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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 19 recordsLinked to original sources
PubMed2006

HRCT shows variations in appearance in disseminated tuberculosis in adults.

OBJECTIVE: To examine patterns of high resolution computed tomography (HRCT) of lungs of adults with disseminated tuberculosis (TB). DESIGN: Disseminated TB was defined as radiological involvement of all lung lobes. RESULTS: The case series illustrated wide variation in HRCT of disseminated TB. Patterns identified on HRCT included (1) miliary TB (haematogenous dissemination), (2) miliary TB with exudative reaction, (3) bronchogenic spread, (4) miliary TB mixed with bronchogenic spread, and (5) bronchogenic spread with multiple cavity formation. CONCLUSION: The HRCT patterns described allow classification of disseminated TB according to the mechanism of spread (haematogenous and/or bronchogenic) and the degree of local lung involvement (reaction or cavitation).

Aged↗
PubMed2004

Elevation of cytokeratin 19 fragment (CYFRA 21-1) in serum of patients with radiation pneumonitis: possible marker of epithelial cell damage.

Cytokeratin 19 fragment (CYFRA 21-1) level in serum have already been documented as a useful tumor marker for lung cancer. In the present study, we hypothesized that CYFRA 21-1 increases in the sera of patients with radiation pneumonitis, resulting from epithelial cell damage. We measured CYFRA 21-1 in the sera of patients with radiation pneumonitis and evaluated the correlation between CYFRA 21-1 level and severity of radiation pneumonitis as well as clinical course. We studied 16 patients diagnosed with radiation pneumonitis associated with primary lung cancer. CYFRA 21-1 levels in the sera of patients with diffuse radiation pneumonitis (n = 6) significantly increased compared to normal smokers (n = 10) or patients with local radiation pneumonitis (n = 10). CYFRA 21-1 values in sera changed according to the progression or improvement of the diffuse radiation pneumonitis. An immunohistochemical study using pulmonary tissues obtained from autopsied patients with radiation pneumonitis demonstrated that the hyaline membrane and proliferating type II pneumocytes were strongly stained by the anti-human cytokeratin 19 antibody. Our data demonstrated that CYFRA 21-1 was increased in patients with diffuse radiation pneumonitis. Since CYFRA 21-1 is widely used as a tumor marker for lung cancer, this evidence should be noted especially in irradiated patients.

Aged↗
PubMed2004

Anti-Salmonella activity of (2E)-alkenals.

AIMS: This study investigated the effect of a series of naturally occurring aliphatic (2E)-alkenals against Salmonella choleraesuis subsp. choleraesuis ATCC 35640 and evaluated their antibacterial action. METHOD AND RESULTS: A homologous series of aliphatic (2E)-alkenals from C5-C13 were tested for their antibacterial activity against Salm. Choleraesuis. The antibacterial action of (2E)-alkenals against Salm. choleraesuis increases with increasing carbon chain length. (2E)-Dodecenal (C12) was the most effective against this food-borne bacterium with minimum bactericidal concentration (MBC) of 6.25 microg ml-1 (34 micromol l-1), followed by (2E)-undecenal (C11) with an MBC of 12.5 microg ml-1 (77 micromol l-1). The activity was found to correlate with the hydrophobic alkyl chain length from the hydrophilic aldehyde group. The time-kill curve study showed that (2E)-dodecenal was bactericidal against Salm. choleraesuis at any growth stage. CONCLUSIONS: The antibacterial activity of (2E)-alkenals against Salm. choleraesuis was found to correlate with the hydrophobic alkyl chain length. The conjugated double bond is not essential in eliciting the activity but is associated with increasing it. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of their easy availability and wide distribution in many edible plants, (2E)-alkenals can be used as anti-Salmonella agents.

Alkenes↗
PubMed2004

CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis.

