(10)B-NMR determination of (10)B-BPA, (10)B-BPA-fructose complex and total (10)B in blood for BNCT.

First spontaneous, noninvasive determination method of (10)B-BPA, (10)B-BPA-fructose complex, and total (10)B in blood is described. (10)B-NMR measurement with 100,000 FT accumulation enables us to obtain the result within 100min/sample. The detection limits for the simultaneous analysis were 3ppm, 3ppm and 6ppm for (10)B-BPA, (10)B-BPA-fructose complex and total (10)B respectively in this study. By this method, we can actually discuss behavior of the (10)B-BPA-fructose complex in blood.

Biological evaluation of dopamine analogues containing phenylboronic acid group as new boron carriers.

As new BNCT reagents, we designed and synthesized dopamine analogues containing phenylboronic acid group, N-3,4-dihydroxyphenethyl-4-dihydroxyborylbenzamide (dopamine-PCBA) and N-[2-(3,4-dihydroxyphenetyl)ethyl]-3-(4-dihydroxyborylphenyl)promionamide (dopamine-CEBA). The efficacies of these compounds have not been investigated for biological samples. Therefore we have carried out experiments with cultured tumor cells and tumor-bearing mice, and evaluated possibility of these compounds as boron carriers. Dopamine-PCBA and dopamine-CEBA were synthesized by coupling between p-carboxyphenylboronic acid (PCBA) or 4-(2-carboxyethyl)benzeneboronic acid (CEBA) and 3,4-(dibenzyloxy)phenethylamine hydrochloride (DBPA-HCl) followed by catalytic hydrogenation using Pd catalyst. The effect of compounds on cell vitality was determined by MTT assay in various cells. In vivo biodistribution of compounds was determined in Balb/c and DDY mice in bearing implanted CT26 cells. These results have demonstrated that dopamine-CEBA was less toxic.

Unusual radiographic appearance of ossifying fibroma in the left mandibular angle.

Ossifying fibroma is usually a unilocular lesion with a well-defined, thinly corticated margin radiographically, although various patterns have been noted. The patient was a 27-year-old woman with a painless radiolucent lesion demonstrated on panoramic radiography to involve the root-apex area of the left lower second and third molars. Radiographically, the lesion had some features of a benign tumour, such as an odontogenic myxoma. However, the deep invaginations towards the interalveolar septa suggested a simple bone cyst, whereas the irregular margin and lack of expansion or mandibular canal displacement were consistent with a malignant lesion. A hard tissue component was confirmed only by soft-tissue mode CT. Although this lesion was histopathologically diagnosed as ossifying fibroma, the conflicting imaging findings were challenging and very intriguing.

Central odontogenic fibroma with osteoid formation showing atypical radiographic appearance.

We recently encountered an interesting tumour, containing both a diffuse sclerotic border and calcified bodies, which was eventually diagnosed as a central odontogenic fibroma. The patient was a 40-year-old man with a painless radiolucent area in the crown area of the unerupted left lower third molar shown by panoramic radiography. Clinically, the lesion was thought to represent an odontogenic tumour involving a calcified body, i.e. calcifying cystic odontogenic tumour, calcifying epithelial odontogenic tumour or ossifying fibroma. Diagnosis by radiographic findings was extremely difficult.

Coronary risk factors in Kawasaki disease treated with additional gammaglobulin.

AIMS: To assess the hypothesis that an additional intravenous gammaglobulin (IVGG) infusion, if administered early, may prevent coronary artery lesions (CAL) in patients with Kawasaki disease (KD) who do not respond to initial IVGG therapy. METHODS: Forty four KD patients (17 with CAL and 27 without CAL), treated with additional IVGG because of persistent or recrudescent fever after initial IVGG therapy, were studied. Main outcome measures were the presence of CAL by echocardiography and the number of febrile days before and after start of additional IVGG infusion (pre- and post-additional IVGG). RESULTS: In univariate analyses, risk factors for CAL were the number of febrile days pre-additional IVGG, the number of febrile days post-additional IVGG, the number of days that initial IVGG was divided over, the white blood cell count pre- and post-additional IVGG, and the C reactive protein concentration pre-additional IVGG. In a multivariate analysis, the only independent risk factor was the number of febrile days pre-additional IVGG (> or =10 days; odds ratio 7.86; 95% CI 1.44 to 42.8; p = 0.02). CONCLUSIONS: Among KD patients with persistent or recrudescent fever after initial IVGG therapy, administration of additional IVGG before the first 10 febrile days was associated with a decreased prevalence of CAL, when compared with the prevalence in those who were retreated later. An additional IVGG infusion, if administered early, may prevent CAL in initial IVGG non-responders.

