Summary: An antibiotic complex produced by Streptomyces kitasatoensis. The complex consists of a mixture of at least eight biologically active components, A1 and A3 to A9. Leucomycins have both antibacterial and antimycoplasmal activities.

Top Publications

  1. Fernandes P, Baker W, Freiberg L, Hardy D, McDonald E. New macrolides active against Streptococcus pyogenes with inducible or constitutive type of macrolide-lincosamide-streptogramin B resistance. Antimicrob Agents Chemother. 1989;33:78-81 pubmed
    ..Thus, 14-membered macrolides can be modified so as to confer a low MIC when tested in vitro. ..
  2. Dutton G. Toxoplasmic retinochoroiditis--a historical review and current concepts. Ann Acad Med Singapore. 1989;18:214-21 pubmed
    ..These measures will decrease the incidence of both eye disease and the more severe manifestations of congenital toxoplasmosis, which include congenital abnormalities, mental retardation, hydrocephalus and blindness. ..
  3. Gomi K, Kobayashi E, Miyoshi K, Ashizawa T, Okamoto A, Ogawa T, et al. Anticellular and antitumor activity of duocarmycins, novel antitumor antibiotics. Jpn J Cancer Res. 1992;83:113-20 pubmed
    ..These results indicate that DUMs possess interesting biological activities as DNA-targeting antitumor antibiotics. ..
  4. Blaha T, Erler W, Burch D. Swine dysentery control in the German Democratic Republic and the suitability of injections of tiamulin for the programme. Vet Rec. 1987;121:416-9 pubmed
    ..There was a significant increase of 0.6 piglets weaned per litter and improvements in weaning weights and growth rates. It was concluded that tiamulin was suitable for inclusion in the swine dysentery eradication programme in the GDR. ..
  5. Hardy D, Hensey D, Beyer J, Vojtko C, McDonald E, Fernandes P. Comparative in vitro activities of new 14-, 15-, and 16-membered macrolides. Antimicrob Agents Chemother. 1988;32:1710-9 pubmed
    ..The MICs of roxithromycin, miocamycin, rokitamycin, and josamycin increased in the presence of human serum, whereas MICs of the other compounds either were unchanged or decreased. ..
  6. Sato H, Narita A, Matsumoto K, Suzuki H, Nakanishi Y, Nakazawa S, et al. [Bacteriological, pharmacokinetic and clinical studies of a rokitamycin syrup in pediatrics]. Jpn J Antibiot. 1988;41:696-711 pubmed
    ..4% was achieved for 43 strains of 7 species isolated from the patients. 5. No abnormal laboratory test values were observed after treatment with drug 4 approximately 14 days. A side effect, stomach discomfort, was observed in 1 patient. ..
  7. Chiang S, Welch J, Rauscher F, Beerman T. Effects of minor groove binding drugs on the interaction of TATA box binding protein and TFIIA with DNA. Biochemistry. 1994;33:7033-40 pubmed
  8. Watanabe T. Ultrastructure of Mycoplasma pneumoniae exposed to macrolide antibiotics during cultivation on a glass surface and in an organ culture, in relation to their mycoplasma-killing activity. Drugs Exp Clin Res. 1988;14:231-51 pubmed
    ..Treatment with four times the MIC of these macrolides decreased the number of organisms and vacuolized filamentous organisms could be seen on the epithelial cells. ..
  9. Boger D, Garbaccio R. Catalysis of the CC-1065 and duocarmycin DNA alkylation reaction: DNA binding induced conformational change in the agent results in activation. Bioorg Med Chem. 1997;5:263-76 pubmed

More Information


  1. Borderon J, Borderon E, Laugier J, Bremond M. [The effect of roxithromycin on the aerobic fecal flora in children]. Pathol Biol (Paris). 1989;37:353-7 pubmed
    ..The bacteria with low MIC (less than or equal to 64 mg/l for EB and less than or equal to 4 mg/l for STR. D) are Escherichia coli and Streptococcus faecium. The MIC increased for the three macrolides tested. ..
