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Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) (OMIM #617481) is an autosomal recessive disease characterized by progressive microcephaly, plagiocephaly, hypotonia, spastic quadriparesis, global developmental delay, intellectual disability, optic features and abnormal brain magnetic resonance imaging (MRI). NMIHBA was recently reported to be caused by PRUNE1 mutations. Eight mutations have been reported in 13 unrelated families. Here, we report 3 PRUNE1 mutations in 1 Caucasian and 3 Japanese families. One recurrent missense mutation (p.Asp106Asn) was previously reported in Turkish and Italian families, while the other 2 mutations (p.Leu18Serfs*8 and p.Cys180*) are novel. We also show that mutant PRUNE1 mRNA can be subject to nonsense‐mediated mRNA decay. The patients presented in this study showed atypical NMIHBA phenotypes with no progressive microcephaly. Furthermore, one Caucasian case had significant macrocephaly; therefore, patients with PRUNE1 mutations can exhibit a broad and heterogeneous spectrum of phenotypes. [ABSTRACT FROM AUTHOR]

The article presents case study of a 52 year old male who was diagnosed with heterozygous truncating Solute Carrier Family 5 Member 7 (SLC5A7) related distal hereditary motor neuropathy 7. Topics discussed include observation of paralyzed vocal cord using rhino-laryngo fiberscopic examination; information on presynaptic choline transporter (CHT) encoded in SLC5A7 which plays an important role in synaptic acetylcholine synthesis; and phenotype-genotype correlation presented by SLC5A7 variant.

In patients with Duchenne muscular dystrophy (DMD), the absence of a functional dystrophin protein results in sarcolemmal instability, abnormal calcium signaling, cardiomyopathy, and skeletal muscle degeneration. Using the dystrophin-deficient sapje zebrafish model, we have identified microRNAs (miRNAs) that, in comparison to our previous findings in human DMD muscle biopsies, are uniquely dysregulated in dystrophic muscle across vertebrate species. MiR-199a-5p is dysregulated in dystrophin-deficient zebrafish, mdx5cv mice, and human muscle biopsies. MiR-199a-5p mature miRNA sequences are transcribed from stem loop precursor miRNAs that are found within the introns of the dynamin-2 and dynamin-3 loci. The miR-199a-2 stem loop precursor transcript that gives rise to the miR-199a-5p mature transcript was found to be elevated in human dystrophic muscle. The levels of expression of miR-199a-5p are regulated in a serum response factor (SRF)-dependent manner along with myocardin-related transcription factors. Inhibition of SRF-signaling reduces miR-199a-5p transcript levels during myogenic differentiation. Manipulation of miR-199a-5p expression in human primary myoblasts and myotubes resulted in dramatic changes in cellular size, proliferation, and differentiation. MiR-199a-5p targets several myogenic cell proliferation and differentiation regulatory factors within the WNT signaling pathway, including FZD4, JAG1, and WNT2. Overexpression of miR-199a-5p in the muscles of transgenic zebrafish resulted in abnormal myofiber disruption and sarcolemmal membrane detachment, pericardial edema, and lethality. Together, these studies identify miR-199a-5p as a potential regulator of myogenesis through suppression of WNT-signaling factors that act to balance myogenic cell proliferation and differentiation. [ABSTRACT FROM AUTHOR]

