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Biomedical subjects

Y Osada

Publications and source records attributed to Y Osada.

At least 109 records · Page 6Linked to original sources

Comparative immunohistochemistry of malignant fibrous histiocytoma and sarcomatoid carcinoma of the urinary tract.

An immunohistochemical analysis using antibodies to cytokeratin, epithelial membrane antigen, alpha-1-antitrypsin, alpha-1-antichymotrypsin and factor XIIIa was performed in four cases of malignant fibrous histiocytoma and five cases of sarcomatoid carcinoma in the urinary tract. All cases of malignant fibrous histiocytoma showed positive staining for factor XIIIa, alpha-1-antitrypsin and alpha-1-antichymotrypsin. No case was positive for factor XIIIa, but one case with sarcomatoid carcinoma stained positive for alpha-1-antitrypsin and alpha-1-antichymotrypsin. All cases showed positive staining for cytokeratin and 4 cases with sarcomatoid carcinoma were positive for epithelial membrane antigen, but no cases with malignant fibrous histiocytoma were positive. Immunohistochemical analysis would thus help to distinguish malignant fibrous histiocytoma from sarcomatoid carcinoma of the urinary tract.

Aged↗

Prognostic factors and value of adjunctive nephrectomy in patients with stage IV renal cell carcinoma.

We reviewed 57 cases of Stage IV renal cell carcinoma to clarify the factors influencing prognosis and to evaluate the value of nephrectomy. Cumulative survival from the initial diagnosis was analyzed with respect to the patients' age, sex, side of primary tumor, initial performance status (PS), site of metastasis, and nephrectomy. Overall survival for the patients was 51 percent at one year, 22 percent at three years, and 11 percent at five years. Age, sex, and side of primary tumor had no influence on survival. Improved survival was correlated with good PS, metastases limited to single organ, and removal of the primary tumor. With regard to histopathologic features in nephrectomized patients, low grade and stage were correlated with longer survival. These factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma.

Aged↗

Active efflux of ofloxacin by a highly quinolone-resistant strain of Proteus vulgaris.

A clinical isolate of Proteus vulgaris, strain 881051, highly resistant to ofloxacin (MIC for ofloxacin; 800 mg/L) possessed three types of resistance mechanisms to ofloxacin. The supercoiling activity of DNA gyrase from this strain was barely inhibited by ofloxacin, the ID50 value of ofloxacin against the enzyme was 2700 times higher than that against the enzyme from a susceptible strain, P. vulgaris 08602. In the outer membrane of this resistant strain, no porin protein of 37 kDa was detectable. In the presence of carbonylcyanide m-chloro-phenylhydrazone (CCCP), we found that the accumulation of ofloxacin in the cells of strain 881051, treated with the drug, was about 40-fold higher than that in the absence of CCCP. The CCCP-induced increase in the intracellular drug was 10 and 30 times higher than those in strain 880561 (a moderately resistant strain, MIC 50 mg/L) and 08602 (a fully sensitive strain), respectively. Simultaneous treatment of the strain 881051 with ofloxacin and CCCP resulted in bactericidal synergy. These results indicated that in addition to alterations of DNA gyrase and outer membrane proteins, the active efflux, as the third mechanism, could operate the resistance of strain 881051 to ofloxacin.

Anti-Infective Agents↗

Significance of the methyl group on the oxazine ring of ofloxacin derivatives in the inhibition of bacterial and mammalian type II topoisomerases.

A study was made of the correlation between the in vitro inhibitory effects of several quinolones, including four ofloxacin derivatives, on bacterial DNA gyrase from Escherichia coli KL-16 and on topoisomerase II from fetal calf thymus. No correlation was observed between the inhibitions of DNA gyrase activity and topoisomerase II activity. On the other hand, the inhibitory effects of these quinolones against topoisomerase II were closely correlated with their inhibition of cell growth. Furthermore, among the oxazine derivatives tested, the derivative with a methyl group at position 3 in an S configuration showed the highest activity against DNA gyrase and derivatives without a methyl group on the oxazine ring were more potent against topoisomerase II than those with a methyl group. Among these derivatives, DR-3355, the S isomer of ofloxacin, showed the highest activity against DNA gyrase and low activity against topoisomerase II. These results indicate that the methyl group on the oxazine ring plays an important role in the inhibitory activities of ofloxacin derivatives for these enzymes.

Animals↗

Inhibition by quinolones of DNA gyrase from Staphylococcus aureus.

