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A 73-year-old man, receiving maintenance continuous ambulatory peritoneal dialysis(CAPD)was admitted to our hospital for chief complaining of heartburn. Gastrointestinal endoscopy disclosed 0- II a on the greater curvature of the upper gastric body. On further examination, the clinical diagnosis was defined as gastric cancer and c-stage I A(cT1aN0M0). The patient was recovered with conservative treatment from the perforated peritonitis after undergoing endoscopic submucosal dissection(ESD). Pathology revealed pT1b, INF b, UL(-), ly2, v0, pHM0, pVM0, for which he underwent total gastrectomy after changed to temporary hemodialysis(HD). On the 3rd postoperative day, blood examination showed WBC and CRP value of 16,100/mL and 20.282mg/dL, respectively. On the 6th postoperative day, nasal endoscopy revealed no anastomotic leakage and started oral take. The patient was discharged on the 20th postoperative day with changed to CAPD from the 7th postoperative day.

Background: Several catheter placement procedures have been described for initiation of peritoneal dialysis, including percutaneous insertion, open surgery, and laparoscopic surgery. However, the optimal approach to catheter placement for peritoneal dialysis remains controversial, because each procedure has specific advantages and disadvantages., Patients and Methods: From June 2010 to October 2014, we performed a nephroscope-assisted "pulling-thread" technique for placement of peritoneal dialysis catheters in 46 patients with end-stage renal disease at our medical center. We retrospectively reviewed the operation-related data, early catheter-related complications during the first month after placement, and longterm technical catheter survival., Results: Catheters in all 46 patients were placed precisely in a single step during surgery. The mean operative time was 63.0±18.2 minutes, and no intra-operative complications occurred in any patient. Early catheter-related complications included only exit-site infection (n=2; 4.3%) and catheter obstruction (n=2; 4.3%). There was a mean follow-up period of 18.3±12.7 months. The probability of catheter survival at 1 year was 97.1% and at 2 years was 80.1%., Conclusion: Our technique has the advantages of simplicity, safety, minimal equipment, low early catheter- related complication rate, and favorable long-term catheter outcome, making it ideal for patients with end-stage renal disease.

High-molecular-weight kininogen (HMWK) deficiency is a very rare hereditary disorder. We herein report a case of HMWK deficiency with splenic infarction. The HMWK activity of the proband was markedly decreased (0.9%). Direct sequencing of his HMWK gene showed a homozygous "TC" insertion at c523-524 in exon 4. This insertion led to an amino acid substitution, Ser175Ser, resulting in a frameshift mutation and a premature stop codon in amino acid 183. Furthermore, the HMWK activity was also reduced in the patient's three children, who exhibited the heterozygous "TC" insertion at c523-524 in exon 4. This is the first report of this gene alteration in a patient with HMWK deficiency.

Purpose: The anti-aquaporin-4 (AQP4) antibody was recently reported to be associated with neuromyelitis optica (NMO). Optic nerve involvements in many NMO cases are bilateral and the prognosis is poor. However, it has been suggested that plasma exchange is effective for those patients when steroid pulse therapy is ineffective. Herein, we report successful treatment of a patient with NMO using double-filtration plasmapheresis (DFPP)., Case: A 22-year-old woman consulted a neurologist for neck pain in March 2008. High-intensity lesions were shown in the cervical spinal cord by T2-weighted magnetic resonance imaging. On July 15, the patient was referred to our department for a headache and pain and blurred vision in the left eye. The best-corrected visual acuity was 20/50 and 20/500 in the right and left eyes, respectively, with visual field defects observed in both. After 3 courses of steroid pulse therapy, anti-AQP4 antibodies were positive. In November, the patient again noticed visual acuity loss in the left eye and was treated by additional steroid pulse therapy, which was not effective. Next, she underwent plasma exchange therapy, though it was stopped due to hypotension and dyspnea. The next day, the patient underwent DFPP treatment and visual function gradually recovered., Conclusion: It is important to consider NMO when steroid pulse therapy is not effective. We successfully and safely treated NMO in a young adult patient using DFPP.