To clarify the mechanisms underlying shockwave-induced osteogenesis, we applied shockwave to rat femoral shafts from the ventral side. We assessed bone mineral content (BMC) and bone mineral density (BMD), and analyzed the spatial and temporal gene expression for pro-α1 (I) collagen (COL1A1), pro-α1 (II) collagen (COL2A1), pro-α1 (X) collagen (COL10A1), osteocalcin (OC) and osteopontin (OPN) using in situ hybridization. On the 21st day post-exposure, BMC and BMD in the exposed femur were elevated by 8.46% and 5.80%, respectively, relative to the unexposed femur. Immediately following exposure, there was evidence of scraping of the cortex and periosteal separation with hemorrhage. On day 4, new periosteal bone formation could be seen on the ventral and dorsal side of the femur. In the newly formed bone, COL1A1, OC and OPN were expressed in osteoblastic cells underlying the periosteum. On day 7, there was progression of periosteal bone and trabeculae formation. COL1A1 and OC were expressed in mature osteoblasts lining the trabeculae, whereas OPN was expressed in immature osteoblastic cells, osteocytes and osteoclasts. On day 14, bone remodeling commenced in the periosteal bone. COL1A1, OC and OPN were still expressed at this stage, however, signals were much weaker. Between 4–7 days, chondrocyte clusters were distributed multi-focally near the exposed site, and there was expression of COL2A1 but not of COL10A1. The results demonstrate that gene expression patterns of shockwave-induced osteogenesis are similar to those of periosteal hard callus formation during fracture healing. Shockwaves can yield dramatic activation of cells in normal long bones, and drive the cells to express genes for osteogenesis. [ABSTRACT FROM AUTHOR]

DQ-2556, a new cephalosporin, showed a broad antibacterial spectrum over Gram-positive and -negative organisms. The activity of DQ-2556 against recent clinical isolates of Gram-positive cocci and Enterobacteriaceae was comparable with that of cefpirome, and superior to that of ceftazidime. DQ-2556 was almost as active as cefpirome against Pseudomonas aeruginosa, but was less active than ceftazidime. With the exception of Ps. aeruginosa, DQ-2556 was bactericidal against various organisms at either the MIC or twice the MIC. DQ-2556 bound preferentially to penicillin-binding proteins (PBPs) 2, 1 and 3 of Staphylococcus aureus, PBPs 3, 1A and 1B of Escherichia coli and PBPs 1A, 3 and 4 of Ps. aeruginosa. DQ-2556 was stable to various penicillinases and cephalosporinases, but was unstable to oxyiminocephalosporinases. The Km values of DQ-2556 for the cephalosporinases of Citrobacter freundii and Enterobacter cloacae were only two- or three-fold higher than those of ceftazidime, indicating that DQ-2556 had a relatively high affinity for these enzymes compared with other recently developed cephalosporins. The MIC of DQ-2556 for Esch. coli increased four-fold in an OmpF-deficient mutant, indicating that the OmpF porin was one of the major routes for penetration of DQ-2556 into Esch. coli cells. [ABSTRACT FROM AUTHOR]

The in-vitro synergistic activity of tazobactam, a new beta-lactamase inhibitor, combined with piperacillin was tested against various beta-lactamase-producing strains. The beta-lactamase inhibitory activity of tazobactam against various known types of beta-lactamase was also tested in comparison with clavulanic acid or sulbactam. Tazobactam caused a remarkable reduction of the piperacillin MICs for penicillinase- and oxyiminocephalosporinase-producing strains and also showed a moderate synergistic effect against cephalosporinase-producing strains. The bactericidal activity of piperacillin was enhanced in combination with tazobactam. Tazobactam inhibited the penicillinases, and the oxyiminocephalosporinase produced by Proteus vulgaris, at low concentration. In these cases its activity was comparable with that of clavulanic acid and stronger than that of sulbactam. Tazobactam demonstrated a better inhibitory capability than sulbactam against the cephalosporinases tested. Tazobactam was able to inactivate intracellular beta-lactamase in Prot. vulgaris and Morganella morganii, confirming its ability to penetrate the cell membrane of these species. [ABSTRACT FROM AUTHOR]

Rabbit antiserum was prepared to the penicillinase of Alcaligenes denitrificans subsp. xylosoxydans GN14062. The antibody gave a single precipitin line in double immunodiffusion assays with the penicillinases from strain GN14062 and from two other A. denitrificans subsp. xylosoxydans strains. The precipitin line given by the GN14062 enzyme gave a reaction of complete identity with the precipitin lines of the penicillinases from the other A. denitrificans subsp. xylosoxydans strains. Furthermore, activity of the penicillinases from all three A. dentrificans subsp. xylosoxydans strains was neutralized by the antiserum to the GN14062 enzyme. Thus it was proved that the penicillinases produced by the three A. denitrificans subsp. xylosoxydans strains were immunologically identical. Penicillinases types I, II, III, IV, V, SHV-1, TEM-1, TEM-2, and the chromosomal penicillinases of Klebsiella pneumoniae GN69 and A. faecalis GN14061 formed no immunoprecipitate with, nor were neutralized by, the antiserum to the GN14062 enzyme. From these results, it was concluded that the penicillinase produced by A. denitrificans subsp. xylosoxydans was immunologically distinct from the penicillinases produced by these other bacteria. [ABSTRACT FROM AUTHOR]