  2. Carlone N, Cufini A, Tullio V, Sassella D. Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro. 2. Chemotaxis and phagocytosis of 3H-Staphylococcus aureus by human macrophages. Microbios. 1989;58:17-25 pubmed
    ..Erythromycin displayed a less stimulating effect. Pre-incubation of macrophages with the drugs caused a depression of staphylococcal uptake by phagocytes. Macrophage chemotaxis was unchanged in the presence of both macrolides. ..
  3. Tietze L, Herzig T, Fecher A, Haunert F, Schuberth I. Highly selective glycosylated prodrugs of cytostatic CC-1065 analogues for antibody-directed enzyme tumor therapy. Chembiochem. 2001;2:758-65 pubmed
    ..The cytotoxicity of the corresponding phenol was rather high, with an ED(50) of 1.3 nM. The diastereomer with a syn orientation at the stereogenic centers was much less toxic. ..
  4. Park H. Evidence for a common molecular basis for sequence recognition of N3-guanine and N3-adenine DNA adducts involving the covalent bonding reaction of (+)-CC-1065. Arch Pharm Res. 2002;25:11-24 pubmed
  5. Fraschini F, Scaglione F, Cicchetti F, Rossi M, Borghi C, Alfano G, et al. Prostatic tissue concentrations and serum levels of Myocamicin in human subjects. Drugs Exp Clin Res. 1988;14:253-5 pubmed
    ..Myocamicin has shown itself to be an antibiotic with optimal capabilities of diffusion in the prostatic tissue, where it rapidly reaches good therapeutic concentrations. ..
  6. Matsui K, Nishikawa A. Effects of the macrolide antibiotic, midecamycin, on Staphylococcus aureus product-induced Th2 cytokine response in patients with atopic dermatitis. J Interferon Cytokine Res. 2004;24:197-201 pubmed
    ..These results suggest that topical administration of MDM might be beneficial in AD lesions infected with S. aureus. ..
  7. Chastre J, Brun P, Fourtillan J, Soler P, Basset G, Manuel C, et al. Pulmonary disposition of roxithromycin (RU 28965), a new macrolide antibiotic. Antimicrob Agents Chemother. 1987;31:1312-6 pubmed
  8. Preac Mursic V, Wilske B, Schierz G, Suss E, Gross B. Comparative antimicrobial activity of the new macrolides against Borrelia burgdorferi. Eur J Clin Microbiol Infect Dis. 1989;8:651-3 pubmed
    ..015-0.06 micrograms/ml). Azithromycin was more potent than the other macrolides in experimental animal infection, eradicating the organism in all animals tested at a dosage of 8 mg/kg. ..
  9. Solenberg P, Cantwell C, Tietz A, McGilvray D, Queener S, Baltz R. Transposition mutagenesis in Streptomyces fradiae: identification of a neutral site for the stable insertion of DNA by transposon exchange. Gene. 1996;168:67-72 pubmed
    ..Recombinants obtained by transposon exchange produced higher yields of Ty. ..
  10. Sawada Y, Tsuno T, Miyaki T, Naito T, Oki T. New cirramycin-family antibiotics F-1 and F-2. Selection of producer mutants, fermentation, isolation, structural elucidation and antibacterial activity. J Antibiot (Tokyo). 1989;42:242-53 pubmed
    ..Based on spectral data, cirramycin F-1 and antibiotic A6888C were found to be identical. Cirramycins F-1 and F-2 are active against Gram-positive bacteria, but less active than cirramycin A1. ..
  11. Couet W, Girault J, Reigner B, Ingrand I, Bizouard J, Fourtillan J. [Pharmacokinetics of ponsinomycin administered in a syrup form in single 400-800 and 1200 mg doses in healthy volunteers]. Pathol Biol (Paris). 1989;37:428-32 pubmed
    ..The pharmacokinetics of Mb12 was linear in the range of doses administered. A dose-dependent effect leading to a reduction of the apparent elimination rate when dose increased was observed with Mb9a and more importantly with Mb6. ..
  12. Haruta T, Tsutsui T, Kuroki S, Okura K, Yamamoto H, Suzuki N, et al. [Clinical studies of rokitamycin dry syrup in the field of pediatrics]. Jpn J Antibiot. 1988;41:914-9 pubmed
    ..abstract truncated at 250 words) ..
