ALK7 expression in prolactinoma is associated with reduced prolactin and increased proliferation.

Prolactinoma represents the most frequent hormone-secreting pituitary tumours. These tumours appear in a benign form, but some of them can reach an invasive and aggressive stage through an unknown mechanism. Discovering markers to identify prolactinoma proliferative and invading character is therefore crucial to develop new diagnostic/prognostic strategies. Interestingly, members of the TGFß-Activin/BMP signalling pathways have emerged as important actors of pituitary development and adult function, but their role in prolactinomas remains to be precisely determined. Here, using a heterotopic allograft model derived from a rat prolactinoma, we report that the Activins orphan type I receptor ALK7 is ectopically expressed in prolactinomas-cells. Through immunohistological approaches, we further confirm that normal prolactin-producing cells lack ALK7-expression. Using a series of human tumour samples, we show that ALK7 expression in prolactinomas cells is evolutionary conserved between rat and human. More interestingly, our results highlight that tumours showing a robust expression of ALK7 present an increased proliferation as address by Ki67 expression and retrospective analysis of clinical data from 38 patients, presenting ALK7 as an appealing marker of prolactinoma aggressiveness. Beside this observation, our work pinpoints that the expression of prolactin is highly heterogeneous in prolactinoma cells. We further confirm the contribution of ALK7 in these observations and the existence of highly immunoreactive prolactin cells lacking ALK7 expression. Taken together, our observations suggest that Activin signalling mediated through ALK7 could therefore contribute to the hormonal heterogeneity and increased proliferation of prolactinomas.

Writing waveguides inside monolithic crystalline silicon with nanosecond laser pulses.

Direct three-dimensional (3D) laser writing of waveguides is highly advanced in a wide range of bandgap materials, but has no equivalent in silicon so far. We show that nanosecond laser single-pass irradiation is capable of producing channel micro-modifications deep into crystalline silicon. With an appropriate shot overlap, a relative change of the refractive index exceeding 10-3 is obtained without apparent nonuniformity at the micrometer scale. Despite the remaining challenge of propagation losses, we show that the created structures form, to the best of our knowledge, the first laser-written waveguides in the bulk of monolithic silicon samples. This paves the way toward the capability of producing 3D architectures for the rapidly growing field of silicon photonics.

Quantitative-phase microscopy of nanosecond laser-induced micro-modifications inside silicon.

Laser-induced permanent modification inside silicon has been recently demonstrated by using tightly focused nanosecond sources at a 1550 nm wavelength. We have developed a quantitative-phase microscope operating in the near-infrared domain to characterize the laser-induced modifications deep into silicon. By varying the number of applied laser pulses and the energy, we observe porous and densified regions in the focal region. The observed changes are associated with refractive index variations |Δn| exceeding 10-3, enough to envision the laser writing of optical functionalities inside silicon.

Accessing Extreme Spatiotemporal Localization of High-Power Laser Radiation through Transformation Optics and Scalar Wave Equations.

Although tightly focused intense ultrashort laser pulses are used in many applications from nano-processing to warm dense matter physics, their nonparaxial propagation implies the use of numerical simulations with vectorial wave equations or exact Maxwell solvers that have serious limitations and thus have hindered progress in this important field up to now. Here we present an elegant and robust solution that allows one to map the problem on one that can be addressed by simple scalar wave equations. The solution is based on a transformation optics approach and its validity is demonstrated in both the linear and the nonlinear regime. Our solution allows accessing challenging problems of extreme spatiotemporal localization of high power laser radiation that remain almost unexplored theoretically until now.