New monobactam compounds with fluoromethyl side chains at the 4-position were synthesized. These compounds showed strong antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa and good stability to various beta-lactamases. The effect of replacement of the 1-carboxy-1-methylethoxyimino residue of aztreonam with various substituted groups, and of the configuration of the 3- and 4-position were examined. Substitution of a carboxycyclopropoxy group in the oxyimino moiety effected the most potent antibacterial activity. The cis congeners were not hydrolysed by any types of beta-lactamases including the oxyiminocephalosporin hydrolysing enzyme. Introduction of a fluorine atom in the methyl group at the 4-position increased the beta-lactamase stability of monobactams. [ABSTRACT FROM AUTHOR]

L-105 (sodium(-)-(6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyimino- acetamido]-3-[1,2,3-thiadiazol-5-yl)thiomethyl]-8-oxo-5-thia-1-aza bicyclo [4.2.0]oct-2-ene-2-carboxylate) is a new semisynthetic cephalosporin derivative. The in-vitro antibacterial activity of L-105 against clinical isolates of 18 bacterial species was compared with those of cefmenoxime, cefoperazone and cefazolin. Its spectrum against Gram-negative bacteria was similar to that of cefmenoxime. Moreover, against Gram-positive bacteria, including Staphylococcus aureus, coagulase negative staphylococci, Streptococcus faecalis, Str. pneumoniae and Str. pyogenes, L-105 was more potent than cefmenoxime and cefoperazone. Against Gram-positive bacteria, including Staph. aureus which is comparatively resistant to most third-generation cephalosporins, it was nearly equal in potency to cefazolin. L-105 was stable to various penicillinases and cephalosporinases. However, this compound was slightly hydrolyzed by oxyiminocephalosporinases, i.e., the enzymes produced by Pseudomonas cepacia and Ps. maltophilia. [ABSTRACT FROM AUTHOR]

The in-vitro antibacterial activity of AMA-1080 against both Gram-positive and Gram-negative clinical isolates was studied in comparison with that of aztreonam, cefotaxime, ceftazidime and cefoperazone. AMA-1080 showed a potent antibacterial activity against Gram-negative bacteria, particularly, the strains of Enterobacteriaceae. In addition, AMA-1080 inhibited the strains of genus Pseudomonas at the low concentrations. However, AMA-1080 showed less active against Gram-positive bacteria. It was found that AMA-1080 was highly resistant to hydrolysis by both chromosomal and plasmid-mediated beta-lactamases. [ABSTRACT FROM AUTHOR]

A penicillin beta-lactamase was purified from a strain of Alcaligenes dentrificans subsp. xylosoxydans resistant to beta-lactam antibiotics. The purified enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis, and its molecular weight was 18,000 from sodium dodecylsulphate-acrylamide gel electrophoresis and gel filtration. Its isoelectric point was 9.8, the optimal pH was 8.5 and the optimal temperature was 35 degrees C. The enzyme hydrolyzed penicillin G and ampicillin more rapidly than cephalosporins. Relative rates, with penicillin G as 100, were: ampicillin, 102; carbenicillin, 15; cloxacillin, less than 1; piperacillin, 9; cephaloridine, 41; cefoperazone, 36; cefpiramide, 36 and cefmenoxime, 14. Clavulanic acid, sulbactam, imipenem, and cephamycins had low affinities for the enzyme. The enzyme activity was inhibited by iodine, Hg2+, clavulanic acid and sulbactam. [ABSTRACT FROM AUTHOR]