  13. Boger D, Hughes T, Hedrick M. Synthesis, chemical properties, and biological evaluation of CC-1065 and duocarmycin analogues incorporating the 5-methoxycarbonyl-1,2,9,9a-tetrahydrocyclopropa. J Org Chem. 2001;66:2207-16 pubmed
  14. Nishimura T, Tabuki K, Aoki S, Takagi M. [Laboratory and clinical studies of rokitamycin in pediatric fields]. Jpn J Antibiot. 1988;41:901-13 pubmed
    ..0%. No significant side effect due to the drug was observed in any cases. In conclusion, RKM was found to be efficacious and safe for the treatment of bacterial infections in children. ..
  15. Enjo J, Castedo L, Tojo G. Photochemistry of tosylstilbenoids in the preparation of complex heterocyclic compounds. Synthesis of a cyclopropafuroindolone analogue of the dna-alkylating section of the antitumor compound CC-1065. Org Lett. 2001;3:1343-5 pubmed
    ..reaction in text] A novel photocyclization of tosylstilbenoids is used in the preparation of a cyclopropafuroindolone analogue of the DNA-alkylating unit of the antitumor compound CC-1065. ..
  16. Pechere J, Auckenthaler R. In-vitro activity of roxithromycin against respiratory and skin pathogens. J Antimicrob Chemother. 1987;20 Suppl B:1-5 pubmed
    ..Chlamydia psittaci and, to some extent, against Pasteurella spp. was also assessed, by suitable in-vitro methods. Roxithromycin has a promising potential for treating selected skin and respiratory infections. ..
  17. Cuffini A, Carlone N, Tullio V, Borsotto M. Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro. 3. Killing of intracellular Staphylococcus aureus by human macrophages. Microbios. 1989;58:27-33 pubmed
    ..At a concentration of half the MIC roxithromycin showed a much more impressive killing capacity on macrophage-ingested live Staphylococcus aureus than did erythromycin, under all the experimental conditions used. ..
  18. Itoh Z. [Effect of rokitamycin on upper gastrointestinal contractile activity. Analysis of side-effects on gastrointestinal tract]. Jpn J Antibiot. 1988;41:823-9 pubmed
    ..0 mg/kg RKM was given intravenously. It was found that intravenous injection of RKM did not evoke any contractions attributable to the direct action of RKM in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  19. Boezeman A, Kayser A, Siemelink R. Comparison of spiramycin and doxycycline in the empirical treatment of acute sinusitis: preliminary results. J Antimicrob Chemother. 1988;22 Suppl B:165-70 pubmed
    ..The data so far available from this study suggest that spiramycin presents an alternative to doxycycline in the treatment of acute sinusitis. ..
  20. Wise R, Kirkpatrick B, Ashby J, Andrews J. Pharmacokinetics and tissue penetration of roxithromycin after multiple dosing. Antimicrob Agents Chemother. 1987;31:1051-3 pubmed
    ..After the final dose, a mean of 10.5% of that dose was recovered in 12 h as microbiologically active compound. ..
  21. Kuenzi B, Segessenmann C, Gerber A. Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against selected gram-positive bacteria and Haemophilus influenzae. J Antimicrob Chemother. 1987;20 Suppl B:39-46 pubmed
    ..Good correlations could be found between the area under the in-vitro concentration-vs-time curve (AUC) and PAEs. The longest PAE of 9.6 h was observed after exposure of Str. pneumoniae to 1.9 mg/l of roxithromycin for 6 h. ..
  22. Villa P, Sassella D, Corada M, Bartosek I. Effects of roxithromycin, a new semisynthetic macrolide, and two erythromycins on drug metabolizing enzymes in rat liver. J Antibiot (Tokyo). 1988;41:563-9 pubmed
    ..50% after EE). At the higher dose microsomal activities were not changed by roxithromycin and only aminopyrine N-demethylation was reduced. ..
  23. Furneri P, Scalia G, Garozzo A, Tempera G. Some pharmacokinetic data on miocamycin. I: Serum, urinary and prostatic levels. Drugs Exp Clin Res. 1988;14:755-62 pubmed
    ..5767 +/- 0.2511 mg/h/l in the first group; 6.7333 +/- 0.6058 mg/h/l in the second group; and 18.6825 +/- 15.1555 mg/h/l in the third. The prostatic levels were five times higher than those in the serum at the same time. ..
