Search PubMed⌕ Search

Biomedical subjects

H Nagano

Publications and source records attributed to H Nagano.

At least 127 records · Page 7Linked to original sources

Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy group at the 8 position in mice irradiated with long-wavelength UV light.

A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy group was substituted at the 8 position of the quinoline nucleus, was very stable under irradiation with long-wave UV light (UVA). Derivatives, a fluoroquinolone with no substitution (the 8-H analog) and one in which a fluorine was substituted (the 8-F analog), were degraded in their solutions by the UVA irradiation. The phototoxic inducibility by these derivatives was further studied in a murine model. When mice were dosed orally with 800 mg of Q-35 (8-OCH3) per kg of body weight, the maximum dose given, and exposed to the UVA light, no inflammatory lesions were observed in their ears. Ear redness was marked in mice given more than 12.5 mg of the 8-F analog or 200 mg of the 8-H analog per kg. Histopathological changes, edema, and infiltration of neutrophils were also observed microscopically in groups receiving the 8-H or 8-F analog but not in groups receiving Q-35 (8-OCH3). Similar inflammatory reactions were observed to occur in a dose-dependent manner with other available fluoroquinolone antibacterial agents such as lomefloxacin, enoxacin, norfloxacin, ciprofloxacin and ofloxacin. These results suggest that the introduction of a methoxy group at the 8 position of the quinolone nucleus is important for the reduction of phototoxicity.

Absorption↗

[Pharmacological studies on human urinary kallidinogenase (SK-827): cerebral protective effects].

We investigated the cerebral protective effects of human urinary kallidinogenase (SK-827) in rabbits. The following results were obtained: 1) At a dose of 5.0 x 10(-3) to 1.25 x 10(-2) PNA U/kg, SK-827 significantly inhibited the decrease of focal cerebral blood flow and the impairment of electrocorticogram (ECoG) activity in infarcted rabbits. 2) SK-827 at a dose of 2.5 x 10(-3) PNA U/kg inhibited the development of infarction area induced by internal carotid arterial injection of glass beads. 3) SK-827 at a dose of 2.5 x 10(-3) to 5.0 x 10(-3) PNA U/kg inhibited the decrease of cerebral cortical pO2 induced by 5% oxygen inhalation. 4) On subacute phase 7 days after the destruction of internal capsule, SK-827 at a dose of 1.25 x 10(-2) PNA U/kg improved the abnormality of spontaneous ECoG. These findings suggest that SK-827 minimizes the reduction of cerebral function induced by ischemia.

Animals↗

[Pharmacological studies on human urinary kallidinogenase (SK-827): effects on cerebral metabolism].

We investigated the effects of human urinary kallidinogenase (SK-827) on cerebral metabolism in normal and infarcted rabbits. SK-827 did not influence cerebral glucose and oxygen uptake in normal rabbits. In infarcted rabbits, cerebral glucose and oxygen uptake significantly decreased. SK-827 tended to inhibit the decrease of cerebral blood flow, and significantly inhibited the decrease of cerebral glucose and oxygen uptake in infarcted rabbits. Thus, SK-827 improved cerebral glucose metabolism in infarcted rabbits.

Animals↗

Dot-blot hybridization using digoxigenin-labeled cDNA probe complementary to the S1 gene of avian infectious bronchitis virus permits discrimination between virus strains.

Digoxigenin-dUTP-labeled DNA probe was prepared from a cDNA clone complementary to the gene encoding S1 region of the spike protein of infectious bronchitis coronavirus (IBV) strain M41. The probe exclusively reacted with four strains at 56 degrees C which were grouped to the same serotype as the strain used for the probe. In contrast, at 68 degrees C, the probe reacted only with the homologous strain and did not react even with the strains belonging to the same serotype. The dot-blot hybridization thus appeared serotype-specific at 56 degrees C and strain-specific at 68 degrees C. In addition, it was revealed that the S1 gene has some nucleotide sequence variation even among strains in the same serotype. This technique should be applied to determining serotypes of the virus isolates and to differentiating field isolates from the vaccine strain.

Animals↗

Photostability and biological activity of fluoroquinolones substituted at the 8 position after UV irradiation.

Q-35 [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methylaminopiperid ine-1-yl)-4-oxoquinoline-3-carboxylic acid], a fluoroquinolone, has absorbance peaks at 333 and 286 nm. No spectral change was observed even when this aqueous solution was irradiated with 3 J of long-wavelength UV light (UVA) per cm2. On the other hand, its derivatives, which are unsubstituted (8-H analog) or which are substituted with fluorine at the 8 position (8-F analog), were found to have decreased antibacterial activities with a simultaneous increase in their cytotoxicities when they were degraded in a dose-dependent manner with respect to UVA irradiation. Similar results were observed with the other available fluoroquinolones. Enoxacin and lomefloxacin exposed to 0.3 J of irradiation per cm2 and norfloxacin, ofloxacin, and ciprofloxacin exposed to 1 J of irradiation per cm2 underwent absorption spectrum changes, an accompanying decrease in antibacterial activity, and an increase in cytotoxic activity. These results suggest that the introduction of a methoxy group into the 8 position of quinolones plays an important role in the stability of fluoroquinolones against irradiation by UV light.

