[Potassium sparing diuretics].
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Diuretics↗
Biomedical subjects
S Hashimoto
Publications and source records attributed to S Hashimoto.
[Clinical problems in the treatment of primary central nervous system malignant lymphoma].
While the treatment of extracerebral lymphomas with the combination of chemotherapy and radiotherapy has drastically improved outcomes, the treatment of primary central nervous system malignant lymphoma(PCNSML) has been disappointing. Because of the variety of clinical presentations, progression of disease, and treatment modalities, careful inspection of factors which influence survival may suggest possible approaches for a more effective management in each case. In this report, clinical problems in the treatment of PCNSML was discussed with presenting cases experienced at Tenri hospital since 1983. There were twenty-one cases of histologically proven PCNSML. Surgical resection was undertaken in 11 patients. The remaining patients underwent biopsy only. All patients received radiation therapy. Various modality of chemotherapy was performed in 14 cases. Tumor recurrence was occurred at one or more CNS sites, including 3 patients who had meningeal relapse and one patient who also relapsed outside the CNS. The median survival time was estimated to be 15 months. Among the 9 patients alive at last contact the median length of follow up was 31.5 months(range 4 to 56 months). The following problems were presented and discussed; 1) varieties of initial clinical presentations, 2) variable recurrence patterns, metastases including CSF dissemination and extracranial metastases, 3) treatment-related leukoencephalopathy.
Adult↗
Inhibition of ATRA-induced myeloid differentiation in acute promyelocytic leukemia by a new protein tyrosine phosphatase inhibitor, 3,4-dephostatin.
We previously reported that the expression and the activity of SHP-1, a non-transmembrane protein tyrosine phosphatase (PTPase) increased during myeloid differentiation of an acute promyelocytic leukemia cell line (HT93) induced by all-trans retinoic acid (ATRA). To examine whether inhibition of SHP-1 activity attenuates myeloid differentiation, we used a new PTPase inhibitor, 3,4-dephostatin, and studied its effect on myeloid differentiation. Suppressive effects on immunoprecipitated SHP-1 phosphatase activity and myeloid cell differentiation were detected. These results suggest that SHP-1 is a substrate for 3,4-dephostatin, and that SHP-1 PTPase activity is closely related to myeloid differentiation.
Cell Differentiation↗
[Temporal and geographical variation in epidemics determined from the results of an infectious disease surveillance system in Japan description of epidemic patterns by data-based criteria for epidemic periods].
OBJECTIVE: After developing criteria for epidemic periods for 16 infectious diseases, we investigated temporal (annual and monthly) and geographical (regional) variation in epidemics. METHODS: Data from an infectious disease surveillance system for the years 1993 to 1997 were used for the analysis. The weekly number of patients per monitoring station was calculated from the data and used in developing criteria for an epidemic period. Based on these latter, we calculated the average number of epidemics occurring at each public health center in a year, an average length of the epidemic period, and the average number of patients per monitoring station reported during an epidemic period. These figures were used to explore temporal (annual, monthly) and geographical (regional) variation. RESULTS: With most diseases, the average number of epidemics occurring at a public health center was 0.3-0.5 per year and the average length of an epidemic period was 6-12 weeks. The average number of patients per monitoring station reported during an epidemic period differed according to the diseases. These indices showed that there were few annual differences, but great monthly differences, in most diseases. The average number of epidemics occurring in a public health center showed regional differences with some diseases. CONCLUSION: Temporal and geographical variation in epidemics for 16 infectious diseases was established by developing criteria for an epidemic period.
Data Collection↗
[Evaluation of social activities of the elderly in 27 regions with use of the 'check list for vivid social activities'].
