient of 7.7 Svedbergunits, an isoelectric point of pH = 4.55 and a molecular weight of approx. 180000 daltons. It was found to consist of three subunits with molecular weights of 75000, 63000 and 56000 daltons. The latter two subunits are most probably common in nitrate reductase A and chlorate reductase C.


The correlation between the protein composition of cytoplasmic membranes and the formation of nitrate reductase A, chlorate reductase C and tetrathionate reductase in Proteus mirabilis wild type and some cholate resistant mutants. Three genotypically different chlorate resistant mutants, chl I, chl II and chl III, appeared to lack completely nitrate reductase A, chlorate reductase C and tetrathionate reductase activity. Fumarate reductase is only partially affected in chl I and chl III and unaffected in chl II. Formate dehydrogenase is only partially diminished in chl II, hydrogenase is diminished in chl I and chl II and completely absent in chl III. Subunits of nitrate reductase A, chlorate reductase C and tetrathionate reductase have been identified in protein profiles of purified cytoplasmic membranes from the wild type and the three mutant strains, grown under various conditions. Only the presence and absence of the largest subunits of these enzymes appeared to be correlated with their repression and derepression in the wild type membranes. On the cytoplasmic membranes of the chl I and chl III mutants these subunits lack for the greater part. In the chl II mutant, however, these subunits are inserted in the membrane all together after anaerobic growth with or without nitrate. A model for the repression/derepression mechanism for the reductases has been proposed. It includes repression by cytochrome b components, whereas the redox-state of the nitrate reductase A molecule itself is also involved in its derepression under anaerobic conditions.


[Pathology and pathogenesis of coli dysentery and coli diarrhea in suckling piglets. 1. Studies on the pathomorphology of the gastrointestinal tract in coli dysentery as well as coli diarrhea in the suckling piglet]. The following findings were obtained from histomorphological examination of 45 piglets with coli-bacillosis (with serotypical Escherichia coli detected) and ten piglets with coli-diarrhoea (with non-serotypical E. coli detected): Diarrhoea accompanying either disease was not attributable to catarrhal or haemorrhagic gastro-enteritis. The mucous membrane of the gastro-insestinal tract remained histomorphologically intact in either disease. No change was recorded particularly from villous or surface epithelia and glandular epithelium, and the villous structure was not basically altered. Different degrees of hyper aemia of the gastro-intestinal mucous membrane and moderate oedematisation of the villous stroma were irregular findings. Adhesion of enteropathogenic E. coli to mucous membrane surface was observed but rarely and did not exhibit any visible relationship with the incidence in E. coli of L-antigen K88. In coli-bacillosis and coli-diarrhoea both the diarrhoea and morphological situation of the gastro-bacillosis tract were in conformity with the cholera-type "intestinal noninflammatory secretory diarrhoea" as caused by enterotoxins. Other issues relating to pathology and diagnosis are also discussed.


[Pathology and pathogenesis of coli dysentery and coli diarrhea in suckling piglets. 2. Studies on the experimental induction of disease through the intragastric administration of coli-enterotoxin]. Fractionated intragastric application of a crude enterotoxin of Escherichia coli O 149:K91 (B) K88 (L) was part of experimental intoxication of 88 nursed piglets, aged between one and three days. The experiment was based on culture filtrate supernatant which had produced positive enterotoxic effect in an intestinal ligature test of swine and rabbit. The results were compared with 50 controls, piglets of the same age with intragastric administration of physiological salt solution. The experiment gave pronounced aquaeous diarrhoea (100 per cent) accoumpanied by exsiccosis, weight loss, rough hair, greyish discoloration of the skin, and other manifestations. The mortality was nine per cent. The clinical and pathomorphological picture of the enterotoxin syndrome was in close agreement with spontaneous coli-bacillosis of nursed piglets. Enterotoxin-caused diarrhoea occurred, with the gastro-intestinal mucous membrane remaining morphologically intact. This intoxication method has proved to be a safe model for experimental induction of coli-bacillosis, and it is likely to be suitable for vaccine testing. It can be used, as well, as a simple qualitative enterotoxin test. Additional issues relating to the pathology and pathogenesis of the coli-enterotoxin syndrome of piglets are discussed.


[Risk of recurrence of several congenital malformations: anencephaly, spina bifida, cleft palate and cleft lip]. Recurrence risks were estimated for some congenital malformation from a multifactorial model according to the method given by Smith (1971). Risks were estimated for cleft lip with or without cleft palate, cleft palate alone, anencephaly and spina bifida from data on frequency and heritability collected in France. Results are given in tables representing risks for some 180 specific family histories.


Analysis of clinical and electrophysiological findings in Jakob-Creutzfeldt disease. Serial EEG and EMG investigations were performed in the course of a histologically verified case of Jakob-Creutzfeldt disease. Some electrophysiologic data, including visual-evoked responses were analyzed using a computer. Correlations between clinical and EEG findings suggest that the generator of the periodic discharges may be localized in some circumscribed area of the upper brain stem, probably the thalamus. The inhibitory effect of various narcotics suggests that the pacemaker of the triphasic discharges has relations to the nonspecific activating system.


The use of agarose gels for the assay of the deoxyribonuclease activity associated with the soluble penton of adenoviruses. Evidence is presented that the excess pool of penton complexes purified from adenovirus type 1-infected HEp-2 cells also carry an endonucleolytic activity. The effect was measured with both E. coli and adenovirus type 1 double-stranded DNA substrates. The use of agarose gels for assaying the endonuclease activity allowed the approximative calculation of the number of penton molecules which might produce one DNA double-strand break under the experimental conditions selected.


[Controlled clinical research on the potassium-retaining action of various diuretic drugs]. The potassium-retaining action was evaluated in its kaliemic reflexes, in two diuretic associations composed respectively of hydrochlorothiazide + spironolactone and hydrochlorothiazide + amiloride. The potassium intraerythrocytic levels were also determined as well as the natriuresis, the natremia and the daily diuresis. Researches carried out on a group of patients affected by congestive heart failure showed that, the diuretic efficacy being equal, the association of hydrochlorothiazide + spironolactone does not significantly interfere, at the various posologic levels, with the potassium balance. On the contrary, in this regard, the associaiton of amiloride + hydrochlorothiazide appeared to be less manageable because therapeutic dosages showed a tendency to hyperdaliemia.