  24. Lin C, Hurley L. Determination of the major tautomeric form of the covalently modified adenine in the (+)-CC-1065-DNA adduct by 1H and 15N NMR studies. Biochemistry. 1990;29:9503-7 pubmed
    ..Parallel 15N NMR experiments on the [6-15N]deoxyadenosine-labeled (+)-CC-1065-12-mer duplex adduct show a triplet-like signal around -276.9 ppm and coupling constants of 91.5 and 85.6 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  25. Bandera M, Fioretti M, Rimoldi R, Lazzarini A, Anelli M. Roxithromycin and controlled release theophylline, an interaction study. Chemioterapia. 1988;7:313-6 pubmed
    ..Results did not show any clinically relevant change in theophylline blood levels, implying the conclusion that the new macrolide roxithromycin can be administered simultaneously with a controlled release theophylline. ..
  26. Vernillet L, Bertault Peres P, Berland Y, Barradas J, Durand A, Olmer M. Lack of effect of spiramycin on cyclosporin pharmacokinetics. Br J Clin Pharmacol. 1989;27:789-94 pubmed
    ..3. Spiramycin may be preferable to other macrolide antibiotics known to interact with cyclosporin such as erythromycin or josamycin. ..
  27. Bergeron M, Lavoie G, Boucher F. Comparative bactericidal activity of cefixime, carumonam, enoxacin and roxithromycin with those of other antibiotics against resistant Haemophilus influenzae including beta-lactam tolerant strains. J Antimicrob Chemother. 1987;20:663-9 pubmed
    ..One tolerant strain was a beta-lactamase producer. Two other strains were tolerant only to co-trimoxazole. ..
  28. Maizumi N, Tamura Y, Kanai H, Tsutsui T. Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts. J Periodontal Res. 2002;37:250-4 pubmed
    ..It is important to note, however, that these findings have yet to be extrapolated to in vivo conditions. ..
  29. Brun Y, Coulet M, Forey F, Fleurette J. [In vitro activity of roxithromycin compared to 5 other macrolides against staphylococci]. Pathol Biol (Paris). 1988;36:613-8 pubmed
    ..This study gives the opportunity to classify the 6 antibiotics in a decreasing order considering their antistaphylococcal activity: RU = ERY, TAO = SPI, JOS = MID. No difference was noticeable between S. aureus and CNS strains. ..
  30. Sun D, Park H, Hurley L. Alkylation of guanine and cytosine in DNA by bizelesin. Evidence for a covalent immobilization leading to a proximity-driven alkylation of normally unreactive bases by a (+)-CC-1065 cross-linking compound. Chem Res Toxicol. 1993;6:889-94 pubmed
  31. Kurihara K, Ajito K, Shibahara S, Ishizuka T, Hara O, Araake M, et al. Cladinose analogues of sixteen-membered macrolide antibiotics. I. Synthesis of 4-O-alkyl-L-cladinose analogues via glycosylation. J Antibiot (Tokyo). 1996;49:582-92 pubmed
    ..The nine novel derivatives have been synthesized by glycosylation with 1-thio sugars. The most active derivative of them showed prolonged antibacterial activity in rat plasma in vitro and improved pharmacokinetics. ..
  32. Ma C, Wu L, Dai J, Zhou H, Li J, Sun X, et al. [Acylation specificity of midecamycin 3-O-acyltransferase within Streptomyces spiramyceticus F21]. Sheng Wu Gong Cheng Xue Bao. 2008;24:2086-92 pubmed
    ..spiramyceticus F21, and this character is possibly limited in Streptomyces mycarofaciens ATCC 21454 for midecamycin biosynthesis. ..
  33. Miura T, Kurihara K, Furuuchi T, Yoshida T, Ajito K. Novel 16-membered macrolides modified at C-12 and C-13 positions of midecamycin A1 and miokamycin. Part 1: Synthesis and evaluation of 12,13-carbamate and 12-arylalkylamino-13-hydroxy analogues. Bioorg Med Chem. 2008;16:3985-4002 pubmed publisher
    ..These compounds were evaluated for in vitro antibacterial activity against respiratory tract pathogens. Some of these analogues exhibited an improved activity compared with the corresponding parent compound. ..