Squamous cell carcinoma antigen (SCCA) is a diagnostic tumor marker for the advanced uterine, cervix and lung tumor. Although SCCA is a prognostic indicator for some tumors, recent progress of this marker has shown that the SCCA could also be found in the serum of nonmalignant disease such as renal failure and others. Here, we report a case of spuriously high level of SCCA in patient without carcinoma, renal failure, head-and-neck disease and lung disease. An early fifties female who had been undergone the diagnostic conization for high-grade cervical intraepithelial neoplasia ten years ago and observed without special treatment with around 20ng/ml level of SCCA. She has no signs of tumor, renal failure, head-and-neck disease or lung disease until now. The high performance liquid chromatography with Superdex 200 showed the molecular weight of the major part of SCCA of the patient is more than 160 kDa and the part of 45 kDa, the same molecular weight as lung tumor, is trace amount. Moreover, the ultrafiltration analysis showed the SCCA of the present case did not penetrate the 100 kDa cut-filter, but SCCAs with other patients with uterine, cervix, lung tumor and renal failure did penetrate the filter. In this case, the analysis of molecular weight of SCCA using HPLC gel filtration and ultrafiltration is useful to rule out spuriously elevated SCCA.

Lipid-lowering therapy with a statin not only powerfully lowers cholesterol but also exerts anti-inflammatory effects by decreasing serum C-reactive protein (CRP). Since an angiotensin II, type-1 receptor antagonist (ARB) also decreases CRP levels, the add-on effect of statins on CRP may be worth exploring. We determined the effect of pitavastatin on serum levels of highly sensitive CRP (hs-CRP) in 30 patients with hypercholesterolemia undergoing treatment with anti-hypertensive medication including ARBs. Pitavastatin, 2 mg daily, was given. The control group consisted of hypertensive patients without hyperlipidemia. The low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hs-CRP were measured at baseline, 1, 3, 6, and 12 months after treatment. For the atherosclerotic index, LDL-C/HDL-C ratios at 12 months were calculated. The LDL-C level was markedly reduced at 1 month and thereafter. The baseline level of hs-CRP in the hyperlipidemia group was significantly higher than that in the control group (1.647 ± 0.210 mg/L vs. 0.666 ± 0.097 mg/L p < 0.0001). After 3 months, the percentage of reduction of hs-CRP was significantly higher than that in the control group. The absolute values of hs-CRP were significantly decreased to a level similar to the control group, and the hs-CRP in both groups was remained at the same level for 12 months. Although the LDL-C/HDL-C ratios of the pitavastatin group was significantly reduced from 3.3 to 1.8, those of the control group were not changed. In conclusion, pitavastatin was found to have powerful anti-inflammatory, add-on effects over the similar effects of ARB as assessed by hs-CRP.

We have reported in this journal in vitro susceptibilities of clinical isolates to antibiotics every year since 1992. In this paper, we report the results of an analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers in Japan to selected antibiotics in 2007 compared with the results from previous years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to macrolides has been increasing every year and this was especially clear this year. Most strains of Enterobacteriaceae except for Escherichia coli showed a high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs and the resistance increased further this year. FQs resistance of methicillin-resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S. aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant coagulase negative Staphylococci (MRCNS) was higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of Enterococcusfaecium was more than 85% except for STFX (58.3%). In clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs resistance was 21-27%, which was higher than that of P. aeruginosa from respiratory tract infections at 13-21%, which was the same trend as in past years. Multidrug resistant strains accounted for 5.6% in the urinary tract and 1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to FQs. The carbapenem resistant strains, which present a problem at present, accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86-88% to FQs. The results of the present survey indicated that although methicillin-resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae showed resistance tendencies, and other species maintained high susceptibility rates more than 90% against FQs, which have been used clinically for over 15 years.

Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express FcgammaRIIIa (CD16) identical to that in NK cells, but with a cell type-specific glycosylation, and these soluble forms (sFcgammaRIIIa) are present in plasma. We measured sFcgammaRIIIa(Mphi) derived from macrophages in plasma from subjects undergoing an annual medical checkup. The levels of sFcgammaRIIIa(Mphi) increased with age, and correlated positively with body mass index, blood pressure, LDL cholesterol to HDL cholesterol ratio, triglycerides, hemoglobin A1c, and creatinine, but negatively with HDL-cholesterol levels. The sFcgammaRIIIa(Mphi) levels were related to the number of risk factors for atherosclerosis: such as aging, current smoking, diabetes, hypertension, hyper-LDL-cholesterolemia, hypo-HDL-cholesterolemia, and family history of atherosclerotic diseases. In addition, the sFcgammaRIIIa(Mphi) levels were correlated with carotid maximum intima-media thickness (IMT). These findings indicate the macrophages are activated during the incipient stage of atherosclerosis, and suggest sFcgammaRIIIa(Mphi) may be used as a predictive marker for atherosclerosis.

Patients with dysfibrinogenemia demonstrate a low concentration of plasma fibrinogen. However, many cases remain a symptomatic and are incidentally identified on a pre-operative or screening test for pregnancy. Therefore, urgent diagnosis is desirable. To diagnose this abnormality, it is important to demonstrate a discrepancy between test results by the Clauss and immunologic methods. We use a single radial immunodiffusion (SRID) method to measure the fibrinogen level immunologically. We present one dysfibrinogenemia case diagnosed by SRID. The present case was 23 year-old pregnant female. She demonstrated a low plasma level of fibrinogen (91 mg/dl by the Clauss method) on a pre-delivery-screening test in the 39th week of pregnancy. We suspected dysfibrinogenemia, and measured the fibrinogen level immunologically with SRID. Briefly, we dissolved agar in 10% PBS solution and added 1 mg/ml anti-fibrinogen antibody. Then, patient plasma and 50-200 mg/dl of control plasma were placed on the agar overnight. The immunoreactive fibrinogen level in this patient was 400 mg/dl. Therefore, we diagnosed her as dysfibrinogenemia. She did not have a bleeding episode during the normal vaginal delivery even through fibrinogen was not transfused. The SRID method is readily available, and requires only an anti-fibrinogen antibody and agar, both of which are usually stocked by a general laboratory. The practical method and application described in this report provide instructive information for hospital laboratories.

A 42-year-old male dialysis patient was infected with hepatitis C virus (HCV), and treated with interferon beta (IFN-beta) for a rapid increase in viral load. After dialysis three times a week, 3 million units of IFN-beta were intravenously infused for 1 h. The treatment was markedly effective, and the virus was eliminated in the sixth week. Therapy was continued for 24 weeks, and HCV negativity has been maintained for more than 6 months after the completion of administration. The blood IFN level slowly decreased immediately after administration. The mean trough level was 37 U/mL, and the half-life was 65 min. No adverse event requiring discontinuation of the treatment occurred, showing that IFN alone may safely eliminate the virus in dialysis patients with high hepatitis C viral load. Many dialysis patients are latently infected with HCV, and the infection affects the prognosis. Therefore, establishment of a therapeutic method is urgently needed.

Marinobufagenin and telecinobufagin have been identified as digitalis-like factors in mammals. In toads, marinobufagenin-related compounds, such as marinobufotoxin (MBT), have been isolated in some tissues but not in mammals, and its biological action has not been elucidated. Herein, we aimed to explore the possible production and/or secretion of MBT and the biological action in rats. First, the MBT in culture supernatant of the adrenocortical-originated cell line Y-1 was analyzed by high-performance liquid chromatography and sensitive ELISA for marinobufagenin-like immunoreactivity. Moreover, the structural information was obtained by mass spectrometry. To determine the biological action, MBT (9.6 and 0.96 microg/kg per day) was intraperitoneally infused via an osmotic minipump for 1 week. Blood pressure and renal excretion of marinobufagenin-like immunoreactivity were measured. Marinobufagenin-like immunoreactivity was found in Y-1 cell culture media, and the concentration increased until 24 hours. The structural analysis suggested that marinobufagenin-like immunoreactivities were marinobufagenin and MBT, and tandem mass spectrum analysis revealed them with the specific daughter ions. The highest sensitive ELISA-positive peak of marinobufagenin-like immunoreactivity in the media was MBT. Continuous administration of MBT in rats for 1 week significantly increased systolic blood pressure and renal excretion of marinobufagenin-like immunoreactivity compared with control rats (135+/-3.0 versus 126+/-2.0 mm Hg and 1.41+/-0.286 versus 0.34+/-0.064 ng/day, respectively). These data suggest that MBT, arginine-suberoyl ester of marinobufagenin, can be a novel digitalis-like factor with hypertensive action and is secreted from the adrenocortical cells.

