Detailed pollution map of an area highly contaminated by mercury containing wastewater from an organic chemical factory in People's Republic of China.
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Biomedical subjects
Publications and source records attributed to Y Yasuda.
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An 8-month-old Japanese Black heifer with severe erythropoietic symptoms was subjected to clinical, histological and cytological examinations. During the 1 month clinical observation period, severe increases in RBC count, packed cell volume and haemoglobin concentration were observed. The plasma erythropoietin (Epo) concentration of the heifer (20.7 mIU/ml) was similar to that observed in normal control heifers. Blood gas examinations of the arterial and venous blood revealed low levels of partial pressure O(2) (PaO(2)), partial pressure CO(2) (PaCO(2)) and O(2) saturation (SaO(2)), while the blood pH was within the normal range. Gross lesions could not be detected. However, microscopic observation revealed severe proliferation of erythroblasts in the bone marrow and in the spleen without evidence of neoplastic changes. Based on these clinical and pathological examinations, we diagnosed the heifer as being the first case of primary erythrocytosis in Japanese Black cattle.
BACKGROUND: The surgical strategy for the treatment of colorectal cancer and synchronous hepatic metastases remains controversial. Many surgeons fear anastomotic leakage and intraperitoneal abscesses when performing a one-step procedure. They prefer a two-step procedure with a liver resection 2 to 3 months after resection of the colorectal primary lesion. SUBJECTS AND METHODS: We analysed medical records from April 1994 to April 2002 for a total of 42 patients with colorectal cancer and synchronous liver metastases who underwent simultaneous liver and colorectal resections with a primary anastomosis. Special attention was paid to data on surgical procedures, postoperative morbidity, and mortality. RESULTS: Forty-two patients, 24 men and 18 women, were studied. Median operating time was 6.50 hours (3.75-11.0 hours), and median blood loss was 1522 ml (range 288 to 5650 ml). Postoperative complications included pleural effusion in 4 patients, ileus in 3, anastomotic leakage in 2, intraperitoneal pelvic abscesses in 1, pneumonia in 1, bile leakage in 1, atelectasis in 1, and wound infection in 1. There was no perioperative mortality. CONCLUSION: Simultaneous colorectal resection with a primary anastomosis and hepatectomy for synchronous liver metastases is considered a safe procedure.
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INTRODUCTION: Self-directed learning (SDL) has been an essential issue in medical education due to the expansion of knowledge, accessibility to information and greater emphasis on reflection. If SDL in educational research lacks a clear definition, terminological confusion may hinder the application of the results to practice. The aim of this study was to review and categorise the various forms of SDL described in the contemporary literature. METHODS: A search of Medline was conducted using the key word "self-directed learning". Articles published between 2000 and 2004 were extracted. Review articles, letters and articles from health profession education other than medical education, were excluded. Sixty-three articles were analysed in 2 stages: first, whether the definition of SDL is explicitly described was investigated and next, contents in the articles on SDL were qualitatively analysed using a framework approach. The concept of a compassionate-empathic physician, as developed by Carmel and Glick (1996), was used as the framework. RESULTS: Only 5 articles (8.0%) had an explicit and concrete definition of SDL. Content analysis showed that 26 (50.0%) of the 52 articles dealt with SDL only in the scientific-technical dimension, 3 (5.8%) dealt with that only in the socio-emotional dimension and 23 (44.2%) did so in both dimensions. CONCLUSION: Although many researchers use the term "self-directed learning", only a few clearly defined it to avoid semantic confusion. Scientific-technical goals tended to be discussed more frequently in SDL. From a patient-centred viewpoint, socio-emotional goals should be stressed more.
AIM: To assess safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis for distal ulcerative colitis. METHODS: Granulocyte and monocyte adsorptive apheresis therapy (five aphereses for 5 consecutive weeks) was performed for 30 consecutive patients with active distal ulcerative colitis. Patient compliance, adverse effects and clinical symptoms were regularly assessed. RESULTS: Adverse effects were noted during nine (6%) apheresis sessions in eight patients; slight headache five, transient abdominal pain with tenesmus two, fever (38 degrees C) one and mild liver dysfunction one. None of these adverse effects was serious and all patients could complete five aphereses. Clinical symptoms (stool frequency and consistency, rectal bleeding, tenesmus and mucus in stools) significantly improved after the third apheresis. Clinical remission (normal stool frequency and no rectal bleeding) was achieved in 21 patients (70%) after five aphereses. The median Disease Activity Index score significantly decreased; from 6 [interquartile range (IQR): 4-7] to 2 (IQR: 1-3) (P < 0.0001). CONCLUSION: In the treatment of active distal ulcerative colitis, granulocyte and monocyte adsorptive apheresis is safe and well-tolerated. Granulocyte and monocyte adsorptive apheresis had a beneficial effect on clinical remission and symptoms. However, randomized-controlled trials would be necessary to assess a definite efficacy of granulocyte and monocyte adsorptive apheresis.
