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Biomedical subjects

T Honma

Publications and source records attributed to T Honma.

At least 73 records · Page 4Linked to original sources
PubMed1999

Pharmacokinetics of etoposide after intrathoracic instillation to lung cancer patients with pleural effusion.

OBJECTIVE: To examine etoposide (VP16) levels in serum and pleural effusion after intravenous infusion or intrathoracic instillation to lung cancer patients. METHODS: Four patients were administered VP16 by intrathoracic instillation and three patients were administered it intravenously. Serum, urine, and pleural effusion were collected and VP16 levels in the biological fluids were determined by HPLC. Pharmacokinetic parameters were calculated. RESULTS: VP16 distributed rapidly into pleural effusion after intravenous infusion. In two of three patients, VP16 levels in pleural effusion were maintained at constant levels more than 24 hours in spite of the decline in serum VP16 levels. After intrathoracic instillation, VP16 in pleural effusion reached high levels and eliminated slowly. Serum levels of VP16 were relatively low compared with those in pleural effusion. CONCLUSION: It was demonstrated that intrathoracic instillation of VP16 might be useful for managing malignant pleural effusion and reducing systemic side-effects by cutting down the dose.

Adenocarcinoma↗
PubMed1999

Antioxidative action of flavonoids, quercetin and catechin, mediated by the activation of glutathione peroxidase.

Antioxidative action of flavonoids have been attracted attention of many investigators and a good deal of studies on it were reported. While their interests were mostly centered to the direct scavenging action of flavonoids against free radicals and active oxygen species, we expected that the interaction of flavonoids and intracellularly occurring antioxidative agents such as glutathione peroxidase (GSH-PO) could synergistically enhance their antioxidative activities. For this purpose, cultured rat hepatocytes (BL-9), which are highly expressing GSH-PO, were employed. One group of the cells were cultured with Se deficient media (Se(-) cells) to diminish the activity and the expression of GSH-PO protein and mRNA, and the other group was cultured with Se supplemented media (Se(+) cells). The oxidative cell damage was induced by the addition of H2O2 and two representative antioxidative flavonoids, quercetin and catechin, were added to the media to test their cytoprotective action. In Se(+) cells, the remarkable cytoprotective activity of those flavonoids were confirmed, whereas none of such activity was evidenced in Se(-) cells. It was proved that the intracellular antioxidative function of flavonoids requires the interaction with GSH-PO, at least in the cells expressing the enzyme. Interestingly, the flavonoid activated GSH-PO clearly, and its mechanism is discussed.

Animals↗
PubMed1998

Structural basis for chemical inhibition of human blood coagulation factor Xa.

Factor Xa, the converting enzyme of prothrombin to thrombin, has emerged as an alternative (to thrombin) target for drug discovery for thromboembolic diseases. An inhibitor has been synthesized and the crystal structure of the complex between Des[1-44] factor Xa and the inhibitor has been determined by crystallographic methods in two different crystal forms to 2.3- and 2.4-A resolution. The racemic mixture of inhibitor FX-2212, (2RS)-(3'-amidino-3-biphenylyl)-5-(4-pyridylamino)pentanoic acid, inhibits factor Xa activity by 50% at 272 nM in vitro. The S-isomer of FX-2212 (FX-2212a) was found to bind to the active site of factor Xa in both crystal forms. The biphenylamidine of FX-2212a occupies the S1-pocket, and the pyridine ring makes hydrophobic interactions with the factor Xa aryl-binding site. Several water molecules meditate inhibitor binding to residues in the active site. In contrast to the earlier crystal structures of factor Xa, such as those of apo-Des[1-45] factor Xa and Des[1-44] factor Xa in complex with a naphthyl inhibitor DX-9065a, two epidermal growth factor-like domains of factor Xa are well ordered in both our crystal forms as well as the region between the two domains, which recently was found to be the binding site of the effector cell protease receptor-1. This structure provides a basis for designing next generation inhibitors of factor Xa.

Binding Sites↗
PubMed1998

Internalization and down-regulation of human muscarinic acetylcholine receptor m2 subtypes. Role of third intracellular m2 loop and G protein-coupled receptor kinase 2.

