Biomedical subjects
Publications and source records attributed to M Arisawa.
Isocucurbitacin B (I), 3-epi-isocucurbitacin B (II), and cucurbitacin B (III) were identified as the principal cytotoxic constituents of Ipomopsis aggregata (Pursh) V. Grant (Polemoniaceae). The structure of the new compound, II, was determined through analysis of its spectrometric characteristics.
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The authors described a case of primary intracranial endodermal sinus tumor (EST), and presented a review of 24 reported cases. From the middle of December 1981, this 15-year-old boy experienced progressive diplopia. At the other hospital, partial removal of the intrasellar tumor was performed by a left frontotemporal craniotomy approximately 2 months after the onset of symptoms. The histological diagnosis was suspected to be a pituitary adenoma, and thereafter, 60Co irradiation was carried out for about a month. On June 5th. 1982, the patient was admitted to the Kochi Medical School Hospital, because of increasing headache with diplopia, hoarseness, dysphagia and limitation of tongue movement. On admission, he had a small stature for his age with moderate diabetes insipidus. Neurological examination showed left abducens, glossopharyngeal and vagal nerve palsies in addition to bitemporal hemianopsia. CT scans revealed a heterogenously enhanced high density mass lesion behind the dorsum sellae with an extension from the upper clivus to the sphenoid sinus. Cerebral angiograms showed posterior displacement of the basilar artery. In the endocrinological examination, panhypopituitarism was recognized with a high level of serum alfa-fetoprotein (AFP). While, serum carcinoembryonic antigen (CEA) and human chorionic gonadotropin (HCG) were in normal range. On July 1st. 1982, a left suboccipital craniectomy was performed. The tumor existed mainly in the extradural space along the clivus, and only a small intradural portion of the tumor was excited.(ABSTRACT TRUNCATED AT 250 WORDS)
External decompression is an effective treatment for acute intracranial hypertension, but the repair of cranial defect by cranioplasty is necessary sooner or later. Various materials have been used for cranioplasty, such as bone, metallic materials and methyl methacrylate. Alumina ceramic (Bioceram), which is known to be extremely compatible with tissues, has already been used in the operations of not only orthopedic and oral surgery but also neurosurgery such as transsphenoidal surgery and anterior cervical fusion. At first, we implanted pieces of ceramic and small titan shield in the parietal bone of mongrel dogs. In this experimental study, tissue compatibility and osteogenesis are investigated in each case. The new bone formation was observed macroscopically and histologically around the ceramic pieces, but there were no osteogenic changes around the titan shields. Then ceramic plates, which were designed just as patients' own bone flaps, and titan shields were used for cranioplasties after decompression surgery, and compared clinically and histologically. The ceramic plate is superior than the titan shield in its strength, tissue-compatibility and excellent fit for cranial defect compared with the titan shield. There was no tissue reaction such as subgaleal fluid collection just as seen in the application of acryl resin. We believe that Alumina ceramic (Bioceram) is a good material for cranioplasty.
Several chalcone derivatives; e.g. Ro 09-0204, Ro 09-0323 and Ro 09-0501 were found to reduce markedly the revertant increase of Salmonella typhimurium TA100 by benzo(a)pyrene during the incubation with S-9 Mix. The antimutagenic activity was 100 - 700 times stronger than that of L-ascorbic acid. Effect on other mutagens, the structure activity relationship and the possible mechanism of action are briefly discussed.
The interaction between 6-acetylmethylenepenicillanic acid (compound Ro 15-1903; AMPA) and TEM-1 beta-lactamase was investigated in order to elucidate the mechanism of action of AMPA. Formation of the enzyme-inhibitor complex (EA) was accompanied by a shift of the absorbance maximum from 292 nm to 303 nm and an increase in the absorption. Regeneration of activity was very slow and incomplete, reaching about one-third of the initial activity after 48 h at 37 degrees C. This behaviour indicated a branched pathway of the decay of the inactivated enzyme. Kinetic and isoelectric-focusing experiments proved this assumption. The first-order constant of regeneration of active enzyme was 6 X 10(-6)-10 X 10(-6) s-1, whereas the rate constant leading to inactive enzyme (EA') was 10 X 10(-6)-15 X 10(-6) s-1 at pH 7.0. Both constants became larger at higher pH. Inactive enzyme (EA') consisted of two major species, with pI 5.36 (EA'1) and 5.30 (EA'2). The former increased at the beginning of incubation but decreased after prolonged incubation. From consideration of these results and previous data [Arisawa & Then (1983) Biochem. J. 209, 609-615], a likely mechanism of inactivation of TEM-1 beta-lactamase by AMPA is discussed.