Inhibition of myo-inositol monophosphatase isoforms by aromatic phosphonates.

alpha-Hydroxyphosphonates are moderately potent (Ki = 6-600 microM) inhibitors of the enzyme myo-inositol monophosphatase (McLeod et al., Med. Chem. Res. 1992, 2, 96). Hydroxy-[4-(5,6,7,8-tetrahydronaphtyl-1-oxy)phenyl]methyl phosphonate (3) was resynthesized and its inhibitory potency towards the recombinant bovine brain enzyme confirmed (Ki = 20 microM). Similar aromatic difluoro-, keto-, and ketodifluorophosphonates (5, 7, 9) were inactive. Compound 3 was 15-fold less active on the human as compared to the bovine enzyme. Molecular modeling suggested that the hydrophobic part of the inhibitor interacts with amino acid side chains that are located at the interface between the enzyme subunits in an area (amino acids 175-185) with low similarity between the two isozymes. Phe-183 in the human enzyme was replaced with leucine, the corresponding residue in the bovine isoform. The three isozymes (human wild-type, bovine wild-type and human F183L) had similar kinetic properties, except that the bovine enzyme was less effectively inhibited by high concentrations of the activator Mg2+. The F183L mutant enzyme had a twofold increased affinity for compound 3 as compared to the human wild-type form. We conclude that residue 183 contributes to the binding of aromatic hydroxyphosphonates to IMPase, but it is not the only determining factor for inhibitor specificity with respect to different isozymes.

Selective mechanism-based inactivation of peptidylglycine alpha-hydroxylating monooxygenase in serum and heart atrium vs. brain.

Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) catalyses the rate-limiting step in the post-translational activation of substance P, among other neuropeptides, from its glycine-extended precursor. Comparative kinetic studies were performed, using trans-styrylacetic acid or trans-styrylthioacetic acid as known mechanism-based inhibitors, of PHM isolated from rat, horse or human blood serum. Distinctive species differences with respect to PHM inactivation were observed: the efficiency of inactivation decreased in the order of horse >> rat > human. Trans-styrylacetic acid was more active than its thioether derivative. Moreover, we studied the differential sensitivity towards mechanism-based inactivation, of soluble PHM from rat blood serum and rat brain by trans-styrylacetic acid or benzylhydrazine, as well as the membrane-associated enzymes from rat brain and heart atrium. For the heart atrium membrane PHM or the soluble PHM from blood serum, inactivation rate constants k(inact)/K(I) of approximately 100 M(-1)sec(-1) were found with trans-styrylacetic acid. However, neither of the two tested compounds, at 100 microM or 12 mM, respectively, could inactivate the soluble or membranous PHMs from rat brain during a 15-min pre-incubation period. Instead, under conditions of reversible inhibition, trans-styrylacetic acid competitively inhibited the soluble or membrane-associated brain PHM with inhibition constants K(I) = 0.6 microM and 1.0 microM, respectively. Organ-selective, time-dependent inactivation of PHM with compounds of the above types might be an important pharmacological tool to control peripheral neuropeptide activation.

Monoaryl- and bisaryldihydroxytropolones as potent inhibitors of inositol monophosphatase.

The first successful preparation of mono- and disubstituted 3,7-dihydroxytropolone involves a four-step synthetic scheme. Thus, bromination of 3,7-dihydroxytropolone (8) followed by permethylation of the resultant products furnished gram quantities of intermediates 13-18. Single or double Suzuki coupling reactions between these permethylated monobromo- and dibromodihydroxytropolone derivatives and a variety of boronic acids delivered the expected products whose deprotection yielded the desired compounds 1a-u and 26a-n, usually in fair to good yields. Tropolones 1 and 26 were found to be potent inhibitors of inositol monophosphatase with IC50 values in the low-micromolar range. The results are discussed in the context of the recently described novel mode of inhibition of the enzyme by 3,7-dihydroxytropolones.

[In vitro antibacterial activity of cefpirome: a new cephalosporin; results of a multicenter study]. / Activité antibactérienne in vitro d'une nouvelle céphalosporine, le cefpirome: résultats d'une étude multicentrique.