This study was performed in order to evaluate the angiogenic effect of implantation of either peripheral blood mononuclear cells (PBMNCs) or bone marrow mononuclear cells (BMMNCs) on diabetic peripheral neuropathy. Streptozotocin (50 mg/kg) was injected intravenously into 6-week-old male Lewis rats. Four weeks after the induction of diabetes, 6 x 10(7) of PBMNCs or 1 x 10(8) of BMMNCs were implanted into the left hindlimb muscle. Motor nerve conduction velocity (MNCV) was monitored before and after implantation. At the end of the experiment, bilateral nerve blood flow (NBF) was measured by laser Doppler and the number of vessels in the sciatic nerves quantified by Factor VIII staining of the sections. Diabetes resulted in an approximately 20% reduction (P < 0.01) in sciatic MNCV. Four weeks after implantation, MNCV was improved by 54% with PBMNCs and by 67% with BMMNCs (both P < 0.01). Moreover, the effects of implantation were almost abolished by administration of VEGF-neutralizing antibody. Sciatic NBF was reduced by approximately 50% by diabetes (P < 0.05). This reduction in perfusion was improved by 74% by implantation of PBMNCs and by 62% by implantation of BMMNCs (P < 0.05 and P < 0.01, respectively). These effects were observed only in the implanted limb. Immunohistochemical staining of sciatic nerve sections for Factor VIII showed no significant increase in the number of vessels in the sciatic nerve following implantation of either PBMNCs or BMMNCs. These data suggest that implantation of hematopoietic mononuclear cell fractions is associated with an improvement in MNCV as a result of arteriogenic effects in the sciatic nerve, and that VEGF may contribute to this effect. This improvement occurred in the absence of angiogenesis. Implantation of these cell fractions may therefore be a potential new therapeutic method for treating diabetic peripheral neuropathy.

An 84-year-old woman undergoing maintenance hemodialysis presented with chest discomfort lasting several days and electrocardiographic abnormalities. She had stopped smoking 2 weeks earlier and was experiencing irritability. Upon admission, electrocardiography showed ST-segment elevation in leads I, II, aVF, and V2-6 and an abnormal Q wave in leads II, III, and aVF. Ultrasound cardiography showed left ventricular anteroapical akinesia and basal hyperkinesia. The chest discomfort disappeared without specific therapy. During hospital days 1-5, the ST-segment elevation gradually improved. Giant negative T waves then developed. The left ventricular asynergy resolved by day 8. Radionuclide imaging with iodine-123-beta-methyl-p-iodophenyl pentadecanoic acid, but not with technetium-99 m-sestamibi, showed an apical defect. Elective coronary angiography showed no stenosis. 'Takotsubo' cardiomyopathy was diagnosed. After discharge, the patient continued regular dialysis without cardiac symptoms. We concluded that endogenously activated sympathetic nerve action in hemodialysis patients, especially those under emotional or physical stress, might be a causative factor for Takotsubo cardiomyopathy.

