[Geriatric medicine of the 21st century--perspectives for the practice, education].
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Forecasting↗
Biomedical subjects
T Kita
Publications and source records attributed to T Kita.
[Dose finding study of paclitaxel and carboplatin for ovarian cancer (JKTB)].
We conducted a dose-finding study for combination therapy of paclitaxel (Taxol; TXL) and carboplatin (Paraplatin; CBDCA). TXL is a novel plant-derived anticancer agent that is a diterpene derivative possessing the taxane ring. The subjects were patients with ovarian carcinoma, who were evaluated by a modified Fibonacci method. The dosage of TXL was 150 to 180 mg/m2. CBDCA was administered by dose escalation from AUC = 4 to 7. The administration schedule was as follows. Pre-medication was administered before TXL was given. TXL was then administered by intravenous infusion over 3 hours, followed by CBDCA. The dose of CBDCA was determined using the Calvert formula: [AUCX (GFR + 25)]. GFR was calculated with the Jelliffe equation. The non-hematological toxicities observed in 15 eligible cases were mainly grade 1, with no grade 3 or above, and no increase in severity was observed with stepping up. The hematological toxicities were grade 3 leukopenia in 5 of 15 cases, neutropenia in 5 cases and thrombocytopenia in 0 cases. No grade 4 toxicity was observed. The lowest counts of leukocytes and neutrophils were reached after 10.8 and 11.7 days, respectively. The toxicities were reversible in most cases with subsequent recovery. The above findings indicate that the recommended dosages for TJ therapy for Japanese ovarian cancer patients should be TXL 180 mg/m2 and CBDCA at a target of AUC = 6.
Adolescent↗
[Usefulness of a simple expiratory gas monitor during sedation under spinal anesthesia].
We introduce a simple expiratory gas monitor during sedation under spinal anesthesia. A small extension tube for infusion used as a gas sampling line is placed in the nasal vestibule. It is necessary to make it sure that the point of the tube should not contact with the mucous membrane of the nose. Our method needs no special equipments such as Capnoxygen or Nazorcap, but a cheap extension tube available in any operating room. Therefore this is a simple method. Expiratory gas monitor can detect apnea early, airway obstruction and stenosis and predict PaCO2 during sedation. The change of fractional concentration of oxygen in inspired gas predicts the change of tidal volume. Increase in the former reflects a decrease in the latter under the administration of oxygen. It is possible to evaluate whether sedation became steady with analysis of respiratory pattern. However, nasal discharge may interrupt monitoring expiratory gas. Our simple method to monitor expiratory gas is useful during sedation under regional anesthesia.
Anesthesia, Spinal↗
[Oxidized fatty acid and PPAR-gamma].
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Animals↗
[Role of RAGE in the development of diabetic microangiopathy and atherosclerosis].
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Arteriosclerosis↗
Effects of carbocysteine on antigen-induced increases in cough sensitivity and bronchial responsiveness in guinea pigs.
Carbocysteine is a mucoactive drug and is being used for both acute and chronic infectious airway diseases. Although carbocysteine can repair the damage of epithelial cells caused by exposure to various agents, the effects of this agent on allergic airway diseases such as asthma and eosinophilic bronchitis with an isolated chronic cough, in both of which epithelial damage may be characteristic, is not clear. We investigated the effects of carbocysteine on antigen-induced cough hypersensitivity to inhaled capsaicin at 48 h and bronchial hyperresponsiveness to inhaled methacholine at 72 h after challenge with an aerosolized antigen in actively sensitized guinea pigs. After measuring bronchial responsiveness, we examined neutral endopeptidase (NEP) activity in the tracheal tissue. Carbocysteine (10, 30, or 100 mg/kg) was given intraperitoneally every 12 h for 3 days after antigen challenge. The number of coughs elicited by an aerosol of capsaicin (10(-4) M) was significantly (p < 0.01) decreased in carbocysteine groups (6.13 +/- 0.59 at 10 mg/kg, 4.88 +/- 0.67 at 30 mg/kg, and 4.50 +/- 0.33 at 100 mg/kg during 3 min measurement) compared with the control group (9.75 +/- 0.53). Furthermore, carbocysteine dose dependently repaired the antigen-induced decrease of NEP activity in the tracheal tissue, but it did not influence the bronchial hyperresponsiveness or bronchoalveolar lavage cell component. These findings suggest that carbocysteine promotes the repair of damaged epithelium by allergic reaction and may be useful in allergic airway diseases accompanied by isolated chronic coughing, especially eosinophilic bronchitis without asthma and tracheobronchitis with cough hypersensitivity.