The in vitro activity of cefpirome, a new injectable cephalosporin was studied against 1,082 clinical isolates in a multicentre study. Minimum inhibitory concentrations were determined using an agar dilution method. Cefpirome was active against Enterobacteriaceae. On naturally non-producing beta-lactamase species, cefpirome was active on most of the strains with MICs < or = 0.5 mg/l, including strains producing an acquired penicillinase: E. coli 0.03-0.06, P. mirabilis 0.06-0.12, Salmonella spp. 0.06-0.06, Shigella spp. 0.016-0.03. MICs of K. pneumoniae (0.06-4) ranged from 0.016 to 32:MICs were high against expanded-spectrum betalactamase producers strains. Against species producing cephalosporinase, cefpirome was also active on most of the strains with MICs < or = 0.5: E. cloacae 0.06-2, Citrobacter spp. 0.03-1, S. marcescens 0.06-0.5, P. indol + 0.06-0.25, P. stuartii 0.12-0.5. Cefpirome was less active on Pseudomonas aeruginosa, (8-32) and on A. baumanii (16-32). MICs of cefpirome were low against Haemophilus spp. betalactamase producing or not (0.01-0.03) and M. catarrhalis (0.6-4). Activity of cefpirome on methicillin-sensitive staphylococci, was higher than other third generation cephalosporins (0.25-2) comparable to that of cephalotin and cefamandol. Methicillin-resistant strains should be considered as resistant. Pneumococci (0.01-0.03), except for penicillin-R strains, and streptococci A, B, C, G (0.01-0.06) were very susceptible. Enterococci were of low sensitivity or resistant. Among anaerobes, C. perfringens appeared often susceptible, and Bacteroides spp. resistant.

[In vitro antibacterial activity of a new oral cephalosporin, ceftibuten. Results of a multicenter study]. / Activité antibactérienne in vitro d'une nouvelle céphalosporine orale, le ceftibutène. Résultats d'une étude multicentrique.

Minimal inhibitory concentration (MIC) of ceftibuten (CBT) were evaluated by agar dilution for 1,416 bacterial strains isolated in 5 hospitals. For Enterobacteriaceae, MIC 50 and 90% were respectively (micrograms/ml): (I) Naturally non beta-lactamase producing species: E. coli 0.12-0.5, Shigella 0.06-0.12 and Salmonella 0.03-0.12, P. mirabilis 0.16-0.03. (II) Chromosomal penicillinase producing species: K. pneumoniae 0.03-0.5 and K. oxytoca 0.03-0.06. (III) Chromosomal cephalosporin producing species: E. cloacae and C. freundii 1- greater than 128: S. marcescens 0.25-2; indole + Proteus 0.06-0.12. Activity of CBT was not modified on plasmid mediated penicillinase producing strains; however, CBT was inactive on cephalosporinase hyperproducing strains, and its activity was variably reduced on broad spectrum beta-lactamases producing strains. CBT was inactive on P. aeruginosa (MIC greater than or equal to 32) and on A. baumannii (8- greater than 128). Haemophilus and Gonococci, regardless on beta-lactamase production status, were very susceptible to CBT (MIC 50 and 90%: 0.06-0.5 and 0.016-0.06); it is the same situation for Meningococci; B. catarrhalis was generally inhibited by 0.03 to 2 (strains susceptible to penicillin G) and 0.12 to 16 (strains resistant to penicillin G). CBT was inactive on Staphylococci. Enterococci and Streptococci B were generally resistant; Streptococci A, C, G were inhibited by low concentrations: 0.06 to 1 (MIC 50 and 90%: 0.25-0.5), whereas MIC for other Streptococci 0.12 to 128 (MIC 50 and 90%: 8-128) and for Pneumococci were 0.25 to 16 (4-8). These antibacterial properties particularly against Enterobacteriaceae placed CBT in excellent position among oral cephalosporins.

Treatment of a meningitis due to an Enterobacter aerogenes producing a derepressed cephalosporinase and a Klebsiella pneumoniae producing an extended-spectrum beta-lactamase.

