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Microbial secondary metabolites with potential use in cancer treatment. (Plasmid involvement in biosynthesis and compounds.

Antibiotics and small molecular enzyme inhibitors produced by micro-organisms are microbial secondary metabolites which have no obvious function in the growth of microorganisms. Involvement of plasmids in their biosyntheses has been studied and the structure of the microbial world where various compounds with widely varying structures have been found has been shown to be due to the presence of a great variety of plasmids. On the basis of this structure of microbial world, the author has found the microbial products which have various activities useful in treatment of cancer or in suppression of carcinogenesis. In this paper, the author reviewed his following studies: the plasmid involvement in biosyntheses of bioactive microbial secondary metabolites; the mechanism of therapeutic effect of bleomycin, and the development of useful analogs and derivatives of bleomycin and anthracyclic antibiotics; the screening method to find compounds affecting immune system, and the action of bestatin in enhancing delayed-type hypersensitivity and therapeutic effects of anticancer agents; enzyme inhibitors with potential utility in treatment or prevention of cancer.

3',5'-Cyclic-AMP Phosphodiesterases↗

Microbial degradation of diethanolamine and related compounds.

Thirteen diethanolamine compounds were tested for their biodegradability employing (1) a bacterium selectively isolated from an industral cutting fluid, and (2) an acclimatized sewage population obtained from a domestic waste treatment plant. Pure culture growth and biochemical oxygen demand studies with the isolate showed that only diethanolamine, methyl-diethanolamine, triethanolamine, and laurylsulphate-diethanolamine were degradable. Biochemical oxygen demand techniques using the acclimatized sewage micro-organisms as seed yielded similar results with only diethanolamine, methyl-diethanolamine, triethanolamine, and laurylsulphate-diethanolamine being oxidized to any meaningful extent. Cyclohexyldiethanolamine, phenyl-diethanolamine, and m-tolyl-diethanolamine had oxygen demands of less than 1% of their theoretically calculated values, while ethyl-diethanolamine and benzyl-diethanolamine accounted for 3.6 and 2.3% of their theoretical values respectively. In both systems employed substitution of the tertiary hydrogen of the amine group with isopropyl, 3-aminopropyl, n-butyl, or t-butyl resulted in biologically recalcitrant compounds.

Bacteria↗

Design of metabolic and enzymic machinery to fit lifestyle and environment.

Biochemical theory, spectacular as its growth has been in the last half-century, finds its experimental basis in a remarkably few organisms. The rat, the ox, the pig, the hen plus a few micro-organisms consitute the primary source of biochemistry's experimental material, while, by contrast, modern systematics estimates a bewildering and often overlooked diversity of over 10(6) animal species. As a result of this highly limited 'sampling' of nature, classical biochemistry has supplied an equally limited insight into how far biochemical mechanisms can be extended or adapted for (1) allowing an organism's exploitation of its environment and (2) accommodating environmental change. The situation has improved in more recent years, so that it is now possible to decipher at least the broad strategic outlines of biochemical adaptation to the environment. This essay focuses particular attention on the influence of O2 availability on muscle metabolic organization and control. By drawing examples of muscle metabolism spanning a range from obligate-anaerobic to obligate-aerobic organization, it is possible to demonstrate that certain kinds of metabolic features are highly conserved, whereas others are changed time and time again, in different combinations and permutations. The latter properties constitute the 'raw material' for adapting metabolism to specific O2 regimes, and include (1) the kinds and amounts of enzymes present in muscle, (2) the fine regulatory circuitry allowing for controlled transition from low to high work loads and (3) compensation mechanisms for the adjustment of enzyme reactions with respect to such external parameters as temperature, pressure, salinity and so forth. Within the inescapable limitations of phylogenetic origins and the time available for responding to specific environmental conditions, adequate adaptations of the fundamental design of muscle metabolism have evolved to exploit environments differing greatly in O2 availability and to accommodate a wide range of muscle functions.

Acetylcholinesterase↗

Peripheral dissemination of bacteria in contaminated wounds; role of devitalized tissue: evaluation of therapeutic measures.

