Colonic stenosis after severe methicillin-resistant Staphylococcus aureus enterocolitis in a newborn.
Explore the source record for details and available documents.
Colonic Diseases↗
Biomedical subjects
M Takada
Publications and source records attributed to M Takada.
Possible role of aldosterone and T(3) in development of amiloride-blockable SCC across frog skin in vivo.
There are inconsistencies between the in vitro and in vivo effects of thyroid hormone and aldosterone (Aldo) on the development of an amiloride-blockable short-circuit current (SCC) across bullfrog skin [Takada, M., H. Yai, and K. Takayama-Arita. Am. J. Physiol. 268 (Cell Physiol. 37): C218-C226, 1995]. To address this issue, tadpoles were raised in Aldo + T(3). An amiloride-blockable SCC developed across the skin before forelimbs appeared. Noise analysis of the characteristics (single-channel current, blocking and unblocking rate coefficients, and apparent dissociation constant) of this amiloride-blockable Na(+) channel showed that it really was of the adult type. A similar SCC developed at stage XIX in the skin of tadpoles raised with Aldo alone. These results strongly support our hypothesis that the crucial hormone in the development of this SCC is Aldo but that a suppression mechanism attenuates its effect on SCC development until it is removed by the increase in the serum concentration of thyroid hormone (which starts at stages XVIII-XIX in vivo).
Acetylcholine↗
Phase I/II study of vinorelbine, mitomycin, and cisplatin for stage IIIB or IV non-small-cell lung cancer.
PURPOSE: To determine the maximum-tolerated doses (MTDs) of vinorelbine (VRB), mitomycin (MMC), and cisplatin (P), given in two courses every 28 days to previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: At least three or four patients were entered at each dose level. The starting dose was 20 mg/m(2) for VRB on days 1 and 8 and 4 mg/m(2) for MMC on day 1, with a fixed dose of P 80 mg/m(2) on day 1 every 4 weeks. MMC was increased to 6 mg/m(2) at dose level 2 and subsequently to 8 mg/m(2) at dose level 4. At dose level 3, VRB was increased to 25 mg/m(2). Twenty-five patients were entered onto the phase I study and 19 patients were entered onto phase II study. RESULTS: Nadir leukocyte and platelet counts decreased at each dose level. At dose levels 1 and 2, the dose-limiting toxicity (DLT) was not seen, but at dose levels 3 and 4, DLT was encountered in two patients. Nearly half the patients at dose level 4 had dose reduction due to grade 4 leukopenia. A mathematic model of all toxicity suggested that dose level 4 (VRB 25 mg/m(2) on days 1 and 8 and MMC 8 mg/m(2) and P 80 mg/m(2) on day 1, every 4 weeks) would be the recommended dose for phase II study at which grade 4 toxicity is expected in </= 25% of patients over two courses. Of the 25 assessable patients in the phase I study, 13 achieved a partial response and one had a complete response for a response rate of 56. 0%. Of the 19 assessable patients in the phase II study, 12 had a partial response (63.2%; 95% confidence interval, 38.4% to 83.7%). Grade 3 and 4 leukopenia was observed in 19 (100%), and grade 3 thrombocytopenia was seen in seven (36.8%). Median survival time was 10.7 months and the 1-year survival rate was 43.2% in the 44 assessable patients. CONCLUSION: The VRB/MMC/P regimen is effective against NSCLC, and its efficacy should be confirmed through a randomized study.
Adult↗
Bioavailability and diuretic effect after administration of retarded capsules of bumetanide in human subjects.
Retarded capsules containing 1 mg bumetanide (BN) were prepared and their in vivo absorption and diuretic effect after oral administration in human subjects were studied. For comparison, commercially available tablets of BN (rapid effect) were administered orally. The mean value of the area under the plasma concentration time curve (AUC) after administration of retarded capsules was about one half that of the tablets. The mean maximum plasma concentration (Cmax) and the mean maximum urinary excretion rate of BN after administration of retarded capsules were also about one half compared to those of the tablets. Cumulative urinary volumes for 24 h, however, were not significantly different between retarded capsules and tablets. Peak times for the urinary excretion rate of BN, urine flow rate and the Cmax after administration of retarded capsules were significantly delayed compared to those of tablets. Clockwise hysteresis relationships between the urine flow rate and plasma concentration or urinary excretion rate of BN were observed after administration of retarded capsules. From these studies, retarded capsules of BN possessed a mild diuresis and its diuretic effect was maintained for a few hours after administration.
Administration, Oral↗
Different absorption behaviors among steroid hormones due to possible interaction with P-glycoprotein in the rat small intestine.