Imipenem, a derivative of thienamycin, a carbapenem antibiotic, has a broad spectrum of activity against aerobic (Gram-positive and Gram-negative) and anaerobic bacteria. It is quite stable to all tested β-lactamases produced by various species of bacteria isolated from clinical specimens, whether plasmid or chromosomally mediated. One exception is its hydrolysis by the β-lactamase produced by Pseudomonas maltophilia which is thus usually resistant to imipenem.Imipenem was found to be hydrolysed by renal dehydropeptidase-I residing on the luminal surface of the renal tubular epithelium. A dehydropeptidase-I inhibitor, cilastatin (MK-0791) was developed with specific inhibitory activity toward the renal dehydropeptidase-I and showed detectable effects in humans. [ABSTRACT FROM PUBLISHER]

Cefotaxime (CTAX), a new cephalosporin derivative, has a broad antibacterial spectrum and is stable to β-lactamases produced by various species of bacteria. However, CTAX is hydrolysed by β-lactamases produced by Proteus vulgaris, Pseudomonas cepacia and Bacteroides fragilis, called cefuroxime-hydrolysing enzyme (Group III). Slightly low activity toward Pseudomonas aeruginosa is probably due to the low penetrability of the drug into the cells. The mechanism of action of CTAX was studied with respect to its binding affinities to penicillin-binding proteins (PBPs) and morphological changes of bacteria treated by CTAX in vitro. Cefotaxime showed especially high affinity for Escherichia coli PBP-1A, -1Bs, -3 and -4 and low affinities for PBP-2, -4, -5 and -6. Similar results were obtained with Ps. aeruginosa, in which this compound showed high affinities for PBP-3, -1A, -1B and 2. These results are compatible with morphological observations that at concentrations near its minimal inhibitory concentration or more, this antibiotic induced the formation of filamentous cells of E. coli and Ps. aeruginosa. At higher concentrations or after prolonged incubation, it induced lysis of the cells. [ABSTRACT FROM PUBLISHER]

Coformycin, which is an inhibitor of adenosine deaminase, significantly inhibited in vitro blastogenic responses of human lymphocytes to both phytohaemagglutinin (PHA) and pokeweed mitogen (PWM), whereas blastogenic responses to bacterial lipopolysaccharide (LPS) were rather enhanced by the addition of coformycin. Blastogenic responses of lymphocytes to PHA and PWM were markedly suppressed by the addition of adenosine, which is a substrate of adenosine deaminase. Allopurinol, which is an inhibitor of xanthine oxidase, inhibited blastogenic responses of human lymphocytes lo PHA, PWM, and bacterial LPS. Inosine (a substrate of purine nucleoside phosphorylase) and hypoxanthine (a substrate of xanthine oxidase) showed no or only a small effect on blastogenic responses of human lymphocytes. These results suggest that adenosine deaminase deficiency is associated with the T-cell response but not with the B-cell response and that the impaired T-cell response in adenosine deaminase deficiency is the result of intracellular retention of adenosine in T cells. The results also suggest that purine nucleoside phosphorylase or xanthine oxidase activity is associated with both T- and B-cell responses. [ABSTRACT FROM AUTHOR]

The in vitro activity of meropenem, a carbapenem antibiotic, combined with eight other β-lactams against methicillin-resistant Staphylococcus aureus (MRSA) was tested. The MICs of these antibiotics alone ranged from 12.5 to 1,600 µg/ml for the 25 clinical isolates of MRSA studied. All combinations with meropenem exhibited marked synergy as determined by the checkerboard method. The MICs in combinations of meropenem with other β-lactams were reduced to 1/4 - 1/64 those of the antibiotics alone. No antagonism was observed for any of the combinations of meropenem with other β-lactams. Synergism between meropenem and cefpiramide was the highest among the combinations tested, the geometric mean of the fractional inhibitory concentration index for this combination being 0.237. This combination also demonstrated strong bactericidal activity, the MBCs decreasing to 1/16 - 1/64 of those for the agents alone. In terms of the fractional inhibitory concentration index, this was the most effective combination against MRSA highly resistant to meropenem alone with synergism for 85 % (81/95) of the strains. In addition, synergism of imipenem with cephalosporins against MRSA was demonstrated. The affinity of meropenem and cefpiramide for MRSA penicillin-binding protein (PBP) 2′ was very low, and the combination of both antibiotics showed an additive increase in affinity for this protein, but not a synergistic increase. Thus, the mechanism of synergism did not seem to be related to affinity for PBP2′. It is possible that there is another factor besides PBP2′ which increases the resistance of MRSA and that the combinations inhibit the unknown factor. [ABSTRACT FROM AUTHOR]