Internalization and down-regulation of human muscarinic acetylcholine m2 receptors (hm2 receptors) and a hm2 receptor mutant lacking a central part of the third intracellular loop (I3-del m2 receptor) were examined in Chinese hamster ovary (CHO-K1) cells stably expressing these receptors and G protein-coupled receptor kinase 2 (GRK2). Agonist-induced internalization of up to 80-90% of hm2 receptors was demonstrated by measuring loss of [3H]N-methylscopolamine binding sites from the cell surface, and transfer of [3H]quinuclidinyl benzilate binding sites from the plasma membrane into the light-vesicle fractions separated by sucrose density gradient centrifugation. Additionally, translocation of hm2 receptors with endocytic vesicles were visualized by immunofluorescence confocal microscopy. Agonist-induced down-regulation of up to 60-70% of hm2 receptors was demonstrated by determining the loss of [3H]quinuclidinyl benzilate binding sites in the cells. The half-time (t1/2) of internalization and down-regulation in the presence of 10(-4) M carbamylcholine was estimated to be 9.5 min and 2.3 h, respectively. The rates of both internalization and down-regulation of hm2 receptors in the presence of 10(-6) M or lower concentrations of carbamylcholine were markedly increased by coexpression of GRK2. Agonist-induced internalization of I3-del m2 receptors was barely detectable upon incubation of cells for 1 h, but agonist-induced down-regulation of up to 40-50% of I3-del m2 receptors occurred upon incubation with 10(-4) M carbamylcholine for 16 h. However, the rate of down-regulation was lower compared with wild type receptors (t1/2 = 9.9 versus 2.3 h). These results indicate that rapid internalization of hm2 receptors is facilitated by their phosphorylation with GRK2 and does not occur in the absence of the third intracellular loop, but down-regulation of hm2 receptors may occur through both GRK2-facilitating pathway and third intracellular loop-independent pathways.

Animals↗
PubMed1998

Analysis of chimeric proteins identifies the regions in the carbohydrate recognition domains of rat lung collectins that are essential for interactions with phospholipids, glycolipids, and alveolar type II cells.

Pulmonary surfactant proteins A (SP-A) and D (SP-D) are collectins in the C-type lectin superfamily. SP-A binds to dipalmitoylphosphatidylcholine and galactosylceramide, and it regulates the uptake and secretion of surfactant lipids by alveolar type II cells. In contrast, SP-D binds to phosphatidylinositol (PI) and glucosylceramide (GlcCer). We investigated the functional region in the carbohydrate recognition domain of rat SP-A and SP-D that is involved in binding lipids and interacting with alveolar type II cells by using chimeric proteins. Chimeras ad3, ad4, and ad5 were constructed with SP-A/SP-D splice junctions at Gly194/Glu321, Gln173/Thr300, and Met134/Cys261, respectively. All three chimeras lost SP-A-specific functions. Chimeras ad3, ad4, and ad5 bound to PI with increasing activity. In contrast, chimeras ad3 and ad4 did not bind to GlcCer, whereas ad5 avidly bound this lipid. From these results, we conclude that 1) the SP-A region of Glu195-Phe228 is required for lipid and type II cell interactions, 2) the SP-D region of Cys261-Phe355 is required for optimal lipid interactions, and 3) the structural requirement for the binding of SP-D to PI is different from that for GlcCer.

Animals↗
PubMed1998

Meningeal melanocytoma in the left frontal region.

We report a rare case of meningeal melanocytoma in the left frontal region. A 45-year-old man complained of a headache. Magnetic resonance (MR) scanning showed characteristic patterns: a slightly high signal intensity mass in the left frontal region on the T1-weighted image and a low signal intensity on the T2-weighted image. The patient underwent gross total removal of the tumor. The postoperative course was uneventful. After two years, there was a small local recurrence. The histological finding of the tumor showed meningeal melanocytoma. To our knowledge, this is the second published report of a meningeal melanocytoma in the supratentorial region.

Brain Neoplasms↗
PubMed1998

Lipidized (foamy) tumor cells in a spinal cord ependymoma with collagenous metaplasia.

