J Dermatol Surg Oncol, 1978 Oct, 4(10), 777 - 9 Dermabrasion by diamond fraises revolving at 85,000 revolutions per minute; Fulton JE; Use of a high-speed, air-driven turbo-grinder equipped with diamond fraises that revolve at 85,000 revolutions per minute has improved results in dermabrasions on the face by, it is estimated, 50% . Dermabrasions have been done with this turbo-grinder for scarring from acne, actinic damage, syringomata, lesions of adenoma sebaceum and some other facial conditions . The rapid evaporation, nonimflammability, nonnarcotic, and excellent freezing properties of Freon 12 eliminate the necessity for auxiliary cooling fans . It is thought too that the incidence of secondary infections and keloids have been decreased by use of an ointment of erythromycin (1%) topically during the healing period. Int J Oral Surg, 1978 Oct, 7(5), 442 - 9 Concentrations of azidocillin, erythromycin, doxycycline and clindamycin in human mandibular bone; Bystedt H et al.; Postoperative complications after surgery in the mandible are still a clinical problem . Levels of four antibiotics--azidocillin, erythromycin, doxycycline and clindamycin--were measured in serum, dental alveolar serum, saliva and mandibular bone in 24 patients undergoing surgical removal of mandibular third molars . The concentration in mandibular bone for azidocillin was 0.8 microgram/g +/- 0.4 microgram/g, erythromycin 0.2 microgram/g +/- 0.1 microgram/g, doxycycline 2.6 microgram/g +/- 2 microgram/g and clindamycin 0.6 microgram/g +/- 0.4 microgram/g . No saliva levels were achieved with azidocillin and erythromycin, whereas doxycycline and clindamycin gave measurable saliva levels. Vet Med (Praha), 1978 Oct, 23(10), 623 - 31 {Distribution of erythromycin following intramuscular administration in laboratory animals}; Vyhnalek J; Levels of erythromycin in the blood and organs of rabbits, rats and mice were determined after the i . m . implantation of the drug Erythromycin inj . ad usum vet . at doses of 10 mg kg-1 live weight (rabbits), and/or 25 mg kg-1 (rats) and 1 mg pro toto--approximately 40 mg kg-1 (mice) . A diffusion plate method and the germ Sarcina lutea CCM 552 were used to find out the antibiotic in samples . Sensitivity of the method used was 0.025 microgram ml-1 (g) . In rabbits the level of the antibiotic was maintained in the blood and examined organs and tissues (lungs, liver, kidney, muscles and the wall of the small intestine) by the above dose for more than 12 hours--except liver . The values obtained for the organs and tissues were mostly higher than those obtained for the blood . The highest levels were found in the kidneys and lungs . Neither did the dose of 20 mg kg-1 l . w . maintain the significant level of erythromycin in the blood serum in the course of 24 hours . The results obtained in rats and mice almost coincided with the distribution of erythromycin in the rabbit organisms, and the affinity of this antibiotic with the pulmonary tissue was proved. J Clin Pathol, 1978 Sep, 31(9), 809 - 16 Pathology of five Scottish deaths from pneumonic illnesses acquired in Spain due to Legionnaires' disease agent; Boyd JF et al.; The pathology and histology are reported of five Scots who died of severe pneumonic illnesses after holidays in Spain, three in 1973 and two in 1977 . There is strong evidence in favour of all the deaths having been due to the newly discovered Legionnaires' disease (LD) agent . The agent (or its soluble antigen) has been visualised in sections of lung tissue by fluorescent-antibody tests in all cases, and the agent has been identified by the Dieterle silver staining method in small numbers in all cases . Serological testing was possible in three of the patients, and two had very high antibody titres against the LD agent . Apart from the extensive and severe nature of the pathological process there is no feature to distinguish pulmonary infection by this agent from that due to more commonly known bacteria capable of causing lobar pneumonia . The severity and extensive nature of the process is partly a reflection of neglect in seeking treatment until late in the infection, and partly a reflection, as revealed in retrospect, on the use of the wrong antibiotic combination during treatment . Erythromycin has been recommended by other workers as the drug of choice against the LD agent . Infection by this organism is not confined to the USA or to Spain and is indigenous also in the United Kingdom. Ann Intern Med, 1978 Sep, 89(3), 297 - 309 Legionnaires' disease: clinical features of 24 cases; Kirby BD et al.; Twenty-four cases of Legionnaires' disease were diagnosed at the Wadsworth Veterans Administration Hospital during a 5-month period . All cases occurred in persons exposed to the hospital environment during the usual incubation period of Legionnaires' disease . The clinical illness was quite characteristic . All patients complained of weakness, malaise, anorexia, and cough . Rigors, diarrhea, and pleuritic pain were frequent symptoms . All patients had a maximum temperature of greater than or equal to 39.4 degrees C . Thirteen of 22 patients had relative bradycardia . Chest roentgenograms documented pneumonia in all patients . Leukocytosis, hyponatremia, hypophosphatemia, and abnormal liver-function test results were typical . Diagnosis was made by serologic criteria in 20 patients, postmortem examination of tissue in two, and both serology and tissue examination in two . Four patients in whom the disease was not suspected died of Legionnaires' disease . One patient died of unrelated causes . Fifteen of 19 survivors received erythromycin therapy . The presentation of Legionnaires' disease was characteristic enough to allow early, specific therapy. Clin Pharmacokinet, 1978 Sep-Oct, 3(5), 337 - 51 Influence of food on the bioavailability of drugs; Melander A; Food intake exerts a complex influence on the bioavailability of drugs . It may interfere not only with tablet disintegration, drug dissolution and drug transit through the gastrointestinal tract, but may also affect the metabolic transformation of drugs in the gastrointestinal wall and in the liver . Different food components can have different effects, and food may interact in opposite ways, even with drugs that are chemically related . Therefore, the net effect of food on drug bioavailability can be predicted only by direct clinical studies of the drug in question . As judged mainly from single meal, single dose studies, food intake enhances the bioavailability of several different drugs, such as propranolol, metoprolol, hydrallazine, hydrochlorothiazide, canrenone (from spironolactone), nitrofurantoin, erythromycin (stearate), dicoumarol, phenytoin and carbamazepine, but reduces that of drugs such as isoniazid, rifampicin, tetracycline, penicillin and ampicillin, while having no consistent effect on the bioavailability of metronidazole, oxazepam, melperone, propylthiouracil, sulphasomidine and sulphonylureas . For some drugs such as digoxin and paracetamol, the rate but not the extent of absorption is reduced . Food may enhance bioavailability even though, or rather because, the rate of gastric emptying is reduced; this is apparently the case with hydrochlorothiazide and nitrofurantoin . The food induced enhancement of bioavailability of propranolol, metoprolol and hydrallazine is probably due to reduced first pass metabolism of these drugs, while food induced improvement of drug dissolution may explain the enhanced bioavailability of carbamazepine, canrenone, dicoumarol and phenytoin . An increased gastrointestinal pH may be in part the cause of the food induced reduction of the bioavailability of drugs such as isoniazid and tetracycline . In addition to single meal effects, repeated intake of protein-rich meals enhance, while carbohydrate-rich meals reduce, the rate of oxidation of antipyrine and theophylline . Moreover, intake of charcoal broiled meat markedly accelerates the oxidation of phenacetin and variably accelerates elimination of theophylline . Thus, food and its components and contaminants may have both short and long term effects on both the absorptive and biotransformation processes influencing systemic availability of drugs. J Pharm Sci, 1978 Aug, 67(8), 1087 - 93 Physical characterization of erythromycin: anhydrate, monohydrate, and dihydrate crystalline solids; Allen PV et al.; Hot-stage microscopy, thermoanalytical methods, and X-ray powder diffraction were used to demonstrate that crystalline erythromycin dihydrate converts to the crystalline anhydrate via a noncrystalline intermediate . X-ray powder diffraction, IR spectral, thermogravimetric, and differential thermal analyses were used to characterize the monohydrate material . The flow interrupt technique, a procedure recently developed to deal with low surface area samples, was employed successfully in obtaining isotherms and specific surface areas for the monohydrate and anhydrate . The relative dissolution rates of the various hydrates were determined in an aqueous solution (0.01 M phosphate buffer, pH 7.5) at 37 degrees . The results showed a significant difference in the dissolution rate of the dihydrate compared to the monohydrate and anhydrate. J Pharm Sci, 1978 Aug, 67(8), 1057 - 9 Pharmacokinetics of intravenous erythromycin; Welling PG et al.; Erythromycin pharmacokinetics were examined following intravenous infusion to male subjects . The biological half-life of erythromycin in serum was 2 hr in individuals with normal renal function . The half-life varied in cases of reduced renal function, with values of 3.9 and 7.0 hr occurring in two subjects with severe renal impairment . Postinfusion serum erythromycin levels were adequately described by two-compartment model kinetics, and values for the distribution volume of the central compartment and the overall distribution are described . Estimated erythromycin distribution volumes in normal individuals may facilitate calculation of absorption efficiencies of erythromycin and its salts after oral doses. Med J Aust, 1978 Jul 29, 2(3), 121 - 3 Oral administration of erythromycin stearate: effect of dosage form on plasma levels; Triggs EJ et al.; The clinical effectiveness of three different oral dose forms of erythromycin stearate was assessed by following plasma levels during continued dosage . The assessment was carried out in 12 volunteers who took 250 mg of the drug every six hours in a cross-over design with intravenous administration of erythromycin lactobionate as a reference . While in some patients levels which were obtained after the initial dose were low, plasma levels sufficient to inhibit the majority of bacterial pathogens which cause acute respiratory tract infections were obtained and maintained after the second dose. Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol Bacteriol Virusol Parazitol Epidemiol, 1978 Jul-Sep, 23(3), 177 - 81 {Antibiograms of Leptospira on solid media in Petri dishes}; Sefer M; The sensitivity of fowl leptospirae to antibiotics was tested by diffusiometry on solid media in Petri dishes . The method includes two stages: 1) visible leptospirae cultures are obtained by central seeding and incubation during 3--5 days at 28 or 37 degrees C; 2) antibiotic tablets are disposed at 2 cm from the visible edge of the multiplication zone of the leptospirae . The edge is marked with a pencil at the moment in which the antibiotics are applied . Incubation is continued at the same temperatures . The results are read after five days taking as reference the position of the marginal multiplication line . The sensitivity of leptospirae to antibiotics is expressed by arrested multiplication and resistance by advance of the marginal multiplication line up to or even beyond the antibiotic tablets . Fowl leptospirae are sensitive to penicillin, tetracyclin, chloramphenicol, streptomycin, novobiocin, polymixin, pristinamycin, neomycin, erythromycin, and resistant to mycostatin, septrin, rifampicin, optoquine, sulphatiazol. Arch Intern Med, 1978 Jul, 138(7), 1156 - 8 Acute respiratory distress caused by erythromycin hypersensitivity; Abramov LA et al.; Severe respiratory distress developed in a patient after ingestion of two tablets of erythromycin (Erythrocin) stearate . Complete atelectasis of the left lung was found . The patient was treated intravenously with 200 mg of prednisolone sodium tetrahydrophthalate . On the same day the patient's condition improved dramatically and repeated chest roentgenograms disclosed an almost complete expansion of the atelectatic lung . Using the indirect mast cell degranulation test and the inhibition of direct mast cell degranulation test, we have shown the presence of IgE and non-IgE antibodies (heat stable) against erythromycin . This suggests that an allergic reaction of type 1 and type 3 participated in the course of the clinical picture. J Pharm Sci, 1978 Jul, 67(7), 1031 - 3 Erythromycin VI: kinetics of acid-catalyzed hydrolysis of erythromycin oxime and erythromycylamine; Lazarevski T et al.; Kinetic data were obtained, by qualitative and quantitative analysis, of the hydrolytic degradation of erythromycin oxime and erythromycylamine separated by TLC . The pseudo-first-order rate constants were determined at three temperatures (17,26, and 36 degrees), and the temperature dependency of the reaction was studied . The activation energy for the hydrolysis and methanolysis of the compounds was calculated . The factors contributing to the differences in the reaction rate are discussed. J Pharm Sci, 1978 Jun, 67(6), 764 - 6 Bioavailability of erythromycin stearate: influence of food and fluid volume; Welling PG et al.; The influence of various test meals and coadministered water volumes on erythromycin stearate bioavailability from orally dosed film-coated tablets was studied in healthy human subjects . Serum erythromycin levels were uniformly reduced by all test meals, with the reduction in mean peak serum levels varying from 47 to 60% . Serum erythromycin levels also were reduced significantly in fasted individuals when the accompanying water volume was reduced from 250 to 20 ml . The apparent drug absorption rate constant was not influenced by treatments . This result is probably due to rapid degradation of solubilized, unabsorbed drug in the GI tract . Higher and more uniform serum erythromycin levels are obtained when erythromycin stearate tablets are given on an empty stomach together with an adequate water volume. Genetics, 1978 Jun, 89(2), 281 - 97 Erythromycin resistance and the chloroplast ribosome in Chlamydomonas reinhardi; Davidson JN et al.; Five classes of erythromycin-resistant mutants of Chlamydomonas reinhardi have been identified . Each class corresponds to a different genetic locus, three nuclear and two chloroplast . The three nuclear loci appear to be unlinked, while Conde et al . (1975) have shown that the two chloroplast loci are linked, but not allelic . Mutants in each class have a unique pattern of cross-resistance in vivo to other antibiotics (lincomycin, carbomycin, and cleocin) that affect chloroplast protein synthesis . The chloroplast ribosomes from each class have a distinctive erythromycin-binding reaction in vitro.