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6-Acetylmethylenepenicillanic acid is a new kinetically irreversible inhibitor of various beta-lactamases. Interaction between 6-acetylmethylenepenicillanate and purified TEM-1 beta-lactamase during the inactivation process was investigated. 6-Acetylmethylenepenicillanate inhibited the enzyme in a second-order fashion with a rate constant of 0.61 microM-1 . S-1. The apparent inactivation constant decreased in the presence of increasing concentrations of the substrate benzylpenicillin. Native enzyme (pI 5.4) was converted into two inactive forms with pI 5.25 and 5.15, the latter form being transient and readily converted into the more stable form with pI 5.15. Even a 50-fold excess of inhibitor over enzyme did not produce any other inactivated species of the enzyme. All the results obtained suggest that 6-acetylmethylenepenicillanate is a potent irreversible and active-site-directed inhibitor of TEM-1 beta-lactamase.
A new prostaglandin D2 (PGD2), which is highly concentrated in the rat hypothalamic-pituitary system, was investigated for its gonadotropin release and synthesis by radioimmunoassay (RIA). Significant increases in the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were observed when the anterior pituitaries were incubated for 4 hours in vitro in the presence of 500 micrograms PGD2/ml incubation medium. Little change in LH and FSH contents in the rat anterior pituitary was observed between the control and PGD2-stimulated groups during incubation. In addition, more than 200 micrograms PGD2/ml induced a marked increase of cyclic adenosine 3',5' monophosphate (cAMP) formation in the rat anterior pituitary, and this was observed within 10 minutes after stimulation by PGD2. These data indicate that PGD2 directly induces a marked release of both LH and FSH from the gonadotrophs, and the mechanism of action of PGD2 could be mediated by cAMP formation.
Several Citrobacter freundii beta-lactamases, discernible by their substrate profiles and sensitivities to inhibition by newer cephalosporins, were inhibited by ceftriaxone in an unusual manner. Inhibition was noncompetitive at low concentrations of cephaloridine but became competitive at concentrations above 600 muM, which is close to the K(m) (570 muM) for cephaloridine.
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To resolve discrepancies between its enzymological activity and its in vitro or in vivo activity, 6-acetylmethylenepenicillanic acid (Ro 15-1903), a potent beta-lactamase inhibitor, was investigated for its chemical stability and its ability to penetrate the bacterial cell envelope. Although Ro 15-1903 was fairly stable in water or saline, it was found to be unstable in a rich medium, in mouse plasma and in human serum. Decomposition half-lives in Tryptic Soy Broth (TSB) and mouse plasma were determined by spectrometry to be 1.3 hours and 12 minutes respectively. These values were confirmed by a biochemical method for determination of Ro 15-1903. Furthermore, a large enhancement of the in vitro activity was noticed when the assay medium was changed from TSB to a synthetic medium in which Ro 15-1903 was more stable. The ampicillin-potentiating activity marginally increased if a permeability mutant harboring the R6K plasmid, which codes for TEM-1 beta-lactamase production, was used instead of the wild-type strain. These results prove that the chemical instability of Ro 15-1903 is the main cause of its disproportionally low activity in vitro and in vivo. Ro 15-1903 is not nonspecifically inactivated by proteins, since it did not lose its activity after incubation with bovine serum albumin (50 mg/ml) for 2 hours at 37 degrees C. It seems to react specifically with beta-lactamase.
In the course of multiple antibiotic treatment of a seriously ill patient, a high level of resistance to cefamandole, cefuroxime and ceftriaxone was found among consecutive isolates of Klebsiella oxytoca, other species isolated remaining susceptible. Susceptibility to cefotaxime was less affected, and the activity of cefoxitin and moxalactam was unchanged. Resistant K. oxytoca strains synthesized a large amount of a broad-spectrum beta-lactamase, able to hydrolyze ceftriaxone, cefuroxime and cefotaxime. The enzyme level as well as the ability to hydrolyze different cephalosporins with different rates explained the in vitro susceptibilities observed reasonably well. The initially susceptible K. oxytoca strain easily converted in vitro to variants producing a high level of beta-lactamase after exposure to ceftriaxone, without concomitant acquisition of high-level resistance to this antibiotic, suggesting that additional and at present unknown factors also contributed to resistance of the clinical isolates.
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Potentiating activity of alafosfalin was examined in detail with 8 cephalosporins and mecillinam against 164 urinary bacteria representing 8 genera. Alafosfalin was generally comparable in activity to cefamandole and mecillinam but superior to other cephalosporins tested. When the minimal fractional inhibitory concentration indices were compared, synergism was observed with all of the beta-lactams tested for all species except Streptococcus faecalis. Marked synergism was observed with Escherichia coli, Citrobacter, and enterobacter and, among the drugs tested, with cefamandole and mecillinam. Although alafosfalin is inactive against Pseudomonas aeruginosa, potentiation was seen with cefsulodin. The most favorable combination ratio of alafosfalin/cephalosporin to elicit potentiation was determined for each species and occurred in a rather narrow range of combinations (1:4 to 4:1 in general).