Immunohistochemical demonstration of chromogranin A in endocrine organs of the rat and horse by use of region-specific antibodies.

Chromogranin A (CgA) is an acidic glycoprotein that is co-stored with hormones or neurotransmitters in granular components of endocrine cells and neurons, and released together with them in response to adequate stimulation. In addition to acting as a packaging protein, CgA functions as a precursor molecule that yields several bioactive peptides by proteolytic cleavage. The purpose of this study is to elucidate how different the processing of CgA is among endocrine tissues by immunostaining using multiple region-specific antisera, and to evaluate the availability of region-specific antisera. When various endocrine organs of rats were immunostained with four region-specific antisera against rat CgA (CgA 1-28, 94-130, 296-314, and 359-389), all amine/peptide-secreting endocrine tissues except the pineal body were stained positively. The adrenal medulla and gastric endocrine cells were equally intensely immunoreactive to all four antisera, while the other endocrine tissues, represented by pancreatic islets, showed different staining patterns depending on the antiserum. These results suggest that the processing of CgA differs from tissue to tissue. An antiserum against horse CgA 335-365, corresponding to rat CgA 359-389 which shows the highest concentration in the plasma and urine of the rat, again stained all endocrine tissues of the horse except the pineal body. Therefore, the anti-horse CgA 335-365 serum is useful for immunohistochemical survey of horse CgA, and may make possible the establishment of a CgA assay system for the measurement of CgA in the plasma, urine and saliva.

Synthesis and biological activity of novel macrocyclic antifungals: acylated conjugates of the ornithine moiety of the lipopeptidolactone FR901469.

A series of acylated analogues of the novel macrocyclic lipopeptidolactone FR901469 has been prepared and evaluated for antifungal and hemolytic activity. Several analogues displayed markedly reduced hemolytic potential and comparable protective effects to the natural product in a mouse model of candidiasis.

Studies on 8-methoxyquinolones: synthesis and antibacterial activity of 7-(3-amino-4-substituted)pyrrolidinyl derivatives.

A series of 8-methoxyquinolones bearing 3-amino-4-methylpyrrolidines or 3-amino-4-fluoromethylpyrrolidines at the C-7 position was synthesized and their physicochemical and biological properties were evaluated. All of the compounds synthesized showed more potent activity than LVFX (3) against both gram-positive and negative bacteria. Increases in lipophilicity of these compounds had desirable effects on their potency of single intravenous toxicity and pharmacokinetic profiles in animals. Among the compounds synthesized, 1-fluorocyclopropyl derivatives 17 and 20, and 7-(cis-3-amino-4-fluoromethylpyrrolidinyl) derivative 19 (DC-756h) showed negative responses in the micronucleus test in mice while 1-cyclopropyl-7-(3-aminopyrrolidinyl) derivative 16 showed a positive response. These results suggested that the introduction of a fluorine atom into the 3-aminopyrrolidinyl substituent resulted in favorable influence on genetic toxicity as well as into the N-1 cyclopropyl substituent.

In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi.

The in vitro antifungal activity and spectrum of FK463 were compared with those of amphotericin B, fluconazole, and itraconazole by using a broth microdilution method specified by National Committee for Clinical Laboratory Standards document M27-A (National Committee for Clinical Laboratory Standards, Wayne, Pa., 1997). FK463 exhibited broad-spectrum activity against clinically important pathogens including Candida species (MIC range, <==0.0039 to 2 microg/ml) and Aspergillus species (MIC range, <==0.0039 to 0.0313 microg/ml), and its MICs for such fungi were lower than those of the other antifungal agents tested. FK463 was also potently active against azole-resistant Candida albicans as well as azole-susceptible strains, and there was no cross-resistance with azoles. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viability after a 24-h exposure at concentrations above 0.0156 microg/ml. The minimum fungicidal concentration (MFC) assays indicated that FK463 was fungicidal against most isolates of Candida species. In contrast, the MFCs of FK463 for A. fumigatus isolates were much higher than the MICs, indicating that its action is fungistatic against this species. FK463 had no activity against Cryptococcus neoformans, Trichosporon species, or Fusarium solani. Neither the test medium (kind and pH) nor the inoculum size greatly affected the MICs of FK463, while the addition of 4% human serum albumin increased the MICs for Candida species and A. fumigatus more than 32 times. Results from preclinical in vitro evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.

Prosthetic restorations with osseointegrated implants after bone grafts to correct large jaw defects caused by extraction of multi-impacted teeth: a case report.