Pulmonary fibrosis is caused by various known and unknown aetiologies, but the key pathogenic mechanisms are still ill-defined. Chemokines are a large family of chemotactic cytokines that play pivotal roles in various inflammatory diseases. In the present study, the roles of chemokines in a rat model of radiation pneumonitis/ pulmonary fibrosis were examined. Accumulation of inflammatory cells and pneumonitis were observed on day 28, and diffuse alveolar wall thickening with extensive fibrosis was observed on day 56. In addition to the previously reported CCL2 (macrophage chemoattractant protein-1) induction, selective upregulation of CCL22 (macrophage-derived chemokine) and CCL17 (thymus and activation-regulated chemokine) were demonstrated for the first time in the irradiated lung tissues. Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages. On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients. Since these two chemokines play pivotal roles in various type-2 T-helper cell-dominant diseases, it was speculated that CCL22, and probably CCL17, are involved in the pathophysiology of radiation pneumonitis/pulmonary fibrosis and idiopathic pulmonary fibrosis through the recruitment of CC chemokine receptor 4-positive type-2 T-helper cells and alveolar macrophages.

Aged↗
PubMed2004

Thallium-201 single-photon emission computed tomography in the detection of retroperitoneal schwannoma.

We describe a patient with retroperitoneal schwannoma whose tumour was detectable by 201Tl single-photon emission computed tomography (SPECT). Physiologic uptake in the alimentary tract did not hamper the interpretation on SPECT images. Uptake by the tumour extending along the spinal nerve root was well recognised in axial and coronal images. Our results suggest that 201Tl SPECT may be useful in the detection of retroperitoneal schwannomas.

Female↗
PubMed2003

Expression of thyroid transcription factor-1 in 16 human lung cancer cell lines.

It has been suggested that thyroid transcription factor-1 (TTF-1) is frequently expressed in human lung cancer, especially in adenocarcinoma and small cell lung cancer, and the TTF-1 expression is closely related with the expression of surfactant protein. We hypothesized that TTF-1 is expressed in human lung cancer cell lines and its expression might be related to the expression of surfactant protein. To test this, expressions of TTF-1 and surfactant protein A (SP-A) were immunohistochemically evaluated in 16 human lung cancer cell lines. In addition, expressions of mRNAs for TTF-1 and SP-A were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. As a result, nuclear staining of TTF-1 was observed in two of six adenocarcinoma cell lines, none of seven small cell lung cancer cell lines, and none of three squamous lung cancer cell lines. Among the 16 cell lines, six cell lines (PC3, LC2/Ad, A549, RERF-LC-OK, HI1017, and PC9) expressed significant amounts of mRNA for TTF-1. In contrast, cytoplasmic staining of TTF-1 was observed in five of six adenocarcinoma cell lines, in six of seven small cell lung cancer cell lines, and in all three squamous cell lung cancer cell lines. One of the two adenocarcinoma cell lines those showed positive nuclear staining and cytoplasmic SP-A staining released a significant amount of SP-A in culture supernatant. Our present study demonstrates that the frequency of TTF-1 expression in the nucleus was very low in human lung cancer cell lines; however, their cytoplasmic positivities should be further investigated.

Adenocarcinoma↗
PubMed2003

Genetic susceptibility to thymic lymphomas and K-ras gene mutation in mice after exposure to X-rays and N-ethyl-N-nitrosourea.