The intestinal absorption of ten steroid hormones was evaluated in the rat small intestine, especially focusing on the interaction with intestinal P-glycoprotein (P-gp). Hydrocortisone, prednisolone, 6alpha-methylprednisolone, and dexamethasone (adrenocortical steroid hormones) all disappeared in a regional-dependent manner (duodenum>jejunum>ileum). The decreased rate of disappearance in the lower small intestine seemed to be due to the involvement of absorption barriers like P-gp. In contrast, all sex hormones including progesterone exhibited very high absorbability in the entire small intestine (duodenum=jejunum=ileum), possibly demonstrating the absence of restricted absorption by intestinal P-gp. Progesterone enhanced the rate of disappearance of vinblastine but did not affect 6alpha-methylprednisolone. In the presence of vinblastine and verapamil, on the other hand, the rate of disappearance of 6alpha-methylprednisolone increased significantly. It was demonstrated that there was a plural P-gp family, which had different substrate specificities, in the rat intestine and that steroid hormones interacted with them as substrates or inhibitors in a very complex manner.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Stereoselective permeation of new fluorinated quinolone derivatives across LLC-PK1 cell monolayers.
We examined the stereoselective membrane permeation of new fluorinated quinolone derivatives (NQs) across LLC-PK1 cell monolayers, using levofloxacin (LVFX) and its R-(+) isomer. LVFX permeation was 1.6-fold greater in the basal-to-apical direction than that in the apical-to-basal direction, suggesting that LVFX permeated LLC-PK1 cell monolayers in a secretory-oriented manner. In contrast to LVFX, the permeation of the R-(+) isomer was almost identical in both directions. LVFX permeation in the basal-to-apical direction was significantly reduced in the presence of guanidine, enoxacin, and L-arginine, whereas tetraethylammonium, D-arginine, D- and L-lysine had no effect on the basal-to-apical permeation of LVFX. Basal-to-apical permeation of the R-(+) isomer was not affected by these compounds. Cellular accumulation of LVFX was inversely increased when guanidine suppressed the appearance of LVFX in the apical medium in a concentration-dependent manner. These results imply that the inhibitory effect of guanidine on the basal-to-apical permeation of LVFX involves the permeation process across the apical membrane. Guanidine trans-stimulated the efflux of LVFX from LLC-PK1 cells but did not affect cimetidine efflux. These results suggest that some NQs, like LVFX and its R-(+) isomer, are stereoselectively secreted across LLC-PK1 cell monolayers and that an organic cation transport system, which favors guanidine as a typical substrate, may be involved in the secretory-oriented permeation of some NQs.
Animals↗
[Decreased plasma levels of omeprazole after coadministration with magnesium-aluminium hydroxide dry suspension granules].
Plasma levels of omeprazole (OPZ) in Japanese male subjects were compared after a single oral administration of 20 mg of OPZ enteric-coated tablets with and without coadministration of Maalox (MLX suspension) or Maalox dry suspension granules (MLX granules). After coadministration of MLX granules, plasma levels of OPZ markedly decreased, and area under the blood concentration-time curve (AUC) decreased to 26% of that of OPZ alone. In contrast, only a slight decrease in AUC was observed after coadministration of OPZ and MLX suspension. Both MLX suspension and MLX granules exhibited similar degrees of the inhibitory effect on the renal excretion of levofloxacin. It was suggested that a specific and unexpected drug interaction occurred between OPZ enteric-coated tablets and MLX granules via a distinct mechanism from that reported for fluoroquinolones and MLX suspension.
Administration, Oral↗
The contribution of nitric oxide to diuretic and natriuretic effects of renal kinins in normotensive rats.
We have reported that diuresis and natriuresis due to increase in renal kinins induced by the neutral endopeptidase 24.11 (NEP) inhibitor were attenuated by nitric oxide (NO) synthase inhibitor. To further clarify the water-sodium excretory mechanism of renal kinins, we estimated NO2+NO3 (NOx) and cGMP in plasma and urine with and without a specific NEP inhibitor, thiorphan. P-aminohippuric acid (PAH) and inulin were injected into male Sprague-Dawley rats. Vehicle (n = 8) or thiorphan (30 mg/kg, n = 10) was injected after the control period. Mean blood pressure (MBP), plasma and urinary PAH, inulin, NOx and cGMP, urinary volume (UV) and urinary sodium excretion (UNaV) were measured before and after injection of the reagents. MBP, renal plasma flow and glomerular filtration rate were not affected by thiorphan. Plasma NOx and cGMP with thiorphan did not differ from the vehicle, while urinary NOx and cGMP increased. None of the variables were affected by vehicle. UV and UNaV were higher with thiorphan than with vehicle. Positive correlation was found between urinary deltaNOx and deltacGMP. Each urinary deltaNOx and deltacGMP was significantly correlated to both deltaUV and deltaUNaV. Urinary NOx and cGMP were increased while maintaining correlations to UV and UNaV, but plasma NOx and cGMP were not affected by thiorphan. This implies that the mechanism of water-sodium excretion induced by NEP inhibitor is mediated by renal NO. Therefore, renal NO may contribute to the diuretic and natriuretic effects of renal kinins.