We report a 49-year-old woman with a spinal cord ependymoma located in the thoracolumbar region. At surgery, a soft dark-grayish tumor, which contained a hard whitish area, was removed. The specimen was a moderately cellular tumor with a central core made up of collagen nodules poor in cellular elements. Many of the tumor cells possessed ground glass-like eosinophilic cytoplasm, and frequently foamy tumor cells were evident. Perivascular pseudorosettes, ependymal rosettes and canals were present, the latter being rare. Many tumor cells, including those with foamy cytoplasm, were positive for glial fibrillary acidic protein. Similar tumor cells were also seen among, and even within, the collagen nodules. The MIB-1 labeling index was 0.66%. Ultrastructurally, the frequent lipidized tumor cells were ependymal in nature; cytoplasmic 10-nm-wide filaments, and intracytoplasmic lumina and intercellular microrosettes lined by microvilli were evident. Cilia were very rare. We considered the present case to be an unusual, lipidized variant of ependymoma. The collagen nodules appeared to be produced by the tumor cells themselves.

Collagen↗
PubMed1998

An evaluation of infants' growth in the Kingdom of Nepal.

BACKGROUND: The His Majesty's Government/Japan International Cooperation Agency Primary Health Care Project began in April 1993 in collaboration with the Saitama Prefectural Government, for the purpose of improving the health status of the people in model districts of the Kingdom of Nepal. Growth monitoring is one of the basic methods that defines the health and nutritional status of children. METHODS: Anthropometric indices were measured in 759 children in the Bhaktapur district. We used the World Health Organization prototype growth chart and national growth standard for Japanese children (1990) to analyze the growth data. RESULTS: We found that the average bodyweight growth curve of children up to 4 months of age followed the 50th percentile reference curve. For children of 5-12 months of age, there was a delay in bodyweight gain and the growth curve reached the 3rd percentile curve. For children more than 1 year old, the growth curve moved below the third percentile curve. Catch-up growth did not occur before the children reached 5 years of age. The main causes of catch-up growth being hampered were chronic undernutrition and inadequate nutritional balance. CONCLUSIONS: As this was the first opportunity to evaluate infant growth in this district, the first important consequence of the results was to analyze the causes of growth faltering and failure-to-thrive in Nepalese children. Even more important, was the need to give appropriate counseling on improving feeding and other health-related practices, and the most important consequence of all was to instruct Nepalese health workers that utilizing the growth charts is an integral part of health care.

Anthropometry↗
PubMed1998

Regulation by uniconazole-P and gibberellins of morphological and anatomical responses of Fraxinus mandshurica seedlings to gravity.

The present study deals with roles of gibberellins (GAs) in gravitropic responses of woody stems of horizontally-positioned, 2-year-old seedling of Fraxinus mandshurica Rupr. var. japonica Maxim. The application of uniconazole-P, an inhibitor of GAs biosynthesis, to stem nodes at various concentrations significantly inhibited not only righting the stems but also wood formation. The application of GAs (GA3 and GA4) in combination with uniconazole-P negated the inhibitory effect of the treatment of uniconazole-P alone. The GAs alone did not affect wood formation, however, both GAs increased wood formation on both the upper and lower sides of horizontal stems with an increase in the concentration of combined uniconazole-P. In all of the seedlings, tension wood was formed on the upper side of stems. The application of uniconazole-P alone at various concentrations did not inhibit the formation of tension wood fibres.

Dose-Response Relationship, Drug↗
PubMed1998

A rapid assay of granisetron in biological fluids from cancer patients.

A convenient high-performance liquid chromatography (HPLC) was developed for the rapid assay of granisetron (GRN) in biological fluids, such as serum, urine, and pleural effusion, from cancer patients. Extrelut-1 was used for the solid-phase extraction. HPLC was carried out using a LiChroCART cartridge column packed with Lichrospher 100 CN and a mobile phase consisting of 0.1 M acetate buffer (pH 3.5) and acetonitrile (7:3). A fluorescence detector of 290 nm for excitation and 365 nm for emission was used. The standard curve was linear over the range of 2 to 100 ng/ml of GRN. Assay precision, expressed as a coefficient of variation (C.V.), was in the range of 0.9-5.4% in the within-day assay and 2.5-6.9% in the between-day assay, respectively. GRN was well separated on the HPLC chromatogram from drugs such as etoposide, metclopramide, ondansetron, and domperidone which are often used together with GRN. It was suggested that the present method is useful for the rapid monitoring of GRN in the serum, urine, and pleural effusion of patients undergoing cancer chemotherapy.