--Haploid and diploid strains containing combinations of different genes affecting the chloroplast ribosome were constructed to probe ribosome structure . New phenotypes were obtained by such combinations, demonstrating interactions between the gene products of a number of loci specifying ribosome components. Eur J Biochem, 1978 May, 86(1), 187 - 91 Characterisation of the binding of virginiamycin S to Escherichia coli ribosomes; de Bethune MP et al.; Virginiamycin S is an inhibitor of protein synthesis in vivo . In this paper we show by equilibrium dialysis that it binds specifically to the 50-S subunit of Escherichia coli ribosomes, with one binding site per subunit . This binding is not altered by the presence of chloramphenicol, tetracycline or puromycin but is competed for by erythromycin . Using the splitting-reconstitution method, it could be demonstrated that protein L16 is absolutely required for the binding of virginiamycin S to the 50-S subunit. Med J Aust, 1978 Apr 22, 1(8), 409 - 10 Non-specific (non-gonococcal) urethritis; Rana C et al.; A report is made of a small study of ureaplasmas and chlamydias in 32 cases of non-specific urethritis . Erythromycin was used as a therapeutic agent and found to be reasonably effective. Mol Gen Genet, 1978 Apr 6, 160(2), 171 - 81 Janus green resistance in Saccharomyces cerevisiae: interaction of nuclear and cytoplasmic factors; Kruszewska A et al.; Janus green B was found to be a specific inhibitor of mitochondrial function in yeast . This is consistent with the Janus green specificity in supravital staining of mitochondria . A mutant of S . Cerevisiae resistant to Janus green B was isolated . It shows cross resistance to oligomycin, ethidium bromide and a weak resistance to chlormaphenicol . The mutant was found to be sensitive to cycloheximide and erythromycin . Genetic analysis of this mutant showed that mitochondrial genes are not involved in the determination of Janus Green resistance . Tetrad analysis suggested that two more more nuclear genes are concerned, but many unusal genetic features suggestive of the involvement of a cytoplasmic element remain to be explained. J Clin Pharmacol, 1978 Apr, 18(4), 194 - 202 Bioavailability of erythromycin ethylsuccinate in pediatric patients; Coyne TC et al.; A parallel treatment group bioavailability study was undertaken in children 6 to 65 months of age, comparing fasting and nonfasting erythromycin serum levels after a single oral dose of erythromycin ethylsuccinate granules . Results demonstrated significantly higher levels in the nonfasting than in the fasting state, while fasting state levels were comparable to those found in studies of adult subjects receiving recommended doses of the same compound. Genetics, 1978 Apr, 88(4 Pt 1), 643 - 50 Nuclear mutation increases streptomycin and spectinomycin sensitivity in Chlamydomonas; Lee RW et al.; A spontaneously arising nuclear mutation, ss-1, has been identified in Chlamydomonas reinhardtii that decreases both streptomycin and spectinomycin resistance levels about 10-fold after its introduction into all wild-type, streptomycin-resistant and spectinomycin-resistant strains examined . The mutations for resistance map to nuclear and uniparentally inherited (chloroplast) loci . In contrast, no modification of erythromycin resistance was detected after introducing ss-1 into wild-type strains or into strains carrying nuclear or uniparentally inherited erythromycin-resistance mutations . We suggest that ss-1 affects the small subunit of the chloroplast ribosome because others have shown that streptomycin and spectinomycin resistance in C . reinhardtii are associated with this subunit, whereas erythromycin resistance is associated with the large subunit . ss-1 shows no linkage with the nuclear locus for streptomycin resistance. Mol Gen Genet, 1978 Mar 20, 160(1), 33 - 40 Genetic damage during thymidylate starvation in Saccharomyces cerevisiae; Barclay BJ et al.; Thymidylate starvation in a yeast mutant auxotrophic for dTMP caused cell death and the induction of mutations in the mitochondrial genome . After 24 h of starvation almost all surviving cells were respiratory deficient petites . In addition, shorter episodes of dTMP starvation induced chloramphenicol and erythromycin resistant mutants, indicating the occurrence of mitochondrial point mutations . Suboptimal concentrations of exogenous thymidylate were also found to induce petites and a decline in cell viability and the magnitude of these effects was acutely dependent upon the dTMP concentration . Cesium chloride gradient analysis of DNA from cells undergoing thymineless incubation revealed a progressive loss of mitochondrial DNA, and a decrease in the molecular weight of nuclear DNA. JAMA, 1978 Feb 13, 239(7), 640 - 1 Sporadic Legionnaires' disease; Jones FL et al.; The first case of Legionnaires' disease recognized in Pennsylvania since the Philadelphia epidemic of 1976 was that of a 53-year-old emphysematous man who had extensive unilateral pneumonia accompanied by high fever, hypoxemia, and disorientation . His illness progressed despite treatment with cephalothin, but he recovered coincident with the administration of gentamicin and erythromycin . The diagnosis was established serologically by a 32-fold rise in antibody titer to the agent of Legionnaires' disease . Similar illness did not affect others in his community, and infection in four family members was excluded clinically and serologically. J Foot Surg, 1978 Winter, 17(4), 150 - 4 Some considerations of antibiosis and drug interactions in podiatric surgery; Stoller MI; Most antibiotics function via two basic and distinctly different mechanisms . The first mechanism is bacteriocidal in which an antibiotic interferes with bacterial cell wall metabolism causing the destruction of the cell through the resulting cell wall lysis . Bacteriocidal drugs include the penicillins, the cephalosporins, and aminoglycosides . The second mechanism is bacteriostatic wherein a drug interferes with protein synthesis within the cell itself thus inhibiting the growth and multiplication of the cell . This basic action should not be confused with direct cellular destruction . Examples of bacteriostatic drugs are erythromycin, lincomycin, clindamycin, chloramphenicol, and the tetracyclines . A good intellectual exercise would be to imagine using a bacteriostatic drug to inhibit cell reproduction and then to finish off the germ with a good bacteriocidal drug . But ability of a bacteriocidal drug to function depends upon its ability to act on a growing and reproducing bacterial cell, otherwise it won't work . So generally, combination therapy involving both classes of drug is not recommended. Scand J Infect Dis, 1978, 10(1), 7 - 9 Treatment of anginose infectious mononucleosis with metronidazole; Hedstrom SA et al.; 16 patients with the anginose type of infectious mononucleosis were treated with metronidazole, and another 3 patients were given clindamycin . Most of the patients had been given penicillin or erythromycin before admittance to hospital . Treatment with metronidazole had a favourable effect on the course of the disease; the body temperature was normalized, signs of tonsillitis disappeared and cervical lymph nodes decreased in size within 3 days in 10 patients and in the remaining 6 within 4 or 5 days . Difficulty in mastication and swallowing was usually relieved within 1 to 2 days of treatment . The period before normalization was significantly shorter than in 10 controls . Two of the 3 patients who were given clindamycin developed exanthems, but otherwise a similar favourable effect as in the metronidazole-treated patients was observed. Arch Dis Child, 1978 Jan, 53(1), 38 - 42 Mycoplasma pneumoniae infections in children; Stevens D et al.; Details are given of all serologically confirmed Mycoplasma pneumoniae infections in children referred to Bristol hospitals during an epidemic lasting 18 months . 44 children, many below school age, had lower respiratory infections . The majority had cough and malaise which had failed to respond to antibiotics given before referral . Chest x-rays showed no pathognomonic features: segmental or patchy consolidation was common; 3 cases of lobar consolidation . Cold agglutinins were raised in 9 out of 12 cases . In the majority of cases the total leucocyte count was normal and the absolute neutrophil count raised . Mean duration of symptoms was 4.2 weeks (range 1-16) . Treatment with erythromycin or tetracycline appeared to have little effect in most cases . Seven nonrespiratory manifestations were seen in 6 children . These were meningitis (2 cases), Stevens-Johnson syndrome (4 cases, 1 case complicated by toxic epidermal necrolysis), and acute haemolytic anaemia (1 case). Res Vet Sci, 1978 Jan, 24(1), 121 - 3 Sensitivity of mycoplasmas of the respiratory tract of pigs and horses to erythromycin and its use in selective media; Lewis J et al.; The ability of erythromycin in liquid medium to suppress the growth of eight species of acholeplasma and of 13 species of mycoplasma was tested . The Acholeplasma spp and two glycolytic Mycoplasma spp from horses--a slow glucose-metabolising (SGM) mycoplasma and a strain N3, related to M mycoides--were sensitive to erythromycin . Thus the growth of acholeplasmas can be suppressed when attempts are made to isolate pathogens from the porcine respiratory tract, but, in the case of horses, erythromycin would suppress not only Acholeplasma spp but also two Mycoplasma spp of unknown pathogenicity in the equine respiratory tract. J Antibiot (Tokyo), 1978 Jan, 31(1), 70 - 3 The effects of trimethoprim and erythromycin on polysome metabolism in Escherichia coli; Roche J et al.; Trimethoprim and erythromycin were shown to have different overall effects on in vivo polysome metabolism in Escherichia coli . In a rel A+-rel A pair of strains, trimethoprim treatment induces a reduction of polysome level to a variable extent, similarly to aminoacyl tRNA deprivation of cells, but persisting polysomes remain dynamic structures in a state of continual turnover . In contrast, erythromycin stabilizes polysome level to a high value in either kind of strain, but maintained polysomes appear as "frozen" structures unable to undergo ribosome translocation. Br J Dis Chest, 1978 Jan, 72(1), 13 - 20 A comparison of ampicillin, erythromycin and erythromycin with sulphametopyrazine in the treatment of infective exacerbations of chronic bronchitis; Willey RF et al.; A comparative study of ampicillin (500 mg four times daily), erythromycin (500 mg four times daily) and sulphametopyrazine (1 g at start of exacerbation) followed by erythromycin (500 mg four times daily) was carried out in infective exacerbations of chronic bronchitis . Ampicillin and erythromycin were found to be equally effective, but the combination of erythromycin and sulphametopyrazine was significantly less effective . Unwanted effects were more frequent with ampicillin and with erythromycin plus sulphametopyrazine than with erythromycin alone. Dermatologica, 1978, 156(2), 105 - 10 Erythromycin stearate in acne vulgaris: its effect on the skin surface lipids and on the activity of purified pancreatic lipase; Hellgren L et al.; To study the mechanism of action of erythromycin stearate in acne vulgaris, the composition of the skin surface lipids was analyzed before, during and after treatment (500 mg daily for 1 week, 250 mg daily for 2 months) in 17 patients . Quantitative thin-layer chromatography showed that the fatty acid fraction in the skin surface lipids decreased significantly during the treatment period . The clinical effect was good in 14 of 17 patients . Further investigations were performed on the effect of erythromycin stearate on purified pancreatic lipase . The enzyme activity was not inhibited by exposure to the drug. Nucleic Acids Res, 1978 Jan, 5(1), 271 - 84 Turbidimetric and potentiometric studies of ribosomal subunits from an erythromycin resistant mutant of Escherichia coli; Kliber JS et al.; Turbidimetric and potentiometric techniques were applied to the analysis of an EryR mutant . Results show that in the mutant, the 30S subunits are drastically altered, as indicated by a higher Mg2+ requirement for subunit association and by an important difference in the titratable groups . Replacement of parental 50S by mutant 50S subunits does not decrease the association capacity with 30S parental subunits, but a structural difference is detected in the mutant 50S with potentiometric measurements . The mutation results in decreased ribosomal in vitro activities at 22 degrees C including lowered polyphenylalanine synthesis, drastic altered initiation step and the loss of erythromycin binding to the ribosomes . The results extend previous observation of a gene eryC part in the maturation of both subunits. Biochim Biophys Acta, 1977 Dec 2, 479(3), 279 - 89 Effects of erythromycin on membrane-bound chloroplast ribosomes from wild-type Chlamydomonas reinhardi and erythromycin-resistant mutants; Hanson MR et al.; 1 . Treatment of wild-type cells of Chlamydomonas reinhardi with high concentrations of erythromycin results in increased recovery of membrane-bound chloroplast ribosomes, presumably by preventing polysomal runoff during harvesting of cells . No such membrane-retention effect is detected if erythromycin is added after harvesting of cultures, before cell breakage . 