Animals↗
Does Group B streptococcal sepsis attenuate endogenous nitric oxide synthesis in neonates?
Explore the source record for details and available documents.
Age Factors↗
[Quantification of cerebral blood flow using 123I-IMP SPECT--a new method of estimating the input function from brain dynamic data].
In order to avoid continuous arterial blood sampling, we estimated input function by the method in that the whole brain time activity curves were fitted by two-term exponential function and differentiated analytically after the injection of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). This method was applied to 4 patients with cerebral infarction and 2 patients with brain tumor. Values of regional cerebral blood flow (rCBF) were calculated from the input function calibrated by one-point arterial sampling at 5 minutes after the injection using microsphere method, and then were compared with those obtained from the table-lookup method. In this study, we used the individual input function for the table-lookup method instead of the standard input function. The overall accuracy errors between two-term exponential functions and the whole brain time-activity curves were about 1%. The values of rCBF calculated by this method were well correlated with those by the table-lookup method (r = 0.901, p < 0.001). Optimal calibration time for this method was between 3-minute and 10-minute after 123I-IMP injection and the deviation of the rCBF values obtained by this method from those obtained by the table-lookup method in which the input function was calibrated at 5 minutes remained within 10%. This method is a less invasive and convenient alternative to the conventional methods which require continuous arterial blood sampling.
Adult↗
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↗
The impact of extranodal spread of lymph node metastases in patients with oral cancer.
A retrospective study of 61 patients with histologically confirmed lymph node metastases was undertaken to evaluate the prognostic significance of extranodal spread (ENS) of metastases on the patterns of treatment failure and survival. ENS was present in 28 (46%) of the 61 patients and it was significantly associated with N stage. T stage, clinical stage, number of positive nodes, level of metastases, mode of treatment, and histological differentiation, however, did not influence the incidence of ENS. The 5-year disease-specific survival rate was 57%. The values for patients with and without ENS were 40% and 72%, respectively, which were statistically significant. The univariate analysis showed that the presence of ENS was a significant predictor of patient survival (P = 0.008). The number and level of positive nodes and postoperative radiotherapy had no prognostic importance. ENS, however, was also associated with an increased risk of distant metastases.
Adult↗
[Sensitivity of sputum eosinophil cationic protein level for monitoring asthmatic patients with normal peak expiratory flow].
Previous studies have shown that eosinophils and eosinophil cationic protein (ECP) levels in the sputum of patients with asthma closely reflect inflammatory activity of the bronchial mucosa. We examined whether the ECP level or eosinophil count in induced sputum provides information useful in determining whether to taper the dose of medications or to terminate treatment especially with inhaled corticosteroids in patients with well controlled asthma. We studied 15 adults with asthma who consistently maintained a peak expiratory flow (PEF) value within 80% or more of their predicted value (green zone) for at least 4 weeks with no asthmatic symptoms. All patients underwent at least two hypretonic saline inhalation tests. Forty sputum samples were obtained for evaluation of cell count and ECP level. Before the tests, patients were requested to record asthmatic symptoms, medications received, and morning and evening PEF values in a diary for more than 3 months. The relations among clinical and laboratory variables, including symptoms scores, medication scores, asthma scores (= symptom scores + medication scores). PEF values, forced expiratory volume (FEV1.0) during the test, and sputum eosinophil count or sputum ECP, were analyzed. The sputum ECP level correlated significantly with the percentage of eosinophils in the sputum (rs = 0.783). There were also significant correlations between the sputum ECP level and the mean weekly symptom scores (rs = 0.500-0.510), medication scores (rs = 0.510-0.540), and asthma scores (rs = 0.509-0.548). However, there were no significant correlations among sputum ECP level, mean morning PEF or evening PEF, daily variation in PEF, and FEV1.0. We conclude that the sputum ECP level is a sensitive laboratory variable useful in monitoring the presence of eosinophilic inflammation in the bronchial mucosa of patients with bronchial asthma, especially those who have mild or no symptoms with normal PEF.
Adult↗
Bilateral involvement of hands and legs in the Gollop-Wolfgang complex.
Explore the source record for details and available documents.
Female↗
Requirement of caspase-3(-like) protease-mediated hydrogen peroxide production for apoptosis induced by various anticancer drugs.
