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Biomedical subjects

M Fukasawa

Publications and source records attributed to M Fukasawa.

171 records · Page 10Linked to original sources

In vitro antibacterial activity of SM-1652, a new broad-spectrum cephalosporin with antipseudomonal activity.

SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bacteria was comparable to that of cefazolin. SM-1652 exceeded cefazolin in potency and broadness of antibacterial activity against such Enterobacteriaceae as indole-positive Proteus spp., Enterobacter cloacae, and Serratia marcescens. A remarkable feature of the spectrum of SM-1652 is its high activity against Pseudomonadaceae. Against 200 clinical isolates of Pseudomonas aeruginosa, SM-1652 was significantly more active than cefoperazone, cefotaxime, and sulbenicillin and as active as cefsulodin. The activities of SM-1652 against Pseudomonas maltophilia and Pseudomonas cepacia were superior to those of cefoperazone, cefotaxime, cefsulodin, sulbenicillin, and gentamicin. SM-1652 was relatively stable to hydrolysis with plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.

Anti-Bacterial Agents↗

Studies of maternal and fetal 11-deoxycorticosterone, corticosterone,18-hydroxycorticosterone and aldosterone in normal and toxemic pregnancy.

Simultaneous determination of maternal and fetal plasma 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO) in normal and toxemic pregnancies was performed by utilizing a newly developed radioimmunoassay. The mean levels of plasma DOC and ALDO in normal term pregnancy were significantly higher than those of nonpregnant women. Comparing the mean levels of umbilical arterial plasma to those in maternal plasma at delivery, DOC and ALDO were consistently higher in the former, while B was higher in the latter, and 18OH-B was largely unchanged. However, no umbilical arteriovenous gradient was found in any corticosteroid measured. In toxemia of pregnancy, the corticosteroid levels in the maternal plasma were lower than those in normal pregnancies, and in umbilical arterial plasma, B was significantly higher and 18OH-B and ALDO remained almost the same as those in normal pregnancy. Thus, it appears that ALDO synthesis in mother in normal term pregnancy was enhanced but in toxemia of pregnancy it was suppressed, while in the fetus, it was enhanced not only in normal pregnancy but also in toxemia of pregnancy.

18-Hydroxycorticosterone↗

Isolation of two types of Pseudomonas aeruginosa mutants highly sensitive to a specific group of beta-lactam antibiotics and with defect in penicillin-binding proteins.

Two types of mutants highly sensitive to beta-lactam antibiotics were obtained from Pseudomonas aeruginosa PAO 2142 by treatment with N-methyl-N'-nitro-N-nitrosoguanidine. One type of mutant showed over 30 times higher sensitivity to mecillinam, carbenicillin and sulbenicillin than did the parent, but not to most other beta-lactam antibiotics tested. In contrast, the other type mutant was about 30 times more sensitive to ampicillin, cephaloridine, cefoxitin and cefmetazole, but resistant to mecillinam, carbenicillin and sulbenicillin at the same level as the parent. Beta-lactamase activity of these mutants ws not different from that of the parent. Defect in either of penicillin-binding proteins 1A/1B or 5 was observed in some mutants of P. aeruginosa highly sensitive to beta-lactam antibiotics.

Bacterial Proteins↗

Histopathologic changes in the infundibular septum after balloon pulmonary valvuloplasty in tetralogy of Fallot.

Balloon pulmonary valvuloplasty (BPV) has been applied to tetralogy of Fallot (TOF) as a palliative procedure. To investigate the histopathologic changes by BPV in the infundibular septum of TOF, we performed histopathologic examinations of the infundibular septum resected at corrective surgery. The subjects were 5 patients with TOF, who underwent BPV at the median age of 2.2 months and the corrective surgery at the median age of 15.0 months (BPV group), and 4 patients with TOF who had no prior BPV and who underwent the corrective surgery at the median age of 14.5 months (control group). There was no significant difference between the two groups in the endocardial thickness, myocardial vacuole degeneration, or fraction of fibrous and interstitial space. However, the specimens from 3 patients in the BPV group had localized dense fibrous lesions in the myocardium. The findings in this limited sample suggest that BPV for TOF does not produce overall histopathologic alterations such as fibrosis, thick endocardium, and myocardial vacuole degeneration, but may sometimes damage the myocardium of the infundibular septum resulting in the formation of localized dense fibrous lesions. The clinical significance of this damage is still unknown, and further cases should be investigated.

Catheterization↗

Degradation of penicillin-binding protein 2' in methicillin-resistant Staphylococcus aureus.