PURPOSE: Ras activation is one of the major mechanisms for the development of murine thymic lymphomas by radiation and chemical carcinogens. To gain insight into the relationship between genetic susceptibility and ras gene mutation, the frequency and spectrum of ras gene mutation was examined in thymic lymphomas from susceptible and resistant mice. MATERIALS AND METHODS: K- and N-ras mutations in thymic lymphomas that arose in X-ray-irradiated and N-ethyl-N-nitrosourea (ENU)-treated mice of susceptible C57BL/6, rather resistant C3H and their hybrid B6C3F1 were analysed by polymerase chain reaction-single-strand conformation polymorphism and subsequent DNA sequencing. RESULTS: C57BL/6 exhibited a higher incidence of thymic lymphomas after exposure to X-rays and ENU than C3H, with B6C3F1 being intermediate. K-ras gene mutations occurred frequently in the pathogenesis of ENU-induced thymic lymphomas in susceptible C57BL/6 as opposed to resistant C3H. The ras mutations were more frequent in ENU-induced thymic lymphomas than X-ray-induced thymic lymphomas, and with the latter, there was no clear evidence for strain differences, suggesting that the genetic susceptibility to X-rays was independent of ras activation. The mutations of K-ras in thymic lymphomas from C57BL/6 were predominantly GGT to GAT in codon 12, whereas this mutation type was never found in those from C3H. No strain difference was observed in the nucleotide sequence or expression levels of O(6)-alkylguanine alkyltransferase, indicating that this enzyme did not account for the genetic susceptibility to ras activation. CONCLUSIONS: The results indicate that there is a clear strain and carcinogen dependency of K-ras mutation and that the frequency of ras mutation might determine the genetic susceptibility to ENU-induced lymphomagenesis, whereas pathways independent of ras activation might determine the susceptibility to X-ray-induced lymphomagenesis.

Alkylating Agents↗
PubMed2001

Very-long-period seismic signals and caldera formation at Miyake Island, Japan.

Over a period of roughly 40 days, starting on 8 July 2000, a caldera structure 1.7 kilometers in diameter developed by means of gradual depression and expansion of the summit crater at Miyake Island, Japan. At the same time, very-long-period (VLP) seismic signals were observed once or twice a day. Source mechanism analyses of the VLP signals show that the moment tensor solutions are smooth step functions over a time scale of 50 seconds, with dominant volumetric change components. We developed a model to explain the caldera and the VLP signals, in which a vertical piston of solid materials in the conduit is intermittently sucked into the magma chamber by lateral magma outflow. This model offers potential for making quantitative estimations of the characteristic physical properties of magma systems.

Journal Article↗
PubMed2001

Novel, potent, and selective phosphodiesterase 5 inhibitors: synthesis and biological activities of a series of 4-aryl-1-isoquinolinone derivatives.

A novel class of potent and selective phosphodiesterase 5 (PDE5) inhibitors, 4-aryl-1-isoquinolinone derivatives, which have been designed by the comparison of the structure of cGMP and a previously reported 1-arylnaphthalene lignan, was disclosed. Among these compounds, methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate dihydrochloride (36a) exhibited potent PDE5 inhibitory activity (IC(50) = 1.0 nM) with high isozyme selectivities (IC(50) ratio: PDE1/PDE5 = 1300, PDE2/PDE5 > 10 000, PDE3/PDE5 > 10 000, PDE4/PDE5 = 4700, PDE6/PDE5 = 28). Compound 36a also showed the most potent relaxant effect on isolated rabbit corpus cavernosum (EC(30) = 7.9 nM). Compound 63 (T-1032), the sulfate form of 36a, was selected for further biological and pharmacological evaluation of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Structure-Activity study of retinoid agonists bearing substituted dicarba-closo-dodecaborane. Relation between retinoidal activity and conformation of two aromatic nuclei.

We have investigated the structure activity relationships of the potent retinoid agonist, 4-[4-(2-propyl-1,2-dicarba-closo-dodecaboran-l-yl)phenylamino]benzoic acid (BR403), which we have previously reported. Substitution of a methyl group on the aromatic nucleus or a methyl group on the nitrogen atom, or replacement of the amino group with ether, methylene, carboxyl or 1,1-ethylene greatly decreased the activity. The relatively planar conformation at the phenyl-N-phenyl moiety seems to play a critical role in the appearance of the biological activity.

Animals↗
PubMed2001

Completely inverse images in dual-isotope SPECT with Tl-201 and I-123 MIBG in a patient with myocarditis.