Administration, Inhalation↗
[Recent trends in studies of the etiology of hypertension: New endocrine regulators of blood pressure].
The literature review reflects new aspects of humoral regulation in hypertension and target-organ damages with special regard to natriuretic peptide system(NPS) and adrenomedullin(AM). NPS and AM are recently discovered regulators which serve as antihypertensive and target-organ protective factors. These peptides have both diuretic and natriuretic properties and a relaxing effect on the vasculature. Moreover, they antagonize the proliferative and hypertrophic stimuli in the vasculature and heart. Recently, progressive technics of molecular biology clearly revealed crucial roles of these peptides for cardiovascular regulation in both normal and pathological states including hypertension and related organ damages. Natriuretic peptides, potentially AM, are new therapeutic tools for heart failure and main targets for further development of new antihypertensive drugs such as vasopeptidase inhibitor.
Adrenomedullin↗
[Transthoracic radical esophagectomy after extensive myocardial infarction].
We experienced the perioperative management of a 47 year-old patient for transthoracic esophagectomy after myocardial infarction. He was admitted to our hospital and diagnosed as having advanced esophageal cancer and he developed extensive myocardial infarction on the day of admission. Revascularization with PTCA was not successful, and circulatory support (IABP) was required for 7 days. Complete occlusion of the right coronary artery and extensive akynesis of the right ventricle occurred. Two months later, transthoracic esophagectomy was scheduled. The patient was monitored with pulmonary artery catheter during perioperative period. The postoperative course was uneventful and the patient was discharged 64 th day after the operation.
Catheterization, Swan-Ganz↗
[Monitoring of cerebral oxygenation status with near-infrared spectroscopy during inferior vena caval reconstruction under extracorporeal circulation].
We report two cases of anesthetic management with monitoring by near-infrared spectroscopy in patients with renal cell carcinoma and with adrenal cortical carcinoma, who had tumor thrombus invading into the inferior vena cava. In inferior vena caval reconstruction, extracorporeal circulation such as veno-veno bypass or cardiopulmonary bypass is frequently required. The hemodynamic unstability under extracorporeal circulation may lead to severe cerebral damage, especially in elderly patients. We monitored cerebral oxygenation state during reconstruction of the vena cava by near-infrared spectroscopy. One patient underwent surgery with veno-veno bypass and another patient with partial cardiopulmonary bypass. Oxygenated hemoglobin decreased during extracorporeal circulation, especially during the use of partial cardiopulmonary bypass compared with veno-veno bypass. However, these decreased oxygenated hemoglobin was restored rapidly at the end of extracorporeal circulation. Both patients showed no post-operative neurological complication. We concluded that near-infrared spectroscopy, which is continuous and non-invasive monitoring of cerebral oxygenation status, is one of the useful monitors during extracorporeal circulation.
Aged↗
[A case of relapsing polychondritis monitored by daily peak flow measurement].
A 55-year-old man was admitted to our hospital with dyspnea and stridor. At presentation, he also had a low grade fever, arthralgia and nasal obstruction. His chest roentgenogram showed diffuse tracheal narrowing, and chest CT revealed a thickened tracheal wall and fractured cricoid and thyroid cartilages. A diagnosis of relapsing polychondritis was made on the basis of his symptoms and in accordance with Damiani's criteria and CT findings. Daily peak flow (PEF) monitoring was carried out to assess the disease condition of the trachea. Methylprednisolone pulse therapy was started, and was followed by oral prednisolone, which improved his condition immediately, but reduction of oral prednisolone led to recurrence. The clinical course was clearly evaluated by PEF monitoring, but the change was undetectable on chest CT. Dapson, cyclophosphamide, and inhaled steroid were administered with oral prednisolone and the patient's condition has since been fair and stable. PEF monitoring may be useful for the early detection of recurrence in cases of relapsing polychondritis.
Humans↗
[Perioperative management for radical esophagectomy in a patient with polycythemia vera].
We experienced perioperative management of a 75 year-old patient with polycythemia vera (PV) who underwent transthoracic esophagectomy. After treatment for 14 days of ranimustine and hydroxycarbamid, the preoperative hemoglobin, hematocrit values and platelet count were 17.9 g.dl-1, 58% and 54 x 10(4).mm-3 respectively. During the perioperative period, phlebotomy, elastic stockings, intermittent pneumatic compression, infusion of nafamostat, and early extubation (the day of operation) were performed to prevent deep venous thrombosis. The postoperative course was uneventful and the patient was discharged 34 days after the operation.