  34. Morikawa K, Zhang J, Nonaka M, Morikawa S. Modulatory effect of macrolide antibiotics on the Th1- and Th2-type cytokine production. Int J Antimicrob Agents. 2002;19:53-9 pubmed
    ..Clarithromycin had the most potent inhibitory effect of the drugs used. The present results suggested that anti-bacterial agents might modify the host's immunological response by interfering with the activity of T helper cells. ..
  35. Fourtillan J, Couet W, Ingrand I, Reigner B, Bizouard J, Girault J. [Influence of food intake on the bioavailability of ponsinomycin administered in a syrup form]. Pathol Biol (Paris). 1989;37:446-50 pubmed
    ..The results suggest that ponsinomycin absorption is faster when administered with food but quantitatively unchanged. ..
  36. Sacristan J, Elviro J, Garcia de Lomas J, Palomino Nicas J, Sobradillo V, Sánchez Gascón F, et al. [Double-blind clinical trial comparing 5 days of dirithromycin versus 7 days of diacetylmidecamycin in acute bronchitis and acute exacerbations of chronic bronchitis]. Enferm Infecc Microbiol Clin. 1997;15:357-60 pubmed
  37. Ozegowski J, Muller P. Metabolism of phosphate-limited cultures of Streptomyces. IV. Protein-phosphorylation of antibiotics-producing cultures. Zentralbl Bakteriol. 1993;279:157-66 pubmed
    ..Protein tyrosyl kinase was demonstrated in the cellular extracts. The results supports the hypothesis that protein phosphorylation possesses a function in the regulation of growth and secondary product formation. ..
  38. Sifrim D, Janssens J, Vantrappen G. Comparison of the effects of midecamycin acetate and clarithromycin on gastrointestinal motility in man. Drugs Exp Clin Res. 1992;18:337-42 pubmed
    ..i.d.) resulted in a statistically significant increase in the postprandial number of antral contractions per hour as well as in the postprandial antral motility index, as compared to placebo. ..
  39. Chin Quee T, Al Joburi W, Lautar Lemay C, Chan E, Iugovaz I, Bourgouin J, et al. Comparison of spiramycin and tetracycline used adjunctively in the treatment of advanced chronic periodontitis. J Antimicrob Chemother. 1988;22 Suppl B:171-7 pubmed
    ..The study was not long enough to determine whether or not the difference in spirochaete level was an indication that the spiramycin group would have maintained the benefits of treatment for a longer time. ..
  40. Minguez F, Ramos C, Loscos A, Chiu M, Prieto J. In vitro killing kinetics and postantibiotic effect of josamycin and other macrolides on several bacteria. Chemotherapy. 1993;39:163-8 pubmed
    ..pneumoniae. Although lower, the PAEs induced on E. coli were significant when high concentrations of the drug were tested. The assayed macrolides showed both more activity and PAEs on S. pneumoniae. ..
  41. Lukhtanov E, Kutyavin I, Gamper H, Meyer R. Oligodeoxyribonucleotides with conjugated dihydropyrroloindole oligopeptides: preparation and hybridization properties. Bioconjug Chem. 1995;6:418-26 pubmed
    ..dTp)8-CDPI1-3 conjugates also formed stabilized duplexes with poly(rA). The extent of stabilization was half that observed with poly(dA). ..
  42. Cong L, Piepersberg W. Cloning and characterization of genes encoded in dTDP-D-mycaminose biosynthetic pathway from a midecamycin-producing strain, Streptomyces mycarofaciens. Acta Biochim Biophys Sin (Shanghai). 2007;39:187-93 pubmed
    ..venezuelae and tylMIII/tylMII in S. fradiae, the product of midH probably functions as an auxiliary protein required by the MidI protein for efficient glycosyltransfer in midecamycin biosynthesis. ..
  43. Desnottes J, Diallo N, Moret G. Effect of spiramycin on adhesiveness and phagocytosis of gram-positive cocci. J Antimicrob Chemother. 1988;22 Suppl B:25-32 pubmed
    ..Although in-vitro results cannot be directly compared with in-vivo data, it is of interest that spiramycin decreases adherence of different Gram-positive cocci and enhances phagocytic capacity of PMNs. ..