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BACKGROUND: We previously reported that an ambient aspartic proteinase is crucial to desquamation of the stratum corneum at pH 5. Identification of this aspartic proteinase by using enzyme inhibitors suggested it to be cathepsin D, although we could not exclude cathepsin E. OBJECTIVES: To determine the identity of this aspartic proteinase and its distribution within the stratum corneum. METHODS: We measured enzyme activities of cathepsin D and cathepsin E in the salt and detergent extracts from callus stratum corneum, using a fluorogenic peptide as a substrate and comparing the effect of addition of Ascaris pepsin inhibitor (specific for cathepsin E) with that of pepstatin A (which inhibits both cathepsin D and cathepsin E). Both enzymes were then extracted and purified from plantar stratum corneum samples and identified by Western blotting. Immunofluorescence microscopy was used to investigate the localization of proteinases within human plantar stratum corneum sample sections. RESULTS: We found that 20% of total aspartic proteinase activity could be attributed to cathepsin E, the remainder to cathepsin D. Two subunits of cathepsin D were identified, a mature active form at 33 kDa and an intermediate active form at 48 kDa; cathepsin E was also identified at 48 kDa, although in a stained band 10-fold weaker in the immunoblot. Immunofluorescence microscopy showed the antibody to cathepsin D to be localized in the lipid envelopes of the stratum corneum, whereas that to cathepsin E stained the tissue diffusely. The labelling for cathepsin D was similar to that observed for desmosomes, and immunoelectron microscopy confirmed that cathepsin D was present on desmosomes. On the other hand, cathepsin E occurred intracellularly within the squames. CONCLUSIONS: We conclude that cathepsin D, and not cathepsin E, causes desquamation by degrading desmosomes.
We report a case of tracheoesophageal fistula (TEF) secondary to chemotherapy for primary thyroid lymphoma. A 65-year-old man with a short history of a rapidly enlarging neck mass was diagnosed as having thyroid lymphoma of diffuse, large B-cell type. The TEF occurred during the first course of chemotherapy including cyclophosphamide, doxorubicin, vincristine and prednisolone. After placing a feeding gastrostomy without oral intake, eight cycles of chemotherapy were completed and complete remission was achieved. Although the cervical mass disappeared, TEF and esophageal stenosis persisted. Total thyroidectomy and resection of the stenotic cervical esophagus were carried out followed by interposition of the revascularized jejunum and its mesenteric patch to cover the TEF. This seems to be the first report of a TEF caused by chemotherapy for primary thyroid B-cell lymphoma. A variety of treatments for TEF including simple closure, tracheal resection, colonic bypass and muscle flap have been reported with low success rates. Our procedure using a jejunal mesenteric patch seems to be unique and may be a new treatment strategy for TEF.
The authors report a 14-year-old boy with Wiskott-Aldrich syndrome complicated by progressive multifocal leukoencephalopathy after allogeneic bone marrow transplantation. Several therapeutic approaches were attempted, but there was no response. The patient died 2 months after the onset of neurologic symptoms. We detected three distinct, rearranged regions of JC virus in the cerebellum, occipital lobe, and brainstem. These findings suggest that the brain lesions had three independent origins.
To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early- and/or late-onset HC (early=29, late=48, both=4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (p=0.0079, odds ratio (OD)=5.109, 95% confidence interval (CI)=1.533-17.030), busulfan (BU) (p=0.0015, OD=3.336, 95% CI=1.584-7.027), BU+CY (p=0.0001, OD=4.369, 95% CI=2.055-9.292), antithymocyte globulin (p=0.0009, OD=3.368, 95% CI=1.642-6.911), nonradiation (p=0.0163, OD=2.564, 95% CI=0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (p=0.0001, OD=7.519, 95% CI=2.847-19.858), and bladder irrigation (p=0.0001, OD=4.950, 95% CI=2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (P<0.001) than Mesna alone (p=0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (p=0.0105, OD=5.301, 95% CI=1.477-19.026) and bladder irrigation (p=0.0001, OD=9.469, 95% CI=3.872-23.156) were significant risk factors of early-onset HC. We conclude that (i). high-dose BU as well as CY is a cause of HC, (ii). protective bladder irrigation has an opposite effect, and (iii). Mesna possibly has a toxic effect on bladder mucosa.
A new advanced glycation end product (AGE), N(omega)-carboxymethyl-arginine (CMA), was found in acid-soluble skin collagen of a newborn bovine prepared by in vitro glycation with 1 M glucose incubation at 37 degrees C for about 30 days [ 1 ]. CMA production was increased with incubation time in parallel, and after 30 days incubation the yield was 100 times higher than that of pentosidine [ 1 ]. This result suggested the importance of CMA as a major AGE in collagen. We have detected and measured the CMA level in human serum proteins by electrospray ionization/liquid chromatography/mass spectrometry (ESI/LC/MS), using CMA standard concentration curve. In this report, we first show the existence of CMA in vivo, and its serum level is significantly elevated in diabetic serum proteins, compared to age-matched control serum proteins. These results provide strong evidence that CMA is a new diagnostic marker of glycation in diabetes.