Animals↗

Cerebral microcirculatory changes after cerebral embolization induced by glass bead injection in rabbits.

The authors investigated microcirculatory changes in cerebral embolization induced by an injection of glass beads (mesh size 20/400, 15 mg/body) using intravital microscopy and reflectance spectrophotometry in normal rabbits. Cerebral embolization with the glass bead injection reduced the inner diameter of cerebral arterioles, the index of cerebral hemoglobin concentration (IHb), and the index of oxygen saturation (ISO2). Moreover, platelet aggregation rates and plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) appreciably increased. During observation of the pial vasculature, "white bodies" became visible at the entrance of arteriolar branchings two to three minutes after the glass bead injection. After indomethacin administration (3 mg/kg, IV), they could not observe white bodies, and platelet aggregation rates were significantly reduced. The plasma levels of TXB2 and 6-keto-PGF1 alpha were also significantly reduced. These findings suggest that glass beads do injury to the microvascular endothelial cells leading to development of white bodies, ie, "flying thrombi." Therefore, the cerebral microvascular embolization induced by the glass bead injection appears to be an experimental model for evaluating efficacy of remedies for the cerebral microcirculatory disorders.

6-Ketoprostaglandin F1 alpha↗

Morphological modifications during long-term survival of Meckel's cartilage hypertrophic chondrocytes transplanted in the mouse spleen.

To examine the ultimate fate of hypertrophic chondrocytes, Meckel's cartilage bars from 18-day-old mouse embryos were transplanted into isogenic mouse spleen for 3, 7, 14 and 21 days and observed at the light and electron microscopic levels. The midportions of these Meckel's cartilage bars were used as explants; they were characterized by many hypertrophic chondrocytes containing euchromatic round nuclei, a large amount of glycogen particles, and some vacuoles. Grafted cartilage adapted well to the splenic tissue, showing intense metachromasia around the territorial matrix. Ultrastructural observations indicated that the number of large vacuoles and glycogen aggregates in the hypertrophic cells became markedly reduced with grafting time, whereas the Golgi apparatus and rough endoplasmic reticulum were well-developed. Needle-like crystals showing initial apatite deposition appeared in association with matrix vesicles; these proliferated as time elapsed after transplantation. On day 14 after transplantation, cells displaying such various structural features as pyknotic nuclei, large vacuoles, and cytoplasmic shrinkage were noted in addition to intact hypertrophic chondrocytes. Following resorption of the calcified cartilage by multinucleated giant cells, many osteoblasts appeared along the border of the calcified matrix. Some remaining hypertrophic cells in the calcified matrix had transformed into osteocyte-like cells. On day 21, the resorbed area of the calcified cartilage was invaded by many blood vessels. Hypertrophic chondrocytes, now exposed from cellular lacunae, and the osteocyte-like cells in the calcified matrix displayed involutional changes. The present study showed that, although the hypertrophic chondrocytes in Meckel's cartilage essentially underwent regressive changes, they retained the ability to stimulate endochondral ossification within the microenvironment of the spleen. In addition, some of these cells were transformed into osteocyte-like cells.

Animals↗

Cyclic appearance of cytoplasmic NOR-silver-stained particles in sea urchin embryos.

When sea urchin embryos were subjected to nucleolar organizer region (NOR)-silver staining, densely stained particles were observed in the cytoplasm. The appearance of these cytoplasmic particles (CPs) was cell-cycle dependent. During early development, the CPs were detected at interphase, but not during mitosis; they disappeared at metaphase and reappeared at telophase. The CPs appeared periodically even when embryos were treated with cytochalasin B or aphidicolin, which inhibits the progression of cytokinesis and nuclear division, respectively. By contrast, CPs were not detected in the colchicine-treated embryos in which both cytokinesis and nuclear divisions were prevented. The CPs were observed only in the embryos whose stage was early blastula (about 6th to 7th cleavage) or earlier; no CPs were detected even at interphase in the embryos at late blastula (about 8th to 9th cleavage) or later. Electron microscopic evaluation showed CPs to be granular structures, similar to heavy bodies. Also, sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) showed that 95-kDa and 38-kDa proteins were the NOR-silver-staining proteins in sea urchin embryos. These proteins existed during the course of the cell cycles. These results suggest that (1) the cyclic appearance of the CPs or heavy bodies is closely related to the cell cycle as well as the programming of the embryogenesis, but independent of the cycle of cytokinesis and nuclear division; (2) 95-kDa and 38-kDa proteins are the major NOR-silver-staining proteins in sea urchin embryos.