[Immunomorphological study of plasmorrhagia in experimental hypertension in rats]. Plasmorrhagia of the arterial wall of various organs in rats with ischemic renal, DOCA-saline, and genetic spontaneous hypertension was studied by the method of fluorescent antibodies according to Coombs with the use of pure antibodies to yamma-globudin of a rabbit. The most pronounced plasmorrhagia was observed in rats with DOCA-saline hypertension in the arterial vessels of the kidneys. In rats with genetic hypertension lesions of the heart vessels were noted.


[Immunofluorescence study of fixed antibodies in experimental allergic polyneuritis]. Determination of globulins in the peripheral nervous system in rabbits with experimental allergic polyneuritis (EAP) was carried out by Coonbs' method with fixation of complement according to Shepherd. Fixation of immunoglobulins in the myelin coats of sensitive ganglions before the appearance of neurologic symptoms of EAP was shown. In the same departments of the peripheral nervous system and at the same time periods there was observed accumulation of immunocompetent cells, which testified to the likelyhood of local formation of specific antibodies that produced a pathogenic action.


[Cytological studies in pulmonary pathology]. Cytological investigations of the bronchial secretion and sputum in particular have acquired in recent years a great practical significance in pulmonary pathology. It is recommended to use cytodiagnosis along with prophylactic X-ray examinations of the population to detect pulmonary pathology, in particular among individuals with a higher risk of developing cancer. A substantiated opinion is put forward that cytodiagnosis should precede examinations of patients with clinico-roentgenologically confirmed changes in the lungs.


[Determination of diagnostic significance of nonspecific morphological signs]. For assessment of diagnostic significance of nonspecific morphological signs the authors suggest to apply calculation of their informativeness according to Kullback's formula. This qualitatively characterizes the degree of difference of crossed signs in differentiating diseases. An initial value is frequency of occurrence of a sign or a degree of its manifestation determined by a relative frequency index according to histometry findings. Calculation of informativeness may be applied only with respect to statistically significant differing aspects. The value of the informativeness index corresponds to diagnostic significance of a sign. The recommended objective method broadens the sphere of application of diagnostic biopsy and may facilitate putting into practice of pathological anatomy of methods of computer diagnosis.


[Histophysiology of the thymus gland].

[Histophysiology of the thymus gland]. The article comprises a survey of the literature data on histophysiology of the thymus gland and a discussion of results of the authors' own observations of this gland in rats line "Vistar" in normalcy and in the presence in the organism of a transplanted tumour RS-1. Problems associated with histophysiology of the thymus, including such as differentiation of thymocytes, their relationships with the reticuloepithelial cells, the capacity of the latter for secretion, the role of the stratified epithelial bodies, the hematothymus barrier, etc., are discussed.


[Ultrastructural changes in mucosa of the distal portion of the large intestine of patients with dysentery]. The ultrastructure of the mucosa of the large intestine was studied in 10 patients with acute dysentery. The group of patients included 7 women and 3 men aged 17--50 years. Diagnosis was confirmed in all cases bacteriologically (by isolation of Sonne shigella in 4 patients and Flexner shigella in 6 patients). The electron-microscopy study of bioptats of the mucosa showed that in the inflammatory process all its cells--prismatic, gobletcells, and enterochromaffin -- took part, although not in the same degree. Early appearance of a great number of prismatic cells with a high functional activity indicated to compensatory abilities of the mucosa already during the first days of the disease.


[Detection of damaged myocardial cells in histological sections by photochemical fluorochroming]. The effect of photochemical fluorochromizing used in the method suggested consists in the following: after the exposure of sections to short-wave ultraviolet irradiation the preparations start to fluorescence intensively in the visible region with the long-wave the myocardium of mice, dogs and section materials showed that following photochemical fluorochroming the intensity of lumenescence of damaged cells of the myocardium increased markedly as compared with that of intact cells. The authors recommend to use the described method in diagnosis of early stages of ischemic lesions of the myocardium.


Anatomical considerations when using endodontic endosseous pins and blade implants. The use of pin and blade implants is evaluated from the point of view of the regional anatomy. Some principles are enunciated and a plea is made for the publication of more clinical analyses.


Denture sore mouth. Aetiological aspects and treatment. Seventy-four patients wearing full upper and lower dentures were examined in the study; 37 exhibited varying degrees of denture sore mouth (DSM) while the remaining 37 patients acted as controls. Denture trauma was more common in the DSM group. Candida was grown from 73 per cent of patients with DSM but only from 22 per cent of controls. Control patients had better denture hygiene than DSM patients. One year later 22 of the original DSM patients wearing newly made dentures were re-examined. Nine out of 22 still exhibited varying degrees of DSM. In the 9 cases persisting, a nystatin-chlorhexidine treatment plan was prescribed, resulting in resolution of 7 further cases. The cases that failed resolve were wearing unstable traumatogenic new dentures.


A survey of patients' attitudes to their dentist. A survey of the dentist-patient relationship, carried out in several Melbourne suburbs, found that the incidence of dentures increases with age; that females visit the dentist more regularly and are more likely to wear partial dentures than males; that the young visit more regularly than the old; and that the wearing of dentures and the expense of treatment are significant factors which deter people from visiting the dentist more regularly. It was found that "fear" and "dislike" of the dentist, "low" confidence in the dentist and a poor dentist attitude to the patient are all associated with poor attendance. "Dislike" is a stronger deterrent than "fear", although "fear" is more common. Confidence in the dentist is high, most have a high opinion of their own dentist, and only a fifth of the respondents consider their dentist to be "rude" or "indifferent". Attitude associations are also discussed.


Home dialysis and renal transplantation in the management of chronic renal failure. In Australia, most patients with terminal renal failure can be offered rehabilitation by home dialysis or renal transplantation, or both. All patients require an initial period of dialysis and this can, in many cases, be carried out in the patient's home. Although the great majority of patients with terminal renal failure will receive a renal transplant, a further period of dialysis will be necessary if this is not successful until a second transplant can be carried out. Home dialysis is especially valuable for these patients, for country patients and for those unlikely to receive a satisfactory renal transplant.


Laboratory diagnosis of urinary tract infection in children. One-third of the total number of 1,500 urine specimens examined each month by the bacteriology department of the Royal Children's Hospital, Melbourne, originate in the General Paediatric Clinic. The patients, presenting with acute symptoms, are similar to those encountered in general practice. This article discusses the laboratory methods used to support a diagnosis of urinary tract infection (UTI) in childhood.