Aged↗
Analyses by comparative genomic hybridization of genes relating with cisplatin-resistance in ovarian cancer.
Cisplatin has played a key-role in the management of ovarian cancer patients. Since the mechanisms of cisplatin-resistance have been reported to be multifactorial, it is quite difficult to predict effectiveness of cisplatin-based chemotherapy. In the present study, we have screened abnormal chromosomal regions in cisplatin-resistant and paclitaxel-resistant human ovarian cancer cell lines using comparative genomic hybridization (CGH). Increased copy number at 6q21-25 and decreased copy number at 7q21-36 and 10q12-15 were observed in the cisplatin-resistant cell line. Increased copy number at 7q11.2-21 was observed in paclitaxel-resistant cell lines. Messenger RNA of MDR1 located on chromosomal region of 7q11.2-21 was overexpressed in the paclitaxel-resistant cell lines and recognized as a potential mechanism of acquired paclitaxel-resistance. In CGH analyses of 28 primary epithelial ovarian cancer patients, gains of 1q21-22 (p = 0.0183) and 13q12-14 (p = 0.0407) were observed in significantly high abundance in the cisplatin-resistant tumor group, compared with the cisplatin-sensitive tumor group. These genetic alterations were suggested to be potential indicators for drug resistance.
Chromosome Aberrations↗
Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages.
Receptor-mediated endocytosis of oxidized low density lipoprotein (OxLDL) by macrophages has been implicated in foam cell transformation in the process of atherogenesis. Although several scavenger receptor molecules, including class A scavenger receptors and CD36, have been identified as OxLDL receptors on macrophages, additional molecules on macrophages may also be involved in the recognition of OxLDL. From a cDNA library of phorbol 12-myristate 13-acetate-stimulated THP-1 cells, we isolated a cDNA encoding a novel protein designated SR-PSOX (scavenger receptor that binds phosphatidylserine and oxidized lipoprotein), which acts as a receptor for OxLDL. SR-PSOX was a type I membrane protein consisting of 254 amino acids, expression of which was shown on human and murine macrophages with a molecular mass of 30 kDa. SR-PSOX could specifically bind with high affinity, internalize, and degrade OxLDL. The recognition of OxLDL was blocked by polyinosinic acid and dextran sulfate but not by acetylated low density lipoprotein. Taken together, SR-PSOX is a novel class of molecule belonging to the scavenger receptor family, which may play important roles in pathophysiology including atherogenesis.
Amino Acid Sequence↗
Small GTPase Rab4 regulates Ca2+-induced alpha-granule secretion in platelets.
Upon activation, platelets release many active substances stored in alpha- and dense-core granules. However, the molecular mechanisms governing regulated exocytosis are not yet fully understood. Here, we have established an assay system using permeabilized platelets to analyze the Ca(2+)-induced exocytosis of both types of granules, focusing on RabGTPases. Incubation with Rab GDP dissociation inhibitor, an inhibitory regulator of RabGTPases, reduced membrane-bound RabGTPases extensively, and caused strong inhibition of the Ca(2+)-induced secretion of von Willebrand factor (vWF) stored in alpha-granules, but not that of [(3)H]5-hydroxytryptamine (5-HT) in dense-core granules. Specifically, Rab4 co-fractionated with vWF and P-selectin (an alpha-granule marker) upon separation of platelet organelles by density gradient centrifugation. Incubation of the permeabilized platelets with cell extracts expressing the dominant negative mutant of His-tagged Rab4S22N, but not with those of similar mutant His-Rab3BT36N, inhibited the vWF secretion, whereas neither of the cell extracts affected the [(3)H]5-HT secretion. Importantly, the inhibition of vWF secretion was rescued by depleting the cell extracts of the His-Rab4S22N with nickel beads. Thus, in platelets, the regulatory mechanisms governing alpha- and dense-core granule secretions are distinct, and Rab4 is an essential regulator of the Ca(2+)-induced exocytosis of alpha-granules.
Bacterial Proteins↗
Oral immunization with size-purified microsphere beads as a vehicle selectively induces systemic tolerance and sensitization.