Objective: Ultrasound (US)-mediated destruction of contrast microbubbles causes capillary rupturing that stimulates arteriogenesis, whereas intramuscular implantation (im) of bone marrow mononuclear cells (BM-MNCs) induces angiogenesis. We therefore studied whether US-targeted microbubble destruction combined with transplantation of BM-MNCs can enhance blood flow restoration by stimulating both angiogenesis and arteriogenesis., Methods and Results: US-mediated destruction of phospholipid-coated microbubbles was applied onto ischemic hindlimb muscle and subsequently BM-MNCs were transfused. A significant enhancement in blood flow recovery after Bubble+US+BM-MNC infusion (34% increase, P<0.05) was observed compared with Bubble+US (25%). The ratio of capillary/muscle fiber increased by Bubble+US+BM-MNC-i.v (260%, P<0.01) than that in the Bubble+US group (172%), into which BM-MNCs were incorporated (angiogenesis). Smooth muscle alpha-actin-positive arterioles were also increased, and angiography showed augmented collateral vessel formation (arteriogenesis). Platelet-derived proinflammatory factors activated by Bubble+US induces the expression of adhesion molecules (P-selectin and ICAM-1), leading to the attachment of transplanted BM-MNCs on the endothelium. Flow assay confirmed that the platelet-derived factors cause the adhesion of BM-MNCs onto endothelium under laminar flow., Conclusions: This study demonstrates that the targeted delivery of BM-MNCs by US destruction of microbubbles enhances regional angiogenesis and arteriogenesis response, in which the release of platelet-derived proinflammatory factors activated by Bubble+US play a key role in the attachment of transplanted BM-MNCs onto the endothelial layer.

Myocardial fibrosis commonly occurs in patients with end-stage renal disease (ESRD) and has proven to be an important predictor for cardiovascular events. In experimental settings, angiotensin II type 1 receptor (AT1-R) antagonists have been shown to have anti-fibrotic effects on the myocardium independent of their antihypertensive effects. In this study, to investigate whether the AT1-R antagonist losartan would have such anti-fibrotic effects in patients, we administered losartan or, for purpose of comparison, the angiotensin-converting enzyme enalapril or Ca2+-antagonist amlodipine to patients with ESRD. Thirty-nine ESRD patients with hypertension were randomly assigned to receive losartan (n=13), enalapril (n=13), or amlodipine (n=13). Ultrasonic integrated backscatter (IBS) and serological markers of collagen type I synthesis and degradation were used to assess the degree of myocardial fibrosis just before and after 6 months of treatment. There were no significant differences in antihypertensive effects among the three agents. In the enalapril- and amlodipine-treated groups, the mean calibrated IBS values increased significantly after 6 months of treatment (enalapril: -31.6 +/- 1.3 to -29.4 +/- 1.2 dB, p=0.011; amlodipine: -30.6 +/- 1.4 to -27.2 +/- 1.2 dB, p=0.012). However, the mean calibrated IBS values in the losartan-treated group did not increase after 6 months of treatment (-31.2 +/- 1.7 to -31.3 +/- 1.4 dB, p=0.88). The ratio of the serum concentration of procollagen type I carboxy-terminal peptide to the serum concentration of collagen type I pyridinoline cross-linked carboxy-terminal telopeptide was significantly reduced in the losartan-treated group (42.6 +/- 4.6 to 34.4 +/- 3.6, p=0.038). The present study indicates that losartan more effectively suppresses myocardial fibrosis in patients with ESRD than does enalapril or amlodipine despite a comparable antihypertensive effect among the three drugs.

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Background and Objectives: There are several potential endogenous digitalis-like factors (EDLF) in mammalian body fluids, and marinobufagenin (MBG) may be the most potent EDLF. Improved assays are needed to confirm the potency of these metabolites. In the present study, we have identified MBG and telocinobufagin (TCB) in human plasma by high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR)., Methods and Results: The high-resolution MS analysis revealed the molecular masses of TCB and MBG to be the same as their respective theoretical values. Using a tandem mass spectrometer, the mass-charge ratio for TCB was determined to be 403.2 for the parent ion and 349.2 for the daughter ion. The mass-charge ratio for MBG was m/z 383.2 and m/z 401.2. The NMR study revealed that the signals for MBG and TCB were the same as those obtained by MS analysis. In human blood, MBG and TCB were also identified by liquid chromatography (LC) as well as MS. In the LC/MS assay, proscillaridin A was used as an internal standard. The plasma was pretreated with Sep-Pak C18, and then 50 microL was applied to the C8 high-performance liquid chromatography (HPLC) column. The mean plasma concentration of MBG in healthy volunteers (0.94 +/- 0.28 ng/mL) was significantly lower than that in patients undergoing regular hemodialysis (3.81 +/- 1.92 ng/mL). The concentration of TCB in the healthy volunteers (1.80 +/- 0.55 ng/mL) was also significantly lower than that in patients with terminal renal failure (6.86 +/- 4.30 ng/mL)., Conclusion: These results indicate that the major EDLF is TCB because its plasma concentration is the highest among the reported endogenous digitalis candidates.