PURPOSE: The aim of this study was to determine the utility of a 'Check list for vivid social activities (Check list)' developed for self-evaluates of social activities by the elderly. In this study, two surveys were made. First, the usefulness of the 'Check list' was evaluated by the person in charge of health and welfare for elderly in each region. Then a survey of the elderly using the 'Check list' was made in some regions to further assess its. METHODS: 1. We conducted a study of 3,255 cities, towns and villages in Japan using a mailed questionnaire. 2. About 4,100 elderly 65 years of age or older from 27 regions filled in the 'Check list'. The participants belonged to various groups such as those receiving physical care and senior citizen organizations. RESULTS: 1. One thousand four hundred and seventy (45.2%) cities, towns and villages responded to our questionnaire. About 50% of those were in favor regarding 'the utility of the Check list' and 'ease of filling in the Check list'. About 25% of them were in favor in terms of 'the efficiency of the Check list for making elderly initiate some social activities'. Forty-four percent of them answered that they intended to take advantage of the 'Check list'. 2. By comparing results from each of the 27 regions, it was possible to evaluate the levels of social activities by the locality. By comparing activities of groups composed of regions with same characteristic, it was possible to characterize social activities at the group. CONCLUSION: These finding suggest utility for the 'Check list'.
Activities of Daily Living↗
N-acetyl-L-cysteine inhibits bleomycin-induced interleukin-8 secretion by bronchial epithelial cells.
OBJECTIVE: Bleomycin (BLM) has proven effective for the treatment of cancers, but the most serious dose-limiting side-effect is the development of pulmonary toxicity. Although the precise mechanism in the pathogenesis of BLM-induced lung injury has not been determined, oxygen radicals and neutrophils are indicated to play a key role in it. Interleukin-8 (IL-8) is thought to be an important mediator of the pathogenesis of acute lung injury. METHODOLOGY: The IL-8 production from bronchial epithelial cell line, BEAS-2B cells was measured by enzyme-linked immunosorbent assays for IL-8. RESULTS: The concentrations of IL-8 were reportedly elevated in BLM-induced lung injury, suggesting the involvement of IL-8 in the pathogenesis of BLM-induced lung injury. In the present study, we showed that BLM induced the expression of IL-8 protein and mRNA in BEAS-2B cells, and N-acetyl-L-cysteine (NAC) inhibited IL-8 expression. In addition, the structurally unrelated antioxidant, pyrrolidine dithiocarbamate (PDTC) also effectively inhibited BLM-induced IL-8 production. CONCLUSION: These results suggest that anti-oxidant-sensitive mechanism might be involved in the inhibition of IL-8 secretion by BLM-stimulated bronchial epithelial cells and that NAC might be useful for the treatment of BLM-induced lung injury.
Acetylcysteine↗
[Anxiolytic effects of serotonin reuptake inhibitors and their mechanism of action].
The purpose of this study was to examine the anxiolytic effects of serotonin (5-HT) reuptake inhibitors and to clarify their action mechanisms and roles in the brain serotonergic system in the psychopathology of anxiety. It has been proposed that conditioned fear stress (CFS)-induced freezing behavior in rats could be used as a model of anxiety. In the experiment using this model, acute treatment with the 5-HT reuptake inhibitors reduced CFS-induced freezing behavior, while acute treatment with the noradrenaline or dopamine reuptake inhibitors failed to alter CFS-induced freezing. CFS elevated extracellular 5-HT levels in the medial prefrontal cortex, and this elevations of 5-HT level was followed by a resolution of the freezing. A dose of 10 mg/kg of a selective 5-HT reuptake inhibitor (SSRI), citalopram, administered 60 min before exposure to CFS increased extracellular 5-HT concentrations immediately and potently, and reduced freezing. The 5-HT1A receptor antagonists, particularly at low doses, enhanced the antifreezing effect of citalopram. While the antifreezing effect of citalopram (10 mg/kg) disappeared by prolongation of the period between conditioning and exposure to CFS, acute challenge of citalopram (10 mg/kg) reduced freezing in the rats into which citalopram (10 mg/kg) had been injected twice daily for 7 days. From these findings, it is indicated that 1) 5-HT reuptake inhibitors decrease anxiety, 2) 5-HT release is increased at the nerve terminal under anxiety conditions, 3) the elevation of 5-HT levels in the terminal has an anxiolytic action which is closely related to the pharmacological effects of SSRI-class of anxiolytics, and 4) 5-HT1A receptor antagonist enhances the antifreezing effect of SSRI by blocking the autoreceptor-mediated negative feedback mechanisms of 5-HT neurons. By prolonging the period between conditioning and exposure to CFS, the author recognized the feasibility to establish an animal model which reflects the psychopathology of anxiety disorder more precisely. Presynaptic 5-HT1A receptor desensitization may account for the mechanism of action of repeated treatment with SSRI.