The role of available therapeutic agents in the management of infection has long been a continuing source of debate. This study assessed the rapidity of lateral dissemination of three common pyogenic organisms from wounds. The Streptococcus spreads peripherally with greater speed than the Staphylococcus or E. coli. Appraisal of the role and effectiveness of jet wound irrigation, debridement, and penicillin provides firm evidence that, of these three therapeutic agents, the only one that can control bacterial proliferation in a contaminated wound is the antibiotic. The primary role of energized jet irrigation is to remove clots and wound debris. The specific function of debridement is removal of devitalized tissue, in which role it has no effective competitor. These studies demonstrate that devitalized tissue in a contaminated wound quickens the rapidity of peripheral spread of all three micro-organisms. Systemic penicillin plus saline irrigation is the most effective therapeutic measure at both the second and fourth postinoculation hours in nondevitalized contaminated wounds. Debridement proved to be the most effective therapeutic device at the second, fourth, and sixth postinoculation hours in devitalized wounds.

Animals↗

[Comparative clinical and experimental studies of various denture cleansers. 2. Testing of antimicrobial efficiency].

Agar diffusion plate tests were performed on five strains of micro-organisms to characterize the disinfecting properties of nine denture cleaners. Furthermore, the liberation of oxygen was determined as a function of time, and the course of pH variation of the various cleaning solutions was studied. The highest oxygen concentrations and the best antimicrobic activities were achieved by the preparations Eladent G and T.

Bacteria↗

Numerical immunotaxonomy of Leishmania. I. Differentiation of four strains of Leishmania by serological tests.

This paper describes the application of numerical methods to the arrangement of four leishmanial strains according to their reactivity and cross-reactivity in tests of parasite agglutination, indirect immunofluorescence and passive cutaneous anaphylaxis with antisera prepared by immunization or infection of rabbits, guinea-pigs and mice. Using corresponding pools of animal sera as test 'reagents' the antigenic reactivity of the four leishmanial strains (L. enriettii, L. tropica major, L. aethiopica and L. mexicana amazonensis) was scaled by reference to end-point serum titres; and antigenic relationships between individual strain pairs were expressed as mean similarity coefficients, giving equal weight to the results of the different serological tests. Overall analysis of the results revealed that L. mexicana amazonensis and L. tropica major were the two most closely related strains, clustering with an overall similarity coefficient of 89%, whereas coefficients of similarity between other strain combinations fell between 75 and 80%. Although different sera had different discriminatory capacity for the leishmanial strains, two combinations of serum reagent and test system yielded relationships between the four strains that most closely approximated to the overall values. These were: (a) immunofluorescence tests with mouse antisera; and (b) agglutination tests with selected rabbit antisera. The results illustrate the use of a number of immunological parameters in relating micro-organisms of a given genus, and reveal a serological classification of the four leishmanial strains at variance with their geographical origin.

Agglutination Tests↗

Bladder defense mechanism.

In order for micro-organisms to infect the urinary tract they must adhere to the vesical mucosa so that they remain after voiding. Experiments in our laboratory demonstrated that the bladder has a self-protective mechanism capable of preventing bacterial adherence to the surface. Histochemical staining demonstrated that this substance is a mucopolysaccharide. Treatment of the mucosa with acid disrupted the protective layer and resulted in a 20 to 100-fold increase in bacterial adherence. Within 24 hours this layer reappeared and binding was again reduced to normal. This phenomenon was not related to microbial species or metabolic activity.

Adhesiveness↗

[Penicillin V potassium in tonsillar tissue and serum (author's transl)].

1.2 mega U Penicillin V potassium was given to 20 patients 2 hours (group 1) and another 19 patients 3 hours (group 2) before tonsillectomy. After the operation biological determinations of the levels of active principle were made from tonsillar tissue and serum with statistical evaluation of the results (Spearman's rank correlation). There was a significant connection between the serum and tonsillar tissue concentrations (in children and adults) in both groups. The level of the active principle in group 2 was only slightly lower than in group 1. Many of the micro-organisms responsible for tonsillitis can be influenced by the concentrations found here, so that application of Penicillin V can often be expected to have a good therapeutic effect.

Adolescent↗

Alpha chain disease: immunoglobulin abnormalities, pathogenesis and current concepts.

The laboratory findings upon which the diagnosis of alpha chain disease relies and the main results of immunochemical, structural and biosynthetic studies of the pathological immunoglobulin are reviewed briefly. The pathogenesis of the disease is discussed in view of its possibly non-malignant nature at the early stage and of its peculiar geographic distribution, suggesting the triggering role of an intestinal micro-organism.