Ribonucleic acid (immune RNA, iRNA), extracted from the spleens of mice immunized with sheep red blood cells (SRBC), induced specific immunological memory. The humoral immune responses of iRNA-treated animals were compared with in vivo and in vitro primary and secondary responses, using the haemolytic plaque-forming cell (PFC) assay. IgM antibody formation was markedly higher in iRNA-treated than in any other mice. The effect of iRNA was antigen-specific and similar materials from non-immunized mice had no activity. [ABSTRACT FROM AUTHOR]

T- and B-cell participation in the immune response induced by immune ribonucleic acid (iRNA) preparations against 1-dependent antigens was studied using athymic nude, neonatally thymectomized (NT) and cyclophosphamide-treated (CY) mice. The IRNA(T + B) preparations were made from the spleen of BALD/c mice immunized with these antigens. Injection of the IRNA into nude or NT mice caused an increase in the number of specific rosette-forming cells (RFC) and of memory cells capable of responding to secondary stimulus with a small dose of the corresponding antigen. Injection with T-dependent antigens or with iRNA(T + B) did not cause any immune response in CY mice, suggesting depletion of the if-cell function. The (RNA(T) and iRNA(B) were prepared, respectively, from the thymuses of BALD/c mice and from the spleens of nude mice which had been immunized with 1-dependent antigens. Injection of nude mice with both IRNA(T) and iRNA(S) caused an increase in the number of specific RFC and the secondary antibody formation response after boosting with a small dose of the corresponding antigen. Injection of IRNA(T) preparation into nude mice could induce the anamnestic response after boosting. However, neither of the iRNA(T) or iRNA(B) preparations could induce in nude mice the proliferation of the number of specific RFC. These results indicate the presence of at least two kinds of IRNA preparations against 1-dependent antigens and that the cooperation of IRNA(T) and IRNA(B) was required for the induction of immune response against T-dependent antigens. [ABSTRACT FROM AUTHOR]

The immune response of congenitally athymic (nude) mice induced by immune ribonucleic acid (IRNA) to lipopolysaceharides of Escherkhia coli 0-55 (LPS) was studied. The thymus-independent nature of the immune response of mice to LPS was confirmed and nude mice responded to LPS in a manner similar to normal mice. An IRNA preparation extracted from the spleen of nude mice immunized with LPS could induce the proliferation of roseue-forming cells (RFC) in nude mice. iRNA preparations were insensitive to treatment with deoxyribonuclease and pronase, but were inactivated by ribonuclease treatment. The active fraction of the iRNA preparation had sedimentation values in a sucrose density gradient between 7 and 16 S and comprised only a small fraction of the total RNA present in the spleen cells, thereby indicating that the active moiety was one or more species of RNA. The anamnestic response was induced by treatment with iRNA made from the spleen of nude mice immunized with LPS. An increase in the number of rosette-forming cells (RFC), plaque-forming cells (PFC) and formation of humoral antibody to LPS was seen after injection with a small amount of LPS 4 weeks after iRNA treatment. [ABSTRACT FROM AUTHOR]