2 . Growth of wild-type cells is inhibited by 10 microgram/ml erythromycin, but a concentration twice as high is required to increase recovery of membrane-bound wild-type ribosomes . On the other hand, the concentrations of erythromycin which inhibit growth of mutant ery-M1b produce a membrane-retention effect . Mutant ery-U1a is resistant to high concentrations of erythromycin and no membrane-retention effect is detectable at concentrations which produce one in wild type and ery-M1b . 3 . These results can be reconciled by a two-point model of the mechanism of erythromycin action on chloroplast ribosomes in Chlamydomonas. Scott Med J, 1977 Dec, 22(5), 405 - 7 The use of erythromycin in a general practice; Grob PR; It would appear that erythromycin is a safe drug to use in general practice; it is indicated, and has advantages, in the treatment of infections of both the upper and lower respiratory tracts. Scott Med J, 1977 Dec, 22(5), 393 - 5 Erythromycin and anaerobic infection; Lambert HP; The theoretical basis of the use of erythromycin in peri-operative prophylaxis after bowel surgery will be discussed and the results of the use of erythromycin in such patients and the sensitivity to the antibiotic of isolates from human peritonitis described . This work will be related to results obtained in a rabbit experimental model for the study of peritonitis. Mol Gen Genet, 1977 Nov 18, 156(3), 267 - 71 Properties of ribosomes from erythromycin resistant mutants of Escherichia coli; Pardo D et al.; We have studied the in vitro properties of ribosomes from several mutants resistant to erythromycin . Mutations in three different genes may confer resistance to erythromycin . Two of them are structural genes for proteins L4 and L22 of the large subunit . The third mutation (in eryC gene) seems to affect mainly the small subunit . The mechanism of action of the antibiotic may involve both subunits. Fortschr Med, 1977 Oct 27, 95(40), 2445 - 7 {Treatment of chlamydial urethro-adnexitis with erythromycin}; Hofstetter A et al.; Besides mycoplasmas and ureaplasmas chlamydias are able to cause an urethro-adnexitis in men . Jeasts, trichomonas and herpes-viruses are in our patients of less importance . Therapy with erythromycine of chlamydial urethroadnexitis is successful. Eur J Biochem, 1977 Oct 3, 79(2), 469 - 72 The involvement of protein L16 on ribosomal peptidyl transferase activity; Bernabeu C et al.; Radioactive ribosomes from Escherichia coli were treated with increasing concentrations of NH4Cl in the presence of 50% ethanol . The resulting particles were tested for peptidyl transferase activity as well as for the binding of (U)C-A-C-C-A-Leu-Ac, (U)C-A-C-C-A-Leu, chloramphenicol, lincomycin and erythromycin . At the same time the proteins present in the particles were quantitatively estimated and the amount of each related to the residual activity displayed by the treated ribosomes . It was found that the loss of protein L16 closely paralleled the inactivation of the particles implying an important role for this protein in the structure of the peptidyl transferase center. J Clin Pharmacol, 1977 Oct, 17(10 Pt 1), 592 - 600 Pharmacokinetics of erythromycin on repetitive dosing; Colburn WA et al.; Serum erythromycin concentration data from several repetitive dosing studies were analyzed with newly developed computer methods for fitting multiple-dose data and generating nonlinear least-squares estimates of pharmacokinetic parameters . This analysis indicates that the pharmacokinetics of erythromycin can be described by a one-compartment linear model with the following characteristics: (a) a lag time between the time of drug administration and the onset of absorption; (b) apparent zero-order rather than first-order absorption; (c) dose-to-dose variability in the rate and extent of absorption; and (d) day-to-day variability in the kinetics of elimination . The bioavailability of the third dose of erythromycin on a given day is considerably lower than that of the second dose or of the fourth and last dose of the day . The average apparent half-life of erythromycin was 1.8 hour on day 1 and 2.6 hours on day 3 of the repetitive dosing regimen. JAMA, 1977 Sep 26, 238(13), 1371 - 3 Comparison of erythromycin base and estolate in gonococcal urethritis; Brown ST et al.; A randomized double-blind trial of 152 men with gonococcal urethritis compared the therapeutic efficacy of erythromycin estolate and erythromycin base . Twenty-one of 86 (24%) men treated with the estolate and 15 of 66 (23%) treated with the base had recurrent or persistent gonococcal infection when seen after a 9-g course of erythromycin . The serum erythromycin activity among estolate-treated patients (3.57 +/- 0.84 microgram/ml) was nearly twice that for base-treated patients (1.76 +/- 0.80 microgram/ml) . Our findings do not support routine use of erythromycin for treatment of pregnant, penicillin-allergic patients. Antibiotiki, 1977 Aug, 22(8), 722 - 6 {Experience with studying suspension media in actinomycete lyophilization}; Semenov SM; Viability, cultural features and antibiotic-production properties of the organisms producing tetracycline, chlortetracycline, erythromycin, neomycin, oxytetracycline and polymyxin were studied after their storage for 2 years in ampoules at a temperature of 4--10 degrees in lyophilized state with the use of sodium glutamate, polyvinylpyrrolidone, their combination and horse serum . The highest growth rate was observed in most of the cultures lyophilized in sodium glutamate . The growth of the cultures lyophilized in the solution of polyvinylpyrrolidone alone was mainly scanty or moderate . The antibiotic production level in some strains lyophilized in sodium glutamate or its combination with polyvinylpyrrolidone was after storage for 2 years somewhat higher than that in the control . The cultural features, i.e . the colour of the aerial and substrate mycelium and pigment secretion did not significantly differ in the lyophilized cultures and the cultures maintained on agarized media. Mol Gen Genet, 1977 Jun 8, 153(2), 199 - 204 A new ribosomal mutation which affects the two ribosomal subunits in Escherichia coli; Pardo D et al.; A new ribosomal mutant resistant to erythromycin is described . The product of the gene eryC seems to be implicated in the assembly of the two ribosomal subunits, particularly in the maturation process of the RNA 23S and 16S. Monatsschr Kinderheilkd, 1977 Jun, 125(6), 634 - 9 {Clinical and radiological findings in 78 children during the 1974/75 mycoplasma-pneumonia-epidemic (author's transl)}; Muller-Wening W et al.; Between August 1974 and October 1975 78 patients with mycoplasma-pneumonia-infection were admitted to the 3 pediatric clinics of Hannover . Their clinical and radiological findings were studied . 20 patients with serological diagnosis of additional viral infection were not included in this study . The clinical diagnosis was confirmed by complement fixation test . The commonest symptoms were fever, coughing and abnormal auscultatory findings over the lungs . Chest roentgenograms showed three different patterns of infiltration: 1 . Disseminated, non homogenous bronchial lines and mottled shadows often with swollen hilar lymphnodes in 46% of all patients.--2 . Homogenous, extensive, opaque infiltrates in 29% of all patients.--3 . Perivascular and peribronchial infiltrates at the hilus with or without swollen lymphnodes in 21% of all patients.--This means that in half of the patients abnormal signs in chestroentgenogram (type 2 and 3) were present, which formerly were described as "atypical pneumonia."--4 . There were no radiological symptoms in 4% of the patients.--Those who were treated with tetracyclin or erythromycin became afebrile within 1--3 days, in those who didn't get antibiotics at all or were treated with other antibiotics fever lasted longer. Aust N Z J Med, 1977 Jun, 7(3), 291 - 3 Erythromycin jaundice: diagnosis by an in vitro challenge test; Cooksley WG et al.; A 53-year-old housewife who had developed severe cholestatic hepatitis following the administration of erythromycin estolate therapy two-and-a-half years previously, was studied by an in vitro "challenge" test in which peripheral venous lymphocytes were cultured in the presence of erythromycin estolate, erythromycin stearate and erythromycin base . Evidence of blastogenesis was observed in response to erythromycin estolate, but not to erythromycin stearate of erythromycin base . This test thus provided evidence that the patient was "sensitized" to erythromycin estolate without exposing her to the risk of in vivo challenge . Furthermore, in contrast to previous studies, the findings provide evidence that erythromycin estolate jaundice is mediated by immunological mechanisms. Biochemistry, 1977 May 31, 16(11), 2349 - 56 Interaction between the erythromycin and chloramphenicol binding sites on the Escherichica coli ribosome; Langlois R et al.; The effects of chloramphenical on the binding kinetics of a fluorescein isothiocyanate derivative of 9(S)-erythromycylamine with 70S and 50S ribosomes have been studied by direct fluorimetric measurements . While chloramphenicol had little effect on the second-order 70S binding rate of the erythromycin analogue, it substantially reduced the dissociation rate of the fluorescent antibiotic-70S ribosome complex . This could be explained by simultaneous binding of both antibiotics to the 70S ribosome . The kinetic results suggest that chloramphenicol-saturated 70S particles bind the erythromycin analogue four times stronger and this was confirmed by direct binding studies . In additon, chloramphenicol causes a twofold increase in the intrinsic fluorescence of the 70S-bound analogue . This increase in fluorescence was used to study the kinetics of chloramphenicol binding to 70S ribosomes containing the fluorescent derivative . The fluorescence change followed first-order kinetics, suggesting that chloramphenicol induces a conformational change in the 70S particle . This could explain both its effect on erythromycin binding and on the fluorescence of bound analogue . Less detailed results with the 50S particle indicate a qualitively similar picture of erythromycin-chloramphenicol interactions. Va Med, 1977 May, 104(5), 319 - 20, 325-8 Otitis media: a review; Perriello VA et al.; We have presented recommendations for diagnosis and management of otitis media in children based on a comprehensive review of the pertinent medical literature . For an entity that is so common, there still remain amazingly large numbers of areas of controversy . We have also attempted to stress the importance of appropriate therapy and adequate followup as being very important in the management of otitis media . Newer concepts, particularly the use of the impedance bridge tympanogram, have been mentioned . With all the above background information in mind and with considerations for what is practical for the patient and the medical community, we would recommend the following as the acceptable minimal care for patients with otitis media . When the diagnosis of the acute otitis media is made on the basis of physical findings of myringitis, and/or middle ear fluid, and/or rupture of the tympanic membrane, the following treatment course is advisable: Neonates Culture of middle ear fluid if possible . Ampicillin 200 mg/kg/day intramuscularly . Gentamicin 3/5mg/kg/day intramuscularly . Hospitalize and treat until well and for minimum