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Biomedical subjects

D Bauer

Publications and source records attributed to D Bauer.

At least 37 records · Page 2Linked to original sources

Molecular cloning of human myelin-associated glycoprotein.

The nucleotide sequence for human myelin-associated glycoprotein (MAG) and its deduced amino acid sequence, obtained by analysis of two overlapping cDNA clones isolated from a human brain cDNA library, is presented and compared to that reported for rat MAG. The sequence provides an open reading frame of 1,878 nucleotides encoding a peptide of 626 amino acids with a calculated molecular weight of 69.1 kD. It is 89% homologous in nucleotide sequence to the large isoform of rat MAG, with 95% homology in the amino acid sequence. It contains 9 potential glycosylation sites, one more than in rat, and shares other key features with rat MAG, including 5 immunoglobulin-like regions of internal homology, an RGD sequence, and potential phosphorylation sites. Its structure appears to be highly conserved in evolution, possibly suggesting a close interdependence between its structure and function. The human gene is located on the proximal long arm of chromosome 19 (19q12----q13.2).

Amino Acid Sequence

Pseudomonas aeruginosa: in vivo (murine) activity of five antimicrobial drugs, with and without human IgG immunoglobulin preparations.

Five antimicrobial drugs (ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin) and two human, intravenously applicable, IgG immunoglobulin preparations (Psomaglobin, Polyglobin N) were examined alone and in various combinations for therapeutic efficacy in myelosuppressed as well as normal NMRI mice following systemic infection with 4 selected strains of Pseudomonas aeruginosa. Both IgG preparations alone invariably failed to passively protect neutropenic and normal mice, even though the preparations contained demonstrable antibodies against purified exotoxin A of P. aeruginosa and against numerous polypeptide and lipopolysaccharide constituents of the 4 test strains of P. aeruginosa. Among the antimicrobial drugs employed alone, ciprofloxacin and imipenem were the most effective. Tobramycin alone occupied an intermediate position, whereas monotherapy with ceftazidime and piperacillin invariably failed. All antimicrobial drug combinations were efficacious in myelo-suppressed as well as normal mice. Both IgG preparations failed to enhance the activities of ceftazidime and piperacillin in neutropenic mice; the activity of tobramycin was augmented against 1 of 2 P. aeruginosa strains, as well as that of ciprofloxacin. Both IgG preparations enhanced the activities of ceftazidime and tobramycin in normal NMRI mice, as well as that of piperacillin against 1 of 2 test strains. It was concluded that the two IgG preparations were more beneficial for normal rather than neutropenic mice, provided that the animals were treated with appropriate antimicrobial drugs as well.

Animals

Susceptibility of Acinetobacter calcoaceticus to antimicrobial drugs, alone and combined, with and without defibrinated human blood.

Twenty-five clinical isolates of Acinetobacter calcoaceticus were examined for susceptibility to 14 antimicrobial drugs. In terms of inhibitory and bactericidal activities, imipenem and polymyxin B were most active, followed by amikacin and ceftazidime. Four isolates were resistant against fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin). The isolates varied in susceptibility to aztreonam, cefotaxime, cotrimoxazole, gentamicin, mezlocillin, netilmicin and piperacillin. Fresh defibrinated human blood from 3 donors revealed similar killing kinetics against 8 selected isolates. In time-kill curve experiments, human blood enhanced the activity of amikacin more than that of ceftazidime, ciprofloxacin and imipenem against A. calcoaceticus. The combinations of amikacin + imipenem and amikacin + ceftazidime in the presence of human blood were effective against this microorganism. Human blood combined with ciprofloxacin + imipenem was more effective than blood with added ceftazidime + ciprofloxacin.

Acinetobacter

An analysis of the relationship between proximal and distal motor control.

The purpose of this investigation was to test the ontogenetic principle that the development of proximal postural stability precedes, and is necessary for, the development of distal fine motor control. The Posture and Fine Motor Assessment of Infants (Case-Smith, 1987) was used to examine the relationship between proximal and distal motor function in 60 normal infants. Low positive partial correlations were found between components of posture and fine motor control. Although all partial correlations, except those between the head component of postural control and the fine motor scores, were significant, they were not strong enough to support the validity of the proximal-distal principle. They appear instead to reflect a functional rather than an ontogenetic relationship. These findings have implications for treatment and further research.