The in-vitro activity of T-5575, 2-carboxypenam, a new parenteral antibiotic and its stability to beta-lactamases were compared with those of ceftazidime and imipenem. The activity of T-5575 was equal or superior to that of ceftazidime or imipenem against Gram-negative bacteria that produced penicillinase with the exception of the enzyme OXA-1. Against strains that produced Cephalosporinase and zinc-dependent beta-lactamase, the activity of T-5575 was superior to that of ceftazidime or imipenem. T-5575 was a poor substrate and had low affinity for beta-lactamases produced by Citrobacter freundii, Enterobacter cloacae and Pseudomonas aeruginosa. The activity of T-5575 was less influenced by the derepressed production of chromosomal enzymes than that of ceftazidime. Overall, T-5575 had excellent activity against Gram-negative pathogens that produced various types of beta-lactamases. [ABSTRACT FROM AUTHOR]

From October 1988 to January 1992, nine isolates of Pseudomonas aeruginosa carrying transferable plasmids encoding imipenem-hydrolyzing β-lactamase (pI = c. 9.5) were recovered from nine different patients in a neurosurgical ward of a hospital in Japan. The β-lactamase activities of the sonicated extracts from the transconjugants were inhibited by EDTA and this was partially reversible by the addition of zinc cation. The substrate specificity and pI of the β-lactamase were similar to those of the metallo β-lactamases from P. aeruginosa and Serratia marcescens TN9106. All strains were resistant to imipenem, carbenicillin and antipseudomonal cephems including ceftazidime, cefsulodin, cefpirome, while four and five strains were susceptible to piperacillin and aztreonam, respectively. Both low level imipenem resistance and high level cephem resistance were co-transferred with the production of metallo β-lactamase, while resistance to piperacillin, aztreonam, and high level imipenem-resistance were not selected. Production of chromosomal cephalosporinase in piperacillin resistant strains was derepressed, and production of outer membrane protein of D2 was diminished in highly imipenem resistant strains. Six strains were isolated in 1991, and the amounts of antipseudomonal agents, especially imipenem, used in the neurosurgical ward increased markedly in this year. Only three of the nine isolates had the same serotype, pyocin type and phage type. Our results suggest that the repeated isolation of imipenem and cephem-resistant P. aeruginosa producing metallo β-lactamase was related to the high usage of antipseudomonal β-lactam antibiotics such as imipenem, and was exacerbated by the dissemination of a plasmid. [ABSTRACT FROM PUBLISHER]

We devised an accurate procedure with which to measure the affinities of beta-lactam antibiotics for penicillin-binding protein (PBP) 2' in methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we used two isogenic strains of MRSA, on heterogeneous and the other homogeneous, derived from the methicillin-susceptible strain FDA209P, harbouring the mecA gene. In these MRSA strains, PBP2' was saturated by [14C]benzylpenicillin (PCG) at a concentration of 300 mg/L. In addition, the saturation of PBP2' by [14C]PCG required an incubation period of 30 min. According to these results, the precise affinities of beta-lactam antibiotics for PBP2' were determined by the 'accurate competition assay', using a high concentration of [14C]PCG and extending the reaction time. This procedure yielded lower IC50 values of beta-lactams than the 'usual competition assay'. However, each beta-lactam had almost the same affinity for PBP2' in heterogeneous and homogeneous strains. These results suggest there is a factor(s) other than PBP2' responsible for controlling resistance levels and the heterogeneity or homogeneity of MRSA strains. [ABSTRACT FROM AUTHOR]

The in-vitro synergic activities of BRL42715, a new beta-lactamase inhibitor, clavulanic acid, sulbactam, and tazobactam combined with ampicillin, piperacillin, cephalothin, or cefoperazone were tested against various bacteria producing known types of beta-lactamase. BRL42715 showed the best synergistic activity among the inhibitors tested against strains producing penicillinases of type I, II, III, V, and that from Klebsiella pneumoniae, cephalosporinases, and oxyiminocephalosporinases (except that from Klebsiella oxytoca). Clavulanic acid combined with the beta-lactams tested showed the best synergic activity of the inhibitors against strains producing type IV penicillinase and oxyiminocephalosporinase from K. oxytoca. The 50% inhibitory doses of BRL42715 were superior to those of clavulanic acid against various types of beta-lactamases except for type IV penicillinase and the oxyiminocephalosporinase from K. oxytoca. The inhibitory activity of BRL42715 against cephalosporinases from various bacteria was 10(4) to 10(6)-fold greater than that of clavulanic acid. The synergic effects of BRL42715 and clavulanic acid on the activity of piperacillin were compared against six clinical isolates of bacteria resistant to piperacillin. The synergic activity of BRL42715 was greater than that of clavulanic acid in all six isolates. [ABSTRACT FROM AUTHOR]