In order to clarify the mechanism of action of quinolones against Staphylococcus aureus, the subunit A and B proteins of DNA gyrase were separately purified from a crude extract of S. aureus FDA 209-P. The reconstituted enzyme exhibited ATP-dependent DNA supercoiling activity. The inhibitory effects of quinolones on the supercoiling activity of the purified enzyme were measured by the quantitative electrophoresis method (17), using plasmid DNA, pBR322 or pUB110, as substrates and expressed as the 50% inhibitory concentrations (IC50s). The IC50s of ofloxacin, DR-3355 (l-ofloxacin), ciprofloxacin, tosufloxacin, sparfloxacin, and DS-4524, a new quinolone derivative, for pBR322 were 63.0, 37.8, 30.5, 46.0, 28.5, and 3.2 micrograms/ml, respectively. These values were closely correlated with antibacterial activity (MIC), with correlation coefficients of 0.953 for pBR322 and 0.938 for pUB110. These results indicate that, in S. aureus, as in gram-negative bacteria, DNA gyrase is likely to be a major target enzyme of quinolones.

4-Quinolones↗

Inhibitory effects of quinolones on murine hematopoietic progenitor cells and eukaryotic topoisomerase II.

The in vitro inhibitory effects of 12 quinolones, including clinically available compounds such as nalidixic acid, ofloxacin and enoxacin, on the murine hematopoietic progenitor cells and topoisomerase II of fetal calf thymus were compared. The quinolones tested inhibited the proliferation of the murine cells in a dose-dependent manner, and the cytotoxicity of quinolones correlated well (r = 0.910) with their inhibitory potency against the topoisomerase II.

4-Quinolones↗

Chromosomal anomalies in cryptorchidism and hypospadias.

We have studied peripheral blood samples for chromosomal anomalies in 110 consecutive patients who had cryptorchidism and/or hypospadias. Of the patients 7 (6.4%) were found to have chromosomal anomalies. The incidence of chromosomal anomalies in patients with cryptorchidism only was 4/83 (4.8%), in patients with hypospadias only the incidence was 1/18 (5.6%) and in concomitant cases the incidence was 2/9 (22.2%). Of 69 patients with cryptorchidism and/or hypospadias who did not have any other congenital abnormalities, 3 patients (4.3%) were found to have sex chromosomal anomalies. However, of 41 patients associated with generalized congenital abnormalities including mental and growth retardation, we found 4 patients (9.8%) with autosomal anomalies. We conclude that most children with multiple associated abnormalities other than cryptorchidism and/or hypospadias should have chromosome analysis. Moreover, attention should be paid to sex chromosomal anomalies, even when patients with cryptorchidism and/or hypospadias do not have any associated generalized physical abnormalities.

Adolescent↗

Immunoreactive endothelin in human kidney.

Using a sensitive and specific radioimmunoassay for endothelin, we examined immunoreactive endothelin in human kidney tissue obtained from three necropsy and three nephrectomy cases. Immunoreactive endothelin was present in high concentrations in human kidney inner medulla (necropsy cases: 1.08 +/- 0.47 pg/mg wet weight:mean +/- SE)(nephrectomy cases: 2.77 +/- 0.46). Characterization by reverse phase high performance liquid chromatography indicated that the only immunoreactive endothelin in human kidney inner medulla is endothelin-1, although immunoreactive endothelin in rat and pig kidney inner medulla comprises both isopeptides endothelin-1 and -3, suggesting that the genetic expression of endothelin differs according to species.

Aged↗

Synthesis and biological activities of analogs of a lipid A biosynthetic precursor: 1-O-phosphonooxyethyl-4'-O-phosphono-disaccharides with (R)-3-hydroxytetradecanoyl or tetradecanoyl groups at positions 2, 3, 2' and 3'.

Two novel analogs of a biosynthetic precursor of lipid A (2) were synthesized. The one analog (3) has acyl groups identical to those of 2, and the other (4) has tetradecanoyl groups in place of the (R)-3-hydroxytetradecanoyl groups of 2. Both 3 and 4 possess an alpha-glycosidically-bound phosphonooxyethyl group in place of the alpha-glycosyl phosphate group of 2. Compounds 3 and 4 exhibited definite antitumor activity against Meth A fibrosarcoma and low toxicity in rabbits, as the original compound 2 does. The replacement of the hydroxytetradecanoyl groups with tetradecanoyl groups barely affected the antitumor activity, but slightly enhanced the toxicity in rabbits.

Animals↗

Synthesis and biological activities of lipid A analogs: modification of a glycosidically bound group with chemically stable polar acidic groups and lipophilic groups on the disaccharide backbone with tetradecanoyl or N-dodecanoylglycyl groups.