Child Development

Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta.

A number of macrophage-derived mediators have been implicated in the vascular changes of inflammation. We recently reported the isolation of a novel monokine, macrophage inflammatory protein 1 (MIP-1), which causes local inflammatory responses in vivo, and induces superoxide production by neutrophils in vitro. Purified native MIP-1 comprises two peptides with very similar physical characteristics. We report here the resolution of MIP-1 into component peptides by SDS-hydroxylapatite chromatography, and compare the NH2-terminal sequences of the two peptides, now referred to as MIP-1 alpha and MIP-1 beta. A synthetic oligonucleotide probe pool corresponding to the NH2-terminal amino acid sequence of MIP-1 beta was used to isolate a cDNA clone containing its coding sequence. The sequence codes for a 109 amino acid-long polypeptide, of which 69 amino acids correspond to the mature product. Comparison of this MIP-1 beta cDNA with our previously cloned MIP-1 alpha sequence reveals that the MIP-1 peptides, members of a growing family of potential inflammatory mediators, are distinct but highly homologous (58.9% sequence identity) products of different genes.

Animals

Effect of spinal immobilization devices on pulmonary function in the healthy, nonsmoking man.

In the prehospital management of trauma, a variety of devices are used for immobilization of the spinal column during extrication and transport. Two of these commonly used immobilizers, the Zee Extrication Device and the long spinal board, use crisscrossing straps over the thorax to affix the patient to the device. Our study was designed to determine if these two devices alter pulmonary function in the healthy, nonsmoking man. We took 15 healthy, nonsmoking male volunteers and tested four pulmonary function parameters: forced vital capacity (FVC), forced expiratory volume in one second (FEV1), the ratio FEV1:FVC, and forced mid-expiratory flow (FEF 25%-75%). A Breon spirometer was used to test these functions both before and after the volunteers were strapped into the two devices. Three separate trials were given for each parameter and the best scores were used for data computation. Strap tension was controlled by placing a sphygmomanometer beneath each strap and adding tension to produce 10 mm Hg pressure. We found a significant difference (P less than .05) between prestrapping and poststrapping values for three of the four functions tested using the long spinal board: FVC (P = .0079), FEV1 (P = .0001), and FEF 25%-75% (P = .0252). Similarly significant differences were found for three of the four parameters using the Zee Extrication Device: FVC (P = .004), FEV1 (P = .0022), and FEF 25%-75% (P = .008). These differences reflect a marked pulmonary restrictive effect. The ratio FEV1:FVC can be normal or even slightly elevated with restrictive airway disease due to proportional reductions of each parameter. Correspondingly, we found no significant difference between prestrapping and poststrapping FEV1:FVC values (P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Failure of polymyxin B nonapeptide to augment bactericidal activities of novobiocin, rifampin, and of defibrinated human blood against Serratia marcescens.

Polymyxin B (PB) and polymyxin B nonapeptide (PBNP), when combined with rifampin or novobiocin, but not vancomycin, yielded additive inhibitory effects against test strains of Serratia marcescens of three varieties: those that produced cocarde growths around PB disks (coc+); those that grew adjacent to PB disks (coc-, 6); and those that yielded clear inhibition zones around PB disks (coc-, clear). However, time kill curve experiments disclosed that only the combination of rifampin + PB exerted a potent bactericidal effect against coc+ strains of S. marcescens; rifampin + PBNP and novobiocin + PB or PBNP merely effected transient decreases of colony counts. Assays involving 50% (v/v) of fresh defibrinated human blood + PB or PBNP revealed that only PB clearly augmented the antibacterial activity of blood against coc+, and less so against coc- test strains of S. marcescens.

Blood Bactericidal Activity

Pseudomonas aeruginosa: in vitro susceptibility to antimicrobial drugs, single and combined, with and without defibrinated human blood.