Dual-isotope myocardial SPECT in a female patient with idiopathic myocarditis showed completely inverse images in Tl-201 and I-123 MIBG SPECT. In the dual-isotope SPECT performed 13 days after her admission, Tl-201 SPECT images showed reduced accumulation in the apex and normal accumulation in the other regions, whereas the corresponding I-123 MIBG SPECT images showed normal findings in the apex and reduced uptake in the other regions. These rare discrepancies were due to the difference in photon attenuation of the two isotopes in the apex and denervated-but-viable myocardium in the basal region, which were suggested by the following findings of gated perfusion SPECT and echocardiography. Gated SPECT with Tc-99m tetrofosmin performed 23 days after admission revealed normal myocardial perfusion and normal wall motion. Iodine-123 MIBG SPECT findings reflected impaired wall motion in echocardiography performed on admission, which resembles a phenomenon called "memory image" in coronary artery disease. The present case indicated a pitfall in interpreting dual-isotope imaging.

3-Iodobenzylguanidine↗
PubMed2001

Inexplicable suppression of hepatic uptake of gallium-67, a case report.

We describe here a case report of a patient with acute lymphocytic leukemia in whom hepatic gallium-67 (Ga-67) uptake was suppressed. The patient was hospitalized with increasing dyspnea. In Ga-67 scintigraphy, there was no hepatic uptake, although other physiological uptake was clearly observed. In addition, the scintigraphy showed increased accumulation in the right lung consistent with infection. We considered possible reasons for these findings. The patient had no history of chemotherapy or blood transfusion, and his iron metabolism was almost normal. He was not receiving any medication which might reduce hepatic blood flow. Blood chemistry suggested normal hepatic and renal function. The patient died from pneumonia 6 weeks later. The autopsy revealed extensive infiltration of the right lung with Bacillus cereus (B. cereus). Metabolic acidosis and/or iron utilization of B. cereus may induce both increased Ga-67 accumulation in the infected lesion and suppressed uptake in the liver, but these mechanisms could not explain normal physiological uptake in the other organs. This case warranted the further study of the hepatic Ga-67 uptake mechanism.

Aged↗
PubMed2001

Comparison of image reconstruction algorithms in myocardial perfusion scintigraphy.

The purpose of this study was to compare the clinical utility of two image reconstruction algorithms in myocardial perfusion SPECT (single-photon emission computed tomography): filtered back-projection (FBP) and ordered subset expectation maximization (OSEM). A rest/stress one-day protocol with 99mTc-MIBI or tetrofosmin was performed on 102 consecutive patients who underwent coronary angiography. After SPECT data acquisition, images were reconstructed with FBP and OSEM algorithms. We assessed diagnostic performance (sensitivity, specificity and accuracy) in detecting coronary artery stenosis and evaluated regional tracer uptake with a 4-point scoring system. Although there were no significant differences in diagnostic performance between FBP and OSEM reconstruction, the OSEM method yielded higher uptake in the RCA area than the FBP method by reducing the count-loss artifact due to hepatic uptake of the tracers. In addition, regional uptake in the LCX area was significantly lower in the OSEM image than in the FBP image; this phenomenon was observed mainly in patients with coronary stenosis and/or infarction in the LCX territory. In conclusion, OSEM and FBP offered comparable diagnostic performance in stress myocardial perfusion SPECT. The OSEM method contributed to reduction of the count-loss artifact in inferior and posterior walls and to easy recognition of hypoperfusion in the LCX area.

Algorithms↗
PubMed2001

C-type natriuretic peptide is synthesized and secreted from leukemia cell lines, peripheral blood cells, and peritoneal macrophages.