of seven days . Observe closely for meningitis and other infections and drug toxicity . These should be handled only by physicians experienced in dealing with patients in this age range . Appropriate work-up for septicemia should precede treatment . Switch to specific antibiotic when cultures and sensitivity available . Children . From 2 months to 6 years of age: Ampicillin 50mg/kg/day . Decongestant (if desired) . Administer for ten days . Every patient with otorrhea, severe otitis and those not clinically well should be seen for followup ten to 14 days later . They should have a minimum of otologic evaluation including drum mobility . In persistent cases, audiometry and otologic referral are necessary . If patient is allergic to penicillin, erythromycin at 20mg/lb/day may be used . Trimethoprim sulfa may hold promise in the future . Tetracycline is never indicated in this age range because of side effects and high relapse rate secondary to resistant organisms . Patients above 6 years of age: Penicillin pheyoxymethyl 250 mg every six hours for ten days . Decongestant (if desired) . Followup and penicillin allergy as above. Eur J Biochem, 1977 Apr 15, 74(3), 521 - 6 Mitochondrial heredity of resistance to 3-(3,4-dichlorophenyl)-1,1-dimethylurea, an inhibitor of cytochrome b oxidation, in Saccharomyces cerevisiae; Colson AM et al.; 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron), an inhibitor of cytochrome b oxidation, has been used for the selection of three resistant mutants (diur) of Saccharomyces cerevisiae . The mutant diur-64 exhibits in vivo cross-resistance to antimycin A while diur-34 and diur-1 are more sensitive to antimycin A than the parental strain . The three mutants exhibit mitochondrial inheritance according to the following criteria: mitotic segregation of diuron-resistant and diuron-sensitive diploids is obtained among the diploid progeny of a cross between diur and dius; non-Mendelian segregation of diuron resistance (4:0) is observed in spores of tetrads issued from diuron-resistant diploid; extensive ethidium bromide treatment leads to the formation of Q- mutants which no longer transmit diur and dius alleles . Evidence for two distinct diuron-resistant loci were obtained by allelism tests . Recombination analysis shows that diuron-resistance is not located in the polar region of the mitochondrial genome . The diur loci are not linked to the erythromycin locus since the upper limit in recombinants frequency (26%) for a non-polar region is obtained between diur and eryr . A low recombinants frequency (3%) is observed in crosses between diur-34 mutation and the two mutants cob1 and cob2 suggesting that diur-34 might be located between these two cytochrome-b-deficient loci . The resistance to diuron is also expressed in vitro since the oxidation rates of succinate by sonicated submitochondrial particles from the mutants are clearly less sensitive to diuron than that of the wild type. Schweiz Med Wochenschr, 1977 Apr 9, 107(14), 455 - 64 {Diphtheria epidemic in eastern Switzerland in 1974}; Wegmann T et al.; A diphtheria epidemic in the eastern part of Switzerland in 1974 and the measures which were taken for its management and eradication are described . In particular it is pointed out that at present diphtheria displays atypical clinical symptoms in Europe, a fact that renders the diagnosis very difficult in many cases . Therefore, it is important to perform a throat swab in every patient with suspected diphtheria; it is also necessary to explicitly require a search for C . diphtheriae . The early recognition and early treatment of diphtheria with penicillin or erythromycin is of the utmost importance in order to avoid neurological and cardiac complications . With regard to the management and eradication of a diphtheria epidemic, the most important measures are rapid antibiotic protection of all contacts and a widespread immunization of the population . Vaccination of adults with a DiTe vaccine containing a reduced amount of Di-toxoid is recommanded. J Cell Biol, 1977 Apr, 73(1), 139 - 48 Characterization of mitochondrial and cytoplasmic ribosomes from Paramecium aurelia; Tait A et al.; The ribosomes extracted from the mitochondria of the ciliate, Paramecium aurelia, have been shown to sediment at 80S in sucrose gradients . The cytoplasmic ribosomes also sediment at 80S but can be distinguished from their mitochondrial counterparts by a number of criteria . Lowering of the Mg++ concentration, addition of EDTA, or high KCl concentrations results in the dissociation of the cytoplasmic ribosomes into 60S and 40S subunits, whereas the mitochondrial ribosomes dissociate into a single sedimentation class at 55S . Furthermore, the relative sensitivity of the two types of ribosome to dissociating conditions can be distinguished . Electron microscopy of negatively stained 80S particles from both sources has also shown that the two types can be differentiated . The cytoplasmic particles show dimensions of 270 X 220 A whereas the mitochondrial particles are larger (330 X 240 A) . In addition, there are several distinctive morphological features . The incorporation of {14C}leucine into nascent polypeptides associated with both mitochondrial and cytoplasmic ribosomes has been shown: the incorporation into cytoplasmic 80S particles is resistant to erythromycin and chloramphenicol but sensitive to cycloheximide, whereas incorporation into the mitochondrial particles is sensitive to erythromycin and chloramphenicol but resistant to cycloheximide. Hautarzt, 1977 Mar, 28(3), 145 - 7 {Syphilis therapy--results of an inquiry}; Leyh F; In order to get some more information about the kind of treatment of syphilis in the F.R.G . a study among the 1578 practising dermatologists (without members of hospital staff) by means of questionaires was made . 1164 (79%) answered the inquiry . The study shows that nearly 50% of the answering dermatologists treat syphilis by several series of penicillin applications . On the other side, only one third of the respective dermatologists performs treatment by one series, giving penicillin from 15 to 21 Mega units . The study shows that the kind of therapy is rather age-dependend insofar as the older dermatologists prefer the multiple therapy series scheme, whereas the younger dermatologists are inclined to use the single series scheme . Furthermore geographical differences could be shown, e.g . most of the Bavarian dermatologists use the single series scheme . The kind of penicillin, way of application and the time intervals were rather uniform related to regions and schemes of therapy . Tetracycline and Erythromycin are used in case of penicillin allergy . In the opinion of less than 50% of dermatologists additional redications are necessary, whereby the younger ones prefere corticosteroides, the older ones potassium iodide . The benefits of uniformly performed therapy of syphilis by the single series scheme are discussed. Strahlentherapie, 1977 Mar, 153(3), 200 - 3 The effect of erythromycin and its thiocarbamide derivative on the induction of meiotic chromosome rearrangements in irradiated male mice; Pecevski J et al.; Antibiotics, erythromycin and a thiocarbamide derivative of erythromycin were tested for their ability to induce chromosome translocations in whole-body irradiated mice with a dose of 600 r . The aim of the present paper was to determine whether these antibiotics might induce by themselves, chromosomal translocations and whether these agents have a protective effect against X-rays-induced chromosomal translocations in the spermatocytes at the first meiotic metaphase . The incidence of translocations in irradiated animals was 9.07%; in animals treated with erythromycine after irradiation it was 3.80%; and in those treated with a thiocarbamide derivative of erythromycin following irradiation was 3.20% . Not a single chromosome rearrangement was scored among the non-irradiated animals, treated with the mentioned antibiotics. Mol Gen Genet, 1977 Feb 28, 151(1), 69 - 76 Manganese mutagenesis in yeast . VI . Mn2+ uptake, mitDNA replication and ER induction: comparison with other divalent cations; Putrament A et al.; A medium was found in which manganese efficiently induces erythromycin-resistant mitochondrial mutations, and which is suitable for measuring Mn2+ uptake and the labelling of DNA (fig . 1) . Mn2+ uptake is stimulated by glucose and slowed down by cycloheximide (Fig 2) . Mg2+ competes with Mn2+ uptake much stronger than does Zn2+ (Fig . 3) . All of the conditions which favour Mn2+ uptake also favour induction of erythromycin-resistant mutations (Tables 3, 4) . Mn2+ strongly inhibits protein synthesis (Table 1) . Nuclear DNA replication is also strongly inhibited by this cation, while mitochondrial DNA replication is only weakly inhibited during the first 3 h of labelling, but there is small if any increase of the label incorporation between the 3rd 6th h of labelling (Table 2) . The relation between label incorporation into mitDNA and mutation induction by manganese is not straightforward (Table 5) . From among 11 divalent cations tested, only Mn2+ was capable of inducing mitochondrial erythromycin-resistant mutations (Table 6). J Chromatogr, 1977 Feb 11, 132(2), 309 - 13 Erythromycin series . V . Quantitative analysis of cladinose and methylcladinoside by densitometry of thin-layer chromatograms; Lazarevski T et al.; A direct, quantitative, thin-layer chromatographic method is described for the determination of sugar cladinose and methylcladinoside in the presence of other acid-degradation products of the antibiotics erythromycin oxime and erythromycyl-amine . Cladinose and methylcladinoside are separated from compounds which cause interference on pre-coated silica gel F254 plates, and are measured directly on the thin-layer plate using a densitometer . Standard graphs obtained for cladinose and methylcladinoside show a linear relation between the square root of the peak area and the logarithm of the amount of substance present in the spot, as well as between the square of the area and the logarithm of the amount . This method is very successful in stability studies on the antibiotics erythromycin oxime and erythromycylamine in an acid medium . The technique seems to be particularly useful in instances in which the usual analytical methods either cannot be applied or can be applied only with difficulty. Mol Cell Biochem, 1977 Feb 4, 14(1-3), 97 - 100 Mitochondrial biogenesis: inhibitors of mitochondrial protein synthesis; Wilkie D; The effects of erythromycin, chloramphenicol, cycloheximide, pyrimethamine, chromate, cadmium, lead, nickel, 4-nitro-quinoline-1-oxide and thioacetamide on yeast and human cells were studied . Inhibition of the synthesis of mitochondrial proteins resulted in the loss of cytochromes as well as in morphological changes in the cellular membranes and mitotic arrest . The data are discussed. Mol Cell Biochem, 1977 Feb 4, 14(1-3), 25 - 9 Mitochondrial recombination in crosses of iso- and anisomitochondrial Saccharomyces cerevisiae; Kaldma J; Mitochondrial mutants resistant to erythromycin, neomycin and monomycin were isolated . Mitochondria were transmitted from different natural strains to the cells of the same nuclear genotype . In bifactorial crosses of such isochromosomal and anisomitochondrial yeasts we tested random samples of diploid colonies . The distribution of mitochondrial markers in parent and recombinant classes has been shown to occur unequally . The asymmetry of parent and the polarity of recombinant classes were observed to differ in different mitochondrial mutants . Anisomitochondrial strain crosses proved that mitochondrial origin essentially influenced both the parent and recombinant classes distribution and the susceptibility of the transmission to the effect of mating type locus . One can distinguish between 'homo- and heterosexual' cross combinations in terms of recombination polarity . The new type of mitochondria was found to occur with high frequency of transmission to the zygote progeny of markers resistant to erythromycin but not of markers resistant to neomycin . The problem of 'sex' in mitochondria is discussed. Mol Cell Biochem, 1977 Feb 4, 14(1-3), 15 - 8 Cytoduction as a new tool in studying the cytoplasmic heredity in yeast; Zakharov IA et al.; When crossing the haploid cells of genetically marked yeast strains we observed the appearance of both normal diploid zygotes and haploid nuclear cytoplasmic hybrids . The latter had the nuclear markers of one and the cytoplasmic marker (rho+) of the other parent . The autonomous cytoplasmic factor transfer was termed as cytoduction . Cytoduction is supposed to be the abortive form of yeast cell mating . Only about 1% of cytoductants in usually observed . Cytoduction can be used as a simple test on cytoplasmic determination of some characters . We observed the transfer into cytoductant cells of not only rho+ marker but of resistance factors to antibiotics (erythromycin, neomycin) and killer factor as well . Cytoduction can be applied towards constructing strains having the identical nucleus genotype with mitochondria and other cytoplasmic factors of different origin . In crossing strains with doubly marked mitochondria recombination of mitochondrial markers in cytoductant haploid cells was observed, the pattern of which was