Resistance of mice to Krebs ascites tumour, sarcoma S180 and PC6 plasmacytoma after immunisation with Salmonella enteritidis 11RX. Resistance to Krebs ascites tumour, sarcoma S180 (ascitic form) and PC6 plasmacytoma can be induced with prior immunisation with live Salmonella enteritidis 11RX. One thousand to ten thousand more tumour cells are needed to give an LD50 after immunisation. Resistance to PC6 could be recalled 137 days after intravenous immunisation with 11RX protein antigen intraperitoneally as measured by prolonged survival or monitoring the death of 5[131I]-iodo-2'-deoxyuridine labelled tumour cells in vivo. The range of tumours to which resistance can be produced by 11RX immunisation suggests that the mechanism of resistance does not involve antigens common to the tumours and Salmonella enteritidis 11RX.


Local and systemic effects in the non-specific tumour resistance induced by attenuated Salmonella enteritidis 11RX in mice. Suppression of growth of a number of different murine tumours, injected subcutaneously or into the foot pad, was induced by prior intraperitoneal or intravenous immunisation with Salmonella enteritidis 11RX. The effect of immunisation on tumour growth was relatively minor, but could be enhanced by addition of 11RX antigen preparations to the suspensions of tumour cells used for challenge. The significance of these findings is discussed.


A role for antibody in the expression of cellular immunity to Salmonella typhimurium C5. Immunisation of mice with alcohol-killed Salmonella typhimurium C5 vaccine before infection with Salmonella enteritidis 11RX enhanced the ability of these mice to control and eliminate a challenge dose of Salmonella typhimurium C5, compared to mice which only received live Salmonella enteritidis 11RX organisms. When alcohol-killed Salmonella enteritidis Se795 vaccine was used instead of the Salmonella typhimurium C5 vaccine, this effect was not observed. These observations imply that both humoral and cellular responses are important in the expression of immunity to slamonella infections. The bearing of these results on the observations of other workers is discussed.


The role of thymus-derived cells in immunity to salmonella infection. The ability of thymus-derived (T) cell depleted mice to eliminate a dose of the normally avirulent 11RX strain of Salmonella enteritidis was compared to that of normal mice by following the fate of the challenge organisms in the liver and spleen of both types of mice. Although the mice did not require normal numbers of T cells to survive infection with Salmonella enteritidis 11RX, T cell depletion reduced the ability of mice effectively to eliminate the organism from their tissues. In addition, T cell depletion abolished the ability of live Salmonella enteritidis 11RX vaccine to protect mice against a subsequent challenge with the virulent C5 strain of Salmonella typhimurium.


The effect of antigenic strength and immunisation on the popliteal lymph node allograft response. The kinetics of the popliteal lymph node response to an allograft of lymphoid cells injected into the foot pad were examined after challenge with strong (Ag-B) and weak (non Ag-B) transplantation antigens. The response to weak antigens was characterised by a lag period of 2 days. The response to strong antigens was more rapid in onset. Active immunisation against weak antigens accelerated the response so that it came to resemble the immediate response to strong antigens. Active immunisation against strong antigens depressed the response. This depression was reproduced by giving passive antiserum to normal recipients. Passive antiserum produced by immunisation against weak antigens was also suppressive. Adoptive transfer of immune lymphoid cells reproduced the effects seen with passive transfer of antiserum. These findings indicate that clonal expansion of antigen-sensitive cells is characteristic of immunity to weak and not to strong antigens and that antibody is produced in both situations and has a similar suppressive effect on the cell-mediated response in addition to its direct effect on the graft.


The responses of the popliteal lymph node of the sheep to Ross River and Kunjin viruses. The responses of popliteal lymph nodes of sheep to Ross River virus (RRV) or Kunjin virus (KV) have been studied by monitoring the cell populations, virus titre, antibody titre and plaque-forming cell (PFC) content of the efferent lymph. In a typical primary response to subcutaneous inoculation in the lower hind limb of either RRV or KV, the flow rate of lymph increased slightly. Increased cell concentrations in the lymph following inoculation caused the hourly cell outputs to rise 5.3- to 10.1-fold above pre-challenge levels. High cell outputs were sustained at greater than 3-fold above pre-challenge figures for up to 10 days. The increased number of large, blastic lymphocytes ranged from 4.0- to 14.9-fold; the increase in these cells usually followed the rise in total number of lymphocytes by 24 to 48 h and remained at greater than 3-fold higher levels for up to 12 days. Ross River virus was recovered in the efferent lymph for at least 36 h after inoculation. Sudden disappearance of the virus from the lymph was correlated with the onset of significant haemagglutination-inhibition antibody titres by 3 to 4 days after infection. In the efferent lymph, PFC were detected 5 to 7 days after primary or secondary inoculation of KV or RRV when lymphocytes were incubated with specific haemagglutinin-coated goose erythrocytes and guinea-pig complement. Antibody levels in the lymph were persistent while the occurrence of PFC was transient.


Salmonella typhimurium colitis.

Salmonella typhimurium colitis. A patient in whom Salmonella typhimurium infection caused a localised colitis is described. Colitis has been demonstrated in experimental animals infected with S. typhimurium and noted at post mortem in patients dying from S. typhimurium infection. However colitis is an infrequently recognised feature of this infection in man, the usual diagnosis being one of gastroenteritis. There have been four other cases reported with radiological evidence of colonic involvement due to salmonella infection. Colitis probably occurs more frequently than is usually recognised in this condition and must be distinguished from ulcerative colitis.


A study of the influence of magnesium ions on the conformation of ribosomal ribonucleic acid and on the stability of the larger subribosomal particle of rabbit reticulocytes. Mg2+ was shown to affect the conformation of rRNA over the range of 0.03-1.2M-KCl. The species studies were Escherichia coli S-rRNA and L-rRNA (the RNA moieties of the smaller and larger subribosomal particles respectively) and rabbits S-rRNA and L-rRNA. 2. The addition of Mg2+ to rRNA in reconstitution buffer (0.35M-KCl0.01M-Tris/HCl, pH7.2) at 20 degrees C let to an increase in bihelical secondary structure through the formation of additional (mainly A-U) base-pairs (e.g. an additional approx. 58 A-U base-pairs per molecule of E. coli S-rRNA as judged by u.v. difference spectrophotometry...


Peptidyltransferase activity of ribosomes and a ribosome precursor from a mutant of Escherichia coli. Escherichia coli strain 15-28 is a mutant with a defect in ribosome synthesis that caused the accumulation of ribonucleoprotein ('47S') particles during exponential growth. These particles are precursors to 50S ribosomes that lack three ribosomal proteins. Peptidyltransferase activity and binding at the peptidyl site of the peptidyltransferase centre are greatly decreased in 47S particles. Both these activities are lower in the 50S and 70S ribosomes of strain 15-28 than in its parent. Unusual assembly of the larger ribosomal subunit in strain 15-28 may produce completed ribosomes with diminished biological activity.