Six novel lipid A analogs were synthesized. The first two analogs, 4 and 5, have an alpha-glycosidically bound carboxymethyl or 1,3-dicarboxyisopropyl group on the disaccharide backbone with four tetradecanoyl groups. The next three analogs, 6, 7 and 8, have two or four N-dodecanoylglycyl groups on the 1-alpha-O-phosphonooxyethylated disaccharide backbone. Analog 6 bears N-dodecanoylglycyl groups on the hydroxyl functions at positions 3 and 3', and tetradecanoyl groups on the amino functions at positions 2 and 2'. Analog 7 is a 2, 3, 2' and 3'-tetrakis(N-dodecanoylglycyl) derivative, and analog 8 resembles compound 6, but the binding of the N-dodecanoylglycyl and tetradecanoyl groups at positions 2, 2' and 3, 3' are reversed. The third analog, 9, has the same acyl group configuration as compound 6, but has a 1,3-dicarboxyisopropyl group at position C-1. Compounds 4 and 5 exhibited definite antitumor activity against Meth A fibrosarcoma, indicating that the phosphate group at the C-1 position in lipid A could be replaced by the carboxylic acid without reducing the antitumor activity. In rabbits, compounds 6 and 9 exhibited potent antitumor activity, but their toxicity was extremely low. On the other hand, compounds 7 and 8 showed no antitumor activity. The levels of antitumor activity of 6 and 9 were similar to those of the natural-type lipid A. The antitumor activities of analogs with a N-dodecanoylglycyl group on the disaccharide backbone depended on the connecting sites of the acyl groups.

Animals↗

Stimulatory effect of romurtide on hematopoiesis in monkeys.

Repeated subcutaneous injections of romurtide (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18), muroctasin; CAS 78113-36-7), a synthetic muramyl dipeptide derivative, increased significantly the number of peripheral neutrophils and monocytes in a dose-dependent fashion in healthy cynomolgus monkeys (Macaca fascicularis). The number of platelets was also increased significantly in monkeys with repeated dosing of romurtide. After single dosing of romurtide (1 mg/head), neutrophils counts showed a marked increase within 24 h and at 120 h after romurtide injection. Monocytes counts were decreased transiently until 8 h, but were increased persistently from 48 to 120 h after injection. Lymphocytes counts were stable throughout the experimental period except for a significant decrease until 24 h. In addition, romurtide stimulated blood neutrophils and monocytes in vivo for enhanced chemiluminescence (CL) responses to opsonized Escherichia coli. When peripheral monocytes from monkeys were incubated with various concentrations of romurtide in vitro, production of colony-stimulating factors (CSFs), interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cells was enhanced significantly, indicating that the augmenting effects of romurtide on the production of various monokines including CSFs by monocytes are involved in the mechanisms of hematopoiesis and enhanced CL generation by phagocytic cells in vivo.

Acetylmuramyl-Alanyl-Isoglutamine↗

Protective role of complement in the development of experimental pneumococcal pneumonia in mice.

To evaluate the role of complement in the lung defense against Streptococcus pneumoniae, mice decomplemented with multiple injections of cobra venom factor were challenged with type 3 pneumococci by inhalation. Without injection of cobra venom factor, the organisms were eliminated rapidly from the lungs in the majority of mice, accompanied by a significant but transient decrease in the serum C3 level. Focal pneumonia developed occasionally in some mice retaining the organisms in the lungs. By decomplementation with cobra venom factor, on the other hand, pneumococci were not eliminated completely from the lungs during the early stage of infection and afterward proliferated extensively. Consequently, the mice developed typical pneumococcal pneumonia with attendant bacteremia, while the serum C3 level has recovered compensatory during the course of infection. Thus, the complement was indicated to play an important role in the lung defense against pneumococci in mice, especially during the early stage of infection.

Animals↗

Evaluation of flow electromyography in patients with benign prostatic hyperplasia.

Combined uroflowmetry and external sphincter electromyography studies were done both preoperatively and postoperatively in patients with benign prostatic hyperplasia. In 56 patients preoperative electromyography during voiding showed silent or markedly suppressed activity in 41 patients (73.2%), while the remaining 15 patients (27.8%) revealed active electromyography. In the postoperative studies, 12 patients revealed active electromyography even after the release of obstruction. The urine flow rate following operation was not drastically improved in the active electromyography group compared to the silent electromyography group. We suppose that long-term urethral obstruction with prostatic adenoma could influence the function of relaxation of the external sphincter muscle in some patients with benign prostatic hyperplasia.

Aged↗

Bilateral pararenal lymphatic cysts associated with hypertension.

A case of bilateral pararenal lymphatic cysts is reported. These cysts surrounded the renal parenchyma in a multilobulated fashion and were contained in the intracapsular space. The lymphangiography showed the communication between cysts and lymphatic channels. Histopathological findings suggested the possible nature of this lesion to be congenital lymphatic anomalies.

Child↗