Diagnosis, Differential↗

[Antibiotic residues in organs and muscle tissues of broilers. I. Bacitracin, flavomycin, spiramycin and viriniamycin residues following administration of diets containing low levels of these antibiotics (author's transl)].

Two groups of broilers were fed two different feed mixtures. A feed containing a mixture of bacitracin, flavomycin, spiramycin and virginiamycin (20 ppm each) was administered to sixity broilers. Sixty other broilers were given a similar feed not containing any antibiotics. After slaughter, samples of kidney, liver and breast were examined for the presence of antibiotic residues. All samples were found to be negative for antibiotic residues. Four micro-organisms were used in performing the tests: Bacillus cereus Kiel, Bacillus subtilis 165, Bacillus subtilis BGA and Micrococcus luteus ATCC 9341.

Aminoglycosides↗

[Veterinary medicine and public health (author's transl)].

Various aspects of current problems in the field of public health will be commented on in an introductory paper. Attention will mainly be paid to three subjects, viz. zoonoses, food hygiene and environmental pollution. Recent developments in the field of so-called classical and currently emerging zoonoses will be briefly discussed with reference to the specific papers which will be presented by specialists during the course of the day. In the field of food hygiene, problems of bacterial and chemical contamination of foods of animal origin will be referred to. Modern aspects related to drastically altered methods of production, distribution and eating habits will be stressed again. Future chief items for further methods studies in this field will be puut forward. In addition to general aspects of problems relating to the environment and pollution, attention will be drawn to the specific contribution of the veterinarian both in the prevention of further pollution and in the possible solution of the highly complicated problems in this field. Real and hypothetical cycles of micro-organisms and chemical constituents in the environment as well as studies designed to disrupt these cycles will be discussed. In considering these problems, reference will be made to more detailed discussions whhich will take place during the course of the day, to the duties of and possibilities for the veterinarian in all these fields of research, to international co-operation and to the research programmes and legal regulations in the Netherlands.

Animals↗

[Discopathies after fractures and destructive vertebral lesions during rheumatismal pelvispondylitis].

In three cases of rheumatic spondylitis, fracture across the disc of an ankylosed spinal segment (C5-C6, D7-D8, and D12-L1 respectively) resulted in rapid development of a discopathy with destruction of the adjacent vertebral bodies. In one of these cases, surgical exposure of the focus permitted anatomical study of the lesion; the changes that had developed after the fracture were inflammatory in appearance, which at first suggested infection by non-specific micro-organisms, an assumption that was rapidly abandoned. This misleading histological appearance largely explains why these destructive discopathies in spondylitis have long been regarded as a consequence of the rheumatic process itself. A review is presented of the arguments which suggest that they have, in fact, a mechanical pathogenesis, often determined by a fracture. From this it may be concluded that the treatment of choice is temporary immobilization in moderate cases and surgery with transplantation in complicated or unstable cases.

Aged↗

[Studies for the presence of Yersinia enterocolitica and Yersinia pseudotuberculosis in clinically normal pigs (author's transl)].

163 clinically normal slaughtered pigs were examined for the presence of Yersinia enterocolitica and Yersinia pseudotuberculosis. The following results were obtained: Yersinia enterocolitica was isolated from the tonsils in twenty-two cases, Yersinia pseudotuberculosis being found to be present in the tonsils in seven cases, Yersinia enterolitica was isolated from the liver in one case and from the caecal contents in eight cases, and Yersinia pseudotuberculosis was isolated from the caecal contents in three cases. These bacteria were not isolated from the mesenteric lymph nodes and muscle tissues. All sixty samples of minced raw pork which were examined, were also negative for these micro-organisms. Almost all strains isolated were of the same serotypes as those isolated from man in the Netherlands. The findings did not suggest that ingestion of raw pork might involve a risk of human yersiniasis. It is doubted, however, whether the methods of isolation were sufficiently selective.

Animals↗

[Ways of microbial contamination in hospital and their importance for hospital infection (authors transl)].