similar to that of mitochondrial recombination in normal zygotes. Int J Clin Pharmacol Biopharm, 1977 Feb, 15(2), 90 - 7 {Acute side effects of erythromycin, lincomycin and clindamycin}; Raab W; After some introductory remarks on the pathogenetic mechanisms of acute undesirable reactions following the administration of antibiotics, the incidence of vascular shock (anaphylactic shock, anaphylactoid shock) is discussed . Investigations were performed to obtain information on the sensitizing capacity of erythromycin and clindamycin in rats and guinea pigs . Although maximation procedures were used, no sensitization could be obtained, in contrast to similar series with penicillin and sulfonamides . In another experimental series, the anaphylactoid properties of erythromycin and clindamycin were studied in vitro . The dye-kick-off test and the mast-cell-degranulation test were used . No pronounced anaphylactoid activity, either of the cellular or of the humoral type, was found in the two antibiotics investigated . The results of the animal experiments and the experiments in vitro are in good accordance with clinical experience: erythromycin and clindamycin rank among the safest antibiotics with regard to the elicitation of acute undesirable actions. Jpn J Antibiot, 1977 Feb, 30(2), 139 - 44 {The therapeutic effect of doxycycline (Vibramycin) on pneumonia due to mycoplasma pneumoniae (author's transl)}; Izumikawa K et al.; Tetracycline is expected to be as effective as erythromycin in the treatment of pneumonia due to Mycoplasma pneumoniae . In this clinical trial 12 cases with pneumonia due to Mycoplasma pneumoniae were given doxycycline (Vibramycin "Pfizer'), a long-acting derivative of tetracycline . Judging from time periods required for defervescence, improvement in symptoms such as cough and disappearance of shadows on chest X-ray, the therapeutic effect of doxycycline was excellent in 8 cases and good in 4 cases. Ann Otol Rhinol Laryngol, 1977 Jan-Feb, 86(1 Pt 1), 9 - 11 Reversible sensorineural hearing loss with intravenous erythromycin lactobionate; Karmody CS et al.; Three patients are presented who developed reversible sensorineural hearing losses during treatment with intravenous erythromycin lactobionate . A fourth patient treated with erythromycin gluceptate did not develop hearing loss . Ototoxicity with erythromycin lactobionate has been previously reported in only three patients, one of whom had medication orally . Withdrawal of the antibiotic resulted in prompt improvement in every case with return of hearing to pretreatment levels. Padiatr Padol, 1977, 12(1), 10 - 8 {Mycoplasma pneumonias in childhood (author's transl)}; Guggenbichler JP et al.; During the winter months 1974/75 we were able to observe a number of unusual respiratory tract infections particularly in children over 6 years of age which appeared as pneumonias . Characteristic clinical findings included a dry, hacky cough, refractive to the usual antitussives, starting 1--2 weeks prior to admission, fever up to 104, malaise, headache, anorexia, shortness of breath and cyanosis . Several Pts were treated prior to admission with a number of antibiotics and failed to respond . Laboratory findings showed a peripheral polymorphonuclear leucocytosis with toxic granulations of neutrophiles . A sedimentation rate above 40 in the first hour occurred in most Pts . X Ray of the lung revealed a characteristic mottled appearance with patchy infiltrations, atelectasis and nodular densities . Frequently a shift of the mediastinum towards the infiltrate was seen . One of the hallmarks on physical examination was the discrepancy between the severity of the clinical illness and the paucity of physical findings . Decreased breath sounds over affected lung areas were often the only findings on auscultation; find rales, rhonchi or dullness on percussion were less often heard . The combination of a typical history, physical examination, laboratory tests and X Ray findings enabled us to make a presumptive clinical diagnosis of Mycoplasma pneumonia before serologic test results were available and to start with the appropriate antibiotic (Erythromycin, Tetracycline) early in the course of the disease . Complement fixation tests with a titer of 1 : 20 and a fourfold rise over the next two weeks or an initial titer of 1 : 80 and above were considered significant for acute disease. J Assoc Off Anal Chem, 1977 Jan, 60(1), 176 - 8 Collaborative study of assay method for erythromycin in pelleted feeds containing binding agents; Winkler VW et al.; A modified method for analysis of erythromycin in feeds containing the pelleting adjuvants bentonite and Masonex has been evaluated by collaborative study . Erythromycin is freed from the binding action of these adjuvants by an aqueous methanolic pH 8 buffer presoak before extraction with methylal . The recovery values for mash and pellets of 6 different sample types range from 86.6 to 103.0% of theory with a grand mean of 96.8% . This modification has been adopted as official first action. Acta Chir Acad Sci Hung, 1977, 18(2), 149 - 53 Ovarian actinomycosis developed during the use of a plastic intrauterine contraceptive device; Csapo Z et al.; PIP: A case report of ovarian actinomycosis developed during the use of a plastic IUD describes diagnosis and treatment . After 7 months use of the Szontagh-Szereday IUD, a 33-year-old patient was admitted with fever and a flat tender mass of apple size, reaching to the right pelvic wall . The patient was treated with chloramphenicol, phenylbutazone, trimethoprim and sulphadimidine, erythromycin, neomycin, colistin, and methicillin which were administered in courses of 4-5 days to treat the septic fever and repeated, but negative punctures of the pelvic mass were made . The patient was transfused and then treated with carbenicillin and penicillin and a few complaint-free days followed . On the 65th day of clinical treatment laparoscopy was performed and a mass was found adhering to the pelvic wall and coecum and enclosing the Fallopian tube and ovary . Chronic inflammation with multiple abscesses were seen histologically and total hysterectomy and bilateral adnexectomy were performed . 1 section of the ovary showed a structure suggesting actinomycosis . The patient was discharged and then readmitted on the 40th postoperative day . Culture of an abscess in the right side of the pelvis revealed macrophages, granulocytes, and typical "sulphur" granules . Actinomycosis was diagnosed and treated with penicillin and methicillin . J Bacteriol, 1977 Jan, 129(1), 326 - 32 Interaction of cytoplasmic membrane and ribosomes in Escherichia coli: spectinomycin-induced disappearance of membrane protein I-19; Mizuno T et al.; Incubation of Escherichia coli with spectinomycin caused the disappearance of a major protein from the cytoplasmic membrane . This protein, called "I-19", was not a ribosomal protein . Its disappearance was not a result of the direct action of spectinomycin on the cytoplasmic membrane, but a result of its action on ribosomes . The disappearance was specifically induced by spectinomycin, and other antibiotics such as neomycin, erythromycin, and chloramphenicol had no effect . Although growth was not required for spectinomycin-induced disappearance of protein I-19 from the cytoplasmic membrane, the disappearance was not observed under conditions where protein synthesis was inhibited completely either by the addition of chloramphenicol or by cooling in ice . It is suggested that at least some ribosomes interact with the cytoplasmic membrane and that a modification of the mode of interaction through the action of spectinomycin on ribosomes caused the deletion of membrane protein I-19. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 158 - 67 Treatment of syphilis in pregnancy; Thompson SE 3rd; Only penicillin has been adequately studied in treating syphilis during pregnancy . It is safe for the fetus and highly effective in doses currently recommended by the USPHS . Since these schedules appear to represent a minimal effective dose, smaller amounts should never be used . Whether higher doses would produce higher cure rates is not known . Penicillin is the drug of choice and the standard against which all others must be measured . Tetracyclines in any dose or form should not be used because of toxicity to both mother and child . Erythromycin (except the estolate) and cephalosporins are promising because of low toxicity, but their efficacy has not been established. Ann Rheum Dis, 1976 Dec, 35(6), 502 - 9 Detection by electron microscope of rod-shaped organisms in synovial membrane from a patient with the arthritis of Whipple's disease; Hawkins CF et al.; Rod-shaped organisms identical to those present in the jejunal mucosa have been found in the synovial membrane of a patient with Whipple's disease . These probably caused inflammatory changes which sere reflected in an increase of the cellular content and high enzyme levels (acid phosphatase and 5-nucleotidase) of the synovial fluid . Tetracycline was effective in controlling the bowel lesion but only had a temporary effect upon the arthritis . Erythromycin controlled both the bowel lesion and the arthritis. Eur J Biochem, 1976 Nov 15, 70(2), 409 - 17 The cytochrome bc) complex of yeast mitochondria . Site of translation of the polypeptides in vivo; Katan MB et al.; 1.Yeast cells were labelled with radioactive amino acids in the presence of cycloheximide and the cytochrome bc1 complex was isolated from them as described in the preceding paper (Katan, M.B.., Pool, L . & Groot, G.S.P . (1976)Eur . J . Biochem, 65, 95-105) . After analysis of this preparation by sodium dodecylsulphate polyacrylamide gel electrophoresis only one band, with an apparent Mr of 32000, was found to have incorporated radioactivity . The amount of label in the band was low, but could be increased approximately 5-fold by preincubating the cells in erythromycin before the labelling period . 2 . Cells were labelled in the presence of chloramphenicol and the cytochrome bc1 complex was isolated by (NH4)2SO4 fractionation . Upon electrophoresis in the presence of sodium dodecylsulphate only four of the six bands that belong to the complex were found to have incorporated radioactivity; no radioactivity was found in the bands with an Mr of 40000 and 17000 . The same result was obtained after labelling in the presence of acriflavin . If, however, the cytochrome bc1 complex was isolated by immunoprecipitation, all bands were found to have incorporated radioactivity in the presence of chloramphenicol . The amount of radioactivity in the Mr 32000 band was now clearly depressed . 3 . It is concluded that of the seven polypeptides of the cytochrome bc1 complex of yeast only one is made on mitochondrial ribosomes . This polypeptide has an Mr of 32000 and is probably associated with cytochrome b. Res Vet Sci, 1976 Nov, 21(3), 318 - 23 Pharmacokinetic interpretation of erythromycin and tylosin activity in serum after intravenous administration of a single dose to cows; Baggot JD et al.; The distribution and elimination kinetics of erythromycin and tylosin, which are macrolide antibiotics, were studied in healthy cows . A single dose (12-5 mg/kg) of drug was administered as an intravenous bolus, and blood samples were collected at precisely timed intervals . The standard cylinder plate bioassay method using Sarcina lutea as test organism was employed to determine antibiotic activity in the serum . The results suggested that these drugs are distributed in at least two kinetically distinct body compartments . By use of established mathematical techniques, values were assigned to the individual rate constants controlling distribution between the central and peripheral compartments and to the rate constant controlling overall elimination (beta) of each drug from the body . The calculated overall tissue to serum drug level ratios (k12/k21) after apparent distribution equilibrium was attained were 2-28 and 2-05 for erythromycin and tylosin, respectively . The half-life (mean+/-SD) of erythromycin was 3-16 h+/-0-44, while that of tylosin was 1-62 h+/-0-17 . The total body clearance (ml/kg/min) values were 2-88+/-0-47 for erythromycin and 7-8+/-2-95 for tylosin . Analogue computer simulated curves of the antibiotic levels in the central and tissue compartments as wel as an elimination curve were generated . The tissue level of erythromycin reached a peak of 43 per cent of the dose at 67 min . At 6 h, the percentages of the dose of erythromycin in the central and tissue compartments and eliminated were 6, 19 and 75, respectively . The peak level of tylosin in the tissue compartment (26-5 per cent of the dose) was present at 30 min . At 4 h, 1 and 5 per cent of the dose were contained in the central and peripheral compartments, respectively, while 94 per cent had been eliminated . This single dose study provides information which is essential for the design of a satisfactory dosage regimen. Antibiotiki, 1976 Nov, 21(11), 1002 - 4 {Erythromycin penetration into the cerebrospinal fluid of patients}; Imshenetskaia VF; Permeability of erythromycin through the barrier of blood-cerebrospinal fluid in neurosurgical patients after its oral administration in a dose of 300-500 mg and intravenous administration in a dose of 200 mg was studied . The erythromycin was