A case of nosocomial meningitis due to a Klebsiella pneumoniae producing a CAZ-5 extended-spectrum beta-lactamase and an Enterobacter aerogenes producing a derepressed cephalosporinase is reported. The intrathecal catheter incriminated was removed and a treatment with ceftazidime (4 g/24 h) and amikacin (1.5 g/24 h) was started. After 24 h ceftazidime was replaced by imipenem (2 then 4 g/24 h). This treatment failed to obtain cerebrospinal fluid sterilization; therefore the imipenem dosage was increased to 8 g/24 h and two intrathecal infusions of amikacin (50 mg) were carried out. Thereafter the patient recovered.

[In vitro antibacterial activity of a new fluoroquinolone, temafloxacin, against hospital isolates. Results of a multicenter study]. / Activité antibactérienne in vitro d'une nouvelle fluoroquinolone, la témafloxacine, sur les bactéries hospitalières. Résultats d'une étude multicentrique.

Minimal inhibitory concentrations (MICs) of temafloxacin (TMF) was determined by agar dilution for 2,510 bacterial strains isolated in 1989 in 9 university hospitals. Activity of TMF against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (mode MIC: 0.06 micrograms/l); like for other FQ, this activity was reduced against NAL intermediate (mode 1) and resistant (R) (mode 4) Enterobacteriaceae. MICs of TMF against P. aeruginosa were between 0.12 and 128 (mode 0.5-1). TMF had also a good activity against NAL S A. baumannii (mode MIC: 0.06-0.12) but this activity is reduced against NAL R Acinetobacter (mode MIC: 16). TMF was highly active against Haemophilus mode MIC: less than or equal to 0.008), Gonococci (mode MIC: 0.008-0.032), Meningococci (mode MIC: 0.08) and B. catarrhalis (mode MIC: 0.016). TMF showed better activity to other fluoroquinolones against methicillin susceptible Staphylococci (mode MIC: 0.06); the resistant strains (mode MIC: 8) are usually methicillin resistant. Comparatively to the currently available FQ, TMF is so more effective against Enterococci (mode MIC: 1), Streptococci (mode MIC: 0.5-1) and Pneumococci (mode MIC: 0.5). Finally, for the anaerobic bacteria, TMF is more active against C. perfringens (mode MIC: 0.5) than against B. fragilis (mode MIC: 2).

The in-vitro activity of cefodizime: a review.

For Enterobacteriaceae, MIC50s and MIC90s of cefodizime (mg/l), respectively, were as follows, for naturally non-beta-lactamase-producing species: Escherichia coli 0.12 and 0.5, Salmonella spp. and Shigella spp. 0.25 and 0.5, Proteus mirabilis 0.016 and 0.03; for chromosomal penicillinase-producing species. Klebsiella spp. 0.25 and 64, and for chromosomal cephalosporinase-producing species. Enterobacter cloacae 1 and 64, Citrobacter freundii 1 and 128, Serratia marcescens 2 and 8: indole-positive Proteus spp. 0.06 and 0.5; and Providencia stuartii 0.5 and 1. The activity of cefodizime was not modified by plasmid-mediated penicillinase-producing strains but cefodizime was inactive against cephalosporinase hyper-producing strains and against expanded broad-spectrum beta-lactamase-producing strains. Cefodizime was noticeably less active against Pseudomonas aeruginosa and Acinetobacter baumannii with MICs ranging from 32 to more than 128 mg/l. Haemophilus spp. and Neisseria gonorrhoeae, regardless of beta-lactamase producing status, as well as N. meningitidis, were highly susceptible (MIC50s and MIC90s less than or equal to 0.008 mg/l). Cefodizime was moderately active against methicillin-susceptible staphylococci (MIC50 and MIC90 8 mg/l) but failed to inhibit methicillin-resistant strains. Enterococci were generally resistant: Streptococcus pyogenes and Str. pneumoniae were inhibited by low concentrations (MIC50 and MIC90 0.12 and 0.5 mg/l). A fairly wide range of MICs was found for anaerobes, with lower values for Clostridium perfringens (MIC50 and MIC90 0.5 and 1 mg/l) than for Bacteroides fragilis (8- greater than 128 mg/l). These results show that cefodizime has similar properties to other third generation cephalosporins and suggest that cefodizime would find a role in the management of hospital infections.