Oral administration of antigens has long been recognized as a method to prevent or delay the onset of diseases associated with untoward immune responses to self and non-self antigens. Although oral administration of antigens offers a convenient way to induce systemic tolerance, its therapeutic potential has been seriously limited by the fact that it requires repeated feeding of a large amount of antigens and that it may deteriorate ongoing autoimmune diseases when autoantigens are employed. We have previously shown that orally administered poly-D,L-lactic acid (PDLLA) microspheres containing an antigen were selectively distributed to Peyer's patches (PP) and systemic lymphoid tissues according to their diameter and then released the antigen over a long period of time. We now report that a single dose of intragastric immunization with a PDLLA microsphere 7-10 micrometer in diameter and containing 2 mg of OVA was as effective as 100 mg of water soluble OVA to suppress OVA-specific IgG and DTH response. This was associated with a large increase of Interferon-gamma production by PPT cells stimulated with an antigen and a small increase in secretory IgA specific to OVA. In contrast, administration of an antigen encapsulated in microspheres 3-4 microm in diameter led to an enhanced OVA-specific IgG response and no significant increase in OVA-specific secretory IgA. Thus, by utilizing microspheres of an appropriate diameter as a vaccination vehicle, we were able to selectively induce both systemic tolerance and sensitization by oral ingestion of single low dose of an antigen.
Administration, Oral↗
Junctional adhesion molecule (JAM) is phosphorylated by protein kinase C upon platelet activation.
Junctional adhesion molecule (JAM) is a member of the immunoglobulin superfamily (IgSF) expressed in tight junctions of epithelial cells and endothelial cells, and implicated in transendothelial migration of leukocytes. Recently, JAM is reported to be constitutively expressed on circulating monocytes, neutrophils, lymphocytes subsets, and platelets. However, the role of JAM is not known. Here, we examined how phosphorylaton of JAM is regulated upon platelet activation. Phosphorylation of JAM was induced by thrombin, collagen, but not by ADP. The phosphorylated amino acids were shown to be serine residues by phosphoamino acid analysis. Inhibition of JAM's phosphorylation by PKC inhibitors and Ca(++) chelator suggests the involvement of conventional types of PKCs. By in vitro kinase assays, we demonstrated that JAM could be directly phosphorylated by cPKCs. We also demonstrated phosphorylation of Ser 284, a putative PKC phosphorylation site, by immunoblotting with anti-phosphoserine-JAM antibody in thrombin-stimulated platelets. In addition to the phosphorylation, JAM seemed to form clusters at several sites of cell-cell contact in aggregated platelets by immunoelectron microscopic study. We speculate that JAM may be directly phosphorylated by cPKC(s)upon platelet activation and that the phosphorylationmight be involved in platelet activation.
Adenosine Diphosphate↗
Evaluation of the effects of alpha-phenyl-N-tert-butyl nitrone pretreatment on the neurobehavioral effects of methamphetamine.
A relationship between formation of reactive oxygen species (ROS) and energy depletion has been proposed to play an important role in mediating methamphetamine (METH)-induced neurotoxicity. To evaluate this relationship, we examined the effect of the spin-trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN) on hyperthermia and self-injurious behavior (SIB) and striatal dopamine (DA) depletion produced by METH (4 injections of 4 mg/kg, 2 hr intervals, s.c.) in BALB/c mice. Repeated administration of METH induced hyperthermia, incidence of SIB and striatal DA depletion (84% after 3 days). Pretreatment with PBN (4 injections of 60 or 120 mg/kg, i.p.) reduced METH-induced hyperthermia, but did not significantly attenuate METH-induced SIB or the striatal DA depletion. On the other hand, pretreatment with high doses of PBN (4 injections of 180 or 240 mg/kg, i.p.) protected against METH-induced hyperthermia and SIB, and PBN (180 mg/kg) also completely protected against the acute striatal DA depletion 60 min after the last injection of the drug. However, the long-lasting striatal DA depletion was only attenuated by 52 or 56%, respectively. These results indicate that METH-induced hyperthermia contributes to, but is not solely responsible for METH-induced neurotoxicity, and supports a role for formation of ROS and other mechanisms in the generation of METH-induced striatal dopaminergic neurotoxicity. In addition, the difference in the efficacy of PBN to protect against the acute or long-lasting striatal DA depletion induced by METH may indicate that both ROS formation and other mechanisms are required for METH-induced neurotoxicity to develop.
Animals↗