Caspase-3(-like) proteases play important roles in controlling mammalian apoptosis. However, the downstream events from the caspase-3(-like) protease activation to death of cells are still unclear. Previously, we reported that hydrogen peroxide (H2O2) was generated by the activation of caspase-3(-like) proteases in the process of tyrosine kinase inhibitor-induced apoptosis in human small cell lung carcinoma Ms-1 cells. In the present study, we examined whether generation of H2O2 is a critical event for the apoptotic pathway downstream of caspase-3(-like) protease activation by various anticancer drugs. Anticancer drugs such as camptothecin, vinblastine, inostamycin, and adriamycin induced activation of caspase-3(-like) proteases and apoptosis. Generation of H2O2 was commonly detected after treatment with each of the four anticancer drugs, and scavenging of H2O2 caused cells to fail to undergo apoptosis. Moreover, anticancer drug-induced H2O2 production was inhibited not only by an inhibitor of caspase-3(-like) proteases but also by diphenyleneiodonium chloride, an inhibitor of flavonoid-containing enzymes such as NADPH oxidase. However, activation of caspase-3(-like) proteases was not inhibited by diphenyleneiodonium chloride. These findings suggest that activation of caspase-3(-like) proteases by various anticancer drugs causes generation of H2O2 presumably through the activation of NADPH oxidase, thereby inducing apoptosis. Therefore, H2O2 may function as a common mediator for apoptosis induced by various anticancer drugs.
Acetylcysteine↗
Specificity of pyridinium inhibitors of the ubiquinone reduction sites in mitochondrial complex I.
Dual binding sites for pyridinium-type inhibitors in bovine heart mitochondrial complex I have been proposed (Gluck, M. R., Krueger, M. J., Ramsay, R. R., Sablin, S. O., Singer, T. P., and Nicklas, W. J. (1994) J. Biol. Chem. 269, 3167-3174). The marked biphasic nature of the dose-response curve for inhibition of the enzyme by MP-6(N-methyl-4-[2-(p-tert-butylbenzyl)propyl]pyridinium) makes this compound the first selective inhibitor of the two sites (Miyoshi, H., Inoue, M., Okamoto, S., Ohshima, M., Sakamoto, K., and Iwamura, H. (1997) J. Biol. Chem. 272, 16176-16183). Modifications of the structure of MP-6 show that a tert-butyl group on the benzene ring, a methyl group attached to the pyridine nitrogen atom, para-substitution pattern in the pyridine ring, and the presence of a branched structure in the spacer moiety are important for the selective inhibition. On the basis of the structural specificity, we synthesized a selective inhibitor, MP-24 (N-methyl-4-[2-methyl-2-(p-tert-butylbenzyl)propyl]pyridinium), which elicits greater selectivity. Characterization of the inhibitory behavior of MP-24 provided further strong evidence for the dual binding sites model.
Animals↗
Effects of explosive brain death on cytokine activation of peripheral organs in the rat.
BACKGROUND: The success rate of transplanted organs from brain-dead cadaver donors is consistently inferior to that of living sources. As cadaver and living unrelated donors are equally genetically disparate with a given recipient, the difference must lie within the donor himself and/or the effects of organ preservation and storage. We have hypothesized that irreversible central nervous system injury may up-regulate proinflammatory mediators and cell surface molecules in peripheral organs to be engrafted, making them more prone to host inflammatory and immunological responses. METHODS: Rats undergoing surgically induced acutely increased intracranial pressure (explosive brain death) were followed for 6 hr. Their peripheral tissues were examined by reverse transcriptase polymerase chain reaction and immunohistology, serum factors were assessed by enzyme-linked immunosorbent assay, and the influence of inflammatory molecules in the blood stream was determined by cross-circulation experiments with normal animals. RESULTS: mRNA expression of both lymphocyte- and macrophage-associated products increased dramatically in all tissues. Similar factors in serum were coincidentally increased; these were shown to be active in vivo by cross-circulation with normal animals. The organs of all control groups, including animals with important ischemic injury and with hemorrhagic shock, were negative. Up-regulation of MHC class I and II antigens and the co-stimulatory molecule B7 suggests increased immunogenicity of the peripheral organs. These changes could be inhibited by: (i) administration of a recombinant soluble P-selectin glycoprotein ligand-Ig, a P- and E-selectin antagonist; and (ii) a fusion protein, cytotoxic T lymphocyte antigen 4-Ig, which blocks B7-mediated T-cell co-stimulation. CONCLUSIONS: Activation of peripheral organs following explosive brain death may be caused by various interrelated events, including the effects of massive acute central injury, hypotension, and circulating factors. Almost complete suppression of these changes could be produced by biological agents. Such interventions, if reproducible in humans, could improve the quality of organs from "marginal" donors, broadening the criteria for donor acceptance.
Animals↗