[Piperacillin-amikacin combinations: killing curves]. / Associations pipéracilline-amikacine: cinétique de bactéricidie.

Bactericidal activity as a function of time of piperacillin (PIP) and amikacin (AKN) alone and in combination was evaluated by killing curves technique on 23 clinical isolates: E. coli (6), K. pneumoniae (5), E. cloacae (6) and P. aeruginosa (6), for which the minimal inhibitory concentrations ranges of piperacillin were 0.25 to 64 mg/l and of amikacin 1 to 8 mg/l. For each species, the strains were chosen according to the most frequent phenotypes: beta-lactams susceptible, penicillinase (Pase), cephalosporinase (Case) and Pase + Case producers. Killing curves were carried out with the following concentrations (mg/l): piperacillin (2, 16, 64); amikacin (4, 8, 16); piperacillin (2) + amikacin (4); piperacillin (16) + amikacin (8); piperacillin (64) + amikacin (16). Antibiotic concentrations corresponded to pharmacokinetics and/or to critical values of piperacillin and amikacin. Bactericidal activity was defined as a 4 log 10 decrease in CFU/ml between 2 and 24 hours. When piperacillin (64) was combined with amikacin (16), the bactericidal effects were nearly the same as those with amikacin alone. But piperacillin (16) + amikacin (8) combination had bactericidal effect for the majority of strains (21/23) and it prevented for some of them the bacterial regrowth observed with amikacin alone at the same concentration. A bactericidal activity without regrowth (until the 24th hour) was obtained for 9 strains; 2 susceptible E. coli, 3 K. pneumoniae (chromosomal Pase producer) and 4 cefotaxime susceptible E. cloacae, with low dose combination piperacillin (2) + amikacin (4). Finally, only combinations piperacillin (64) + amikacin (16) or piperacillin (16) + amikacin (8) had bactericidal activity on 2 Ticarcillin-resistant P. aeruginosa, the two antibiotics being separatedly bacteriostatic.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic studies with myo-inositol monophosphatase from bovine brain.

The kinetic properties of myo-inositol monophosphatase with different substrates were examined with respect to inhibition by fluoride, activation or inhibition by metal ions, pH profiles, and solvent isotope effects. F- is a competitive inhibitor versus 2'-AMP and glycerol 2-phosphate, but noncompetitive (Kis = Kii) versus DL-inositol 1-phosphate, all with Ki values of approximately 45 microM. Activation by Mg2+ follows sigmoid kinetics with Hill constants around 1.9, and random binding of substrate and metal ion. At high concentrations, Mg2+ acts as an uncompetitive inhibitor (Ki = 4.0 mM with DL-inositol 1-phosphate at pH 8.0 and 37 degrees C). Activation and inhibition constants, and consequently the optimal concentration of Mg2+, vary considerably with substrate structure and pH. Uncompetitive inhibition by Li+ and Mg2+ is mutually exclusive, suggesting a common binding site. Lithium binding decreases at low pH with a pK value of 6.4, and at high pH with a pK of 8.9, whereas magnesium inhibition depends on deprotonation with a pK of 8.3. The pH dependence of V suggests that two groups with pK values around 6.5 have to be deprotonated for catalysis. Solvent isotope effects on V and V/Km are greater than 2 and 1, respectively, regardless of the substrate, and proton inventories are linear. These results are consistent with a model where low concentrations of Mg2+ activate the enzyme by stabilizing the pentacoordinate phosphate intermediate. Li+ as well as Mg2+ at inhibiting concentrations bind to an additional site in the enzyme-substrate complex. Hydrolysis of the phosphate ester is rate limiting and facilitated by acid-base catalysis.