Twelve clinical isolates of Pseudomonas aeruginosa of distinct pyocin type varied in susceptibility to 14 of 17 antimicrobial drugs. The 2 x MIC concentrations of 16 antimicrobial drugs combined with 55% (v/v) of fresh, defibrinated human blood yielded additive effects. Additive effects were noted with blood plus the MIC concentrations of all drugs tested except cefoperazone, gentamicin, and netilmicin. Blood combined with subinhibitory (1/2 MIC) concentrations of aztreonam, ceftazidime, ciprofloxacin, fleroxacin, imipenem, and tobramycin, respectively, yielded additive effects; indifferent effects were observed with the remaining 10 blood plus 1/2 MIC drug combinations. The following drug combinations additively augmented the antibacterial activity of 65% (v/v) of human blood against two selected isolates of P. aeruginosa: tobramycin (1 microgram/ml) plus the MIC or 2 x MIC concentrations of azlocillin, aztreonam, ceftazidime, ciprofloxacin, imipenem, norfloxacin, ofloxacin, piperacillin, and ticarcillin, respectively. Imipenem (8 micrograms/ml) combined with ceftazidime, cefoperazone, and piperacillin, but not aztreonam, enhanced the bactericidal activity of human blood. Rifampin (2 micrograms/ml) plus tobramycin (0.5-1 microgram/ml) combined with 8 or 16 micrograms/ml of azlocillin, aztreonam, cefoperazone, ceftazidime, imipenem, and piperacillin, respectively, enhanced blood-mediated killing of three representative multiple-drug-resistant P. aeruginosa isolates. Additional effective triple-drug combinations with human blood were rifampin + tobramycin + polymyxin B, rifampin + ciprofloxacin + imipenem, and rifampin + amikacin + imipenem. Ciprofloxacin (2 micrograms/ml) was the most potent intraphagocytic bactericidal drug of 16 tested agents (greater than or equal to 2 x MBC concentrations) against P. aeruginosa control strain ATCC 27853.

Anti-Bacterial Agents

Morphometric characteristics of hepatocellular dysplasia.

Morphometric study of liver biopsies from six entities (normal tissue, post-hepatitis cirrhosis, post-alcoholic cirrhosis, cancer-related cirrhosis, hepatocellular adenoma and hepatocellular adenocarcinoma) confirmed that this technique can be a valuable adjunct to histopathologic study in the examination of such specimens. As expected, measurements in cirrhotic nodules showed two populations of cells. The so-called "large dysplastic cells" had nuclear and cellular areas close to those of normal hepatocytes and should thus be considered to be hyperplastic elements, not precancerous elements. The smaller dysplastic cells had morphometric values close to those of the corresponding hepatocellular carcinomas, indicating that these cells are the truly precancerous ones. Therefore, while the study confirmed that hepatic cirrhosis is a precancerous lesion, it also showed that the term hepatocellular dysplasia must be restricted to the smaller type of cells found in such nodules.

Adenoma

[Assay of erythrocyte, platelet and serum superoxide dismutase, glutathione peroxidase and catalase in rheumatoid polyarthritis].

The authors present a study of superoxide dismutase, catalase and glutathione peroxidase in hemolysis product, platelets and serum of 23 patients with rheumatoid polyarthritis and 11 healthy subjects. The nature of the treatment enables to divide the 23 patients into 3 groups: group I (8 cases): no treatment; Group II (7 cases): steroid therapy alone; group III (8 cases): basic treatment associated (3 cases) or not (5 cases) to steroid therapy. Statistical analysis shows no significant difference, whatever the environment and the treatment contemplated. The significance of these results is discussed and compared with literature data concerning only enzymatic activities and not the blood levels as in the present study.

Adult

Active immunization of NMRI mice against Serratia marcescens. II. K-antigen extracts.

The minimal active immunogenic doses (intraperitoneal administration) of crude K-antigen extracts of Serratia marcescens for NMRI mice were 80 ng. Following ultracentrifugation (300,000 x g, 16 h), supernatant fluids of three K-antigen extracts were free of contaminating DNA, RNA, and 2-keto-3-deoxy-D-manno-octonic acid (KDO), and the contents of Limulus amoebocyte lysate-reactive lipopolysaccharide (LPS) had been reduced from 100- to 1000-fold. The minimal active immunogenic doses of two ultracentrifuged K-antigen extracts were 2 and 10 micrograms, respectively. A mucoid strain of S. marcescens (SM 20-M; serotype O6/O14:H12) yielded nonmucoid (= SM 29-NM) variants that had lost most of the O6/O14 O-antigen (LPS) and all of the SM 29-M K-antigen extract reactivity (ELISA test) and which were ca. 5-fold less mouse-virulent. Crude K-antigen extracts from S. marcescens strain SM 29-M and variant SM 29-NM failed to protect NMRI mice against strain SM 29-M.