Background: We evaluated usefulness of the postexercise systolic blood pressure (SBP) response for detecting coronary artery disease (CAD) in hemodialysis patients., Methods: A treadmill exercise testing was done, and the SBP response was measured in 44 hemodialysis patients (30 men, 14 women; age 41 to 81 years). The postexercise SBP response was defined as the ratio of SBP after 3 minutes of recovery to SBP at peak exercise., Results: The SBP ratio of the 25 subjects with coronary artery stenosis (1.01+/- 0.13) was significantly greater (p<0.01) than 19 subjects without coronary artery stenosis (0.83+/- 0.10). An SBP ratio greater than 0.92 identified CAD with higher sensitivity, specificity, and accuracy than did the conventional ST-segment depression criterion (76 vs. 56%, 90 vs. 53%, and 82 vs. 55%, respectively)., Conclusion: Determination of the SBP ratio is a clinically useful, noninvasive method for accurately detecting CAD in hemodialysis patients., (Copyright (c) 2005 S. Karger AG, Basel.)

S100A12, also called EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) or calcium-binding protein in amniotic fluid-1, is a ligand for RAGE. It has been shown that S100A12 induces adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in the vascular endothelial cell and mediates migration and activation of monocytes/macrophages through RAGE binding and that infusion of lipopolysaccharide into mice causes time-dependent increase of S100A12 in the plasma. Therefore, circulating S100A12 protein may be involved in chronic inflammation in the atherosclerotic lesion. In this study, we developed an ELISA system that uses specific monoclonal antibodies against recombinant human S100A12 to measure plasma S100A12 levels in patients with diabetes. On using our S100A12 ELISA system, the coefficients of variation of intra- and interassay were less than 4 and 9%, respectively. The analytical lower detection limit was 0.2 ng/ml. When plasma S100A12 levels were measured by this system, the concentrations were more than twice as high in the patients with diabetes, compared with those without. Using univariate analysis in all subjects, plasma S100A12 concentrations correlated with hemoglobin A1c, fasting glucose, high-sensitivity C-reactive protein and white blood cell count. Stepwise multiple regression analyses, however, revealed that only white blood cell count and hemoglobin A1c remained significant independent determinants of plasma S100A12 concentration. These results suggest that plasma S100A12 protein levels are regulated by factors related to subclinical inflammation and glucose control in patients with type 2 diabetes.

Various etiologic factors have been identified in tubulointerstitial nephritis (TIN), including allergic drug reaction, infection, and immune-mediated disease. Immune-mediated TIN without significant glomerular involvement has been reported to occur as a renal complication secondary to Sjögren's syndrome, lupus nephritis, and antitubular basement membrane antibody-related disease. We present a first case of acute TIN associated with autoimmune-related pancreatitis (AIP). A 64-year-old man was referred to our division from a surgeon for the close examination of renal dysfunction. The pancreatic and biliary imaging showed segmental narrowing of the pancreatic duct with localized swelling of the pancreatic head, suggesting the carcinoma of the pancreatic head at that time. However, the laboratory findings also showed renal dysfunction with high level of serum immunoglobulin G and hypocomplementemia. Renal biopsy was performed to investigate the etiology of the renal dysfunction. The renal biopsy specimen showed acute TIN. The patient had no drug history, which may cause TIN. Oral corticosteroid therapy improved the renal function as well as histological damage, the pancreatic imaging study, and the laboratory tests of pancreatic and hepatobiliary enzyme. Although the pancreatic biopsy has not performed in our patient, his clinical course confirmed us that AIP was the final diagnosis for his pancreatic lesion. Despite further examination, there was no evidence of other autoimmune-related diseases such as Sjögren's syndrome. To our knowledge, this is the first report of acute TIN associated with AIP. We suggest that AIP may be an etiologic factor in some cases of TIN.