[In vitro antibacterial activity of lomefloxacin, a new fluoroquinolone, against hospital strains. Results of a multicenter study]. / Activité antibactérienne in vitro d'une nouvelle fluoroquinolone, la loméfloxacine, sur les bactéries hospitalières. Résultats d'une étude multicentrique.

Minimal inhibitory concentrations (MICs) of lomefloxacin (LOM) was determined by agar dilution for 2,819 bacterial strains isolated in 1988 in 9 university hospitals. Activity of LOM against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of pefloxacin (PEF) (mode MIC: 0.12-0.25 micrograms/ml); like for PEF, this activity was reduced against NAL resistant (R) Enterobacteriaceae (mode MIC: 4). MICs of LOM against P. aeruginosa were between 0.5 and 16 (mode: 2). LOM had also a good activity against NAL S A. baumannii (mode MIC: 0.5) but this activity is reduced against NAL R Acinetobacter (MICs : 4 to 128). LOM was highly active against Haemophilus (mode MIC: 0.06), Gonococci (mode MIC: 0.008), Meningococci (mode MIC: 0.03), Branhamella (mode MIC: 0.12-0.25). LOM showed activity similar to PEF against methicillin susceptible Staphylococci (mode MIC: 0.5-1); the resistant strains are usually methicillin resistant. Similar to the currently available quinolones, LOM is less effective against L. monocytogenes (mode MIC: 8), Enterococci (mode MIC: 4), Streptococci (mode MIC: 4) and Pneumococci (mode MIC: 8). Finally, for the anaerobic bacteria, LOM is more active against Clostridium perfringens (mode MIC: 1) than against Bacteroides fragilis (mode MIC: 32).

Comparative in-vitro activity of meropenem against clinical isolates including Enterobacteriaceae with expanded-spectrum beta-lactamases.

Meropenem, a new parenteral carbapenem, was tested in vitro by an agar-dilution method against 373 standard strains (aerobes and anaerobes) and against nine expanded-spectrum beta-lactamase-producing strains and their transconjugants (5 CTX-1, 2 CAZ-1, 2 CAZ-2). Meropenem was compared with methicillin, imipenem, piperacillin, cefoxitin, cefotaxime, ceftazidime, gentamicin, chloramphenicol, clindamycin, ciprofloxacin, vancomycin and metronidazole. Meropenem and imipenem exhibited an extended spectrum of activity, with low MICs. Only methicillin-resistant staphylococci, and Pseudomonas (Xanthomonas) maltophilia were resistant. Of the carbapenems, imipenem was more active against methicillin-susceptible staphylococci, streptococci and Enterococcus faecalis, but meropenem was markedly more active against all the Enterobacteriaceae and some pseudomonads. Both had similar activity against Ps. aeruginosa, Acinetobacter spp. and anaerobes. The carbapenem MICs were very low for Enterol acteriaceae producing the expanded-spectrum beta-lactamases. Against CTX-1-producing strains resistant to cefotaxime and ceftazidime and against CAZ-1 or CAZ-2-producers highly resistant to ceftazidime meropenem was the most active, with MICs lower (0.03-0.12 mg/l) than those of imipenem (0.06-0.5 mg/l), for wild type producers and their transconjugants.

[In vitro antibacterial effect of a new oral cephalosporin, cefixime. Results of a multicenter study]. / Activité antibactérienne in vitro d'une nouvelle céphalosporine orale, le céfixime. Résultats d'une étude multicentrique.