determined after the antibiotic single administration at intervals of 40 minutes to 6 hours . A total of 31 observations were performed . Low penetration of erythromycin into the cerebrospinal fluid of the patients was shown . The administration route (oral or intravenous) practically had no effect on the antibiotic penetration level into the subarachnoidal spaces . The highest liquor levels were observed within the period of 3 to 6 hours after the drug administration . The maximum index of penetration from the blood into the cerebrospinal fluid was about 10 per cent . The erythromycin penetration increased in cases with inflammatory changes in the meninges. J Cell Biol, 1976 Nov, 71(2), 497 - 514 Periodic variations in the ratio of free to thylakoid-bound chloroplast ribosomes during the cell cycle of Chlamydomonas reinhardtii; Chua NH et al.; The ratio of free to thylakoid-bound chloroplast ribosomes in Chlamydomonas reinhardtii undergoes periodic changes during the synchronous light-dark cycle . In the light, when there is an increase in the chlorophyll content and synthesis of thylakoid membrane proteins, about 20-30% of the chloroplast ribosomes are bound to the thylakoid membranes . On the other hand, only a few or no bound ribosomes are present in the dark when there is no increase in the chlorophyll content . The ribosome-membrane interaction depends not only on the developmental stage of the cell but also on light . Thus, bound ribosomes were converted to the free variety after cultures at 4 h in the light had been transferred to the dark for 10 min . Conversely, a larger number of chloroplast ribosomes became attached to the membranes after cultures at 4 h in the dark had been illuminated for 10 min . Under normal conditions, when there was slow cooling of the cultures during cell harvesting, chloroplast polysomal runoff occurred in vivo leading to low levels of thylakoid-bound ribosomes . This polysomal runoff could be arrested by either rapid cooling of the cells or the addition of chloramphenicol or erythromycin . Each of these treatments prevented polypeptide chain elongation on chloroplast ribosomes and thus allowed the polyosomes to remain bound to the thylakoids . Addition of lincomycin, an inhibitor of chain initiation on 70S ribosomes, inhibited the assembly of polysome-thylakoid membrane complex in the light . These results support a model in which initiation of mRNA translation begins in the chloroplast stroma, and the polysome subsequently becomes attached to the thylakoid membrane . Upon natural chain termination, the chloroplast ribosomes are released from the membrane into the stroma. Eur J Biochem, 1976 Sep, 68(1), 301 - 11 Analysis of proteins synthesized in mitochondria of cultured mammalian cells . An assessment of current approaches and problems in interpretation; Jeffreys AJ et al.; 1 . The conditions which enable highly efficient utilization of {35S}methionine by cultured mammalian cells and the resolution of selectively labelled mitochondrial products are described . 2 . Analysis of mitochondria purified from cells labelled in the presence or absence of inhibitors of cytoplasmic (or mitochondrial) protein synthesis indicated that about 5% of the {35S}methionine incorporated into mitochondrial proteins results from synthesis on mitoribosomes . 3 . The electrophoretic profile of the detergent-solubilized proteins of mitochondrial isolated from cells which were labelled in the presence of 50 mug/ml emetine was similar to those obtained with extracts prepared by direct solbuilization of the intact cells after incorporation of label . 4 . Pulse-labelling studies suggested that the components resolved by electrophoresis and autoradiography under the conditions described, apparently represent discrete and stable end products radiography under the conditions described, apparently represent discrete and stable end products of mitochondrial protein synthesis . No post-synthetic modification or degradation of these products was detected . 5 . Erythromycin was found to suppress the synthesis of additional labelled products which were detected in extracts of one cell line, when analysed by procedures which normally detected only mitochondrially synthesized proteins . These additional bands were attributed to the synthetic activity of Mycoplasma. Ann Trop Med Parasitol, 1976 Sep, 70(3), 253 - 8 The chemotherapy of rodent malaria, XXIV . The blood schizontocidal action of erythromycin upon Plasmodium berghei; Warhurst DC et al.; Erythromycin inhibits chloroquine-induced pigment clumping in Plasmodium berghei in vitro . The drug was therefore tested against infections of P . berghei in mice and was found to be active at non-toxic doses . Given orally, the stearate salt was more effective than the base, but subcutaneously the base was more effective than the stearate . Erythromycin potentiated the action of chloroquine against two chloroquine-resistant strains of rodent malaria, the mildly resistant NS, and the highly resistant RC strains of P . berghei, but not against the drug-sensitive N strain. JAMA, 1976 Aug 16, 236(7), 859 - 60 Erythema chronicum migrans in the United States; Mast WE et al.; Four cases of erythema chronicum migrans occurred within a one-month period in southeastern Connecticut . The syndrome may include advancing erythematous rash stemming from an apparent insect bite, hyperesthesias, myalgias, malaise, fever, lymphadenopathy, and, rarely, meningitis . Treatment with penicillin, the tetracycline, or, in our experience, erythromycin usually results in prompt resolution. Biochim Biophys Acta, 1976 Aug 2, 442(1), 76 - 87 Ferredoxin biosynthesis in Euglena gracilis; Matson RS et al.; Analysis of ferredoxin content in cultures of Euglena gracilis grown in the presence of selective antibiotic inhibitors of protein synthesis resulted in the following conclusions: 1 . Ferredoxin is synthesized from cytoplasmic (80s-type) ribosomes; cycloheximide, a potent inhibitor of 80s translation completely abolished the synthesis, while the inhibitors of 70s translation chloramphenicol and erythromycin were not effective . In addition, ferredoxin was detected in a streptomycin-bleached mutant that lacks the chloroplast structure and chloroplast DNA . 2 . Ferredoxin's transcript is presumably of nuclear origin; rifampicin, an inhibitor of chloroplast DNA-dependent RNA polymerase did not inhibit synthesis, while the streptomycin-bleached mutant continued to synthesize ferredoxin without chloroplast DNA. Mol Gen Genet, 1976 Aug 2, 146(3), 261 - 8 The conditions required for the induction of petite yeast mutants by fluorinated pyrimidines; Oliver SG et al.; Cytoplasmic petite mutagenesis by 5-fluorouracil (5FU) was prevented by temperature sensitive mutations which blcoked either nuclear transcription or cytoplasmic translation . However, 5FU was also ineffective in resting cells and in cells exposed to alpha-mating factor, showing that cell division or nuclear DNA synthesis is required for the mutagenic event to take place . In addition, the mutagenic effect of 5FU was completely prevented by daunomycin, and since this agent preferentially inhibits respiratory growth and was shown to selectively block RNA synthesis in the mitochondria, it was concluded that petite mutagensis resulted from incorporation of 5FU into mitochondrial RNA . Since inhibition of mitochondrial protein synthesis by erythromycin had little immediate effect on the mutagenicity of 5FU, it was deduced that the RNA in question is not directly involved in mitochondrial translation, and may have a regulatory function. Acta Pathol Microbiol Scand {B}, 1976 Aug, 84(4), 170 - 6 The diagnostic value of determination of IgM antibodies against Mycoplasma pneumoniae by the indirect immunofluorescent antibody test; Skaug K et al.; The indirect fluorescent antibody technique for specific IgM and IgG antibodies was applied to paired sera from 33 patients with a current M . pneumoniae infection, along with the complement fixation test . A roughly parallel increase in antibody titres in all the three tests was observed; the ratio of IgM/IgG titres was, however, higher in patients below 20 years of age than in older patients . Rises in antibody titres were regularly observed in spite of the fact that most of the patients were treated with tetracycline or erythromycin during the acute phase of the disease . Serum specimens from 15 other patients lacking clinical data of a recent M . pneumoniae infection, but with stationary complement fixation titres, all showed IgG antibodies with stationary titers and, with the exception of three patients, a negative IgM antibody test . Sera from 20 individuals lacking complement fixing antibodies were also without demonstrable IgG and IgM antibodies . Sampling of serum from 9 of the pneumonia patients was repeated . The last IgM positive sample was collected up to six months after onset of the disease and all were found to be negative in the IgM test 8 to 10 months after onset of the illness in these treated patients . The implications of these findings for the serological diagnosis of M . pneumoniae infections are discussed. Antibiotiki, 1976 Aug, 21(8), 675 - 8 {Dependence of erythromycin biosynthesis on the active acidity of the medium}; Brinberg SL et al.; Dependence of erythromycin biosynthesis on the medium active acidity was studied by the following methods: by changing pH of the initial medium, by changing the concentration of the medium components determining the active acidity of the culture, by using buffer mixtures by automatic control of pH . It was found that pH of the initial medium within 5.7-8.1 had no effect on the culture growth . Biosynthesis of erythromycin markedly decreased at pH 6.3 or lower . The values of pH within 6.6-7.5 (optimal values 6.7-6.9) were favourable for the antibiotic biosynthesis . At pH 6.2-6.3 the antibiotic accumulation was equal to 5-10 per cent of the control. Biochim Biophys Acta, 1976 Jul 16, 435(4), 333 - 9 Effect of viomycin on dihydrostreptomycin binding to bacterial ribosomes; Masuda K et al.; Viomycin, a peptide antibiotic, reduced the amounts of dihydrostreptomycin bound to ribosomes of Myobacterium smegmatis and Escherichia coli, although they have different modes of action . The {3H}dihydrostreptomycin binding to ribosomes could not exchanged with streptomycin or dihydrostreptomycin, but not with unrelated antibiotics, namely, kanamycin, neomycin, spectinomycin, capreomycin, tuberactinomycin-N, chloramphenicol and erythromycin . We suggest that there is a significant interaction between the binding sites of viomycin and streptomycin on ribosomes. Mol Gen Genet, 1976 Jul 5, 146(1), 61 - 78 Electron microscopy of analysis of circular repetitive mitochondrial DNA molecules from genetically characterized rho- mutants of Saccharomyces cerevisiae; Lazowska J et al.; 1 . We have studied mtDNA purified from nine p- petite mutants in which most of the wild type sequence has been deleted but the genetic markers conferring resistance to erythromycin of oligomycin or paromomycin have been retained . 2 . All mtDNA contained numerous circular molecules . The size distribution of the circles conformed to a multimeric series which was characteristic for each mutant . We conclude that any one region of the wild type mtDNA molecule, when maintained in a p- clone, while other regions are deleted, can give rise to a multimeric series of circles . 3 . In tandem straight repetitive mtDNAs the circles contain odd and even number of unit sequence repeats . In palindrome repetitive mtDNAs the circles contain mostly even number of unit sequence repeats . Thus, one straight or two inverted repeats constitute the monomeric unit of circularization . 4 . We found that the frequency distribution of circles follows on a number basis a simple rule: frequency of numeric circles = 1/n frequency of monomeric circles, for n = 2, 3 and 4 . Thus, on a mass basis each class represents the same fraction of total mtDNA and the mitochondrial genome has the same probability to constitute one monomeric circle or to be a part of n-meric circle . We interpret this finding that in vivo all molecules are circular . 