Animals↗
[Radiation exposure to patient and radiologist during transcatheter arterial embolization for hepatocellular carcinoma].
PURPOSE: To evaluate radiation exposure to patients and radiologists during transcatheter arterial embolization(TAE) for hepatocellular carcinoma. MATERIALS AND METHODS: In 39 TAE procedures performed at eight institutes, skin doses were evaluated with thermoluminescence dosimeters at the patient's back(entrance surface) and lower abdomen, and at the radiologist's forehead and abdomen. Real-time dosimeters were also used to evaluate patient skin dose. RESULTS: The patients' mean entrance surface dose was 973 +/- 681 mGy(range, 185 to 3543 mGy) with the mean fluoroscopic time of 21 minutes and 6 digital subtraction angiography(DSA) acquisitions. The dose at the patients' lower abdomen was 0.98 +/- 0.77 mGy. Doses for the radiologists were 0.04 +/- 0.04 mGy at the forehead and 0.15 +/- 0.19 mGy and 0.005 +/- 0.01 mGy at the abdomen over and under the apron, respectively. Fifty-six percent of the patients' skin dose was from DSA and 44% from fluoroscopy. CONCLUSIONS: Patient skin dose may occasionally exceed the dose for transient erythema. Because a patient may have repeated TAEs, skin doses or X-ray conditions should be recorded. The exposed doses of radiologists were considered to be acceptable with proper techniques. Further efforts to reduce radiation should be directed toward both DSA and fluoroscopy.
Aged↗
[A Warthin's tumor showing extensive necrosis].
Warthin's tumors are one of the most easily recognizable tumors using light microscopy. However, histopathological diagnosis is difficult in a few cases when characteristic cystic cavities with papillary walling and underlying lymphoid stroma are obscured by reactive changes. We describe a case of an extirpated Warthin's tumor of the right parotid gland which demonstrated extensive necrosis, squamous metaplasia and xanthomatous inflammation. No characteristic structure for this tumor was noticed in a section of an initially sampled specimen. As a result, a destroyed fistula was suspected. An additional sampling was performed to confirm the diagnosis and the sampled specimen fortunately demonstrated the diagnostic structure of a Warthin's tumor excluding malignancy. An awareness of the morphological variation seen in this tumor should lead to additional sampling of specimens, thereby preventing erroneous interpretation.
Adenolymphoma↗
[Three cases of primary acute pulmonary cavitation in sarcoidosis].
Sarcoidosis has a variety of pulmonary manifestations including the nodular, or infiltrative form. However, primary cavitary formation is rare. In this report, we describe three cases of sarcoidosis with primary acute pulmonary cavitations. All three patients were young adults (2 men and 1 woman) and chest radiography and chest CT showed bilateral Hilary lymphadenopathy, multiple cavitations with thin, smooth walls, and diffuse granular shadows. Primary acute pulmonary cavitation of sarcoidosis was diagnosed, since a transbronchial biopsy specimen revealed sarcoid granuloma, and there was no evidence of infection, emphysematous change, or fibrotic or cystic bronchiectatic changes on chest radiography in any case. Corticosteroid therapy was given in all cases for severe extrathoracic disease (2 of severe uveitis and 1 of CNS involvement). After the treatment, the multiple cavities and diffuse granular shadows in the lung fields disappeared. We accordingly suggest that corticosteroid therapy is effective for primary acute cavitation in sarcoidosis.