Minimal inhibitory concentrations (MIC) of cefixime (CXM) were evaluated by agar dilution against 2,469 bacterial strains isolated in 10 hospitals. For Enterobacteriaceae, MIC 50 and 90% micrograms/ml were respectively: (I) naturally non beta lactamase producing species: E. coli and Shigella 0.25-0.5; Salmonella 0.06-0.25; P. mirabilis 0.008-0.032. (II) chromosomal penicillinase producing species: Klebsiella 0.06-2. (III) chromosomal cephalosporinase producing species: E. cloacae and C. freundii 1-greater than 128; S. marcescens 0.25-16; indole + Proteus 0.06-4; P. stuartii 0.032-0.5. Activity of CXM was not modified against plasmid-mediated penicillinase producing strains, but CXM was inactive on cephalosporinase hyperproducing strains and on broad spectrum beta lactamases producing strains. CXM was inactive on P. aeruginosa (MIC 50 and 90%: 64-128) and on A. baumannii (16-128). Haemophilus and Gonococci, regardless of beta-lactamase production status, and Meningococci were very susceptible to CXM (MIC 0.008-0.12). B. catarrhalis was generally inhibited by 0.03 to 0.5. CXM was poorly active on methicillin susceptible Staphylococci (MIC 50 and 90%: 1-64) and inactive on methicillin resistant strains. Enterococci were generally resistant whereas Streptococci and Pneumococci were inhibited by low concentrations: 0.008 to 1. These antibacterial properties place CXM in excellent position among oral cephalosporins.

[In vitro antibacterial activity of a new macrolide, miokamycin. Results of a multicenter study]. / Activité antibactérienne in vitro d'un nouveau macrolide, la miokamycine. Résultats d'une étude multicentrique.

Minimal inhibitory concentration (MIC) of miokamycin (M) were evaluated by agar dilution for 1,024 bacterial strains isolated in 6 hospitals and classed as a function of susceptibility and resistance to macrolides, lincosamides, streptogramins group (MLS). MIC of M ranged from 0.25 to 4 micrograms/ml (mode MIC 1-2) on Staphylococcus susceptible to MLS and on MLSB inducible strains; M was inactive on MLSB constitutive strains. MIC of M ranged from 0.016 to 4 micrograms/ml (mode MIC 0.12 to 0.5) for Streptococci and Pneumococci susceptible to erythromycin (E) and from 0.12 to greater than 128 for strains resistant to E. Enterococci susceptible to E were inhibited by 0.5 to 2 micrograms/ml (mode MIC 1) and strains resistant to E by 4 to greater than 128. Haemophilus were inhibited by 2 to 64 micrograms/ml (mode MIC 32), Neisseria by 0.12 to 4 (mode MIC 0.5-1) and B. catarrhalis by 0.12 to 8 (mode MIC 1). L. pneumophila was very susceptible to M: MIC 0.016 to 0.12 (mode MIC 0.06). MIC of M ranged generally from 0.5 to 2 micrograms/ml (mode MIC 1) for C. perfringens and from 0.03 to 2 (mode MIC 1) for B. fragilis. Thus, M was shown to be among macrolide antibiotics of resistance non-inducing type on MLSB inducible resistance strains. Its activity was similar to that of spiramycin slightly superior on Staphylococci, slightly inferior on Streptococci and Enterococci, similar on Pneumococci, very superior on Neisseria, Legionella and anaerobes. M had a good activity on Branhamella and, as others macrolides, was poorly active on Haemophilus.

Purification and properties of myo-inositol-1-phosphatase from bovine brain.

myo-Inositol-1-phosphatase from bovine brain was purified over 2000-fold. The native enzyme has a Mr of 59,000, and on SDS/polyacrylamide-gel electrophoresis the subunit Mr was 31,000. Thus the native enzyme is a dimer of two apparently identical subunits. The enzyme, purified to a specific activity of more than 300 units/mg of protein (1 unit of enzyme activity corresponds to the release of 1 mumol of Pi/h at 37 degrees C), catalysed the hydrolysis of a variety of phosphorylated compounds, the best one, in terms of V/Km, being D-myo-inositol 1-phosphate. Kinetic constants of compounds tested, including both isomers of glycerophosphate and two deoxy forms of beta-glycerophosphate, were measured. They show the importance of the two hydroxyl groups which are adjacent to the phosphate in myo-inositol 1-phosphate. With a wide variety of substrates Li+ was found to be an uncompetitive inhibitor whose Ki varied with substrate structure.