5 . Four mutants displayed a single multimeric series of circles ranging from 0.3 mum to 2.4 mum monomer circle length . Five mutants displayed multiple different multimeric series . In the latter case, the longest unit sequence repeat length was equal to the sum of the two shorter unit sequence repeat lengths . Sorting out, recombination and internal deletions of circular repetitive p- mtDNA molecules are discussed. Mol Gen Genet, 1976 Jul 5, 146(1), 5 - 16 Effects of elevation of strain-ploidy on transmission and recombination of mitochondrial drug resistance genes in Saccharomyces cerevisiae; Gunge N; In order to study the effects of strainploidy on the transmission and recombination of the mitochondrial genes C, E and O conferring the resistance to chloramphenicol, erythromycin and oligomycin, respectively, haploids were crossed to diploids and the results of genetic analysis were compared with those from haploid X haploid crosses . All haploid X haploid crosses showed an increased transmission of diploid derived alleles, relative to haploid derived ones, but the pattern of increase differed between homosexual and heterosexual crosses . In omega-haploid X omega-diploid homosexual crosses, the increase was of roughly equal magnitude at the C, E and O LOCI: there was a polar co-transmission of the diploid derived alleles . In omega plus haploid by omega-diploid heterosexual crosses, on the contrary, a differential increase was observed at the different loci, the magnitude being the smallest at the C locus and the largest at the O locus . As a result, there was a preferential transmission in favor of the haploid derived C alleles and of the diploid derived O alleles . A near equal transmission from both parents was observed for the E alleles . A decrease and an increase in the recombination frequency were noticed in the above haploid by diploid homosexual and heterosexual crosses, respectively . The above phenomena were ascribed to different dosages of mitochrondrial genomes from parents . Experimental data were well accorded with the theoretical expectation which were obtained on the assumptions that diploids contain twice as many mitochondrial genomes as haploids, and that random pairings and recombination would occur among mitochrondrial genomes from parents . The elevation of strain-ploidy did not affect the recombination polarity which is under the control of the omega gene . It was theoretically predicted that a preferential transmission in favor of diploid derived alleles at all the C, E and O loci would be seen in omega-haploid x omega plus diploid heterosexual crosses as well as in omega plus haploid x omega plus diploid homosexual crosses, but that the magnitude of the polar transmission would vary depending upon the loci in the former crosses, while it would be the same at all the loci in the latter ones . The recombination frequency was predicted to decrease in both of these crosses. Antibiotiki, 1976 Jul, 21(7), 604 - 8 {Prevalence of markers characteristic for penicillinase plasmids in clinical strains of straphylococci}; Ponomareva TR et al.; Occurrence of the markers of penicillin and erythromycin resistance in the clinical strains of Staph . aureus, as well as their connection with the determinants of resistance to the heavy metal salts and sodium arsenate was studied . 79 per cent of Staph . aureus were resistant to penicillin and 47 per cent to erythromycin . All erythromycin resistant strains were also resistant to penicillin . More than a half of the strains of Staph . aureus of the phage groups I, III and the mixed phage group had a set of markers: pen, asa, cad, mer, ego . The rate of elimination of the above markers with ethidium bromide was high . The presence of the penicillinase plasmid determining a rather low level of resistance to erythromycin (20--50 gamma/ml) was characteristic of the strains belonging to the phage group I . The presence of the plasmid determining a high level of resistance to that drug (500--1000 gamma/ml) was characteristic of the phage group III and the mixed phage group . The erythromycin sensitive strains of Staph . aureus were almost always sensitive to mercuric ions. J Infect Dis, 1976 Jul, 134(1), 93 - 6 Relative efficacy of clindamycin, erythromycin, and penicillin in treatment of Treponema pallidum in skin syphilomas of rabbits; Brause BD et al.; The currently recommended antibiotic for treatment of fetal syphilis in pregnant women who are allergic to penicillin is erythromycin . However, clindamycin crosses the placenta more effectively than erythromycin . Therefore, an in vivo rabbit model of intradermal syphilomas was used to determine the effect of clindamycin compared with the effects of erythromycin and penicillin on the growth of virulent Treponema pallidum . The average number of motile treponemes in two, paired, mature lesions was determined before and after therapy in groups of four rabbits per dosage . Single intramuscular doses of clindamycin (15 and 40 mg/kg) and erythromycin (12 and 40 mg/kg) did not decrease treponeme counts significantly . Single injections of penicillin (10,000 units/kg) reduced treponemal counts by more than 250-fold . Multiple intramuscular injections of clindamycin reduced counts by five- to sevenfold, whereas multiple doses of erythromycin and penicillin decreased treponeme counts by greater than 300-fold . These studies indicate that clindamycin is far less active than erythromycin or penicillin in treatment of established syphilitic lesions in rabbits. J Biol Chem, 1976 Jun 10, 251(11), 3392 - 8 Peptidyl transfer RNA dissociates during protein synthesis from ribosomes of Escherichia coli; Menninger JR; Growing cultures of mutant Escherichia coli with temperature-senstive peptidyl-tRNA hydrolase were shifted to nonpermissive 4o degrees . There followed a roughly linear increase in a fraction of isolated tRNA (over 50% after 20 min) whose amino acid-accepting activity was masked until treatment with active peptidyl-tRNA hydrolase . The ionophoretic mobility of amino acid label associated with this fraction could be altered by treatment with the hydrolase, trypsin, RNAse, and alkali . The rate of accumulation of this fraction could be altered by treating the growing cells with chloramphenicol, which reduced the rate, or erythromycin, which enhanced it . It is concluded that peptidyl-tRNA dissociates from ribosomes of the mutant cells during protein biosynthesis . The primary metabolic role of peptidyl-tRNA hydrolase is to prevent the accumulation of dissociated peptidyl-tRNA, which inhibits protein synthesis . The rate of dissociation of peptidyl-tRNA from ribosomes was estimated at between 1 per 90 and 1 per 2600 peptide elongation steps in the absence of antibiotics, depending on the level of inhibition of protein synthesis . After 20 min at 40 degrees, the size distribution of peptides found on tRNA was heterogeneous, with over 74% having a molecular weight greater than 8 X 10(2) . The effect of erythromycin suggests that its mechanism of action is to destabilize the peptidyl-tRNA/ribosome interaction and thereby stimulate the dissociation of peptidyl-tRNA . The mechanism of inhibition of protein synthesis by accumulating peptidyl-tRNA and reasons why peptidyl-tRNA dissociates from ribosomes are discussed in terms of the current data. Clin Exp Immunol, 1976 Jun, 24(3), 483 - 91 Changes in intra-vascular complement and anti-treponemal antibody titres preceding the Jarisch-Herxheimer reaction in secondary syphilis; Fulford KW et al.; Six patients with secondary syphilis and one control subject were observed over a period of up to 8 hr following the administration of either penicillin or erythromycin . Serial clinical observations were made and blood samples obtained for complement and serological analysis . The patients showed Jarisch-Herxheimer reactions (JHR) of varying intensity which were found to be preceded by and to parallel in degree certain changes in complement and syphilitic antibody titres . Falls in total haemolytic complement, in C4, C3, C6 and C7 and a marked drop in C1INH were observed . There was no change in total GBG/GGG or evidence of conversion of GBG to GGG . Associated falls occurred in the titres of the QFTA and the QTPHA antibodies but not of the QVDRL or QTPI antibodies . C3 conversion was found in the two patients that suffered severe reactions . Immune complexes were not detected and it is suggested that complement activation occurred in the extra-vascular body compartment . The significance of these changes in relation to other plasma enzyme systems and to the development of the full clinical picture of the JHR is discussed. Mol Gen Genet, 1976 Apr 23, 145(1), 7 - 17 Deletion mapping of mitochondrial transfer RNA genes in Saccharomyces cerevisiae by means of cytoplasmic petite mutants; Fukuhara H et al.; Mitochondrial transfer RNA genes have been ordered relative to the position of five mitochondrial drug resistance markers, namely, chloramphenicol (C),1 erythromycin (E), oligomycin I and II (OI, OII), and paromomycin (P) . Forty-six petite yeast clones that were genetically characterized with respect to these markers were used for a study of these relationships . Different regions of the mitochondrial genome are deleted in these individual mutants, resulting in variable loss of genetic markers . Mitochondrial DNA was isolated from each mutant strain and hybridized with eleven individual mitochondrial transfer RNAs . The following results were obtained: i) Of the seven petite clones that retained C, E, and P resistance markers (but not O1 or O11), four carried all eleven transfer RNA genes examined; the other three clones lost several transfer RNA genes, probably by secondary internal deletion; ii) Prolyl and valyl transfer RNA genes were located close to the P marker, whereas the histidyl transfer RNA gene was close to the C marker; iii) Except for a glutamyl transfer RNA gene that was loosely associated with the O1 region, no other transfer RNA genes were found in petite clones retaining only the O1 and/or the OII markers; and iv) Two distinct mitochondrial genes were found for glutamyl transfer RNA, they were not homologous in DNA sequence and were located at two separate loci . The data indicate that the petite mitochondrial genome is the result of a primary deletion followed by successive additional deletions . Thus an unequivocal gene arrangement cannot be readily established by deletion mapping with petite mutants alone . Nevertheless, we have derived a tentative circular map of the yeast mitochondrial genome from the data; the map indicates that all but one of the transfer RNA genes are found between the C and P markers without forming a tight cluster . The following arrangement is suggested: -P-pro-val-ile-(phe, ala, tyr, asp)-glu2- (lys-leu)-his-C-E-O1-glu1-OII-P-. Br J Ophthalmol, 1976 Apr, 60(4), 245 - 52 Severe endemic trachoma in Tunisia; Dawson CR et al.; In two villages in southern Tunisia where trachoma was endemic 7 per cent and 14 per cent of adults respectively had visual acuity of 20/400 or less . In both villages active trachoma affected most children under the age of two, reached a peak in two- to five-year-olds, then declined to age 15 . The chronic inflammatory disease in childhood appeared to produce irreversible scarring of the eyelids, and loss of vision occurred in adult life due to corneal scarring caused by inturned eye lashes and loss of tears (dry-eyed syndrome) . Economic development in one village was associated with a decline in active, infectious disease . In the second village, whose traditional economy was unchanged, there was the same prevalence of active disease over a three-year period . Unless economic development or public health control programmes reduce the prevalence of severe and moderate trachoma children now affected will develop the same blinding lesions as their parents . With the increasing numbers of children who survive there will probably be a dramatic increase in the numbers of the blind from trachoma in 10 to 20 years . Since active inflammatory trachoma in childhood responds to tetracyclines, erythromycin, and sulphonamides the disease should be attacked in those undeveloped rural areas where it continues to lead to blindness. Med Biol, 1976 Apr, 54(2), 146 - 9 Goniomitosis in rats affected by mycoplasma or macrolides; Lastikka L et al.; Infection with Mycoplasm pulmonis caused a slight increase in the incidence of chromosome breaks in goniomitotic cells of the rat testis . No differences existed between healthy and infected rats in the frequency of mitotic divisions, measured as the number of metaphases per slide . The macrolide antibiotics erythromycin and tylosin are widely used as antimycoplasmal drugs . Erythromycin was given to healthy rats intramuscularly at a concentration of 20 mg/kg, and tylosin perorally in the drinking water at a concentration of 0.1%, both for 10 days . Neither drug induced an increase in the incidence of chromosome breaks in the spermatogonia . But both these macrolides caused a definite reduction in the therapy of cell division . With erythromycin, this effect had disappeared 18 days after the end of treatment. Obstet Gynecol, 1976 Apr, 47(4), 492 - 4 Congenital syphilis after maternal treatment with erythromycin; Fenton LJ et al.; A case is reported in which erythromycin was used successfully to treat maternal syphilis but failed to adequately treat the fetus . This report and similar studies suggest that oral erythromycin is not a reasonable alternative drug for the treatment of lues in the penicillin-allergic gravid female. Farmaco {Sci}, 1976 Apr, 31(4), 254 - 63 Polymorphism of erythromycin studied by differential thermal analysis; Pelizza G et al.; The polymorphism of erythromycin has been studied by differential thermal analysis . Three main forms, two crystalline (I and SI) and one amorphous have been characterized . Solvation and imbibition water can be differentiated . Solvates from 2-propanol (SII), trichloromethane (SIII) and tetrachloromethane (SIV) have been characterized . The physical stability of the various forms both in the dry state and in aqueous suspension are discussed. Cutis, 1976 Apr, 17(4), 799 - 801 Acne: treatment with minocycline; Coskey RJ; Forty-seven patients with acne, unresponsive to tetracycline and erythromycin, were treated with 100 mg minocycline daily . About one-quarter showed a 50% improvement or better . Five patients became dizzy during the first week of therapy, making it necessary to