Adult↗
Effect of subchronic lithium carbonate treatment on anxiolytic-like effect of citalopram and MKC-242 in conditioned fear stress in the rat.
We investigated the effect of citalopram [selective serotonin (5-HT) reuptake inhibitor] and MKC-242 (5-[3-¿(2S)-(1, 4-Benzodioxan-2-ylmethyl) amino¿propoxy]-1, 3-benzo-dioxol hydrochloride; a selective 5-HT(1A) receptor agonist) on the expression of conditioned freezing, an index of anxiety, following treatment with subchronic lithium carbonate (LiCO(3)). Male Sprague-Dawley rats were used in these experiments. Acute administration of citalopram (subcutaneously, s.c.) reduced freezing significantly at a high dose (30 mg/kg), while showing no effect at lower doses (3 and 10 mg/kg). Acute administration of MKC-242 (s.c.; 0.1-10 mg/kg) dose dependently reduced freezing. Subchronic LiCO(3) treatment (1 week; 0.05% or 0.2% LiCO(3) in diet; p.o.) showed no effect on freezing behavior. Acute treatment with both citalopram (3 and 30 mg/kg) and MKC-242 (1 mg/kg) after subchronic treatment with the higher, but not the lower concentration of LiCO(3) (1 week), reduced freezing markedly and significantly, as compared with either drug alone. These results suggest that subchronic LiCO(3) treatment enhanced the anxiolytic-like effects of these serotonergic drugs by facilitating central 5-HT neurotransmission at clinically therapeutic plasma lithium levels.
Animals↗
Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling.
Bruton's tyrosine kinase (Btk) is a critical component in the B-cell antigen receptor (BCR)-coupled signaling pathway. Its deficiency in B cells leads to loss or marked reduction in the BCR-induced calcium signaling. It is known that this BCR-induced calcium signaling depends on the activation of phospholipase Cgamma (PLCgamma), which is mediated by Btk and another tyrosine kinase Syk and that the SH2 and pleckstrin homology (PH) domains of Btk play important roles in this activation process. Although the importance of the PH domain of Btk has been explained by its role in the membrane targeting of Btk, the functional significance of the SH2 domain in the calcium signaling has remained merely a matter of speculation. In this report, we identify that one of the major Btk-SH2 domain-binding proteins in B cells is BLNK (B-cell linker protein) and present evidences that the interaction of BLNK and the SH2 domain of Btk contributes to the complete tyrosine phosphorylation of PLCgamma.
Agammaglobulinaemia Tyrosine Kinase↗
Serial analysis of gene expression in human monocytes and macrophages.
Monocytes/macrophages serve as sentinels involved in chronic inflammation and the eradication of various pathogens. To define molecularly the differentiation of blood monocytes into macrophages, we conducted serial analysis of gene expression (SAGE) in human blood monocytes/macrophages induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) or M-CSF. SAGE analysis of 57,560, 57,463, and 55,856 tags from monocytes, GM-CSF-, and M-CSF-induced macrophages, respectively, allowed identification of 35,037 different transcripts. Interestingly, the genes with the highest expression during differentiation from monocytes into macrophages were genes involved in lipid metabolism. Both CSF-induced macrophages expressed similar sets of genes except for several genes such as monocyte-derived chemokine (MDC), legumain, prostaglandin D synthetase, and lysosomal sialoglycoprotein. The identification of specific gene expression in human monocytes, GM-CSF-, or M-CSF-induced macrophages provides novel methods to define macrophage subsets and the maturation and activation stage of cells of macrophage lineage and, possibly, to diagnose diseases in which macrophages play a major role. This study represents the first extensive serial analysis of gene expression for any type of human hematopoietic cells.