Effects of dicyclohexylcarbodi-imide on proton translocation coupled to fumarate reduction in anaerobically grown cells of Escherichia coli K-12. The addition of dicyclohexylcarbodi-imide to anaerobic cells of Escherichia coli K12 decreases both the observed extent of proton translocation coupled to fumarate reduction by endogenous substrates and the t 1/2 of proton re-entry after such translocation, but does not affect fumarate uptake. Dicyclohexylcarbodi-imide also inhibits fumarate reductase activity in cell extracts.


Mineral imbalances in farm animals and their study and diagnosis with isotopic tracers. Twenty-two mineral elements are known to be essential for animal life. These are calcium, phosphorus, sulphur, potassium, sodium, chlorine, magnesium, iron, iodine, copper, manganese, zinc, cobalt, molybdenum, selenium, chromium, tin, vanadium, fluorine, silicon, nickel and arsenic. Naturally occurring and man-made dietary imbalances of many of these elements and their interactions with other minerals are described and their functions and requirements by farm animals are outlined. The nature and importance of metabolic interactions among the mineral elements are discussed and the important concept stressed that there is no single minimum requirement or safe tolerance of a particular mineral, but a series of such minimum requirements and safe tolerances depending on the extent to which other minerals with which it interacts is present or absent from the diet. Radioactive tracer elements are shown to be of great value in the determination of mineral nutrient availability to the animal and for following mineral metabolic movements in the body. They are also shown to have considerable potential for the diagnosis of mineral imbalances. Various in vivo and in vitro techniques, involving both radioactive and stable tracers developed for the early diagnosis of mineral deficiencies are described and the strengths and weaknesses of such techniques in comparison with standard biochemical tests, are discussed. The need for further critical studies with isotopic tracers in the detection and diagnosis of mineral imbalances is emphasized. The main types of biochemical criteria used in the diagnosis of mineral deficiencies and excesses are given, with appropriate examples of their use.


Comparative mutagenicity test of dyes on E. coli WP2 and S. typhimurium as indicator organisms. The mutagenic activity of some industrial dyes has been studied. None of these chemical substances reverted E. coli WP2 and S. typhimurium, regardless of their chemical structure, either in the direct test or in the liver microsomal assay.


[Simple and rapid method for direct coliform analysis in seawater]. A simple and rapid test for the fecal coliform analysis in seawaters by means of the direct seeding on selective-differential m-FC agar medium is described. The data set fourth show a good yield for the test insofar as test sensitivity, specificity and reliability are concerned. Consequently, its use is proposed along with, or at variance with, the traditional techniques MPN and FM which are not always of practical and easy carrying out, under particular operative conditions (need to customarily analyse a high number of samples).


[Possible use of the platelet as the cell system for the control of enteropathogenicity of E. coli and of other enterobacteria. Preliminary approach]. After an introduction concerning the assays employed in vitro and in vivo to determine enterotoxigenic activity of E. coli, the A. suggests a new in vitro model as a preliminary approach based upon the influence of LT enterotoxin of Escherichia coli on platelet aggregation (inhibitory effect) as expression of stimulation of adenylatecyclase activity evoked by this fraction and eventually other cholera-like fractions released from enterobacteria.


Pharmacokinetics of methohexitone following intravenous infusion in humans. A sensitive method, using gas chromatography with nitrogen selective detection, has been developed for the accurate measurement of methohexitone, in plasma, in concentrations of less than 0.05 mug/ml, and which makes it possible to study the pharmacokinetics of the drug after clinical doses in man. Methohexitone sodium 3.0 mg/kg was administered by zero-order infusion to healthy volunteers and plasma concentrations were measured during and after infusion. The decrease in the plasma concentration of methohexitone can be described by two-compartment kinetics. The terminal elimination half-life of the drug is relatively short (70-125 min), which is a result of a high metabolic clearance rate (657-999 ml plasma/min). It was concluded that uptake of the drug by adipose tissue does not contribute significantly to its pharmacokinetics in man. In addition to the initial redistribution of an anaesthetic dose of methohexitone, the quick recovery of patients is a result of rapid metabolism of the drug.


Cyanide and thiocyanate concentrations following sodium nitroprusside infusion in man. Twenty-six patients, receiving an infusion of sodium nitroprusside (SNP) during surgery, had considerable increases in both red cell and plasma cyanide concentration, but only small changes in plasma thiocyanate concentration. There was a linear relationship between both plasma and RBC cyanide concentrations and the total dose of SNP. The expired cyanide concentration followed the changes in the plasma. We believe that the development of metabolic acidosis, and the recent fatalities involving SNP, are attributable to histotoxic hypoxia as a result of excessive plasma concentrations of cyanide. On the basis of our results, we recommend that the total dose of SNP should not exceed 1.5 mg/kg during short-term infusions and that the plasma cyanide should not exceed 300 nmol%. Plasma thiocyanate concentrations are, in general, an unreliable indication of extent of exposure to cyanide, although they may become important during long-term infusions.


Recovery from methohexitone, halothane and diazepam. Five motor and six cognitive tests were performed once before and then serially after anaesthesia with halothane and nitrous oxide of both short and long duration, methohexitone anaesthesia, and diazepam sedation with local anaesthesia. An untreated control group was also tested. The results suggest that, in the first hour, recovery was most rapid after short-duration halothane and nitrous oxide, was less rapid after methohexitone alone and was least rapid after long-duration halothane and nitrous oxide. Recovery after diazepam with local anaesthesia was prolonged and was incomplete at 3 h.


Lysogenization by bacteriophage lambda IV inhibition of phage DNA synthesis by the products of genes cII and cIII. In direct measurements of phage lambda DNA synthesis, we have detected an inhibition caused by the cII and cIII gene products. This inhibition was more clearly observed when P amber phages were grown in a permissive host, presumably because of the limitation in DNA synthesis due to uncomplete suppression. The inhibition takes place in cells infected at high multiplicity, but not in cells infected at low multiplicity. To explain these findings, we propose a model in which the bacterial population is heterogeneous with respect to its ability to support phage DNA synthesis. An initial limitation caused by host factors would be amplified by the action of the cII and cIII products, at high multiplicity only, and the resulting inhibition would be essential in the "choice" towards lysogeny.