OBJECTIVE: C-type natriuretic peptide (CNP) is the third member of the natriuretic peptide family. Cultured endothelial cells secrete CNP, and its secretion rate from the endothelial cells is augmented by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha, which participate in the pathophysiology of inflammation. In this study, we investigated the regulation of CNP secretion from monocytes and macrophages to estimate its contribution to the progression of inflammation. MATERIALS AND METHODS: CNP secretion rates from two human leukemia cell lines (THP-1 and HL-60), human peripheral blood lymphocytes, granulocytes, monocytes, monocyte-derived macrophages, and mouse peritoneal macrophages were measured under conditions with or without stimulation. Immunoreactive CNP levels in the culture media of these cells were measured by a specific radioimmunoassay. RESULTS: The secretion rates of CNP from THP-1 and HL-60 cells were augmented according to the degree of their differentiation into macrophage-like cells under the stimulation with phorbol ester. Peripheral blood monocytes also increased the CNP secretion rate after their differentiation into macrophages. Retinoic acid elicited synergistic effects on the CNP secretion rate from HL-60 cells when administered with lipopolysaccharide, interferon-gamma, interleukin-1beta, tumor necrosis factor-alpha, or phorbol ester. In contrast, the phorbol ester-stimulated CNP secretion rate from THP-1 cells was suppressed with dexamethasone, which inhibits monocyte differentiation into macrophage. CONCLUSIONS: The secretion rate of CNP from monocytes was shown to be regulated based on the degree of their differentiation. This study provides evidence that the monocyte/macrophage system is one of the sources of CNP, especially under inflammatory conditions.

Animals↗
PubMed2001

Effects of food intake and age on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic. Comparison with cefpodoxime proxetil.

The effects of food intake and age on intestinal absorption of AS-924, a novel prodrug-type cephem antibiotic, were examined in 16 healthy adult volunteers (eight young volunteers and eight elderly volunteers) by the cross-over method, using cefpodoxime proxetil (CPOD-PR) as the control drug. The gastrointestinal absorption of AS-924 and CPOD-PR was increased slightly by food intake and the extent of increase was slightly greater after administration of CPOD-PR. The absorption of AS-924 was not affected by age, whereas intestinal absorption of CPOD-PR increased with age. In conclusion, these results confirmed that AS-924 has the unique characteristics as a novel prodrug and that its absorption is less likely to be affected by food intake and age.

Administration, Oral↗
PubMed2001

Effect of antacid pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic--comparison with cefteram-pivoxil.

The effect of pretreatment with ranitidine, an antacid, on the absorption of AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime (CTIZ), was examined in eight healthy adult male volunteers by the cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. The C(max) and area under the concentration (AUC) values and cumulative urinary excretion rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreased by 32, 38 and 37%, respectively, in the ranitidine pretreatment group whereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibiotics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affected by pretreatment with ranitidine largely due to inactivation of this antibiotic in the gastrointestinal tract at high pH rather than to a decrease in solubility. In contrast, isomerization of AS-924 was hardly induced by the elevation of pH, thus demonstrating that AS-924 was less likely to be affected by pretreatment with antacids.

Absorption↗
PubMed2001

Potent estrogen agonists based on carborane as a hydrophobic skeletal structure. A new medicinal application of boron clusters.

BACKGROUND: Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable thermal stability and exceptional hydrophobicity. Applications of the unique structural and chemical properties offered by icosahedral carboranes in boron neutron capture therapy have received increasing attention over the past 30 years. However, these features of carboranes may allow another application as a hydrophobic pharmacophore in biologically active molecules that interact hydrophobically with receptors. RESULTS: We have designed candidate estrogen-receptor-binding compounds having carborane as a hydrophobic skeletal structure and synthesized them. The most potent compound bearing a carborane cage exhibited activity at least 10-fold greater than that of 17beta-estradiol in the luciferase reporter gene assay. Estrogen receptor-alpha-binding data for the compound were consistent with the results of the luciferase reporter gene assay. The compound also showed potent in vivo effects on the recovery of uterine weight and bone loss in ovariectomized mice. CONCLUSION: Further development of the potent carborane-containing estrogenic agonists described here, having a new skeletal structure and unique characteristics, should yield novel therapeutic agents, especially selective estrogen receptor modulators. Furthermore, the suitability of the spherical carborane cage for binding to the cavity of the estrogen receptor-alpha ligand-binding domain should provide a basis for a similar approach to developing novel ligands for other steroid receptors.

Animals↗