  44. Cornaglia G, Ligozzi M, Pelosi E, Canepari P, Fontana R. In vitro activity of lomefloxacin (SC-47111) against enterobacteriaceae, enterococci and staphylococci. J Chemother. 1989;1:84-90 pubmed
    ..The new drug was also active against staphylococci having an MIC50 and MIC90 of 0.5 and 2 micrograms/ml, respectively. It was bactericidal at the MIC for 62% of the strains and at twofold the MIC for all the others. ..
  45. Motohiro T, Aramaki M, Oda K, Kawakami A, Tanaka K, Koga T, et al. [Clinical studies of rokitamycin dry syrup on skin and soft tissue infections in the pediatric fields]. Jpn J Antibiot. 1988;41:1503-16 pubmed
    ..2%. Ratings were determinable on the fifth and the seventh days of treatment in 24 and 21 cases, respectively, with all the cases judged good or excellent.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  46. De Luca M. Clinical and microbiological effects of in vivo miocamycin therapy on oral infections and in surgical prophylaxis. Drugs Exp Clin Res. 1988;14:659-63 pubmed
    ..1% of the cases) and the occurrence of side-effects (10% of the cases). Among the patients who underwent surgical therapy, only 11 out of 80 showed small problems (slight fever and swelling). ..
  47. Agache P, Amblard P, Moulin G, Barriere H, Texier L, Beylot C, et al. Roxithromycin in skin and soft tissue infections. J Antimicrob Chemother. 1987;20 Suppl B:153-6 pubmed
    ..Clinical effectiveness was 92% for roxithromycin and 82% for doxycycline, and bacteriological effectiveness also 92% and 82% respectively, the differences not being statistically significant. ..
  48. Furuuchi T, Kurihara K, Yoshida T, Ajito K. Synthesis and biological evaluation of novel leucomycin analogues modified at the C-3 position. I. Epimerization and methylation of the 3-hydroxyl group. J Antibiot (Tokyo). 2003;56:399-414 pubmed
    ..3-O-Methylrokitamycin (16b) showed enhanced antibacterial activity in vitro and 3,3''-di-O-methyl-4''-O-(3-methylbutyl)leucomycin V (22) exhibited improved metabolic stability in rat plasma in vitro. ..
  49. Skinner M, Kanfer I. High-performance liquid chromatographic analysis of josamycin in serum and urine. J Chromatogr. 1988;459:261-7 pubmed
    ..The recoveries at the upper and lower ends of the calibration range for serum were 77% and 70%, respectively, and those for urine were 76% and 80%, respectively. ..
  50. Searcey M. Duocarmycins--natures prodrugs?. Curr Pharm Des. 2002;8:1375-89 pubmed
    ..A simple analysis of the approaches that could be taken to vary the structure for targeting is suggested...
  51. Xia H, Wang Y, Sun J. Characterization of polyketide ketoreductase gene (MPKR) from midecamycin-producing strain (Streptomyces mycarofaciens 1748). Chin J Biotechnol. 1994;10:169-78 pubmed
    ..The deduced amino acid sequences of MPKR gene consisted of 261 aa residues. Its amino acid were compared with actIII gene coding protein sequences. The similarity was 77.4% and the identity was 66.7%. ..
  52. Kavi J, Webberley J, Andrews J, Wise R. A comparison of the pharmacokinetics and tissue penetration of spiramycin and erythromycin. J Antimicrob Chemother. 1988;22 Suppl B:105-10 pubmed
    ..8 h. Spiramycin persisted in the inflammatory fluid with a mean elimination half-life of 7.7 h compared to 2.2 h for erythromycin. Twenty-four hour urinary recovery of the administered dose of each antimicrobial agent was less than 5%. ..
  53. Motohiro T, Aramaki M, Oda K, Kawakami A, Tanaka K, Koga T, et al. [Microbiological, pharmacokinetic and clinical studies of rokitamycin dry syrup in the pediatric field]. Jpn J Antibiot. 1988;41:920-59 pubmed
    ..1. The GA-test produced pH values indicating that amounts of gastric acid were mostly either normal or high in 42 of the 43 subjects tested (97.7%), and only one low acid case (2.3%) was observed.(ABSTRACT TRUNCATED AT 400 WORDS) ..