We detected a novel protein with [14C]benzylpenicillin (PCG)-binding capacity and a molecular mass of about 60 kD in methicillin-resistant Staphylococcus aureus using a high concentration of [14C]PCG and extending the reaction time. However, the fluorogram showed that the band density of penicillin-binding protein 2' (PBP2') decreased gradually with incubation time. The appearance of the 60-kD protein and the reduction of the band density of PBP2' were stoichiometrically linked, and the binding profiles of beta-lactams for PBP2' and the 60-kD protein corresponded. These results suggested that the 60-kD protein is a degradation product of PBP2'.

Anti-Bacterial Agents↗

Meropenem resistance in Pseudomonas aeruginosa.

Two genetically distinct classes of meropenem-low-susceptibility Pseudomonas aeruginosa PAO2152 mutants, which arose spontaneously, were isolated. Two meropenem resistance genes, mpmA and mpmB, were mapped near ilvB/C and proC, respectively, on the P. aeruginosa PAO chromosome. The mpmA was thought to be identical to oprD2 because of the cross-resistance to carbapenems and the association with the loss of the outer membrane protein D2 (OprD2). The mpmB mutation conferred a 4-fold increase in resistance to meropenem, and cross-resistance to various types of antimicrobial agents, e.g. carbenicillin, norfloxacin and chloramphenicol. However, the mpmB mutant was susceptible to imipenem. This mutant still possessed OprD2 and showed increased expression of a 48-kD outer membrane protein, although its profiles of beta-lactamase activity and affinities of penicillin-binding proteins for beta-lactams were indistinguishable from those of the parent strain. The resistance gene mpmB was considered to be an allele of nalB (or cfxB or oprK) from the results of the transductional analysis. The mutation frequency of mpmA:mpmB was in the ratio of 4:1. The same results were obtained in another clinically isolated P. aeruginosa strain. Meropenem resistance caused by both mpmA and mpmB mutations seemed to be due to the reduction in permeability of antibiotics through the outer membrane. These findings suggest a new pathway for the translocation of meropenem other than that mediated by OprD2 across the outer membrane. Thus, meropenem showed about 4- to 8-fold higher activity than imipenem against OprD2-deficient P. aeruginosa.

Bacterial Outer Membrane Proteins↗

Inhibition of postsurgical adhesions in a standardized rabbit model: intraperitoneal treatment with tissue plasminogen activator.

The direct effects of tissue plasminogen activators (TPA) delivered locally into the peritoneal cavity at the site of injury on the subsequent formation of postsurgical adhesions in rabbits were studied. A 3 x 5 cm flap of parietal peritoneum (approximately 1 mm thick) was sharply dissected from the right lateral peritoneal sidewall. The serosal surface of the adjacent small bowel was abraded with a scalpel until punctate bleeding developed. Alzet minipumps containing varying doses of TPA were sewn into the subcutaneous space with their polyethylene catheter tips leading from the pump into the peritoneal cavity, 2-3 mm over the injury test site. Within 7 days after the implantation of the pumps, the rabbits were killed and the extent of adhesions was determined. The threshold dosage at which significant beneficial antiadhesion properties are obtained was between 0.015 and 0.05 mg TPA/mL of buffer at 6 x 10(-4) mg/kg/day. Effective adhesion prevention occurred with only two days of treatment beginning the day of surgery.

Animals↗

Inhibition of postsurgical adhesions in a standardized rabbit model: II. Intraperitoneal treatment with heparin.

The formation of adhesions after peritoneal trauma is thought to result from the deposition of fibrin and its subsequent organization by fibroblast ingrowth and, in some cases, neovascularization and reepithelialization. Since heparin is an effective anticoagulant, and clotting is a major contributor to postsurgical fibrin deposition, we studied the effects of heparin delivered locally into the peritoneal cavity at the site of the injury on the subsequent formation of postsurgical adhesions. A flap of parietal peritoneum (approximately 1 mm thick) was dissected from the right lateral peritoneal sidewall of New Zealand white female rabbits. The serosal surface of the adjacent small bowel was abraded with a scalpel to produce punctuate bleeding. This area between the excised parietal peritoneum and adjacent small bowel serosa was then used for evaluating the efficacy of heparin for adhesion prevention. Alzet minipumps containing phosphate-buffered saline with varying doses of heparin were sewn into the right dorsal subcutaneous space with Vicryl sutures. A polyethylene catheter tip leading from the pump into the peritoneal cavity was placed 2-3 mm over the injury test site. Within seven days after the implantation of the pumps, the rabbits were killed and the extent of adhesions determined, according to a qualitative grading system. The threshold dosage at which significantly beneficial antiadhesion properties were obtained was 1.5 x 10(-2) U/hour or 7.5 x 10(-3) U/kg/day. Effective adhesion prevention occurred with only two days of treatment beginning the day of surgery. At this dose, no postsurgical bleeding occurred. These findings suggest that local intraperitoneal administration of low-dose heparin throughout the immediate postoperative interval may result in adhesion-free healing.

Animals↗