Dependence of the sedimentation of high molecular weight DNA on centrifuge speed. A theory by Zimm [B.H.Zimm, Biophys. Chem. 1-(1974)279] predicts that for a given centrifuge speed, there is a broad maximum in a plot of the sedimentation coefficient of DNA against molecular wight. Experimental measurements of these maxima for various centrifuge speeds were made for double-helical DNA in neutral sucrose gradients and singlestrand DNA in alkaline gradients. The measurements are in quantitative agreement with the theory, providing good evidence for its validity. The existence of the maximum shows that there is a limit to the sedimentation rate under specified conditions for KNA in the linear form. By implication, DNA observed to sediment faster than this limit is not in the linear form to which most sedimentation theory is applicable.


[Colicin El synthesis in a cell-free system of paired transcription--translation]. Proteins were synthesized in the cell-free coupled transcription-translation systen (S30) under the control of the DNA-templates of plasmid ColEl, phages T2 and Sd. The most active templates were phage T2 DNA and closed plasmid DNA. Plasmid DNA induced synthesis of 8 individual proteins, one of which was a biologically active antibiotic of protein nature--colicin. The titre of colicin synthesized in such a cell-free system reached 1024 U/ml, this being about 100 times greater than the titre of this antibiotic in the colicinogenic bacteria cultures.


[Immunohistochemical demonstration of the localization of melatonin and N-acetylserotonin in enterochromaffin cells]. Employing the immunohistochemical method with the use of specific antisera to melatonin and to N-acetylserotonine the authors showed the presence of these substances in the enterochromaffine cells of the gastrointestinal. It is emphasized that in the organism there exists a group of melatonin-producing cells whose principal link is served by the enterochromatoffine cells playing an important role in the maintenance of homeostasis due to their function--that of melatonin production.


[Marie Philibert Constant Sappey (1810-1896). The man and the lymphologist]. About one hundred years ago, the two major lymphological works of the XIXth century were published by SAPPEY; this gives the opportunity to recall who was the man who studied: Plagiostoma, Sharks, Teleosts, domestic Mammals and Man.


[Closing volume and inhomogeneity of the ventilatory mechanical system (author's transl)]. The use of the closing volume (VF) to detect small airway lesions is based on physiological data : it would reflect a special and physiological distribution of the pulmonary inhomogeneity. The aim of this work is to discuss the closing volume as used to determine a pathological process or, in other words, the relationship between the observed profile of closing volume and other functional parameters, whose abnormalities are likely to reflect the inhomogeneity of the ventilatory mechanical system. In 126 patients, who represent a wide range of pathological processes, the authors calculated the closing volume and the following functional parameters : the VC/theoretical VC ratio, the RV measured by dilution method and by plethysmography, the FEV1.0/VC ratio, the expiratory total pulmonary resistance (RPTE), the efficient resistance (R), the airway resistance (Raw), the effective compliance (Ce) measured at the spontaneous respiratory frequency, and its variation in relation with respiratory frequency (f), and a distribution index of inspired gas. After discussion of the procedure and of the reproducibility of the closing volume measurements, the authors recall the significant of the lack of phase IV during the closing volume estimation and expose the reasons which allow to think that closing volume extent and inhomogeneity of the ventilatory mechanics have a parallel evolution. The increase in distribution inhomogeneity of the pulmonary time constants (shown by the slope of the Ce variation in relation with f and gas distribution index) is concomitant with an increase in closing volume. The results show that although the lack of phase IV does not have a univocal signification (and this is a limit to the utilization of the closing volume alone as a detection test) the quantification of the closing volume brings, as the Ce, f relation does, an original element, but the evaluation of Ce, f is more difficult to realize in practice.


[A comparative trial of bronchodilator effects of fenoteral and sch 1000 in chronic bronchitis (author's transl)]. In a group of 20 patients with chronic bronchitis, bronchodilator effects of fenoterol (400 mug), SCH 1000 (40 mug), and their combination (fenoterol 400 mug msch 1000 40 mug) have been evaluated and compared by measuring total pulmonary capacity (CPT), intrthoracic gas volume (VGT), forced expiratory volume in one second (VEMS), specific airways resistance (SRva) and maximun expiratory flow at a lung volume for which the initial flow was 0.1 l/s (Vo.iv). Measurements have been made before and 30, 60, 120 and 180 min after administration of the drug. With each of the three drugs, the improvement of the five functional parameters is statistically significant at all time intervals. Changes in CPT, VGT, VEMS and SRva are not statistically different when using the different drugs, whereas the Vo.1v changes suggest a lesser bronchodilator effect of SCH 1000 than fenoterol (p less than 0.05 at 180 min), and especially than fenoterol-SCH 1000 combination (p less than 0.05 at all time intervals). The combination is lightly but not significantly better than fenoterol only. On account of these results and the very high tolerance for the two drugs, a new medication combining SCH 1000 and fenoterol is desirable. The authors emphasize the sensitivity of maximum expiratory flow measurements at low lung volumes for trials on bronchodilators and the necessity to consider the possible reduction in CPT for flows comparison at an identical absolute lung volume.


[Pulmonary collateral circulation in lung cancer: a case of error in the measurement of cardiac output with dyes]. In a series of 40 cases of lung cancer, we recorded arterial dilution curves before and after unilateral occlusion of the pulmonary artery (on the pathologic side) following injection of dye into the pulmonary arterial trunk ("arterial curves") and in the capillary wedge position ("capillary curves"). In one case, a large pulmonary collateral circulation (PCC) is obvious, i.e., the dilution curve shows the characteristic shape of an early recirculation before and a normal shape after occlusion. In three cases, the PCC is likely to exist for: 1) decreasing of the capillary curves is abnormally slow during control; 2) transit time of capillary curves is obviously longer during control; 3) the surface under the arterial curve is 9 to 20 % larger during control than during occlusion. This surface undoubtly corresponds to the first dye circulation during pulmonary artery occlusion while, during control, it is increased by the PCC inspite of the exponential shape of the decreasing slope. Therefore the dye dilution method cannot be used to calculate precisely the PCC flow. Practically, in lung cancer measurements of the cardiac flow by dye dilution curves is erroneous about once out of 10 times. This conclusion can be extended to other lung diseases where a PCC may develop.