A case is reported of a 21-year-old Japanese man examined for unerupted molar teeth on the left side of both jaws. Intraoral examination revealed edentulous regions from the second premolar to the molar, with moderate atrophy of the upper alveolar ridge. A panoramic X-ray revealed eight impacted teeth. The impacted mandibular teeth were extracted through decortication and bone replacement. The impacted maxillary teeth were extracted following reflection of a mucoperiosteal flap. The large defects caused by the extractions in both jaws were filled with autogenous cancellous marrow and bone chips. Eleven months later, in the first stage of the Branemark implant procedure, fixtures were placed in the edentulous regions of both jaws, with simultaneous additional corticocancellous block onlay bone grafting in the maxilla to correct slight resorption. After another seven months, second-stage abutment surgery was performed. Occlusion was then restored through a prosthetic procedure. Next, orthodontic treatment was commenced, using the implant supported teeth as an anchor. Despite the slight resorption in the maxilla, implantation was successful and occlusion was restored in the previously edentulous regions. This suggests that application of a simultaneous corticocancellous block onlay bone graft is a valuable basis for implant procedures in the maxilla.

Effect of lavage with injection of sodium hyaluronate for patients with nonreducing disk displacement of the temporomandibular joint.

OBJECTIVE: The purpose of this study was to determine whether lavaging of the superior joint space with injection of sodium hyaluronate can be used as an alternative treatment method for nonreducing disk displacement of the temporomandibular joint. STUDY DESIGN: In 26 patients with nonreducing disk displacement of the temporomandibular joint, the superior joint space was rinsed with 1% xylocaine, and then sodium hyaluronate was injected there (experimental group). As a control group, 50 patients with nonreducing disk displacement of the temporomandibular joint who received no treatment were used (control group). The frequency of the patients with successful clinical resolution was evaluated in each group during 6 months. RESULTS: The frequency of the patients with successful clinical resolution in the experimental group (73.1%) was significantly higher than that in the control group (36.0%) at the 6-month follow-up (chi-squared test, p < 0.05). CONCLUSIONS: This therapy appears to represent an alternative treatment method for nonreducing disk displacement of the temporomandibular joint.

Studies on 3'-quaternary ammonium cephalosporins--IV. Synthesis and antibacterial activity of 3'-(2-alkyl-3-aminopyrazolium) cephalosporins related to FK037.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3'-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-am ino-2-(2 -hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In particular, the in vivo activity against MRSA of FK037 was the highest of all the beta-lactam antibiotics tested.

Studies on 3'-quaternary ammonium cephalosporins--III. Synthesis and antibacterial activity of 3'-(3-aminopyrazolium) cephalosporins.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]cephalos porins bearing N-mono or dialkyl and carbamoyl aminopyrazolium, and five- or six-membered rings fused to the 3-aminopyrazolium methyl groups at the 3-position, are described. Aminopyrazolium methyl cephalosporins (23e, f, i), with fused saturated and unsaturated rings were especially effective against Staphylococcus strains compared to 3-amino-2-methylpyrazolium methyl cephalosporin (1). Among the cephalosporins prepared in this work, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(4,5, 6, 7-tetrahydro-1-pyrazolo[1,5-a]pyrimidinio)methyl-3-cephem-4-carbox ylate (23f) showed a good balance of antibacterial activity against both Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria including P. aeruginosa. An imidazopyrazolium group at the 3-position in, for example, cephalosporin (23i) was particularly effective for improving antibacterial activity against MRSA.

Multinucleated giant cells recruited by implantation of octacalcium phosphate (OCP) in rat bone marrow share ultrastructural characteristics with osteoclasts.

The ultrastructural characteristics of multinucleated giant cells (MNGCs) on octacalcium phosphate (OCP) and hydroxyapatite (HA) were investigated in comparison with those of osteoclasts, when the synthetic OCP and HA were implanted in rat bone marrow. The morphological difference in the MNGCs were shown between OCP and HA implants in 2 weeks after implantation. The MNGC on the implanted OCP (i-OCP) developed the ruffled border-like structure and the clear zone-like structure. The i-OCP was frayed where it was in contact with the ruffled border-like structure. The MNGC on the implanted HA (i-HA) developed the clear zone-like structure, whereas no ruffled border was seen. The surface of i-HA associated with the MNGC was smooth and not frayed. Bone formed directly on the OCP or HA implants. The interface between the i-OCP and bone matrix interdigitated, whereas that between the i-HA and bone matrix was comparatively smooth. The present study suggested that the i-OCP could be resorbed by the MNGCs which share some ultrastructural characteristics with osteoclasts.

A case of hemangiopericytoma of the buccal mucosa.

We report a 46-year-old woman who presented with a hemangiopericytoma in the buccal mucosa. At the 2-year postoperative examination, there was no evidence of recurrence or metastasis. The findings in the present case are compared with previous reports in the Japanese literature, with regard to patient age and sex, and lesion size, location, malignancy, local recurrence and metastasis.