Both activation of phospholipase A2 causing arachidonic acid release and tyrosine phosphorylation have been proposed to be involved in neuronal functions. Previously, we reported that orthovanadate (Na3VO4), an inhibitor of tyrosine phosphatases, stimulated tyrosine phosphorylation in proteins and enhanced Ca2+-induced noradrenaline release in rat pheochromocytoma PC12 cells. However, the role of tyrosine phosphorylation on phospholipase A2 activity and/or arachidonic acid release in neuronal cells has not been well established. The effects of Na3VO4 on arachidonic acid release and prostaglandin F(2alpha) formation were investigated in two types of neuronal cell lines. In PC12 cells, addition of Na3VO4 stimulated [3H]arachidonic acid release and prostaglandin F(2alpha) formation in a concentration-dependent manner. Co-addition of 5 mM Na3VO4 enhanced ionomycin-stimulated [3H]arachidonic acid release. Na3VO4 also enhanced ionomycin-stimulated [3H]arachidonic acid release from GH3 cells, a clonal strain from rat anterior pituitary. These findings suggest that the tyrosine phosphorylation pathway regulates arachidonic acid release by phospholipase A2 and prostaglandin F(2alpha) formation in neuronal cells.
We have recently shown that malignant tumours from the ovary and uterus expressed erythropoietin (Epo) and its receptor (EpoR), and that deprivation of Epo signal in tumour blocks induced death of malignant cells and capillary endothelial cells in vitro (Yasuda et al, submitted). These in vitro results prompted us to examine the effect of Epo-signal withdrawal on tumours in vivo. RT-PCR analysis demonstrated the expression of mRNAs for Epo and EpoR in the transplants of uterine and ovarian tumours in nude mice. Then we injected locally anti-Epo antibody or soluble form of EpoR into the transplants. At 12 h, 1, 7 or 14 days after the injection, all transplants were resected and examined macro- and microscopically. Tumour size was reduced in Epo signal-deprived transplants. Immunohistochemical examinations revealed destruction of Epo-responding malignant and capillary endothelial cells through apoptotic death. The degree of tumour regression correlated well with the dose and frequency of the injections. Control xenografts with saline injection or needle insertion showed well-developed tumour masses. This Epo response pathway will have profound implications for our understanding of the development and progression of malignant tumours and for the use of Epo-signal deprivation as an effective therapy.
The role of protein kinase C (PKC) and transforming growth factor (TGF)-beta in the proliferation of vascular smooth muscle cells (SMCs) under a high glucose condition was investigated. [3H]-thymidine incorporation under 20 mM glucose was significantly accelerated compared with that under 5.5 mM glucose, and this increase was inhibited by an anti-TGF-beta antibody or a PKC-beta specific inhibitor, LY333531. The amount of active and total TGF-beta1 in the conditioned media did not differ between 5.5 and 20 mM glucose. However, the expression of TGF-beta receptor type II under 20 mM glucose was significantly increased, but that of the TGF-beta receptor type I was not. This increased expression of the TGF-beta receptor type II was prevented by LY333531. These observations suggest that the increased expression of the TGF-beta receptor type II via PKC-beta plays an important role in the accelerated proliferation of SMCs under a high glucose condition, leading to the development of diabetic macroangiopathy.
Recombinant cholera toxin B subunit (rCTB) produced by Bacillus brevis carrying pNU212-CTB has been previously found to be a potent mucosal adjuvant to aluminium-non-adsorbed tetanus toxoid (nTT) and diphtheria toxoid (nDT) co-administered intranasally, and the possibility of needle-free inoculation of these vaccines with rCTB has been suggested. In this paper we examined the potentiality of rCTB as a mucosal adjuvant to aluminium-non-adsorbed yeast-derived recombinant hepatitis B surface antigen (rHBs) being a particulate antigen when administered intranasally with rCTB. In-house ELISA showed that a mixture of rHBs (1 or 5 microg) and rCTB (10 microg) elevated not only systemic responses but also mucosal immune responses at the nasal cavity, the lung, the saliva, the small intestine and the vagina against rHBs, and these could be further increased with higher doses of antigen. With antibody isotypes of IgG, there were equally high levels of serum HBs-specific IgG1, IgG2a and IgG2b antibodies and induction of mixed Th1- and Th2-type responses was considered to occur in combination of rHBs and rCTB. Serum anti-HBs titres in almost all mice obtained from sandwich EIA using a commercial kit were higher than 1000 milli-international units ml(-1) (mIU ml(-1)). These results show that rCTB is also very effective as a mucosal adjuvant for a particulate antigen like rHBs, as well as soluble antigens like nTT and nDT reported previously, suggesting the possibility of intranasal immunization with rHBs plus rCTB in humans.