Lung function after neonatal respiratory distress syndrome. Functional residual capacity (FRC), dynamic lung compliance (CLdyn) and lung resistance (RL) were measured in a group of 51 healthy children aged 18 months to 6 years (group A) and in a group of 69 survivors of the respiratory distress syndrome (RDS) of the same age (group B). Forty-four per cent of the latter had clinical and radiological abnormalities. In the healthy children significant correlations were found between FRC and height (p less than 0.01), CLdyn and height (P less than 0.01) and CLdyn and FRC (p less than 0.01) but a poor correlation existed between RL and height (p greater than 0.05). There was no significant difference between groups A and B in the slopes of the regression lines for FRC, CLdyn and RL against height, but the intercept for the regression lines relating to CLdyn and RL was lower in group B than in group A. Group B was divided into two subgroups according to the length of exposure to artificial ventilation with an FIO2 in excess of 60 %. A lower value for CLdyn was found in the sub-group with the longer exposure (greater than 120 hours) to a high FIO2, suggesting that this is an additional factor in causing lung damage.


The management of deeply infiltrating (T3) bladder carcinoma: controlled trial of radical radiotherapy versus preoperative radiotherapy and radical cystectomy (first report). The preliminary results are presented of a multicentre, co-operative randomised trial, sponsored by the Institute of Urology, London, in which radical irradiation (6,000 rads in 6 weeks) is compared with preoperative irradiation (4,000 rads in 4 weeks) plus radical cystectomy for deeply infiltrating carcinoma of the bladder (Stage T3 or B2C). 189 of the 199 cases entered into the trial between 1966 and 1975 were eligible for study. The overall 3- and 5-year survival rates for combined treatment were 41% and 33%, respectively, compared with 28% and 21% for radical radiotherapy. The operative mortality was 7.8%. The difference between the two treatments in favour of the combined treatment has not yet reached the generally accepted level of significance (P less than 0.05), the p factors for the 3- and 5-year results being 0.064 and 0.077, respectively. Of patients receiving the protocol combined treatment, reduction in tumour stage was found in the surgical specimen in 47% of cases. The overall incidence of nodal metastases was 23% (against the usual figure of 40-50%), and in the presence of a good response of the primary tumour to irradiation, only 8%. The 3- and 5-year survival rates for the down-staged cases were 66% and 55%, respectively, compared with 29% and 22% for patients showing no stage reduction in the surgical specimen. The aim of our future studies is to find effective radiosensitising and cytotoxic agents with which to try and increase the incidence and degree of tumour response to pre-operative irradiation in the combined modality treatment of T3 bladder cancers.


Hypothermic prostatic resection.

Hypothermic prostatic resection. A simple method of markedly reducing blood loss during T.U.R. is reported. Cooling of the irrigant solution to 2 degrees C by placing the glycine in a domestic refrigerator reduces the operative blood loss 6-fold.


Further studies on aspartate transcarbamoylase: molecular weight of the c3r6 complex and analysis of succinate inhibition in the native enzyme. The complex which is formed when excess regulatory subunits (r2) of aspartate transcarbamoylase (EC2.1.3.2) are added to a dilute solution of the catalytic subunit (c3) has been studied by gel-filtration on Sephadex G-200. The elution volume indicates a Stokes' radius of between 5.42 and 5.92 nm, depending on the method of calculation. Using the sedimentation coefficient of 7.7S previously determined, the molecular weight is estimated to be close to 200 000, in support of the c3r6 structure proposed earlier for the complex. The calculated frictional coefficient indicates abnormal hydrodynamic properties which are probably due to unusual structure characteristics. The pattern of succinate inhibition of native aspartate transcarbamoylase has also been analyzed. At low concentrations, succinate activates the enzyme, presumably by converting it from the taut state to the relaxed (r) state. Further increase in the succinate concentration leads to competitive inhibition of the R state. Using a novel procedure for analysis of the data, the Michaelis constant for aspartate of the R state has been estimated to be about 7mM. This value is close to the Km of c3r6 for aspartate, measured under identical conditions. The result therefore provides further evidence suggesting that the c3r6 complex resembles the R state of the native enzyme.


The origin and role of blood-borne monocytes in rats with a transplanted myelogenous leukaemia. The growth of a transplantable myeloid leukaemia into its syngeneic host is accompanied by a progressive increase in the number of blood monocytes. These were shown to be of host origin and were not derived from the inoculated leukaemia cells. The host response which is responsible for the monocytosis differs from that associated with the entry of monocytes into immunogenic sarcomas.


Testing of some benzidine analogues for microsomal activation to bacterial mutagens. Analogues of benzidine were assayed for mutagenic activity towards Salmonella typhimurium TA 1538 in the presence and absence of a liver enzyme preparation. Purified 3,3'-dichlorobenzidine and the technical grade material had some direct mutagenic activity, but this was increased over 50-fold by addition of a liver mixed function oxidase preparation. In the presence of the liver preparation, 3,3'-dichlorobenzidine was approximately 10 times more active than benzidine, while 3,3',5,5'-tetrafluorobenzidine was of approximately equipotency. On the other hand, 3,3',5,5'-tetramethylbenzidine had no mutagenic activity alone or in conjunction with a liver preparation. 3,3'-Dianisidine had slight mutagenic activity in the presence of liver but none in its absence.


Rejection of sarcoma cells at the site of an inflammatory reaction: macrophages are not the only effector cells. Purified protein derivative (PPD) (a soluble protein from tubercle bacilli), when injected together with sarcoma cells into syngeneic mice that had been immunized previously with Bacillus Calmitte-Guérin (BCG), prevents tumour toxic to sarcoma cells [4]. However, non-adherent mononuclear peritoneal exudate cells from BCG-treated mice were also found on addition of PPD to become cytotoxic to sarcoma cells. In vivo assays indicate that such cells may play a major role in the in vivo destruction of tumours at the site of a delayed hypersensitivity reaction.


N'-hydroxy-2-aminofluorene: the principal mutagen produced from N-hydroxy-2-acetylaminofluorene by a mammalian supernatant enzyme preparation. A Salmonella typhimurium TA 1538 culture system wasused to monitor the production of mutagen from N-hydroxy-2-acetylaminofluorene by soluble liver enzymes. When benzene was used to extract the mutagen, no mutagenic activity remained in the liver enzyme preparation. The benzene extract contained approximately two-thirds of the total mutagenic activity produced by the liver enzyme preparation. Using thin layer and column chromatography to analyze the benzene extract, we deduced that N-hydroxy-2-aminofluorene accounted for the mutagenic activity which resulted from the incubation of N-hydroxy-2-acetylaminofluorene with soluble liver enzymes.