stop the medication in four instances . Two patients stopped treatment after several months because of esophagitis in one and headaches in another . Vestibular side effects are the most common complication of treatment . Patients should be warned about this side effect and if it occurs should avoid driving or handling machines . In some instances, dizziness may be so severe that the drug will have to be discontinued. J Pharm Sci, 1976 Apr, 65(4), 497 - 502 Gastric acid inactivation of erythromycin stearate in solid dosage forms; Boggiano BG et al.; The effect of hydrochloric acid at pH 1.2-3.2 ON ERYTHROMYCIN STEARATE AND COMMERCIAL DOSAGE FORMS OF ERYTHROMYCIN STEARATE WAS STUDIED . Under all conditions examined, erythromycin was readily dissolved from the stearate as hydrochloride, and rapidly lost its biological activity in solution . The inclusion of pepsin in the test systems did not affect the results . Although formulation differences somewhat affected the rate of destruction, acid lability was exhibited by all products examined, except enteric-coated tablets . Amounts of acid considered to be normal in the fasting stomach contents of adults during the time likely for a dose to remain in the stomach caused 70-90% destruction within 15 min after the shells started to rupture . Amounts of hydrochloric acid appreciably less than 1 mEq, representing abnormally small quantities even in the fasting state, caused destruction ranging from 30 to 70% of the doses in 15 min . These results are not reconcilable with published statements that the sensitivity of erythromycin to gastric acid is overcome by providing the antibiotic in the form of stearate salt. J Pharm Sci, 1976 Mar, 65(3), 417 - 9 Intestinal secretion of erythromycin base; Holland DR et al.; Erythromycin fluxes into rabbit midjejunal segments were studied . When erythromycin was infused into the jugular vein of anesthetized rabbits, the antibiotic was secreted into the segments at a rate of 0.0136 +/- 0.0023 mg/min . Preloading of the segments with five and 20 times the plasma concentration did not diminish this secretion . Protein binding of the antibiotic within the lumen could not explain this secretion, since both ultrafiltration and chromatography of luminal solutions indicated that the biological activity was free erythromycin . Moreover, the transmural potential across the intestinal mucosa is likely to be theprincipal driving force, since greater than 80 mv would be required to sustain the observed secretion against an imposed 20-fold concentration difference between blood and lumen . The best explanation for the intestinal secretion of erythromycin appears to be an active transport pathway capable of concentrating erythromycin in the lumen . It is not clear what endogenous substances are transported by this pathway. Mol Gen Genet, 1976 Feb 2, 143(3), 301 - 6 Binding of erythromycin to the 50S ribosomal subunit is affected by alterations in the 30S ribosomal subunit; Saltzman L et al.; Expression of resistance to erythromycin in Escherichia coli, caused by an altered L4 protein in the 50S ribosomal subunit, can be masked when two additional ribosomal mutations affecting the 30S proteins S5 and S12 are introduced into the strain (Saltzman, Brown, and Apriion, 1974) . Ribosomes from such strains bind erythromycin to the same extent as ribosomes from erythromycin sensitive parental strains (Apirion and Saltzman, 1974) . Among mutants isolated for the reappearance of erythromycin resistance, kasugamycin resistant mutants were found . One such mutant was analysed and found to be due to undermethylation of the rRNA . The ribosomes of this strain do not bind erythromycin, thus there is a complete correlation between phenotype of cells with respect to erythromycin resistance and binding of erythromycin to ribosomes . Furthermore, by separating the ribosomal subunits we showed that 50S ribosomes bind or do not bind erythromycin according to their L4 protein; 50S with normal L4 bind and 50S with altered L4 do not bind erythromycin . However, the 30S ribosomes with altered S5 and S12 can restore binding in resistant 50S ribosomes while the 30S ribosomes in which the rRNA also became undermethylated did not allow erythromycin binding to occur . Thus, evidence for an intimate functional relationship between 30S and 50S ribosomal elements in the function of the ribosome could be demonstrated . These functional interrelationships concerns four ribosomal components, two proteins from the 30S ribosomal subunit, S5, and S12, one protein from the 50S subunit L4, and 16S rRNA. Contact Dermatitis, 1976 Feb, 2(1), 43 - 44 The safety of topical erythromycin; Fisher AA; The prevention of allergic complications depends on the use of topical medications which have proved to be rare sensitizers . This is particularly true for stasis ulcers and eczemas which are notoriously readily sensitized . Topical erythromycin has proved to be such a non-sensitizing topical antibiotic . In a series of 60 patients with stasis ulcers, erythromycin in the form of Ilotycin ointment (erythromycin in petrolatum) was applied . Not a single instance of allergic sensitization occurred . No instances of sensitization with positive patch tests to topical erythromycin have been reported . Maximization tests with topical erythromycin did not produce sensitization . Topical erythromycin, an effective antibiotic, should be substituted for neomycin which is a common sensitizer. Mol Gen Genet, 1976 Jan 16, 143(2), 197 - 201 Interspecies transfer of mitochondria in Paramecium aurelia; Beale GH et al.; Erythromycin-resistant mitochondria from species 1, 5 and 7 of P . aurelia were injected into erythromycin-sensitive paramecia of each of the same three species . Mitochondria from species 1 and 5 were successfully transferred to all three species, but species 7 mitochondria failed to develop in species 1 and 5 . Minor differences were indicated in the frequency of successful transfers of species 1 mitochondria into species 1 and 5 cells . From studies on the transferability of mitochondria from "hybrid" cells, containing mitochondria from one species and nuclei from another, it was concluded that mitochondrial compatibility was mainly under control of the nuclear genome, with a possible minor control also by the mitochondrial genome. J Biol Chem, 1976 Jan 10, 251(1), 108 - 15 Regulation of mitochondrial protein synthesis at the polyribosomal level; Ibrahim NG et al.; Polysomes consisting of two to eight monosomes were isolated from yeast mitochondria by lysing the mitochondria with Triton X-100 and centrifugation in a 20 to 40% linear sucrose gradient . When yeast spheroplasts were pulse-labeled with {3H}-Leucine in the presence of cycloheximide to block cytoplasmic protein synthesis, radioactivity which was trichloroacetic acid-precipitable was present mainly in the polysome region . Incorporation of leucine was blocked by erythromycin, a specific inhibitor of mitochondrial protein synthesis . Release of radioactivity to the top of the gradient resulted from treating labeled polysomes with either puromycin or ribonuclease (in the latter case with the breakdown of polysomes), indicating that the radioactivity was present in nascent polypeptide chains . Yeast cells were grown in chloramphenicol for 3 hours and in fresh medium for 1 hour and then pulse-labeled with either {3H}leucine or {14C}formate . Three parameters showed a 2-fold increase in cells grown in chloramphenicol prior to pulse labeling: the polysome to monosome ratio, the amount of labeled precursor incorporated into proteins, and the rate of polypeptide chain initiation as judged by the formation of fMet-puromycin . Conversely, these parameters were all decreased approximately 50% in cells treated with cycloheximide prior to pulse labeling . Mitochondria were also isolated from cells previously grown in chloramphenicol or cycloheximide and incubated in vitro with {3H}leucine under optimal conditions . Acid-precipitable radioactivity in the polysome region was increased 3-fold in mitochondria from cells grown previously in chloramphenicol and decreased 75% in those grown in cycloheximide . Furthermore, chain initiation was deomonstrated in the isolated mitochondria by formation of fMet-puromycin . The rate of chain initiation in vitro was increased 2-fold in mitochondria isolated from chloramphenicol-treated cells. Infection, 1976, 4(1 Suppl), 4 - 8 The use of organ cultures and animal models in the study of Mycoplasma pneumoniae infections; Taylor-Robinson D; Organ cultures of ciliated tracheal epithelium derived from various animal species have been used to study several different mycoplasma infections . Human and hamster tracheal cultures have been used in particular to study Mycoplasma pneumoniae which, of all the human mycoplasmas, is the only one which damages the cultures . One reason for this is the capacity of the virulent organisms to attach to the cells; strains which are prevented from attaching or have lost this capacity do not damage the cultures . The organ culture system is therefore valuable in looking at the organisms-cell relationship but it is necessary to use animal models to study immunological processes . Hamsters, and more recently guinea pigs, have been used in this respect . The hamster model has been used to study the pathogenesis of M . pneumoniae pneumonia and also recovery from and resistance to infection . Humoral immune mechanisms seem more important than cell-mediated mechanisms in resistance, and the probable importance of local immunity is discussed . It is pointed out that it should be possible to establish the mechanisms underlying the development of M . pneumoniae sequelae where conditions, similar to those seen in man, occur in animals . Finally, the way in which the hamster model has been used to study the effect of tetracycline and erythromycin on the course of disease is discussed . As in man, therapy often improves the pneumonia but does not eradicate the organisms . This is probably due, at least in part, to the fact that the antibiotics are only mycoplasmastatic . Drugs with mycoplasmacidal properties are needed and the animal model would obviously prove helpful in evaluating these. Vet Med Nauki, 1976, 13(1), 113 - 7 {Sensitivity of 30 strains of E . coli isolated from calves to chemotherapeutic agents}; Kokosharov T; Escherichia coli strains were isolated from calves and were biochemically and serologically identified in terms of their sensitivity to antibiotics . An exclusively high frequency of sensitivity was established to sulfonamides (100 per cent), tetracicline, erythromycin, oleandomycin (86.6 per cent) ampicillin, and streptomycin (70 per cent) . Well expressed was their sensitivity to nitrofurans, canamycin, neomycin, and polymyxin . It was demonstrated through serial dilutions that there exists a high level of resistance to sulfanilamides, oleandomycin, erytromycin, tetracycline, streptomycin, chloramphenicol (more than 512 mug/cm3) . The prevalence of such polyresistand E . coli strains in calves is the reason for concern in the district of Haskovo. Dermatologica, 1976, 152(3), 177 - 80 Bullous fixed drug eruption presumably due to erythromycin; Naik RP et al.; A case of bullous fixed drug eruption involving upper lip, tongue and foot, presumably due to erythromycin, is reported . It is perhaps the first report of erythromycin to be very likely the cause of fixed drug eruption. Drug Metab Dispos, 1976 Jan-Feb, 4(1), 8 - 16 Binding of organic compounds to rat liver and lung; Ludden TM et al.; The binding of various radioisotopically labeled organic compounds to rat liver and lung was investigated in vitro . Pieces of rat lung and slices of rat liver were incubated at 37 degrees C under a nitrogen atmosphere in a modified Krebs-Ringer phosphate solution (pH 7.4) CONTAININg the compound to be studied . Of the neutral compounds investigated, digitoxin, digoxin and dexamethasone were highly bound to both liver and lung tissue, whereas the degree of binding of amitrole, erythritol, and ouabain was 20% or less . The weak acids which were bound to the greatest extent in both liver and lung were phenobarbital, pentobarbital, and diphenylhydantoin . Barbital was poorly bound, and there was no evidence for the binding of 5,5-dimethyloxazolidine-2,4-dione or p-aminohippuric acid in either tissue . Binding of the cardiac glycosides and the barbiturates directly paralleled their lipid solubilities . The degree of binding of neutral compounds and weak acids to lung and liver tissue did not vary greatly with concentration, even though broad concentration ranges were studied . This was also true of the weak base morphine . On the other hand, the binding to liver and lung of the organic bases nicotine, pilocarpine, d-amphetamine, lidocaine, erythromycin, and chloroquine, did vary with concentration . The quaternary ammonium compound decamethonium was bound only to liver, and this binding also varied with concentration . Two additional quaternary ammonium compounds, tetraethylammonium and N1-methylnicotinamide, were not significantly bound to either tissue . Comparisons on the basis of equal content of solids revealed that the binding of diverse organic compounds in liver is greater than or equal to that in lung. Surg Clin North Am, 1975 Dec, 55(6), 1335 - 41 Preoperative pre