Antiemetics↗
PubMed1998

Correlations between interleukin-8, and myeloperoxidase or luminol-dependent chemiluminescence in inflamed mucosa of ulcerative colitis.

Interleukin-8 (IL-8) is a peptide which induces not only chemotaxis of neutrophils but also the release of reactive oxygen metabolites from the neutrophils. There are few reports which clarify the relationships between IL-8 and mucosal infiltration of neutrophils or reactive oxygen metabolites produced by neutrophils in the colonic mucosa of ulcerative colitis (UC). Biopsy specimens of colonic mucosa obtained from 26 patients with active UC and 21 patients with inactive UC were studied in order to clarify the relationships among the inflammation factors in UC. Levels of IL-8 and myeloperoxidase in organ culture media of the biopsy specimens from active UC (measured by ELISA and EIA) were significantly higher than those from inactive UC and controls. Reactive oxygen metabolites of biopsy specimens in active UC (measured by luminol-dependent chemiluminescence) were also markedly increased compared to those in inactive UC and controls. The levels of IL-8 were closely correlated to luminol-dependent chemiluminescence or myeloperoxidase levels. However, the levels of IL-8 and myeloperoxidase did not correlate with the grades of activity on colonoendoscopic findings. These findings suggest that IL-8 may play a role in the pathophysiology of UC but it does not define the endoscopic activity grades of UC.

Adolescent↗
PubMed1998

Correlation of lethal doses of industrial chemicals between oral or intraperitoneal administration and inhalation exposure.

Correlations of lethal doses of industrial chemicals between oral or intraperitoneal administration and inhalation exposure in rats and mice were investigated. LC50 values for inhalation exposure and LD50 values for oral and intraperitoneal administration were obtained from the Registry of Toxic Effects of Chemical Substances. LC50 and LD50 values were plotted on ordinate and abscissa, respectively, using logarithmic scales. A correlation coefficient of r = 0.624 (n = 146, p < 0.001) was obtained for LC50 (ppm) and LD50 (mg/kg) values with oral administration (oral LD50) in rats. This correlation was improved by converting the units of LC50 from ppm to ppm h (cumulative dose), and by converting the units of LD50 from mg/kg to mmol/kg. The correlation coefficient was r = 0.742 when ppm*hr and mmol/kg were adopted for LC50 and LD50, respectively. A similar improvement in correlation coefficients by the same unit conversion was also observed between LC50 and LD50 with intraperitoneal (i.p.) administration (i.p. LD50) in rats. Correlations between LC50 and oral LD50 in mice were also improved by the same unit conversion. The correlations between LC50 and i.p. LD50 were higher than those between LC50 and oral LD50 both in rats and mice. In these correlations, coefficients obtained in rats were greater than corresponding coefficients in mice. We calculated equations to estimate LC50 values accompanied by confidence limits from oral or i.p. LD50 values.

Administration, Oral↗
PubMed1998

Influence of 2-bromopropane on reproductive system--2-bromopropane inhibits forced ovulation in mice.

The influence of 2-bromopropane, an alternative to freon, on ovulation was examined using superovulation induced by pregnant mare's serum gonadotropin and human chorionic gonadotropin (PMSG-hCG) treatment. Three groups of mice were injected intraperitoneally 8 times with 2-bromopropane (2-BP) at 500, 1,000 or 2,000 mg/kg and were induced to ovulate by PMSG-hCG treatment. Injection of 2-BP caused the number of ovulated ova in the 1,000 mg/kg and 2,000 mg/kg groups to decrease remarkably. Uterus weight was also decreased in the 2,000 mg/kg group on the terminal day of the experiment. This result was consistent with cases of human intoxication in which reproductive toxicity was observed.