Influence of five different postnatal lifelong treatments on the transplacental carcinogenicity of ethylnitrosourea in Sprague-Dawley rats. Sprague-Dawley rats received in 10 mg/kg body weight (group I) or 30 mg/kg body weight (group II) ethylnitrosourea (ENU) orally on the 19th day of pregnancy. Their offspring were treated with Bacille Calmette-Guerin, human albumin, hydrocortisone, cyclophosphamide or nicotine starting on the 6th day of life. The ENU treatment significantly reduced the life expectancy of all offspring. Treatment of the offspring did not influence tumor frequency, induction time or localization of neurogenic malignant tumors. Cyclophosphamide treatment of group II offspring increased the number of females bearing mammary carcinomas.


Noninvasive monitoring of adriamycin cardiotoxicity by "Sphygmo-Recording" of the pulse wave delay (QKd interval). Eighty patients with Ewing's sarcoma, bronchogenic carcinoma, and other neoplasms receiving adriamycin were monitored by a Sphygmo-Recording of the pulse wave delay (QKd time interval). The QKd interval, which is the sum of the cardiac pre-ejection period and the pulse transmission time, is sensitive to changes in myocardial contractility and stroke output. The patients were also followed by serial physical examinations, electrocardiograms, chest roentgenograms, serum enzymes, and thyroid function tests; none of these changed during the study period except in a few patients with congestive heart failure (CHF) and/or transient arrhythmias. QKd showed a significant prolongation (greater than 30 msec) within 1-3 weeks after adriamycin administration in a high percentage of patients followed closely. The QKd interval usually returned to pretreatment baseline levels within 4-7 weeks after adriamycin administration. The QKd often showed repeated and sustained elevations after courses of therapy at 3-week intervals. After adriamycin therapy was discontinued the QKd usually returned to normal levels. No statistically significant changes in the QKd were seen in a control group. There were no acute changes in QKd during adriamycin infusions. Of seven patients receiving cumulative doses of adriamycin greater than 550 mg/m2, three developed CHF. QKd intervals in all three of these patients had failed to return to the baseline values 2-3 months prior to any other evidence of CHF. This suggests that failure of QKd to return to pretreatment baseline levels may be of prognostic value. The QKd interval appears to reflect a high incidence of subclinical adriamycin cardiotoxicity. The technique is simple, noninvasive, rapid, and potentially useful for monitoring patients receiving adriamycin and other potentially cardiotoxic drugs.


Phase II studies of dianhydrogalactitol and VP-16-213 in colorectal cancer. Phase II chemotherapy trials of dianhydrogalactitol and VP-16-213 were conducted in patients with metastatic colorectal cancer who had measurable malignant disease which served as indicators of response to therapy. Dianhydrogalactitol was given in a 5-day course at a dosage of 30 mg/m2/day. Toxic reactions included nausea, vomiting, leukopenia, thrombocytopenia, and anemia. There was a definite tendency to a compounding of hematologic toxicity with repeated courses. No evidence of objective therapeutic response was observed among 30 patients treated. VP-16-213 was given at a dosage of 130 mg/m2 on Days 1, 3, and 5. Toxic reactions included nausea, vomiting, alopecia, leukopenia, thrombocytopenia, and anemia. Hematologic toxicity was more severe in patients with elevated serum bilirubin levels. No evidence of objective therapeutic response was observed among 28 patients treated.


Comparison of 5-fluorouracil and ftorafur. I. Quantitative and qualitative differences in toxicity to mice. 5-Fluorouracil (5-FU) was compared to ftorafur, a fraudulent nucleoside analog which acts as a depot form of 5-FU, with respect to influence of dosage level and schedule of administration on toxicity in mice. When the drugs were administered daily and the duration of treatment was varied from a single dose to 32 daily treatments, the toxicity of 5-FU proved to be somewhat more than cumulative. On the other hand, the toxicity of ftorafur on daily treatment was less than cumulative. As a single treatment ftorafur was about half as toxic as 5-FU on an mg/kg basis. When the drugs were administered daily for 12 days the LD50 of ftorafur was about sevenfold that of 5-FU. When the drugs were administered as two treatments and the interval between the two treatments was varied from 0 to 14 days, it was found that 5-FU was considerably more toxic at an interval of 2-7 days than when two doses were administered simultaneously. Appreciable recovery of mice from the initial dose of 5-FU did not occur until sometime between 7 and 10 days. Host recovery from ftorafur toxicity was apparent by 2 days. The dose-mortality curves form both drugs were steep. The decreased toxicity with repeated treatment with ftorafur relative to 5-fu was not due to a decrease in the metabolism of ftorafur to 5-FU, which was much more extensive in mice compared to previously reported pharmacokinetic studies in other species. At equitoxic doses on a daily X 5 schedule, 5-FU and ftorafur had similar myelosuppressive activity. Ftorafur was, however, clearly less suppressive to both humoral and cell-mediated immunity than was 5-FU.


Comparison of 5-fluorouracil and ftorafur. II. Therapeutic response and development of resistance in murine tumors. The therapeutic activity of ftorafur was compared to that of 5-fluorouracil (5-FU) in a number of tumor systems. The drugs were active against ip L1210 leukemia when administered ip, sc, or orally. Administration every fourth day x 3 proved to be the most effective treatment schedule for both drugs, although significant activity was seen on all treatment schedules tested. Both congeners had activity against sc implanted L1210 leukemia as well as a limited effect on the ic implanted tumor. 5-FU produced greater increases in lifespan of mice bearing L1210 leukemia than did ftorafur. 5-FU was also more effective against ip B16 melanoma and ip Gardner 6C3HED lymphosarcoma. Ftorafur was ineffective in the treatment of mice bearing ip P388 leukemia, a tumor which is quite sensitive to 5-FU. At approximately equimolar doses both drugs produced a persistent inhibition of 2'-deoxyuridine incorporation into DNA of L1210 cells in vivo. Ftorafur produced a greater inhibition of uridine incorporation into RNA than did 5-FU, which may account for the lower therapeutic activity of ftorafur. In combination chemotherapy of L1210 leukemia 5-FU plus ftorafur was no more effective than 5-FU alone, neither of the congeners was synergistic with either adriamycin or actinomycin D, and in combination with methotrexate therapeutic synergism was observed with 5-FU but not with ftorafur. After eight transplant generations of exposure to ftorafur, a subline of L1210 leukemia became totally resistant to ftorafur and simultaneously cross-resistant to 5-FU. Doses of ftorafur and 5-FU which were optimally effective in mice bearing the parental L1210 line were lethal to mice implanted with the ftorafur-resistant subline. When treatment of the resistant subline was discontinued after nine transplant generations of exposure to ftorafur, sensitivity to 5-FU returned after three transplant generations without ftorafur. The subline retained its resistance to ftorafur until eight transplant generations after cessation of ftorafur treatment. Another subline of L1210 leukemia exposed to 5-fU for 20 transplant generations proved to be completely resistant to 5-fu and cross-resistant to ftorafur. The mutual cross-resistance between ftorafur and 5-FU supports the contention that ftorafur acts primarily as a depot form of 5-FU.