The stability of the new carbapenem antibiotics, panipenem, meropenem and LJC 10,627, against porcine and human renal dehydropeptidase-I (DHP-I) was compared with that of imipenem. The order of stability to hydrolysis by renal DHP-I was: LJC 10,627 greater than meropenem greater than panipenem greater than imipenem. After incubation of the drugs with porcine or human enzyme at 30 degrees C for 4 h, the percentages of residual activity were as follows: LJC 10,627, 73.7% and 95.6%, respectively; meropenem, 0.2% and 28.7%, respectively; panipenem, 0% and 4.3%, respectively; and imipenem, 0% and 0.1%, respectively. These results demonstrate that LJC 10,627 has extremely high stability against renal DHP-I. [ABSTRACT FROM AUTHOR]

The effect of cyanide, arsenate, Mg++ or EDTA on the uptake of norfloxacin in Escherichia coli was measured. Uptake of norfloxacin was suppressed by either 0.1 mM MgSO4 or 0.1 mM EDTA, while the presence of 0.1 mM MgSO4 increased the minimum suppressive concentration of EDTA from 0.1 to 0.2 mM. Increased uptake in the presence of 10 mM cyanide was observed, but the addition of 10 mM arsenate had no significant effect. Concentration of norfloxacin in bacterial cells was observed even when uptake was suppressed by the addition of 10 mM EDTA. Uptake in mini-cells was comparable to that in whole cells. These results suggest that the uptake of norfloxacin in E. coli, in addition to influx by simple diffusion and energy-dependent efflux, is influenced by binding of norfloxacin to the cell surface as a result of chelating activity to Mg++, together with an unknown concentration step resulting from binding to cell components other than the chromosome. [ABSTRACT FROM AUTHOR]

Antibody production in the African clawed toad (Xenopus laevis) against Salmonella flagella and the immunochemical properties of the antibodies were studied. The titre of the serum antibodies increased slowly and reached a maximum at 3 weeks after immunization and they were detectable even 20 weeks after antigenic stimulation. No protein components were electrophoretically demonstrated at the region corresponding to the IgG of mammalian antibodies. Two types of antibodies were found; the one produced early after immunization was heat- labile and the other produced later was heat-stable. The former was of low molecular weight (7S component) and the latter was macromolecular (19S component). Both antibodies moved electrophoretically to the cathode and were sensitive to 2-mercaptoethanol (2-ME) treatment, and their antigenicities were not identical. The low molecular weight antibody did not fix complement in the presence of antigen, in contrast to the macromolecular antibody. The low molecular weight antibody did not correspond to the IgG type of mammalian antibodies in the following properties; 2-ME sensitivity, heat-sensitivity, electrophoretic mobility and absence of complement-fixing ability. [ABSTRACT FROM AUTHOR]

We report here a case of thromboembolism occurring in a 29-year-old woman with transient eosinophilia. Eosinophilia for at least 11 days was followed by pulmonary embolism. Both reperfusion of pulmonary arteries and disappearance of deep vein thrombi were obtained by treatment with urokinase, tissue plasminogen activator, and heparin. Although the causes of eosinophilia were not specified, we suggested a causative correlation of elevated serum levels of eosinophil granule proteins with the development of thromboembolism. [ABSTRACT FROM AUTHOR]

We report here a case of thromboembolism occurring in a 29-year-old woman with transient eosinophilia. Eosinophilia for at least 11 days was followed by pulmonary embolism. Both reperfusion of pulmonary arteries and disappearance of deep vein thrombi were obtained by treatment with urokinase, tissue plasminogen activator, and heparin. Although the causes of eosinophilia were not specified, we suggested a causative correlation of elevated serum levels of eosinophil granule proteins with the development of thromboembolism. [ABSTRACT FROM AUTHOR]