Animals↗
PubMed1998

Ultrastructure of blood vessel regression in involution of foreign-body granuloma.

The diversity of endothelial cell deletion in regressing blood vessels during involution of granulation tissue was investigated in foreign-body granulomas induced by a collagen sponge implanted into the dorsum of the rat. Small blood vessel density counts were performed to determine the degree of blood vessel regression in the involution of granulation tissue in foreign-body granuloma. The density of these small blood vessels significantly decreased between 100 and 130 days after sponge implantation. The detachment of endothelial cells from their underlying basement membrane and the consequent protrusion into and/or out of the lumen in the vascular network of granulation tissue was observed by electron microscopy. Based on the pattern of manifestation in the endothelium and the characteristic deformation of nuclei, the detached endothelial cells were classified into two groups: 1) the endothelial cell apoptosis group and 2) the endothelial cell degeneration group. The essential difference between the two groups was easily distinguishable as the nucleus of the former group displayed chromatin condensation and margination as the hallmark of early apoptotic changes, while the nucleus of the latter group displayed a pinch structure and intranuclear pocket formation. However, the process by which the detached endothelial cells were shed into the vascular lumen and eventually eliminated from circulation was the same in both groups. The occurrence of both groups increased on the 90th day after sponge implantation and reached a maximum on the 110th day, indicating that the appearance of the groups was synchronized. These results suggest that the two major processes of apoptosis and degeneration of endothelial cells occur during endothelial cell deletion as a mechanism contributing to blood vessel regression.

Animals↗
PubMed1998

[Langerhans cell histiocytosis in the hypothalamus: a case report].

A case of Langerhans cell histiocytosis (LCH) in the hypothalamus is presented. A 52 year old man with eosinophilic granuloma of the lung was referred to our hospital. He complained of headache, easy fatigability, high fever, and voiding large quantities of urine, but was otherwise asymptomatic. T1-weighted images demonstrated a small mass in the hypothalamus. After about six months, the mass had grown to 2 cm in diameter. Surgery was performed by a pterional approach and a biopsy specimen was collected. Light microscopic examination of sections of the biopsy specimen showed polymorphous cellular infiltration by histiocytic cells, eosinophils, neutrophils, and lymphocytes. Electron microscopy showed Langerhans cells and Birbeck granules in the cytoplasm. The histological diagnosis was LCH, multifocal type. After low-dose radiation therapy, the mass gradually decreased in size. The clinicopathological features, neuroradiological findings, and treatment are briefly discussed.

Combined Modality Therapy↗
PubMed1998

[Collagen diseases and gastrointestinal bleeding].

The main lesion of the collagen diseases involves blood-connective tissue, so every collagen disease is a accompanied by gastrointestinal bleeding to some degrees. The concept of systemic vasculitis had been confused, but recently, the criteria for each disease has been established. In addition to these vasculitis, antiphospholipid syndrome, amyloidosis, NSAIDs, steroid and secondary infection caused by the use of immunosuppressant are the candidates for the cause of gastrointestinal bleeding in the collagen diseases. In this paper, we described concisely about the gastrointestinal bleeding in SLE, RA, and systemic vasculitis.

Anti-Inflammatory Agents↗
PubMed1997

A novel type of binding specificity to phospholipids for rat mannose-binding proteins isolated from serum and liver.

Mannose-binding protein (MBP) belongs to the collectin subgroup of C-type lectins with specificity for mannose and N-acetylglucosamine sugars. We investigated whether rat MBPs isolated from serum (S-MBP) and liver (L-MBP) interact with phospholipids using antibody against each MBP. Both S- and L-MBPs bound to phosphatidylinositol coated onto microtiter wells in a concentration- and a Ca2+-dependent manner. L-MBP also bound to phosphatidylglycerol and weakly to phosphatidylserine. MBPs interacted with liposomes composed of these lipids. S- and L-MBPs bound to phosphatidylinositol 4-monophosphate. L-MBP also bound to cardiolipin. These results provide evidence for a novel type of ligand binding specificity for MBPs, and raise the possibility that phospholipids are ligands for collectins.

Acute-Phase Proteins↗