EN-RAGE is a ligand for the receptor for advanced glycation end products (RAGE) and may be involved in the development of diabetic macro- and micro-angiopathy. This study is designed to investigate the regulation of EN-RAGE gene expression in human macrophages. The amounts of EN-RAGE mRNA were measured in cultured human THP-1 macrophages after treatment with various stimuli known to modulate atherosclerosis. First, interleukin-6 (IL-6), a proinflammatory cytokine, increased the level of EN-RAGE mRNA by approximately 2-fold in a time- and a dose-dependent fashion. EN-RAGE protein was detected in the cultured medium and increased significantly by the addition of IL-6. The induction was abolished by pretreatment with the JAK kinase inhibitor and cycloheximide, but not with the MEK kinase inhibitor. Second, pioglitazone (PIO), a thiazolidinedione, decreased the level of EN-RAGE mRNA by approximately 25% of the basal in a time- and a dose-dependent fashion. Pioglitazone also inhibited the induction of EN-RAGE mRNA by IL-6. These results indicate the production of EN-RAGE is induced by IL-6 through de novo protein synthesis via the JAK-STAT kinase pathway and inhibited by the activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) in human macrophages., (Copyright 2003 Elsevier Ireland Ltd.)

Fibrosis of left ventricle commonly occurs in end stage renal disease(ESRD) patients and is an independent risk factor of cardiovascular events. Angiotensin II type 1 receptor antagonist may be able to reverse fibrosis of left ventricle in ESRD patients. Ultrasonography-integrated backscatter(IBS) of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. In this study, 30 chronically hemodialyzed patients with hypertension were randomly allocated to receive antihypertensive therapy with either angiotensin II type 1 receptor(AT1-R) antagonist losartan(n = 10), angiotensin-converting enzyme(ACE) inhibitor enalapril(n = 10) or calcium antagonist amlodipine(n = 10). IBS of posterior wall of left ventricule were measured by IBS before and after 6 months treatment. Baseline demographic and clinical characteristics did not differ in three subgroups. Although losartan(34.2 +/- 1.8 to 30.2 +/- 2.4 dB: p = 0.0094) treatment demonstrated significant reduce of IBS values, enalapril(30.3 +/- 1.5 to 31.7 +/- 1.4 dB: p = 0.3268) and amlodipine (31.6 +/- 1.6 to 33.1 +/- 1.9 dB: p = 0.4632) did not changed it significantly before and after 6 months treatment. All three groups reduced left ventricular mass index(Losartan 154.5 +/- 9.9 to 114.6 +/- 5.8 g/m2: p = 0.0002) (enalapril 155.6 +/- 14.3 to 135.3 +/- 10.4 g/m2: p = 0.0275) (amlodipine 156.6 +/- 7.3 to 137.2 +/- 4.1 g/m2: p = 0.0589). Three groups manifested a similar significant decrease in the mean blood pressure. Plasma angiotensin II concentration was markedly increased by 5.0-fold relative to the control levels before treatment in Losartan treatment, in contrast unchanged in enalapril and only 2.0-fold increased in amlodipine treatment. This study indicates that losartan reduce of fibrosis of left ventricule and this effect may be via an anti-AT1-R effect.