Transmission of micro-organisms in hospitals may occur by the air as well as by direct or indirect contact with infected patients and through germ reservoirs where an additional multiplication of germs takes place. Depending on the kind of infections of the respiratory system, germs are mainly transmitted by the air. Sources of germs are, besides people, mainly medicotechnical equipment, as for instance cold atomisation devices for inhalation. In case of wound infections, smear infections do have the greatest share, however, there are also transmissions by air. Urinary tract infections mainly follow contact infections. The same is true for infections via catheters and similar devices or for infections of the gastrointestinal tract.

Carrier State↗

[Immunotherapy of malignant growths (author's transl)].

Our knowledge of antigens which are associated with different types of malignant tumours is steadily increasing. These antigens exist in considerable numbers, but, so far with few exceptions, only their presence can be demonstrated by certain methods; to isolate and identify them has not yet been possible. These antigens are, therefore, suitable not so much for the primary diagnosis, but rather, like the carcinoembryonic antigen, the tissue-polypeptide antigen or the alpha-feto-protein, for assessing the success of treatment. Active immunization has recently received a fresh impulse by the use of the enzyme neuraminidase, derived from Vibrio cholerae, in the treatment of tumour cells. There is no passive specific immunotherapy in human cancer. As to specific active immunotherapy BCG, Corynebacterium parvum and preparations of these and other micro-organisms together with polynucleotides, levamisol, statolon, tilorone have been employed. Although the results are not uniform they are promising. Attempts at cellular transfer of immunity are not very encouraging. It should be emphasized that the findings apply to human cancer. Experimental studies have produced very interesting results.

Animals↗

[Present aspects of bacterial endocarditis in infants and children. Observation during the years 1969-1976 (author's transl)].

21 infants and children with proven bacterial endocarditis were observed at the Unviersity Children Hospital of Düsseldorf from January 1969 to December 1976. There was high incidence of cases in the infant group and again among the 6 to 8 years old children. Some important aspects of the disease were characteristic for the infant group (N=5): No congenital cardiac abnormality was present, but a surgical cerebro-atrial connection in two cases of hydrocephalus and a prolonged artifical respiration in a third patient could have been predisposing factors. Staphylococci were the pathologic organisms in three infants. The course of the disease consistently resembled that of septicemia and the outcome was always lethal. The diagnosis of bacterial endocarditis was disclosed only by the post mortem examination. The mitral and the tricuspid valves were affected twice respectively, the pulmonary cusps only once. In the children group (N=16) fifteen patients had a congenital malformation of the heart confirmed by previous catheterization. 8 were cyanotic and 5 of them had a tetralogy of Fallot with previous aorto-pulmonary shunting procedure (Waterston). Unlike the spectrum of micro-organisms presently found in adults, the streptococcus viridans prevailed as before, it was isolated in 11 of the 13 blood cultures which yielded positive results. The disease displayed a subacute course and mortality remained with 3 deaths relatively low. In 3 other cases a valve lesion subsisted, in two instances severe enough to necessitate surgery (aortic valve prosthesis, mitral annular narrowing). No relapse was observed during the mean follow up period of 2;8 years.

Adolescent↗

[Annual production of bacterioplankton in the deep sea area of Southern Baikal].

The time of generation of bacterioplankton in the pelagic zone of Baikal differs in various seasons of the year: the minimum time is in December (25 hours), the maximum time is in October of 1970 (580 hours) and in June of 1971 (560 hours). Monthly production of bacteria for a layer of 0 to 50 m varies from 0.07 g in January to 49 g of wet weight per 1 m2 in September. Annual production of bacterioplankton in a layer of 0 to 50 m is 118.5 g of wet weight per 1 m2 of the lake surface. The P/B coefficient of micro-organisms varies from 0.02 in January to 1.1 in December. The most favourable conditions for bacterial growth therefore are in April, July--September, and December. The annual P/B is 4.42.

Bacteria↗

[A mathematical model of inhibition of the growth of Candida utilis by heavy metal ions].

A mathematical model described in this paper, contrary to other models, takes into account transport effects during penetration of the inhibitor into the cell of a micro-organism, and also a possibility of partial inactivation of the inhibitor during formation of complexes. It changes into models of Monod and Monod--Jerusalimsky at extreme values of parameters. Theoretical steady-state concentrations of the biomass in chemostat predicted on the basis of this model coincided with values obtained in experiments with limitation of growth of Candida utilis by silver ions and copper ions.

Candida↗