Cells, Cultured↗
Serial analysis of gene expression in human monocyte-derived dendritic cells.
Dendritic cells (DCs) are professional antigen-presenting cells in the immune system and can be generated in vitro from hematopoietic progenitor cells in the bone marrow, CD34(+) cord blood cells, precursor cells in the peripheral blood, and blood monocytes by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4, and tumor necrosis factor-alpha. We have performed serial analysis of gene expression (SAGE) in DCs derived from human blood monocytes. A total of 58,540 tag sequences from a DC complementary DNA (cDNA) library represented more than 17,000 different genes, and these data were compared with SAGE analysis of tags from monocytes (Mo) and GM-CSF-induced macrophages (M open diamond). Many of the genes that were differentially expressed in DCs were identified as genes encoding proteins related to cell structure and cell motility. Interestingly, the highly expressed genes in DCs encode chemokines such as TARC, MDC, and MCP-4, which preferentially chemoattract Th2-type lymphocytes. Although DCs have been considered to be very heterogeneous, the identification of specific genes expressed in human Mo-derived DCs should provide candidate genes to define subsets of, the function of, and the maturation stage of DCs and possibly also to diagnose diseases in which DCs play a significant role, such as autoimmune diseases and neoplasms. This study represents the first extensive gene expression analysis in any type of DCs.
Antigen Presentation↗
Effects of conditioned fear stress on serotonin neurotransmission and freezing behavior in rats.
In an attempt to clarify the role of the brain serotonergic system in the psychopathology of anxiety, we examined the effect of a psychological stress, conditioned fear stress, on extracellular serotonin (5-hydroxytryptamine, 5-HT) concentrations in the rat medial prefrontal cortex using the method of in vivo microdialysis, while simultaneously observing conditioned fear stress-induced freezing behavior, an index of anxiety. Conditioned fear stress increased extracellular 5-HT levels in the medial prefrontal cortex, and this 5-HT level increase was followed by a resolution of the freezing behavior. A dose of 10 mg/kg of a selective 5-HT reuptake inhibitor, citalopram, administered 60 min before exposure to conditioned fear stress increased extracellular 5-HT concentrations immediately and potently, reducing freezing behavior. These findings strongly suggest that facilitation of brain 5-HT neurotransmission decreases anxiety, which is in agreement with the clinical reports that selective 5-HT reuptake inhibitors are effective in the treatment of anxiety disorders.
Animals↗
Influence of age and gender on exercise training-induced blood pressure reduction in systemic hypertension.
Regular exercise has been reported to lower blood pressure in young and older adults with essential hypertension. However, it is not known how age and gender influence the hypotensive effects of exercise. A total of 109 sedentary subjects with stage 1 or 2 essential hypertension performed exercise training at mild intensity for 8 weeks with a combination of various exercises at 22 fitness clubs. Blood pressure (BP) was reduced significantly during the program in all of the 4 exercise subgroups classified by age and gender (-15/-11 mm Hg in men aged 30 to 49 years, -10/-5 mm Hg in men aged 50 to 69 years, -16/-14 mm Hg in women aged 30 to 49 years, and -10/-6 mm Hg in women aged 50 to 69 years). There was a significant (p <0.01) age x time interaction for both systolic and diastolic BP. However, no significant gender x time interaction was observed over the same time period. After adjustment for baseline BP, exercise duration, and changes in body mass and salt intake, a significant (p <0.01) age effect difference also was observed with reduction in BP at weeks 4 and 8. There were no significant changes in any of these variables in the 42 other hypertensive control subjects. Thus, (1) a clinically significant reduction in BP was produced with the combination of various exercises performed at fitness clubs, (2) older hypertensive subjects experienced smaller reductions in BP than younger counterparts at weeks 4 and 8, and (3) gender did not influence the efficacy of physical activity for lowering elevated BP.