Recombination between bacterial plasmids leading to the formation of plasmid multimers. We report here the formation of plasmid multimers in E. coli. Multimers are covalently closed, circular molecules composed of tandem repeats of the monomer plasmid. Multimer formation occurs at high frequency in rec+, recB-C-, and recF- hosts. Multimer formation is not detected in recA- hosts and occurs at reduced frequency in recB-C-F- hosts. We conclude that multimer formation is mediated by a single reciprocal recombination event occurring at homologous regions on the two plasmids.


Carbohydrate metabolism in liver disease. Most forms of liver disease are probably associated with impaired gluconeogenesis, although hypoglycaemia is rarely an important clinical feature. Blood concentrations of the gluconeogenic precursors, lactate, glycerol and alanine are elevated although, in certain situations, alanine levels may be decreased. Abnormal glucose tolerance is present in both acute and chronic liver disease, but is usually not of clinical importance. The mechanism of glucose intolerance remains uncertain, with diminished hepatocyte mass, portal diversion and insulin resistance the major postulates. Indeed, the importance of the liver in disposing of an oral glucose load, is still questioned. Both hyperinsulinism and hypoinsulinism are found in liver disease, with hyperinsulinism common in cirrhosis and acute viral hepatitis. This is accompanied by insulin resistance. The hyperinsulinism is probably due to defective hepatic clearance of insulin rather that to over-production. The cause of the insulin resistance remains to be established. Glucagon levels are raised and may contribute to this resistance. Growth hormone levels are also increased but are associated with low somatomedin levels and the role of growth hormone in insulin resistance is therefore questionable. Future developments include use of new animal models, studies of biopsy specimens and studies of hepatic hormone receptors.


[Human and animal parasitic diseases in the New Hebrides]. New-Hebrides Condominium, an archipelago in the South Pacific, is a country with a special socio-political environment, due to the duality of its French-British regime. This state of affairs is felt in all areas including Public Health, where we find French, British and Condominial personnel. The pathology of parasitic diseases is essentially tropical with a strong predominance of paludism, at times fatal, and intestinal nematodes; however we rarely find amibiasis or human hydatid disease. Strongyloidiasis as well as specific ascaris of each species are very frequent in animals. In general cattle is relatively healthy, which is fortunate for a country whose economy is turning more and more to breeding.


Carbohydrate metabolism in cardiovascular disease. Carbohydrate metabolism is temporarily disturbed in acute myocardial infarction. The degree of hyperglycaemia and failure of response of insulin appears to be related to the severity of the infarction. The underlying hormonal changes probably include increased secretion of catecholamines and of glucagon. Circulating free fatty acids (FFA) are generally increased by the same metabolic and hormonal factors which promote glucose intolerance. In the zone of developing infarction in the heart, there is a complex metabolic situation with glucose metabolism both being accelerated and inhibited by different factors. Continued uptake of FFA is associated with intracellular accumulation of activated long-chain FFA, acyl CoA, which tends to inhibit mitochondrial metabolism. The metabolism of glucose is thought to be beneficial and that of FFA detrimental to the infarcting tissue. Thus the glucose intolerance and the high circulating FFA occurring as part of the general metabolic response to myocardial infarction, are thought to be harmful to the ischaemic tissue. Increased provision of glucose by dichloroacetate, and inhibition of FFA metabolism by nicotinic acid analogues decrease the extent of experimental infaraction, while glucose--insulin--potassium and propranolol act both by increasing glucose uptake and decreasing that of FFA. Glucose intolerance is also common in peripheral vascular disease. The reasons for this are obscure. However, the alterations in circulating insulin concentration which accompany this intolerance may be involved in the development of arterial lesions either directly through an effect on arterial wall synthesis or indirectly through an effect on circulating lipid levels. Defects may also be found in arterial wall mucopolysaccharide or sorbitol metabolism. The role of sex hormones and catecholamines remains speculative. At present the most cogent view is that in peripheral vascular disease a multi-hormonal disorder exists which may be contributing to the development of arteriosclerosis.


Carbohydrate metabolism in trauma.

Carbohydrate metabolism in trauma. During the initial shock or 'ebb' phase of injury, body glucose (serum glucose concentration X glucose space) is significantly increased but mass flow to peripheral tissue is only slightly altered. During the 'flow' or hypermetabolic phase of injury, mass flow of glucose is markedly increased, related to the extent of injury and directed primarily by increased sympathetic nervous system activity. Increased hepatic gluconeogenesis provides glucose which is converted to three-carbon precursors in the periphery and returns to the liver for reconversion to new glucose, utilising the Cori and alanine cycles. Increased ureagenesis is a consequence of skeletal muscle amino acids contributing to this cycle system. This energy shuttle system produces heat, and the rate of six- to three-carbon cycling correlates closely with the increased oxygen consumption of the injured patient. The glucose cycle may be altered by hormonal administration, food intake, exercise, weight loss, pharmacological manipulation and infection, but the basic reset in hepatic glucose production and energy demands in the injured patient appears essential for the inflammatory response and tissue repair.


The use of isotope turnover techniques in the study of carbohydrate metabolism in man. It now appears that the bulk of methodological, analytical and interpretative problems associated with the use of isotope turnover techniques for the study of carbohydrate metabolism in man are resolved. As illustrated by a number of examples of the use of these techniques for the assessment of carbohydrate metabolism they seem, to the author, to have been more critically useful in the resolution of questions of (a) mechanism of hormone and drug action and (b) of interactions between metabolites, than they have been in defining pathological states, although the volume of information that is being accumulated is sure to prove useful for future research. Although it is this author's opinion that the employment of the radioactive isotopes at the low levels allowed by todays technology does not impose an unreasonable risk to the research subject, the promise of increased sensitivity for the detection of stable isotopes and the promise of their increased availability in a wide variety of compounds are factors that are sure to provide impetus for the wider use of these most valuable techniques in medical research.