Animals↗

[Postoperative change of serum protease inhibitor and C-reactive protein level--with special reference to surgical resection of liver cirrhosis].

Changes in the activities of blood protease inhibitors and acute-phase reactive substances during surgical resection of liver cirrhosis were investigated by measuring the pre- and postoperative blood concentrations of alpha 1-antitrypsin (alpha 1AT), alpha 2-macroglobulin (alpha 2MG), pancreatic secretory trypsin inhibitor (PSTI), urinary trypsin inhibitor (UTI) and C-reactive protein (CRP), in patients with liver cirrhosis who underwent hepatectomy (Group A, n = 19), those without liver cirrhosis who underwent hepatectomy (Group B, n = 6) and those without liver cirrhosis who underwent surgeries other than hepatectomy (Group C, n = 5). On examining the preoperative blood levels of protease inhibitors, Group A had an increased level of alpha 2MG and a decreased level of UTI compared to Groups B and C. alpha 1AT and CRP began to increase on the first day following hepatectomy and formed peaks on the third postoperative day. The increases were significantly higher in Group B than Group A (p less than 0.01). To investigate factors causative of these differences, alpha 1AT and CRP on the third postoperative day were compared in relation to the time of operation, amount of intraoperative bleeding, weight of the resected liver and preoperative ICGR15. alpha 1AT and CRP were significantly correlated to only preoperative ICGR15. PSTI was increased postoperatively but showed no difference between Groups A and B.

Aprotinin↗

Successful surgical management of pulmonary and adrenal metastases from hepatocellular carcinoma.

This article reports a rare case of successful surgery for both lung and adrenal metastases after hepatic resection of hepatocellular carcinoma (HCC). A 55-year-old Japanese man with a 5-year history of chronic liver disease was admitted with an elevated serum alpha-fetoprotein (AFP) value and a liver tumour detected by ultrasonography. Hepatic angiogram showed a tumour stain with the right hepatic vein as a venous drain from the tumour. He underwent posterior-inferior subsegmentectomy of the right hepatic lobe following preoperative chemoembolization. Sixteen months after the first operation, he received pulmonary resection for a solitary metastasis in the right lung. A further 10 months later, a metastatic tumour was detected in the left adrenal gland without any recurrent or metastatic foci, and he underwent left adrenalectomy as his third operation. He is still alive, 8 months after his last operation, and 34 months after hepatic resection, with a normal value of AFP and without any recurrent or metastatic foci. This may be the first report of a patient who underwent successful surgery for pulmonary and adrenal metastases of HCC.

Adrenal Gland Neoplasms↗

Injection of isolated centriolar complex to induce mitosis in starfish eggs.

When centriolar complex isolated from starfish spermatozoa was injected into starfish immature oocytes (fully grown, germinal vesicle stage) followed by treating the latter with 1-methyladenine, mitotic events such as condensation and division of chromosomes of the female pronucleus and cytokinesis following completion of meiosis were observed. No cortical reaction detected in the oocytes. Essentially the same was noted for mature oocytes (pronuclear stage) into which the centriolar complex had been injected. The oocytes that had received sperm tail fraction or buffer alone did not initiate cleavage. It would thus appear that sperm centriolar complex is significantly essential to the initiation of cleavage.

Animals↗

Mature cystic teratoma of the uterine cervix.

A rare case of extragonadal teratoma which occurred primarily in the uterus is described. The tumor developed in the uterine cervix to form a polypoid appearance, and consisted of ectodermal, mesodermal and endodermal derivatives. This is the 14th such tumor to be recorded in world literature. A review of the literature and its possible histogenesis are briefly described.

Adult↗

An outbreak of bovine ephemeral fever in Nagasaki Prefecture in 1988.

In October, 1988, bovine ephemeral fever (BEF) occurred in Nagasaki Prefecture and throughout Kyushu island, with the exception Miyazaki Prefecture. The first outbreak occurred in Hirado-shi on October 17. The total number of diseased cattle was 24 in 24 farms in Nagasaki Prefecture. The clinical findings were mainly sudden fever, anorexia, and instability in standing. The serum neutralizing antibodies against BEF virus (BEFV) rose in all infected cattle. Twelve strains of the virus were isolated in HmLu-1 cell cultures made directly from the heparinized blood of 17 infected cattle. The buffy coat was mainly collected from the samples and washed three times with phosphate buffered saline. These isolates were all neutralized by an antiserum against BEFV (Yamaguchi strain). With the aid of an electron microscope, a representative of isolates named Hirado-9 with a length of 150 nm was seen in the sample of infected HmLu-1 cell cultures. Both Hirado-9 and Yamaguchi strains reacted with antisera. The outbreak of BEF in 1988 was the first since 1971 in Nagasaki Prefecture. The result proved that BEFV can be easily isolated in HmLu-1 cell culture from the washed blood cells of infected cattle.

Animals↗