Animals

Growth curves of Clostridium perfringens in Schaedler and brain heart infusion broths.

Four Clostridium perfringens strains recovered from clinical specimens, four strains obtained from faecal specimens of healthy adults, and control strain ATCC 13124 were inoculated into Schaedler and Brain Heart Infusion broths, respectively, and incubated anaerobically at 35 degrees C for 24 h. The exponential growth phase usually lasted from 2 to 6 h following inoculation; the generation times averaged 23 min at 2 to 4 h and 27 min between 4 and 6 h of incubation. The early stationary growth phase (generation time between 6 and 8 h = 89 min) was reached at 8 h following inoculation. All strains displayed essentially identical in vitro growth rates, even though they differed in murine virulence.

Animals

Active immunization of NMRI mice against Serratia marcescens. I. Phenol-water lipopolysaccharide fractions and purified metalloproteases.

The minimal intraperitoneal (i.p.) immunogenic doses of phenol-hot water lipopolysaccharide (P-W- LPS) preparations from three strains of Serratia marcescens for juvenile NMRI mice ranged from 3.2 to 16 ng following i.p. challenge infection with homologous strains. Dual autoclaving (121 degrees C, 15 min) abolished the cross-immunogenicity of two selected P-W LPS extracts. Four purified metalloproteases from S. marcescens strains SF 178, SH 186, SV O1, and SE 182 shared the following properties: a) inhibition of proteolytic (azocasein hydrolysis) activity by 50 mM of EDTA; b) heat-lability (60 degrees C, 15 min); c) identical molecular weights (54,000 Daltons = 54 K) as documented with the SDS-PAGE procedure; d) close serologic relatedness (ELISA technique, polyclonal rabbit immune sera); and e) uniform reactivity of the 54 K polypeptide bands with polyclonal rabbit anti-metalloprotease immune sera (Western blots). The minimal immunogenic dose of metalloprotease SF 178, the sole significantly murine immunogenic enzyme, was 1000 ng = 1 microgram.

Animals

Interactions of purified Serratia marcescens metalloproteases with fresh human serum and with purified human serum proteins.

Exposure of fresh human serum to two purified metalloproteases of S. marcescens strains SF 178 and SH 186 (both of serotype O6/O14:H12) at 35 degrees C, 3 h, resulted in altered electrophoretic mobility of the protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin, alpha 2-HS-glycoprotein, and complement (C) components C1q, C1s, C3a, C3c, C4, C5, and C9, but not C6, C7, C8, and properdin, as determined with electroimmunoassays (Laurell technique). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) documented the partial degradation of the heavy (H) chain of purified human immunoglobulin IgG by the metalloproteases of S. marcescens strains SF 178 and SV O1 (serotype O13/O19:H1), but not by the metalloproteases of strains SH 186 and SE 182 (serotype O9B:H11) following extended incubation (35 degrees C, 22 h). Human IgA and IgM were refractory. Purified human C components, C3, C4, C5, C6, C7, C8, and C9, as well as purified human alpha 1-antitrypsin, alpha 2-macroglobulin, transferrin, and lactoferrin were attacked by the S. marcescens metalloproteases SF 178 and SH 186 at 35 degrees C for 5 h, as demonstrated with the SDS-PAGE procedure; haptoglobin and C-reactive protein were resistant.

Acute-Phase Proteins

Outer membrane protein alterations in Serratia marcescens resistant against aminoglycoside and beta-lactam antibiotics.

Six isolates of Serratia marcescens were recovered sequentially from the respiratory tract of a single patient. The first three isolates were of the 'opaque' (wild-type) colony type and were susceptible to amikacin, cefotaxime, and lamoxactam. The following three isolates were of the small, 'gray' colony variety, significantly less susceptible to the three antibiotics, and revealed three altered outer membrane proteins, as determined with the SDS-PAGE procedure.

Aminoglycosides