Background: Preclinical studies have established that implantation of bone marrow-mononuclear cells, including endothelial progenitor cells, into ischaemic limbs increases collateral vessel formation. We investigated efficacy and safety of autologous implantation of bone marrow-mononuclear cells in patients with ischaemic limbs because of peripheral arterial disease., Methods: We first did a pilot study, in which 25 patients (group A) with unilateral ischaemia of the leg were injected with bone marrow-mononuclear cells into the gastrocnemius of the ischaemic limb and with saline into the less ischaemic limb. We then recruited 22 patients (group B) with bilateral leg ischaemia, who were randomly injected with bone marrow-mononuclear cells in one leg and peripheral blood-mononuclear cells in the other as a control. Primary outcomes were safety and feasibility of treatment, based on ankle-brachial index (ABI) and rest pain, and analysis was per protocol., Findings: Two patients were excluded from group B after randomisation. At 4 weeks in group B patients, ABI was significantly improved in legs injected with bone marrow-mononuclear cells compared with those injected with peripheral blood-mononuclear cells (difference 0.09 [95% CI 0.06-0.11]; p<0.0001). Similar improvements were seen for transcutaneous oxygen pressure (13 [9-17]; p<0.0001), rest pain (-0.85 [-1.6 to -0.12]; p=0.025), and pain-free walking time (1.2 [0.7-1.7]; p=0.0001). These improvements were sustained at 24 weeks. Similar improvements were seen in group A patients. Two patients in group A died after myocardial infarction unrelated to treatment., Interpretation: Autologous implantation of bone marrow-mononuclear cells could be safe and effective for achievement of therapeutic angiogenesis, because of the natural ability of marrow cells to supply endothelial progenitor cells and to secrete various angiogenic factors or cytokines.

1. The effect of vasodilatory beta-adrenoceptor blockers on regional blood flow in the major organs of anaesthetized rats was investigated using radioactive microspheres. The administration of propranolol and saline was used as a control. 2. Intravenous injections of carvedilol (2 mg/rat), celiprolol (20 mg/rat) and bopindolol (1 mg/rat) equally decreased systemic blood pressure (SBP) by approximately 20 mmHg, whereas propranolol (1 mg/rat) decreased SBP only slightly but not significantly. 3. Heart rate was significantly decreased by carvedilol, celiprolol, bopindolol and propranolol. 4. Coronary blood flow was markedly increased by carvedilol, but not by the other three drugs. 5. Cardiac output tended to decrease following the administration of all four drugs. 6. Total peripheral vascular resistance was not significantly affected by carvedilol, celiprolol and bopindolol, but was markedly increased following propranolol. 7. Renal blood flow was markedly increased by carvedilol. 8. Blood flow in the brown fat was markedly increased by carvedilol and bopindolol, but not by celiprolol and propranolol. 9. These findings indicate that the newer vasodilatory beta-blockers, such as carvedilol and bopindolol, have a beneficial effect on the regional circulation in contrast with the classical beta-blocker propranolol. 10. The regional haemodynamic effects observed in the present study following intravenous injection of the beta-blockers may help explain the clinical experience that vasodilatory beta-blockers increase insulin sensitivity and decrease mortality in patients with congestive heart failure.

Left ventricular hypertrophy (LVH) commonly occurs in patients with end-stage renal disease (ESRD) and is an independent risk factor for cardiovascular events. Angiotensin II type 1 receptor (AT1-R) antagonists may be able to reverse LVH independent to the hypotensive effect in the ESRD setting. Thirty chronically hemodialyzed uremic patients with hypertension were randomly assigned to receive the AT1-R antagonist losartan (n = 10), the angiotensin-converting enzyme (ACD) inhibitor enalapril (n = 10), or calcium antagonist amlodipine (n = 10). Left ventricular mass (LVM) index was measured by echocardiography before and 6 months after treatment. The baseline demographic and clinical characteristics did not differ between the three groups. The mean baseline LVM index also did not differ in the three groups. After 6 months of treatment, losartan treatment significantly reduced the LVM index (-24.7 +/- 3.2%) than amlodipine (-10.5 +/- 5.2%) or enalapril (-11.2 +/- 4.1%) therapy. All three groups had a similar decrease in the mean blood pressure with treatment. The plasma angiotensin II concentration increased 5-fold with losartan treatment. In contrast, the plasma angiotension II concentration did not change with enalapril and only increased 2-fold with amlodipine. Thus, the present study indicates that losartan more effectively regresses LVH in patients with ESRD than do enalapril and amlodipine despite a comparable depressor effect between the three drugs., (Copyright 2002 S. Karger AG, Basel)