Adult↗
Intraoperative radiation therapy to the upper mediastinum and nerve-sparing three-field lymphadenectomy followed by external beam radiotherapy for patients with thoracic esophageal carcinoma.
BACKGROUND: In patients with thoracic esophageal carcinoma, radical dissection of the upper mediastinal lymph nodes often leads to complications such as recurrent laryngeal nerve palsy and subsequent pulmonary disorders. Intraoperative radiation therapy (IORT) to the upper mediastinum and nerve-sparing three-field lymphadenectomy followed by external beam radiotherapy has been developed to improve the locoregional control rate without resulting in these major postoperative complications. METHODS: Three-field lymphadenectomy, including cervical, mediastinal, and abdominal lymph node dissection, was performed. Dissection of the upper mediastinum was conservative to preserve recurrent laryngeal nerve function. IORT of 12-25 grays (Gy) was applied to the upper mediastinum. Postoperative radiation therapy (PORT) of 45 Gy in 16 fractions over 4 weeks was applied to the entire neck and upper mediastinum using an external X-ray beam. Between 1989-1996, 121 patients with thoracic esophageal carcinoma underwent surgery and received IORT, and 103 of these patients underwent PORT as part of their treatment schedule. RESULTS: The surgical mortality rate was 0.8% (1 of 121 cases). The overall 5-year survival rate was 34.4% and the cause specific 5-year survival rate was 54.8%. The cause specific 5-year survival rate for pN0 tumors was 79.4% and was 43.8% for pN1 tumors. No patients died with locoregional recurrence in the mediastinal lymph nodes. Recurrent laryngeal nerve palsy was observed in 25 patients (21%), but the palsy remained for > 1 month in only 13 patients (11%). Mechanical ventilation support for > 48 hours was required for 22 patients (18.2%). Fatal tracheal ulcers occurred in 4 of 18 patients who received the highest IORT dose of 25 Gy. CONCLUSIONS: Three-field lymphadenectomy to preserve recurrent laryngeal nerves and IORT using 12-20 Gy followed by 45-Gy PORT effectively reduced locoregional recurrence, recurrent laryngeal nerve palsy, and pulmonary complications caused by radical surgical dissections. The minimally effective dose of IORT appears to be < or = 15 Gy, a factor that will be further evaluated with longer follow-up.
Adult↗
Ultrasound-guided follicle aspiration: effect of the frequency of a linear transvaginal probe on the collection of bovine oocytes.
The effect of the frequency of an ultrasonic linear transvaginal probe on the collection of bovine oocytes by transvaginal ultrasound-guided follicle aspiration was investigated. Probes with different frequencies (7.5 or 5.0 MHz) were applied to examine the clarity of follicles on the monitor using ovaries of slaughtered cows in Experiment 1. The follicles were visualized on the monitor and divided into small (3- to 5-mm diameter) and large (6- to 10-mm) groups. They were also divided into 2 groups according to the clarity of their outline (clear or obscure). The number of small follicles visualized with a clear outline was greater (P < 0.01) with the 7.5 MHz probe than with the 5.0 MHz probe (9.0 vs 3.2). Oocyte aspiration from live cows was performed using the 7.5 or 5.0 MHz probe in Experiments 2 and 3. The recovered oocytes were divided into 3 categories: cumulus-oocyte-complexes (COCs), denuded oocytes and all others. In Experiment 2, the number of oocytes collected per donor cow was assessed, and in Experiment 3 the number of oocytes per aspirated follicle was examined by aspirating a constant number of follicles per aspiration session. The numbers of oocytes and COCs per donor cow obtained with the 7.5 MHz probe (11.2 and 9.0, respectively) were greater (P < 0.01) than those obtained with the 5.0 MHz probe (4.3 and 3.5). This difference between probes was due to the greater clarity of the follicle images obtained with the 7.5 MHz probe.
Animals↗